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1

Nuclear envelope protein MAN1 regulates clock through BMAL1  

PubMed Central

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

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

2014-01-01

2

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

SciTech Connect

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

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

2010-03-19

3

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

PubMed

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

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

2015-01-15

4

Glucagon-CREB/CRTC2 Signaling Cascade Regulates Hepatic BMAL1 Protein.  

PubMed

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

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

2015-01-23

5

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

E-print Network

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

Boyer, Edmond

6

Smooth-muscle BMAL1 participates in blood pressure circadian rhythm regulation.  

PubMed

As the central pacemaker, the suprachiasmatic nucleus (SCN) has long been considered the primary regulator of blood pressure circadian rhythm; however, this dogma has been challenged by the discovery that each of the clock genes present in the SCN is also expressed and functions in peripheral tissues. The involvement and contribution of these peripheral clock genes in the circadian rhythm of blood pressure remains uncertain. Here, we demonstrate that selective deletion of the circadian clock transcriptional activator aryl hydrocarbon receptor nuclear translocator-like (Bmal1) from smooth muscle, but not from cardiomyocytes, compromised blood pressure circadian rhythm and decreased blood pressure without affecting SCN-controlled locomotor activity in murine models. In mesenteric arteries, BMAL1 bound to the promoter of and activated the transcription of Rho-kinase 2 (Rock2), and Bmal1 deletion abolished the time-of-day variations in response to agonist-induced vasoconstriction, myosin phosphorylation, and ROCK2 activation. Together, these data indicate that peripheral inputs contribute to the daily control of vasoconstriction and blood pressure and suggest that clock gene expression outside of the SCN should be further evaluated to elucidate pathogenic mechanisms of diseases involving blood pressure circadian rhythm disruption. PMID:25485682

Xie, Zhongwen; Su, Wen; Liu, Shu; Zhao, Guogang; Esser, Karyn; Schroder, Elizabeth A; Lefta, Mellani; Stauss, Harald M; Guo, Zhenheng; Gong, Ming Cui

2014-12-01

7

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

SciTech Connect

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

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

2007-02-23

8

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

SciTech Connect

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.

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

2011-07-15

9

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

PubMed Central

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

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

2013-01-01

10

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

PubMed Central

Circadian timing is generated through a unique series of autoregulatory interactions termed the molecular clock. Behavioral rhythms subject to the molecular clock are well characterized. We demonstrate a role for Bmal1 and Clock in the regulation of glucose homeostasis. Inactivation of the known clock components Bmal1 (Mop3) and Clock suppress the diurnal variation in glucose and triglycerides. Gluconeogenesis is abolished by deletion of Bmal1 and is depressed in Clock mutants, but the counterregulatory response of corticosterone and glucagon to insulin-induced hypoglycaemia is retained. Furthermore, a high-fat diet modulates carbohydrate metabolism by amplifying circadian variation in glucose tolerance and insulin sensitivity, and mutation of Clock restores the chow-fed phenotype. Bmal1 and Clock, genes that function in the core molecular clock, exert profound control over recovery from insulin-induced hypoglycaemia. Furthermore, asynchronous dietary cues may modify glucose homeostasis via their interactions with peripheral molecular clocks. PMID:15523558

2004-01-01

11

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

PubMed Central

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

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

2014-01-01

12

BMAL1 controls the diurnal rhythm and set point for electrical seizure threshold in mice  

PubMed Central

The epilepsies are a heterogeneous group of neurological diseases defined by the occurrence of unprovoked seizures which, in many cases, are correlated with diurnal rhythms. In order to gain insight into the biological mechanisms controlling this phenomenon, we characterized time-of-day effects on electrical seizure threshold in mice. Male C57BL/6J wild-type mice were maintained on a 14/10 h light/dark cycle, from birth until 6 weeks of age for seizure testing. Seizure thresholds were measured using a step-wise paradigm involving a single daily electrical stimulus. Results showed that the current required to elicit both generalized and maximal seizures was significantly higher in mice tested during the dark phase of the diurnal cycle compared to mice tested during the light phase. This rhythm was absent in BMAL1 knockout (KO) mice. BMAL1 KO also exhibited significantly reduced seizure thresholds at all times tested, compared to C57BL/6J mice. Results document a significant influence of time-of-day on electrical seizure threshold in mice and suggest that this effect is under the control of genes that are known to regulate circadian behaviors. Furthermore, low seizure thresholds in BMAL1 KO mice suggest that BMAL1 itself is directly involved in controlling neuronal excitability. PMID:25018707

Gerstner, Jason R.; Smith, George G.; Lenz, Olivia; Perron, Isaac J.; Buono, Russell J.; Ferraro, Thomas N.

2014-01-01

13

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

PubMed Central

ID2 is a rhythmically expressed HLH transcriptional repressor. Deletion of Id2 in mice results in circadian phenotypes, highlighted by disrupted locomotor activity rhythms and an enhanced photoentrainment response. ID2 can suppress the transactivation potential of the positive elements of the clock, CLOCK-BMAL1, on mPer1 and clock-controlled gene (CCG) activity. Misregulation of CCGs is observed in Id2?/? liver, and mutant mice exhibit associated alterations in lipid homeostasis. These data suggest that ID2 contributes to both input and output components of the clock and that this may be via interaction with the bHLH clock proteins CLOCK and BMAL1. The aim of the present study was to explore this potential interaction. Coimmunoprecipitation analysis revealed the capability of ID2 to complex with both CLOCK and BMAL1, and mammalian two-hybrid analysis revealed direct interactions of ID2, ID1 and ID3 with CLOCK and BMAL1. Deletion of the ID2 HLH domain rendered ID2 ineffective at inhibiting CLOCK-BMAL1 transactivation, suggesting that interaction between the proteins is via the HLH region. Immunofluorescence analysis revealed overlapping localization of ID2 with CLOCK and BMAL1 in the cytoplasm. Overexpression of CLOCK and BMAL1 in the presence of ID2 resulted in a significant reduction in their nuclear localization, revealing that ID2 can sequester CLOCK and BMAL1 to the cytoplasm. Serum stimulation of Id2?/? mouse embryonic fibroblasts resulted in an enhanced induction of mPer1 expression. These data provide the basis for a molecular mechanism through which ID2 could regulate aspects of both clock input and output through a time-of-day specific interaction with CLOCK and BMAL1. PMID:20861012

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

2010-01-01

14

Genome-Wide Profiling of the Core Clock Protein BMAL1 Targets Reveals a Strict Relationship with Metabolism?  

PubMed Central

Circadian rhythms are common to most organisms and govern much of homeostasis and physiology. Since a significant fraction of the mammalian genome is controlled by the clock machinery, understanding the genome-wide signaling and epigenetic basis of circadian gene expression is essential. BMAL1 is a critical circadian transcription factor that regulates genes via E-box elements in their promoters. We used multiple high-throughput approaches, including chromatin immunoprecipitation-based systematic analyses and DNA microarrays combined with bioinformatics, to generate genome-wide profiles of BMAL1 target genes. We reveal that, in addition to E-boxes, the CCAATG element contributes to elicit robust circadian expression. BMAL1 occupancy is found in more than 150 sites, including all known clock genes. Importantly, a significant proportion of BMAL1 targets include genes that encode central regulators of metabolic processes. The database generated in this study constitutes a useful resource to decipher the network of circadian gene control and its intimate links with several fundamental physiological functions. PMID:20937769

Hatanaka, Fumiyuki; Matsubara, Chiaki; Myung, Jihwan; Yoritaka, Takashi; Kamimura, Naoko; Tsutsumi, Shuichi; Kanai, Akinori; Suzuki, Yutaka; Sassone-Corsi, Paolo; Aburatani, Hiroyuki; Sugano, Sumio; Takumi, Toru

2010-01-01

15

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

PubMed Central

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

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

2014-01-01

16

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

PubMed Central

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

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

2011-01-01

17

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

PubMed

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

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

2014-09-12

18

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

PubMed Central

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

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

2014-01-01

19

Generation of myometrium-specific Bmal1 knockout mice for parturition analysis.  

PubMed

Human and rodent studies indicate a role for circadian rhythmicity and associated clock gene expression in supporting normal parturition. The importance of clock gene expression in tissues besides the suprachiasmatic nucleus is emerging. Here, a Bmal1 conditional knockout mouse line and a novel Cre transgenic mouse line were used to examine the role of myometrial Bmal1 in parturition. Ninety-two percent (22/24) of control females but only 64% (14/22) of females with disrupted myometrial Bmal1 completed parturition during the expected time window of 5p.m. on Day 19 through to 9a.m. on Day 19.5 of gestation. However, neither serum progesterone levels nor uterine transcript expression of the contractile-associated proteins Connexin43 and Oxytocin receptor differed between females with disrupted myometrial Bmal1 and controls during late gestation. The data indicate a role for myometrial Bmal1 in maintaining normal time of day of parturition. PMID:22697126

Ratajczak, Christine K; Asada, Minoru; Allen, Gregg C; McMahon, Douglas G; Muglia, Lisa M; Smith, Donté; Bhattacharyya, Sandip; Muglia, Louis J

2012-01-01

20

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

PubMed Central

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

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

2014-01-01

21

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

PubMed

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

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

2013-06-01

22

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

PubMed Central

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

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

2013-01-01

23

Circadian sensitivity to the chemotherapeutic agent cyclophosphamide depends on the functional status of the CLOCK/BMAL1 transactivation complex.  

PubMed

The circadian clock controls many aspects of mammalian physiology, including responses to cancer therapy. We find that wild-type and circadian mutant mice demonstrate striking differences in their response to the anticancer drug cyclophosphamide (CY). While the sensitivity of wild-type mice varies greatly, depending on the time of drug administration, Clock mutant and Bmal1 knockout mice are highly sensitive to treatment at all times tested. On the contrary, mice with loss-of-function mutations in Cryptochrome (Cry1-/-Cry2-/- double knockouts) were more resistant to CY compared with their wild-type littermates. Thus, both time-of-day and allelic-dependent variations in response to chemotherapy correlate with the functional status of the circadian CLOCK/BMAL1 transactivation complex. Pharmacokinetic analysis of plasma concentration of different CY metabolites shows that, in contrast to the traditional view, circadian variations in drug sensitivity cannot be attributed to the changes in the rates of CY metabolic activation and/or detoxification. At the same time, mice of different circadian genotypes demonstrate significant differences in B cell responses to toxic CY metabolites: B cell survival/recovery rate was directly correlated with the in vivo drug sensitivity. Based on these results, we propose that the CLOCK/BMAL1 transcriptional complex affects the lethality of chemotherapeutic agents by modulating the survival of the target cells necessary for the viability of the organism. PMID:15689397

Gorbacheva, Victoria Y; Kondratov, Roman V; Zhang, Renliang; Cherukuri, Srujana; Gudkov, Andrei V; Takahashi, Joseph S; Antoch, Marina P

2005-03-01

24

From The Cover: Circadian sensitivity to the chemotherapeutic agent cyclophosphamide depends on the functional status of the CLOCK\\/BMAL1 transactivation complex  

Microsoft Academic Search

The circadian clock controls many aspects of mammalian physiology, including responses to cancer therapy. We find that wild-type and circadian mutant mice demonstrate striking differences in their response to the anticancer drug cyclophosphamide (CY). While the sensitivity of wild-type mice varies greatly, depending on the time of drug administration, Clock mutant and Bmal1 knockout mice are highly sensitive to treatment

Victoria Y. Gorbacheva; Roman V. Kondratov; Renliang Zhang; Srujana Cherukuri; Andrei V. Gudkov; Joseph S. Takahashi; Marina P. Antoch

2005-01-01

25

Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration  

PubMed Central

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

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

2013-01-01

26

The Zebrafish Period2 Protein Positively Regulates the Circadian Clock through Mediation of Retinoic Acid Receptor (RAR)-related Orphan Receptor ? (Ror?).  

PubMed

We report the characterization of a null mutant for zebrafish circadian clock gene period2 (per2) generated by transcription activator-like effector nuclease and a positive role of PER2 in vertebrate circadian regulation. Locomotor experiments showed that per2 mutant zebrafish display reduced activities under light-dark and 2-h phase delay under constant darkness, and quantitative real time PCR analyses showed up-regulation of cry1aa, cry1ba, cry1bb, and aanat2 but down-regulation of per1b, per3, and bmal1b in per2 mutant zebrafish, suggesting that Per2 is essential for the zebrafish circadian clock. Luciferase reporter assays demonstrated that Per2 represses aanat2 expression through E-box and enhances bmal1b expression through the Ror/Rev-erb response element, implicating that Per2 plays dual roles in the zebrafish circadian clock. Cell transfection and co-immunoprecipitation assays revealed that Per2 enhances bmal1b expression through binding to orphan nuclear receptor Ror?. The enhancing effect of mouse PER2 on Bmal1 transcription is also mediated by ROR? even though it binds to REV-ERB?. Moreover, zebrafish Per2 also appears to have tissue-specific regulatory roles in numerous peripheral organs. These findings help define the essential functions of Per2 in the zebrafish circadian clock and in particular provide strong evidence for a positive role of PER2 in the vertebrate circadian system. PMID:25544291

Wang, Mingyong; Zhong, Zhaomin; Zhong, Yingbin; Zhang, Wei; Wang, Han

2015-02-13

27

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

PubMed

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

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

2013-10-01

28

Circadian rhythms regulate amelogenesis.  

PubMed

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

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

2013-07-01

29

Changes in pH and NADPH Regulate the DNA Binding Activity of Neuronal PAS Domain Protein 2, a Mammalian Circadian Transcription Factor.  

PubMed

Neuronal PAS domain protein 2 (NPAS2) is a core clock transcription factor that forms a heterodimer with BMAL1 to bind the E-box in the promoter of clock genes and is regulated by various environmental stimuli such as heme, carbon monoxide, and NAD(P)H. In this study, we investigated the effects of pH and NADPH on the DNA binding activity of NPAS2. In an electrophoretic mobility shift (EMS) assay, the pH of the reaction mixture affected the DNA binding activity of the NPAS2/BMAL1 heterodimer but not that of the BMAL1/BMAL1 homodimer. A change in pH from 7.0 to 7.5 resulted in a 1.7-fold increase in activity in the absence of NADPH, and NADPH additively enhanced the activity up to 2.7-fold at pH 7.5. The experiments using truncated mutants revealed that N-terminal amino acids 1-61 of NPAS2 were sufficient to sense the change in both pH and NADPH. We further analyzed the kinetics of formation and DNA binding of the NPAS2/BMAL1 heterodimer at various pH values. In the absence of NADPH, a change in pH from 6.5 to 8.0 decreased the KD(app) value of the E-box from 125 to 22 nM, with an 8-fold increase in the maximal level of DNA binding for the NPAS2/BMAL1 heterodimer. The addition of NADPH resulted in a further decrease in KD(app) to 9 nM at pH 8.0. Furthermore, NPAS2-dependent transcriptional activity in a luciferase assay using NIH3T3 cells also increased with the pH of the culture medium. These results suggest that NPAS2 has a role as a pH and metabolite sensor in regulating circadian rhythms. PMID:25526362

Yoshii, Katsuhiro; Tajima, Fumihisa; Ishijima, Sumio; Sagami, Ikuko

2015-01-20

30

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

PubMed Central

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

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

2013-01-01

31

Class IIa Histone Deacetylases Are Conserved Regulators of Circadian Function*  

PubMed Central

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

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

2014-01-01

32

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

PubMed Central

In this study, we demonstrate that the lack of retinoic acid-related orphan receptor (ROR) ? or ? expression in mice significantly reduced the peak expression level of Cry1, Bmal1, E4bp4, Rev-Erb? and Per2 in an ROR isotype- and tissue-selective manner without affecting the phase of their rhythmic expression. Analysis of ROR?/ROR? double knockout mice indicated that in certain tissues ROR? and ROR? exhibited a certain degree of redundancy in regulating clock gene expression. Reporter gene analysis showed that ROR? was able to induce reporter gene activity through the RORE-containing regulatory regions of Cry1, Bmal1, Rev-Erb? and E4bp4. Co-expression of Rev-Erb? or addition of a novel ROR antagonist repressed this activation. ChIP-Seq and ChIP–Quantitative real-time polymerase chain reaction (QPCR) analysis demonstrated that in vivo ROR? regulate these genes directly and in a Zeitgeber time (ZT)-dependent manner through these ROREs. This transcriptional activation by RORs was associated with changes in histone acetylation and chromatin accessibility. The rhythmic expression of ROR?1 by clock proteins may lead to the rhythmic expression of ROR?1 target genes. The presence of ROR? binding sites and its down-regulation in ROR??/? liver suggest that the rhythmic expression of Avpr1a depends on ROR? consistent with the concept that ROR?1 provides a link between the clock machinery and its regulation of metabolic genes. PMID:22753030

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

2012-01-01

33

The cardiomyocyte molecular clock, regulation of Scn5a, and arrhythmia susceptibility  

PubMed Central

The molecular clock mechanism underlies circadian rhythms and is defined by a transcription-translation feedback loop. Bmal1 encodes a core molecular clock transcription factor. Germline Bmal1 knockout mice show a loss of circadian variation in heart rate and blood pressure, and they develop dilated cardiomyopathy. We tested the role of the molecular clock in adult cardiomyocytes by generating mice that allow for the inducible cardiomyocyte-specific deletion of Bmal1 (iCS?Bmal1). ECG telemetry showed that cardiomyocyte-specific deletion of Bmal1 (iCS?Bmal1?/?) in adult mice slowed heart rate, prolonged RR and QRS intervals, and increased episodes of arrhythmia. Moreover, isolated iCS?Bmal1?/? hearts were more susceptible to arrhythmia during electromechanical stimulation. Examination of candidate cardiac ion channel genes showed that Scn5a, which encodes the principle cardiac voltage-gated Na+ channel (NaV1.5), was circadianly expressed in control mouse and rat hearts but not in iCS?Bmal1?/? hearts. In vitro studies confirmed circadian expression of a human Scn5a promoter-luciferase reporter construct and determined that overexpression of clock factors transactivated the Scn5a promoter. Loss of Scn5a circadian expression in iCS?Bmal1?/? hearts was associated with decreased levels of NaV1.5 and Na+ current in ventricular myocytes. We conclude that disruption of the molecular clock in the adult heart slows heart rate, increases arrhythmias, and decreases the functional expression of Scn5a. These findings suggest a potential link between environmental factors that alter the cardiomyocyte molecular clock and factors that influence arrhythmia susceptibility in humans. PMID:23364267

Lefta, Mellani; Zhang, Xiping; Bartos, Daniel; Feng, Han-Zhong; Zhao, Yihua; Patwardhan, Abhijit; Jin, Jian-Ping; Esser, Karyn A.; Delisle, Brian P.

2013-01-01

34

Social Defeat during Adolescence and Adulthood Differentially Induce BDNF-Regulated Immediate Early Genes  

PubMed Central

Stressful life events generally enhance the vulnerability for the development of human psychopathologies such as anxiety disorders and depression. The incidence rates of adult mental disorders steeply rises during adolescence in parallel with a structural and functional reorganization of the neural circuitry underlying stress reactivity. However, the mechanisms underlying susceptibility to stress and manifestation of mental disorders during adolescence are little understood. We hypothesized that heightened sensitivity to stress during adolescence reflects age-dependent differences in the expression of activity-dependent genes involved in synaptic plasticity. Therefore, we compared the effect of social stress during adolescence with social stress in adulthood on the expression of a panel of genes linked to induction of long-term potentiation (LTP) and brain-derived neurotrophic factor (BDNF) signaling. We show that social defeat during adolescence and adulthood differentially regulates expression of the immediate early genes BDNF, Arc, Carp, and Tieg1, as measured by qPCR in tissue lysates from prefrontal cortex, nucleus accumbens, and hippocampus. In the hippocampus, mRNA levels for all four genes were robustly elevated following social defeat in adolescence, whereas none were induced by defeat in adulthood. The relationship to coping style was also examined using adult reactive and proactive coping rats. Gene expression levels of reactive and proactive animals were similar in the prefrontal cortex and hippocampus. However, a trend toward a differential expression of BDNF and Arc mRNA in the nucleus accumbens was detected. BDNF mRNA was increased in the nucleus accumbens of proactive defeated animals, whereas the expression level in reactive defeated animals was comparable to control animals. The results demonstrate striking differences in immediate early gene expression in response to social defeat in adolescent and adult rats. PMID:22065953

Coppens, Caroline M.; Siripornmongcolchai, Taweeporn; Wibrand, Karin; Alme, Maria Nordheim; Buwalda, Bauke; de Boer, Sietse F.; Koolhaas, Jaap M.; Bramham, Clive R.

2011-01-01

35

Regulation of period 1 expression in cultured rat pineal  

NASA Technical Reports Server (NTRS)

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

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

2002-01-01

36

CLOCK-controlled polyphonic regulation of circadian rhythms through canonical and noncanonical E-boxes.  

PubMed

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

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

2014-05-01

37

Kruppel-like Factor KLF10 Targets Transforming Growth Factor-?1 to Regulate CD4+CD25? T Cells and T Regulatory Cells*  

PubMed Central

CD4+CD25+ regulatory T cells (T regs) play a major role in the maintenance of self-tolerance and immune suppression, although the mechanisms controlling T reg development and suppressor function remain incompletely understood. Herein, we provide evidence that Kruppel-like factor 10 (KLF10/TIEG1) constitutes an important regulator of T regulatory cell suppressor function and CD4+CD25? T cell activation through distinct mechanisms involving transforming growth factor (TGF)-?1 and Foxp3. KLF10 overexpressing CD4+CD25? T cells induced both TGF-?1 and Foxp3 expression, an effect associated with reduced T-Bet (Th1 marker) and Gata3 (Th2 marker) mRNA expression. Consistently, KLF10?/? CD4+CD25? T cells have enhanced differentiation along both Th1 and Th2 pathways and elaborate higher levels of Th1 and Th2 cytokines. Furthermore, KLF10?/? CD4+CD25? T cell effectors cannot be appropriately suppressed by wild-type T regs. Surprisingly, KLF10?/? T reg cells have reduced suppressor function, independent of Foxp3 expression, with decreased expression and elaboration of TGF-?1, an effect completely rescued by exogenous treatment with TGF-?1. Mechanistic studies demonstrate that in response to TGF-?1, KLF10 can transactivate both TGF-?1 and Foxp3 promoters, implicating KLF10 in a positive feedback loop that may promote cell-intrinsic control of T cell activation. Finally, KLF10?/? CD4+CD25? T cells promoted atherosclerosis by ?2-fold in ApoE?/?/scid/scid mice with increased leukocyte accumulation and peripheral pro-inflammatory cytokines. Thus, KLF10 is a critical regulator in the transcriptional network controlling TGF-?1 in both CD4+CD25? T cells and T regs and plays an important role in regulating atherosclerotic lesion formation in mice. PMID:19602726

Cao, Zhuoxiao; Wara, Akm Khyrul; Icli, Basak; Sun, Xinghui; Packard, René R. S.; Esen, Fehim; Stapleton, Christopher J.; Subramaniam, Malayannan; Kretschmer, Karsten; Apostolou, Irina; von Boehmer, Harald; Hansson, Göran K.; Spelsberg, Thomas C.; Libby, Peter; Feinberg, Mark W.

2009-01-01

38

Mistimed sleep disrupts circadian regulation of the human transcriptome.  

PubMed

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

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

2014-02-11

39

Mistimed sleep disrupts circadian regulation of the human transcriptome  

PubMed Central

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

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

2014-01-01

40

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

PubMed

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

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

2009-11-01

41

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

PubMed Central

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

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

2014-01-01

42

Influence of sex on genetic regulation of "drinking in the dark" alcohol consumption.  

PubMed

The ILSXISS (LXS) recombinant inbred (RI) panel of mice is a valuable resource for genetic mapping studies of complex traits, due to its genetic diversity and large number of strains. Male and female mice from this panel were used to investigate genetic influences on alcohol consumption in the "drinking in the dark" (DID) model. Male mice (38 strains) and female mice (36 strains) were given access to 20 % ethanol during the early phase of their circadian dark cycle for four consecutive days. The first principal component of alcohol consumption measures on days 2, 3, and 4 was used as a phenotype (DID phenotype) to calculate QTLs, using a SNP marker set for the LXS RI panel. Five QTLs were identified, three of which included a significant genotype by sex interaction, i.e., a significant genotype effect in males and not females. To investigate candidate genes associated with the DID phenotype, data from brain microarray analysis (Affymetrix Mouse Exon 1.0 ST Arrays) of male LXS RI strains were combined with RNA-Seq data (mouse brain transcriptome reconstruction) from the parental ILS and ISS strains in order to identify expressed mouse brain transcripts. Candidate genes were determined based on common eQTL and DID phenotype QTL regions and correlation of transcript expression levels with the DID phenotype. The resulting candidate genes (in particular, Arntl/Bmal1) focused attention on the influence of circadian regulation on the variation in the DID phenotype in this population of mice. PMID:25559016

Vanderlinden, Lauren A; Saba, Laura M; Bennett, Beth; Hoffman, Paula L; Tabakoff, Boris

2015-02-01

43

Regulation of core clock genes in human islets.  

PubMed

Nearly all mammalian cells express a set of genes known as clock genes. These regulate the circadian rhythm of cellular processes by means of negative and positive autoregulatory feedback loops of transcription and translation. Recent genomewide association studies have demonstrated an association between a polymorphism near the circadian clock gene CRY2 and elevated fasting glucose. To determine whether clock genes could play a pathogenetic role in the disease, we examined messenger RNA (mRNA) expression of core clock genes in human islets from donors with or without type 2 diabetes mellitus. Microarray and quantitative real-time polymerase chain reaction analyses were used to assess expression of the core clock genes CLOCK, BMAL-1, PER1 to 3, and CRY1 and 2 in human islets. Insulin secretion and insulin content in human islets were measured by radioimmunoassay. The mRNA levels of PER2, PER3, and CRY2 were significantly lower in islets from donors with type 2 diabetes mellitus. To investigate the functional relevance of these clock genes, we correlated their expression to insulin content and glycated hemoglobin levels: mRNA levels of PER2 (? = 0.33, P = .012), PER3 (? = 0.30, P = .023), and CRY2 (? = 0.37, P = .0047) correlated positively with insulin content. Of these genes, expression of PER3 and CRY2 correlated negatively with glycated hemoglobin levels (? = -0.44, P = .0012; ? = -0.28, P = .042). Furthermore, in an in vitro model mimicking pathogenetic conditions, the PER3 mRNA level was reduced in human islets exposed to 16.7 mmol/L glucose per 1 mmol/L palmitate for 48 hours (P = .003). Core clock genes are regulated in human islets. The data suggest that perturbations of circadian clock components may contribute to islet pathophysiology in human type 2 diabetes mellitus. PMID:22304835

Stamenkovic, Jelena A; Olsson, Anders H; Nagorny, Cecilia L; Malmgren, Siri; Dekker-Nitert, Marloes; Ling, Charlotte; Mulder, Hindrik

2012-07-01

44

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

PubMed

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

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

2015-02-01

45

SIRT1 regulates circadian clock gene expression through PER2 deacetylation.  

PubMed

The mammalian circadian timing system is composed of a central pacemaker in the suprachiasmatic nucleus of the brain that synchronizes countless subsidiary oscillators in peripheral tissues. The rhythm-generating mechanism is thought to rely on a feedback loop involving positively and negatively acting transcription factors. BMAL1 and CLOCK activate the expression of Period (Per) and Cryptochrome (Cry) genes, and once PER and CRY proteins accumulate to a critical level they form complexes with BMAL1-CLOCK heterodimers and thereby repress the transcription of their own genes. Here, we show that SIRT1, an NAD(+)-dependent protein deacetylase, is required for high-magnitude circadian transcription of several core clock genes, including Bmal1, Rorgamma, Per2, and Cry1. SIRT1 binds CLOCK-BMAL1 in a circadian manner and promotes the deacetylation and degradation of PER2. Given the NAD(+) dependence of SIRT1 deacetylase activity, it is likely that SIRT1 connects cellular metabolism to the circadian core clockwork circuitry. PMID:18662546

Asher, Gad; Gatfield, David; Stratmann, Markus; Reinke, Hans; Dibner, Charna; Kreppel, Florian; Mostoslavsky, Raul; Alt, Frederick W; Schibler, Ueli

2008-07-25

46

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

SciTech Connect

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

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

2013-05-03

47

Library Regulations Library Regulations  

E-print Network

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

Birmingham, University of

48

Specificity in Circadian Clock Feedback from Targeted Reconstitution of the NuRD Corepressor.  

PubMed

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

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

2014-12-18

49

INSURANCE REGULATION  

Microsoft Academic Search

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

Seth J. Chandler

50

Evidence for an Overlapping Role of CLOCK and NPAS2 Transcription Factors in Liver Circadian Oscillators?  

PubMed Central

The mechanisms underlying the circadian control of gene expression in peripheral tissues and influencing many biological pathways are poorly defined. Factor VII (FVII), the protease triggering blood coagulation, represents a valuable model to address this issue in liver since its plasma levels oscillate in a circadian manner and its promoter contains E-boxes, which are putative DNA-binding sites for CLOCK-BMAL1 and NPAS2-BMAL1 heterodimers and hallmarks of circadian regulation. The peaks of FVII mRNA levels in livers of wild-type mice preceded those in plasma, indicating a transcriptional regulation, and were abolished in Clock?/?; Npas2?/? mice, thus demonstrating a role for CLOCK and NPAS2 circadian transcription factors. The investigation of Npas2?/? and Clock?19/?19 mice, which express functionally defective heterodimers, revealed robust rhythms of FVII expression in both animal models, suggesting a redundant role for NPAS2 and CLOCK. The molecular bases of these observations were established through reporter gene assays. FVII transactivation activities of the NPAS2-BMAL1 and CLOCK-BMAL1 heterodimers were (i) comparable (a fourfold increase), (ii) dampened by the negative circadian regulators PER2 and CRY1, and (iii) abolished upon E-box mutagenesis. Our data provide the first evidence in peripheral oscillators for an overlapping role of CLOCK and NPAS2 in the regulation of circadianly controlled genes. PMID:18316400

Bertolucci, Cristiano; Cavallari, Nicola; Colognesi, Ilaria; Aguzzi, Jacopo; Chen, Zheng; Caruso, Pierpaolo; Foá, Augusto; Tosini, Gianluca; Bernardi, Francesco; Pinotti, Mirko

2008-01-01

51

Investigation of Circadian Clock in Peripheral Tissues and Immune-Circadian Interaction in the Domestic Fowl, Gallus Domesticus  

E-print Network

RTPCR) assays. We investigated the avian spleen for daily and circadian control of core clock genes and regulation of the inflammatory response by the spleen clock. The core clock genes, bmal1, bmal2, per2, per3 and clock displayed both daily and circadian...

Kallur, Sailaja

2012-12-07

52

44 Academic Regulations Academic Regulations  

E-print Network

. Because students are responsible themselves for meeting academic goals and requirements, they are urged with their advisors to discuss academic, personal and professional goals; to review the academic regulations44 · Academic Regulations Academic Regulations The Honor System Among the most significant

Shaw, Leah B.

53

Expression of Clock genes in the pineal glands of newborn rats with hypoxic-ischemic encephalopathy?  

PubMed Central

Clock genes are involved in circadian rhythm regulation, and surviving newborns with hypoxic-ischemic encephalopathy may present with sleep-wake cycle reversal. This study aimed to determine the expression of the clock genes Clock and Bmal1, in the pineal gland of rats with hypoxic-ischemic brain damage. Results showed that levels of Clock mRNA were not significantly changed within 48 hours after cerebral hypoxia and ischemia. Expression levels of CLOCK and BMAL1 protein were significantly higher after 48 hours. The levels of Bmal1 mRNA reached a peak at 36 hours, but were significantly reduced at 48 hours. Experimental findings indicate that Clock and Bmal1 genes were indeed expressed in the pineal glands of neonatal rats. At the initial stage (within 36 hours) of hypoxic-ischemic brain damage, only slight changes in the expression levels of these two genes were detected, followed by significant changes at 36–48 hours. These changes may be associated with circadian rhythm disorder induced by hypoxic-ischemic brain damage.

Sun, Bin; Feng, Xing; Ding, Xin; Bao, Li; Li, Yongfu; He, Jun; Jin, Meifang

2012-01-01

54

Government Regulation  

E-print Network

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

Ashford, Nicholas

2005-01-01

55

Gene Regulation  

NSDL National Science Digital Library

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

Robert Frederick (AAAS;)

2008-03-28

56

PPARs Integrate the Mammalian Clock and Energy Metabolism  

PubMed Central

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

Chen, Lihong; Yang, Guangrui

2014-01-01

57

Regulation 28: Library REGULATION 28: LIBRARY  

E-print Network

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

Sussex, University of

58

Charge regulation circuit  

DOEpatents

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

Ball, Don G. (Livermore, CA)

1992-01-01

59

Does the circadian system regulate lactation?  

PubMed

Environmental variables such as photoperiod, heat, stress, nutrition and other external factors have profound effects on quality and quantity of a dairy cow's milk. The way in which the environment interacts with genotype to impact milk production is unknown; however, evidence from our laboratory suggests that circadian clocks play a role. Daily and seasonal endocrine rhythms are coordinated in mammals by the master circadian clock in the hypothalamus. Peripheral clocks are distributed in every organ and coordinated by signals from the master clock. We and others have shown that there is a circadian clock in the mammary gland. Approximately 7% of the genes expressed during lactation had circadian patterns including core clock and metabolic genes. Amplitude changes occurred in the core mammary clock genes during the transition from pregnancy to lactation and were coordinated with changes in molecular clocks among multiple tissues. In vitro studies using a bovine mammary cell line showed that external stimulation synchronized mammary clocks, and expression of the core clock gene, BMAL1, was induced by lactogens. Female clock/clock mutant mice, which have disrupted circadian rhythms, have impaired mammary development and their offspring failed to thrive suggesting that the dam's milk production was not adequate enough to nourish their young. We envision that, in mammals, during the transition from pregnancy to lactation the master clock is modified by environmental and physiological cues that it receives, including photoperiod length. In turn, the master clock coordinates changes in endocrine milieu that signals peripheral tissues. In dairy cows, it is clear that changes in photoperiod during the dry period and/or during lactation influences milk production. We believe that the photoperiod effect on milk production is mediated, in part by the 'setting' of the master clock with light, which modifies peripheral circadian clocks including the mammary core clock and subsequently impacts milk yield and may impact milk composition. PMID:22436218

Plaut, K; Casey, T

2012-03-01

60

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

PubMed Central

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

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

2013-01-01

61

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

PubMed

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

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

2014-01-01

62

Emerging models for the molecular basis of Mammalian circadian timing.  

PubMed

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

Gustafson, Chelsea L; Partch, Carrie L

2015-01-20

63

Incentive regulation and the regulation of incentives  

SciTech Connect

This thesis explores the regulatory problem of incentives and the question of how to create a regulatory framework that most nearly aligns the firm's private interests with the public good. The main themes are: (1) an efficiency loss is inherent in the regulatory relationship, as long as the regulator knows less about the firm's operations than the firm itself; and (2) regulation itself is an incentive mechanism, so that the regulator can choose how to motivate the firm but now whether to do so. An analytical model is used to show the tradeoff between inducing efficient production and efficient pricing. The thesis surveys and analyzes incentive regulation mechanisms adopted by state utility commissions, using a Washington state plan as a case study. A natural extension of incentive regulation is discussed, in which the firm's reward depends on the total gain in consumer surplus rather than just the reduction in expenditures. The ability of the regulator to commit to future actions is central to incentive regulation, as well as many other aspects of regulation.

Blackmon, B.G. Jr.

1991-01-01

64

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

PubMed

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

Vriend, Jerry; Reiter, Russel J

2015-01-01

65

3 Library Regulations Definitions  

E-print Network

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

Mottram, Nigel

66

Regulation and Administered Contracts  

Microsoft Academic Search

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

Victor P. Goldberg

1976-01-01

67

Load regulating expansion fixture  

DOEpatents

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

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

1998-12-15

68

Load regulating expansion fixture  

DOEpatents

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

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

1998-01-01

69

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

Federal Register 2010, 2011, 2012, 2013

...DEPARTMENT OF THE TREASURY Office of Foreign Assets Control 31 CFR Parts 500 and 505 Foreign Assets Control Regulations; Transaction Control Regulations (Regulations Prohibiting Transactions Involving the Shipment...

2011-06-20

70

Regulating the regulator of ROS production.  

PubMed

Balancing inflammatory reactive oxygen species (ROS) production is essential for safely eliminating pathogenic microbes. The newly described protein Negative Regulator of ROS (NRROS) dampens ROS production by restricting NOX2 availability, and thus "cools-off" inflammation. PMID:24839902

Bonini, Marcelo G; Malik, Asrar B

2014-08-01

71

Regulation of brain aquaporins.  

PubMed

Emerging evidence suggests that brain aquaporins (AQP) play important roles for the dynamic regulation of brain water homeostasis and for the regulation of cerebrospinal fluid production. This review deals with the short- and long-term regulation of AQP4 and AQP9, both expressed in astrocytes, and of AQP1, expressed in the choroid plexus. AQP1 and 4 have in other cell types been shown to be regulated by phosphorylation. Phosphorylation affects the gating of AQP4 and the trafficking and insertion into membrane of AQP1. Mercury inhibits the water permeability of AQP1 and AQP9, but not AQP4. The permeability of AQP4 is increased by lead. AQP4 is also regulated by protein-protein interaction. The assembly between AQP4 and syntrophin is required for the proper localization of AQP4 in the astrocyte plasma membrane that faces capillaries. There is evidence from studies on peripheral tissues that steroid hormones regulate the expression of AQP1, AQP4 and AQP9. There is also evidence that the expression of AQP1 can be regulated by ubiquitination, and that osmolality can regulate the expression of AQP1, AQP4 and AQP9. Further insight into the mechanisms by which brain AQPs are regulated will be of utmost clinical importance, since perturbed water flow via brain AQPs has been implicated in many neurological diseases and since, in brain edema, water flow via AQP4 may have a harmful effect. PMID:15561410

Gunnarson, E; Zelenina, M; Aperia, A

2004-01-01

72

Novel regulators of spermatogenesis.  

PubMed

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

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

2014-05-01

73

Regulation of natural monopolies  

E-print Network

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 ...

Joskow, Paul L.

2005-01-01

74

Plant Growth Regulation  

NSDL National Science Digital Library

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

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

75

Melatonin affects nuclear orphan receptors mRNA in the rat suprachiasmatic nuclei.  

PubMed

The pineal hormone melatonin nocturnal synthesis feeds back on the suprachiasmatic nuclei (SCN), the central circadian clock. Indeed, daily melatonin injections in free-running rats resynchronize their locomotor activity to 24 h. However, the molecular mechanisms underlying this chronobiotic effect of the hormone are poorly understood. The endogenous circadian machinery involves positive and negative transcriptional feedback loops implicating different genes (particularly period (Per) 1-3, Clock, Bmal1, cryptochrome (Cry) 1-2). While CLOCK:BMAL1 heterodimer activates the rhythmic transcription of per and cry genes, the PER and CRY proteins inhibit the CLOCK:BMAL1 complex. In previous studies, we observed that the immediate resetting effect of a melatonin injection at the end of the subjective day on the SCN circadian activity did not directly involve the above-mentioned clock genes. Recently, nuclear orphan receptors (NORs) have been presented as functional links between the regulatory loops of the molecular clock. These NORs bind to a retinoic acid receptor-related orphan receptor response element (RORE) domain and activate (RORalpha) or repress (REV-ERBalpha) bmal1 expression. In this study, we investigated whether melatonin exerts its chronobiotic effects through transcriptional regulation of these transcription factors. We monitored roralpha, rorbeta and rev-erbalpha messenger RNA (mRNA) expression levels by quantitative in situ hybridization, up to 36 h following a melatonin injection at circadian time (CT) 11.5. Results clearly showed that, while roralpha was not affected by melatonin, the hormone partially prevented the decrease of the rorbeta mRNA expression observed in control animals during the first hours following the injection. The major result is that the rev-erbalpha mRNA expression rhythm was 1.3+/-0.8-h phase-advanced in melatonin-treated animals during the first subjective night following the melatonin administration. Moreover, the bmal1 mRNA expression was 1.9+/-0.9-h phase-shifted in the second subjective night following the melatonin injection. These results clearly suggest that the NOR genes could be the link between the chronobiotic action of melatonin and the core of the molecular circadian clock. PMID:17067745

Agez, L; Laurent, V; Pévet, P; Masson-Pévet, M; Gauer, F

2007-01-19

76

International Master regulation International Master regulation  

E-print Network

- COMMUNICATION & COMPUTER SECURITY - MULTIMEDIA INFORMATION TECHNOLOGIES ACADEMIC REGULATION 2014-2015 EURECOM, projects and an internship. The academic program (courses, projects) takes place over a period of nine activities is mandatory. The internship takes place over a six-month period. The internship itself must last

Gesbert, David

77

The Right to Regulate  

NASA Technical Reports Server (NTRS)

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

Vittek, J. F.

1972-01-01

78

Plant Growth Regulators.  

ERIC Educational Resources Information Center

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

Nickell, Louis G.

1978-01-01

79

PARKING AND TRAFFIC REGULATIONS  

E-print Network

UNIVERSITY POLICE #12;1 THE PARKING AND TRAFFIC REGULATIONS FOR THE UNIVERSITY OF NEW ORLEANS ARE IN EFFECT regulations which are in effect 24 hours a day/seven days a week. Pedestrians have the right of way; all will reduce the number of crimes on campus. Motor vehicle accidents must be reported to University Police

Li, X. Rong

80

Health practitioner regulation  

Microsoft Academic Search

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

IAN FRECKELTON

81

Proposed EEOC Regulations.  

ERIC Educational Resources Information Center

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

Farrell, Michael

1978-01-01

82

International Regulation Database  

NSDL National Science Digital Library

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

83

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...

84

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

85

Alginate Gene Regulation  

Microsoft Academic Search

\\u000a Alginate is an important virulence factor of Pseudomonas aeruginosa, and so our understanding of alginate gene regulation is best understood in this species. Expression of the algD operon for alginate biosynthesis is only highly expressed in mucoid clinical isolates that usually have pathoadaptive mucA mutations. The three major regulators of the algD promoter (PalgD) are AlgR, AlgB, and AmrZ. Each

Dennis E. Ohman

86

Diversification and Regulated Monopoly  

Microsoft Academic Search

\\u000a Although the merits of diversification by regulated utilities into competitive markets have been widely debated by economists,\\u000a regulators, and public interest advocates, the efficiency consequences of relaxing line-of-business restrictions remains unclear.1 One argument, most recently advanced by Baumol and Willig [1985] and McAvoy and Robinson [1985], contends that diversification restrictions are both unnecessar’ and result in significant inefficiencies through the

Michael A. Crew; Keith J. Crocker

87

Epigenetic Regulation in Drosophila  

Microsoft Academic Search

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

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

88

The Impact of Regulating Social Science Research with Biomedical Regulations  

ERIC Educational Resources Information Center

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

Durosinmi, Brenda Braxton

2011-01-01

89

The Hippo pathway: regulators and regulations  

PubMed Central

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

Yu, Fa-Xing; Guan, Kun-Liang

2013-01-01

90

A fast ac voltage regulator  

Microsoft Academic Search

The study and implementation of an AC voltage regulator is presented in this paper. Traditionally an AC voltage regulator is made with a transformer tap changer or with an AC-AC converter based on buck topologies, recently the developments in ac-ac converter makes feasible the implementation of voltage regulator with other topologies. In this paper is analyzed an ac voltage regulator

N. Vazquez; A. Velazquez; C. Hernandez; E. Rodriguez; R. Orosco

2008-01-01

91

MicroRNA biogenesis: Regulating the Regulators  

PubMed Central

MicroRNAs (miRNAs) function as 21–24 nucleotide guide RNAs that use partial base-pairing to recognize target messenger RNAs and repress their expression. As a large fraction of protein-coding genes are under miRNA control, production of the appropriate level of specific miRNAs at the right time and in the right place is integral to most gene regulatory pathways. MiRNA biogenesis initiates with transcription, followed by multiple processing steps to produce the mature miRNA. Every step of miRNA production is subject to regulation and disruption of these control mechanisms has been linked to numerous human diseases, where the balance between the expression of miRNAs and their targets becomes distorted. Here we review the basic steps of miRNA biogenesis and describe the various factors that control miRNA transcription, processing and stability in animal cells. The tremendous effort put into producing the appropriate type and level of specific miRNAs underscores the critical role of these small RNAs in gene regulation. PMID:23163351

Finnegan, Emily F.; Pasquinelli, Amy E.

2012-01-01

92

Mechanisms regulating melanogenesis*  

PubMed Central

Skin pigmentation is an important human phenotypic trait whose regulation, in spite of recent advances, has not yet been fully understood. The pigment melanin is produced in melanosomes by melanocytes in a complex process called melanogenesis. The melanocyte interacts with endocrine, immune, inflammatory and central nervous systems, and its activity is also regulated by extrinsic factors such as ultraviolet radiation and drugs. We have carried out a review of the current understanding of intrinsic and extrinsic factors regulating skin pigmentation, the melanogenesis stages and related gene defects. We focused on melanocyte-keratinocyte interaction, activation of melanocortin type 1 receptor (MC1-R) by peptides (melanocyte-stimulating hormone and adrenocorticotropic hormone) resulting from proopiomelanocortin (POMC) cleavage, and mechanisms of ultraviolet-induced skin pigmentation. The identification and comprehension of the melanogenesis mechanism facilitate the understanding of the pathogenesis of pigmentation disorders and the development of potential therapeutic options. PMID:23539007

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

2013-01-01

93

Androgen receptor genomic regulation  

PubMed Central

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

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

2014-01-01

94

Metabolic regulation of yeast  

NASA Astrophysics Data System (ADS)

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

Fiechter, A.

1982-12-01

95

Precision voltage regulator  

NASA Technical Reports Server (NTRS)

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

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

1972-01-01

96

Water Regulation I. Osmoregulation  

E-print Network

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

Dever, Jennifer A.

97

Water Regulation I. Osmoregulation  

E-print Network

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

Dever, Jennifer A.

98

Water Regulation I. Osmoregulation  

E-print Network

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

Dever, Jennifer A.

99

Water Regulation I. Osmoregulation  

E-print Network

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

Dever, Jennifer A.

100

Regulating intraflagellar transport.  

PubMed

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

Pedersen, Lotte B; Christensen, Søren T

2012-09-01

101

Regulation and behavior  

NSDL National Science Digital Library

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

Domain, Teachers

2002-01-01

102

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 ...

103

Regulation and Behaviour  

NSDL National Science Digital Library

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

2010-01-01

104

CODE OF FEDERAL REGULATIONS  

EPA Science Inventory

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

105

Aptamers for allosteric regulation  

Microsoft Academic Search

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

Jan L Vinkenborg; Nora Karnowski; Michael Famulok

2011-01-01

106

Regulation of inflammasome signaling  

Microsoft Academic Search

Innate immune responses have the ability to both combat infectious microbes and drive pathological inflammation. Inflammasome complexes are a central component of these processes through their regulation of interleukin 1? (IL-1?), IL-18 and pyroptosis. Inflammasomes recognize microbial products or endogenous molecules released from damaged or dying cells both through direct binding of ligands and indirect mechanisms. The potential of the

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

2012-01-01

107

TABLE OF CONTENTS CALIFORNIA CODE OF REGULATIONS ADMINISTRATIVE REGULATIONS  

E-print Network

.............................................................................................31 Section 115 -- Natural Gas Central Furnaces, Cooking Equipment, and Pool and Spa Heaters: Pilot#12;#12;i TABLE OF CONTENTS CALIFORNIA CODE OF REGULATIONS ADMINISTRATIVE REGULATIONS Section 10 Section 10-102 -- Definitions

108

FDA 101: Regulating Biological Products  

MedlinePLUS

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

109

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...

110

Regulation of Meiotic Recombination  

SciTech Connect

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

Gregory p. Copenhaver

2011-11-09

111

Regulation of inflammasome signaling  

PubMed Central

Innate immune responses have the ability to both combat infectious microbes and drive pathological inflammation. Inflammasome complexes are a central component of these processes through their regulation of interleukin 1? (IL-1?), IL-18 and pyroptosis. Inflammasomes recognize microbial products or endogenous molecules released from damaged or dying cells both through direct binding of ligands and indirect mechanisms. The potential of the IL-1 family of cytokines to cause tissue damage and chronic inflammation emphasizes the importance of regulating inflammasomes. Many regulatory mechanisms have been identified that act as checkpoints for attenuating inflammasome signaling at multiple steps. Here we discuss the various regulatory mechanisms that have evolved to keep inflammasome signaling in check to maintain immunological balance. PMID:22430786

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

2012-01-01

112

Redox regulated peroxisome homeostasis  

PubMed Central

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

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

2014-01-01

113

Chloroplast translation regulation  

Microsoft Academic Search

Chloroplast gene expression is primarily controlled during the translation of plastid mRNAs. Translation is regulated in response\\u000a to a variety of biotic and abiotic factors, and requires a coordinate expression with the nuclear genome. The translational\\u000a apparatus of chloroplasts is related to that of bacteria, but has adopted novel mechanisms in order to execute the specific\\u000a roles that this organelle

Julia Marín-Navarro; Andrea L. Manuell; Joann Wu; Stephen P. Mayfield

2007-01-01

114

Simple proportional temperature regulator  

SciTech Connect

A simple proportional temperature regulator for heating devices and controlled cryostats of low power is described that consists of stock devices: a PP-63 potentiometric bridge, an Shch68000 digital voltmeter, and a B5-43 variable power supply. When a copper-constantan thermocouple is used, the temperature drift is not over 0.1 K/h in the range of 80-300 K.

Borisov, B.A.

1987-06-01

115

Regulating financial conglomerates  

Microsoft Academic Search

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

Xavier Freixas; Gyöngyi Lóránth; Alan D. Morrison

2007-01-01

116

Regulation of Protein Translation  

NSDL National Science Digital Library

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

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

2006-03-07

117

Temperature controlled high voltage regulator  

DOEpatents

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

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

2004-04-20

118

The Theory of Economic Regulation  

Microsoft Academic Search

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

George J. Stigler

1971-01-01

119

Regulation of biomedical products.  

PubMed

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

Gillett, Grant; Saville-Cook, Donald

2010-05-01

120

Improving CS regulations.  

SciTech Connect

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

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

1980-10-01

121

Restructuring nuclear regulations.  

PubMed Central

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

Mossman, Kenneth L

2003-01-01

122

Redox-Regulated Chaperones  

PubMed Central

Redox regulation of stress proteins, such as molecular chaperones, guarantees an immediate response to oxidative stress conditions. This review focuses on the two major classes of redox-regulated chaperones, Hsp33 in bacteria and typical 2-Cys peroxiredoxins in eukaryotes. Both proteins employ redox-sensitive cysteines, whose oxidation status directly controls their affinity for unfolding proteins and therefore their chaperone function. We will first discuss Hsp33, whose oxidative stress-induced disulfide bond formation triggers the partial unfolding of the chaperone, which, in turn, leads to the exposure of a high-affinity binding site for unfolded proteins. This rapid mode of activation makes Hsp33 essential for protecting bacteria against severe oxidative stress conditions, such as hypochlorite (i.e., bleach) treatment, which leads to widespread protein unfolding and aggregation. We will compare Hsp33 to the highly abundant eukaryotic typical 2-Cys peroxiredoxin, whose oxidative stress-induced sulfinic acid formation turns the peroxidase into a molecular chaperone in vitro and presumably in vivo. These examples illustrate how proteins use reversible cysteine modifications to rapidly adjust to oxidative stress conditions and demonstrate that redox regulation plays a vital role in protecting organisms against reactive oxygen species-mediated cell death. PMID:19368357

Kumsta, Caroline; Jakob, Ursula

2009-01-01

123

Differential role of melatonin in restoration of age-induced alterations in daily rhythms of expression of various clock genes in suprachiasmatic nucleus of male Wistar rats.  

PubMed

Aging is associated with changes in several basic parameters of circadian rhythms in mammals leading to circadian dysfunction. The hypothalamic Suprachiasmatic nucleus (SCN) regulates neuronal, endocrine and behavioral rhythms through the expression of various clock genes and release of melatonin from pineal gland. In the present study, we investigated the effect of aging on daily rhythms of various clock genes such as rPer1, rPer2, rCry1, rCry2 and rBmal1 in the SCN of male Wistar rats. The m-RNA expression levels of these genes were studied by using quantitative Polymerase Chain Reaction (qPCR) in 3 age groups [3 (adult), 12 and 24 month (m)] at variable time points (Zeitgeber time (ZT)-0, 6, 12 and 18). The m-RNA expression for all genes studied was rhythmic in SCN of adult rats with maximum for rPer1 at ZT-6, rPer2, rCry1 and rCry2 at ZT-12 and rBmal1 at ZT-18. However in 12 and 24 m, the phases of expression of these genes were significantly altered with abolition of daily rhythms of rCry1, rCry2 and rBmal1 in 24 m. Melatonin, messenger of darkness, an endogenous synchronizer of rhythm, an antioxidant and an antiaging drug, declines with aging. We therefore studied the effects of melatonin administered subcutaneously at 1 h before the onset of darkness (ZT-11) for 11 days on age induced desynchronization in expression of these genes. We report here differential restoration of daily rhythm, phase, levels and stoichiometric interaction of m-RNA expression of these genes in various age groups in rat SCN with melatonin treatment. PMID:24619734

Mattam, Ushodaya; Jagota, Anita

2014-06-01

124

Effective doses, guidelines & regulations.  

PubMed

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

Burch, Michael D

2008-01-01

125

Growth regulation by macrophages  

SciTech Connect

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

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

1982-01-01

126

Genes and gene regulation  

SciTech Connect

Genetics has long been a central topic for biologists, and recent progress has captured the public imagination as well. This book addresses questions that are at the leading edge of this continually advancing discipline. In tune with the increasing emphasis on molecular biology and genetic engineering, this text emphasizes the molecular aspects of gene expression, and the evolution of gene sequence organization and control. It reviews the genetic material of viruses, bacteria, and of higher organisms. Cells and organisms are compared in terms of gene numbers, their arrangements within a cell, and the control mechanisms which regulate the activity of genes.

MacLean, N.

1988-01-01

127

Gastrointestinal hormones regulating appetite  

PubMed Central

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

Chaudhri, Owais; Small, Caroline; Bloom, Steve

2006-01-01

128

Abortion and fertility regulation.  

PubMed

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

Kulczycki, A; Potts, M; Rosenfield, A

1996-06-15

129

[Regulation of terpene metabolism  

SciTech Connect

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.

Croteau, R.

1992-01-01

130

Variable orifice flow regulator  

NASA Technical Reports Server (NTRS)

A flow regulator for high-pressure fluids at elevated temperatures includes a body having a flow passage extending between inlet and outlet openings. First and second orifice members are arranged in the flow passage so at least one of the orifice members can be moved transversely in relation to the flow passage between one operating position where the two orifice openings are aligned for establishing a maximum flow rate of fluids flowing through the flow passage and at least one other operating position in which the two openings are moderately misaligned with one another for establishing a predetermined reduced flow rate of fluids flowing through the flow passage.

Christianson, Rollin C. (inventor)

1991-01-01

131

Epigenetic regulation in plants.  

PubMed

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

Pikaard, Craig S; Mittelsten Scheid, Ortrun

2014-12-01

132

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

PubMed

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

2014-07-28

133

Rapamycin regulates biochemical metabolites  

PubMed Central

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

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

2013-01-01

134

[Regulation of terpene metabolism  

SciTech Connect

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.

Croteau, R.

1991-01-01

135

Mycotoxins – Limits and Regulations  

PubMed Central

Since early years, a need has always been felt for some control on the quality of foodstuffs. With the discovery of aflatoxins in the early sixties, health authorities in man countries have become active in establishing regulations to protect their citizens and livestock fro t potential harm caused by mycotoxins. FDA mycotox-ins-in-foods sampling program is continuing with an objective to remove those foods from interstate commerce that contain Aflatoxins “at levels judged to be of regulator significance” Aflatoxins, Fumonisin B1 and B2, Deoxynivalenol (DON) Ochratoxin A and Patulin occur in a number of food products. FDA workers were instructed to sample and analyze all products for different types of mycotoxins. All baby foods should always be analyzed for all type of mycotoxins. The limits of Aflatoxins B1,B2,! < G2, and M1 in foods and feed stuffs varies from (0-40) ppb for foods & 0-1000ppb for food); for Ochratoxin A(0-50 ppb in food and 0-1000ppb in feed); for Don (500-2000ppb in food & 5-10,000 ppb in feed); for Zearalenone (0-1000 ppb in food); for Patulin (0-50 ppb in foods), for Diacetoxyscirpenol (0-100 ppd in feed); for chetomin (0ppb I feed); for stachybotryotoxin (0ppb in feeds and for Fumonisins (0-1000 ppb in food 5000-50,000 ppb in feedstuffs). PMID:22557007

Mazumder, Papiya Mitra; Sasmal, D.

2001-01-01

136

Emotion Regulation and Anxiety Disorders  

PubMed Central

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

Amstadter, Ananda B.

2009-01-01

137

Transcriptional regulation during Drosophila spermatogenesis  

PubMed Central

Drosophila spermatogenesis has become a paradigmatic system for the study of mechanisms that regulate adult stem cell maintenance, proliferation and differentiation. The dramatic cellular differentiation process from germline stem cell (GSC) to mature sperm is accompanied by dynamic changes in gene expression, which are regulated at transcriptional, post-transcriptional (including translational) and post-translational levels. Post-transcriptional regulation has been proposed as a unique feature of germ cells. However, recent studies have provided new insights into transcriptional regulation during Drosophila spermatogenesis. Both signaling pathways and epigenetic mechanisms act to orchestrate the transcriptional regulation of distinct genes at different germ cell differentiation stages. Many of the regulatory pathways that control male gamete differentiation in Drosophila are conserved in mammals. Therefore, studies using Drosophila spermatogenesis will provide insight into the molecular mechanisms that regulate mammalian germ cell differentiation pathways. PMID:23087835

Lim, Cindy; Tarayrah, Lama; Chen, Xin

2012-01-01

138

Orbit utilization - Current regulations  

NASA Astrophysics Data System (ADS)

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

Lepkowski, R. J.

139

Serotonin regulates rhythmic whisking.  

PubMed

Many rodents explore their environment by rhythmically palpating objects with their mystacial whiskers. These rhythmic whisker movements ("whisking"; 5-9 Hz) are thought to be regulated by an unknown brainstem central pattern generator (CPG). We tested the hypothesis that serotonin (5-HT) inputs to whisking facial motoneurons (wFMNs) are part of this CPG. In response to exogenous serotonin, wFMNs recorded in vitro fire rhythmically at whisking frequencies, and selective 5-HT2 or 5-HT3 receptor antagonists suppress this rhythmic firing. In vivo, stimulation of brainstem serotonergic raphe nuclei evokes whisker movements. Unilateral infusion of selective 5-HT2 or 5-HT3 receptor antagonists suppresses ipsilateral whisking and substantially alters the frequencies and symmetry of whisker movements. These findings suggest that serotonin is both necessary and sufficient to generate rhythmic whisker movements and that serotonergic premotoneurons are part of a whisking CPG. PMID:12873389

Hattox, Alexis; Li, Ying; Keller, Asaf

2003-07-17

140

Factors regulating microglia activation  

PubMed Central

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

Kierdorf, Katrin; Prinz, Marco

2013-01-01

141

POTENT REGULATORS OF METABOLISM  

PubMed Central

Retinoids (vitamin A and its analogs) are highly potent regulators of cell differentiation, cell proliferation, and apoptosis. Because of these activities, retinoids have been most extensively studied in the contexts of embryonic development and of proliferative diseases, especially cancer and skin disease. Recently, there has been considerable new research interest focused on gaining understanding of the roles that retinoids and/or retinoid-related proteins may have in the development of metabolic diseases, primarily obesity, diabetes, and dyslipidemia. This review will summarize recent advances that have been made in these areas, focusing on the role of retinoids in modulating adipogenesis, the roles of retinoids and retinoid-related proteins as signaling molecules linking obesity with the development of type II diabetes, the roles of retinoids in pancreatic ?-cell biology/insulin secretion, and the actions of retinoids in hepatic steatosis. PMID:23281051

Brun, Pierre-Jacques; Yang, Kryscilla Jian Zhang; Lee, Seung-Ah; Yuen, Jason J.; Blaner, William S.

2012-01-01

142

Magnetostrictive Pressure Regulating System  

NASA Technical Reports Server (NTRS)

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

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

2013-01-01

143

TFEB regulates lysosomal proteostasis.  

PubMed

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

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

2013-05-15

144

[Regulation of terpene metabolism  

SciTech Connect

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

Croteau, R.

1989-11-09

145

Regulation XXII: GENERAL REGULATIONS AS TO ACADEMIC APPEALS  

E-print Network

Regulation XXII: GENERAL REGULATIONS AS TO ACADEMIC APPEALS 1. A student may apply under-considered in the light of new evidence. GROUNDS FOR APPEAL 2. For these purposes, `new evidence' is defined as: (i before the examination. These are the only grounds on which representations can be made. Appeals

146

An epithelial circadian clock controls pulmonary inflammation and glucocorticoid action  

PubMed Central

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

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

2014-01-01

147

ROS Stress Resets Circadian Clocks to Coordinate Pro-Survival Signals  

PubMed Central

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

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

148

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

PubMed

In the hippocampus of Siberian hamsters, dendritic length and dendritic complexity increase in the CA1 region whereas dendritic spine density decreases in the dentate gyrus region at night. However, the underlying mechanism of the diurnal rhythmicity in hippocampal neuronal remodeling is unknown. In mammals, most daily rhythms in physiology and behaviors are regulated by a network of circadian clocks. The central clock, located in the hypothalamus, controls melatonin secretion at night and melatonin modifies peripheral clocks by altering expression of circadian clock genes. In this study, we examined the effects of acute melatonin treatment on the circadian clock system as well as on morphological changes of hippocampal neurons. Male Siberian hamsters were injected with melatonin in the afternoon; 4 h later, mRNA levels of hypothalamic and hippocampal circadian clock genes and hippocampal neuron dendritic morphology were assessed. In the hypothalamus, melatonin treatment did not alter Period1 and Bmal1 expression. However, melatonin treatment increased both Period1 and Bmal1 expression in the hippocampus, suggesting that melatonin affected molecular oscillations in the hippocampus. Melatonin treatment also induced rapid remodeling of hippocampal neurons; melatonin increased apical dendritic length and dendritic complexity in the CA1 region and reduced the dendritic spine density in the dentate gyrus region. These data suggest that structural changes in hippocampal neurons are regulated by a circadian clock and that melatonin functions as a nighttime signal to coordinate the diurnal rhythm in neuronal remodeling. © 2014 Wiley Periodicals, Inc. PMID:25160468

Ikeno, Tomoko; Nelson, Randy J

2015-02-01

149

Technological Change in Regulated Industries.  

ERIC Educational Resources Information Center

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

Capron, William M., Ed.

150

Regulating Pornography: A Public Dilemma.  

ERIC Educational Resources Information Center

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

Thompson, Margaret E.; And Others

1990-01-01

151

The Universities and Federal Regulation.  

ERIC Educational Resources Information Center

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…

Crowley, John C.

152

Gravity and body mass regulation  

NASA Technical Reports Server (NTRS)

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

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

1997-01-01

153

Affect and Self-Regulation  

ERIC Educational Resources Information Center

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

Malmivuori, Marja-Liisa

2006-01-01

154

Redox regulation in cancer  

PubMed Central

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

Das, Ila; Chandhok, Des

2010-01-01

155

Regulating the regulator: Rsp5 ubiquitinates the proteasome.  

PubMed

In this issue of Molecular Cell, Isasa et al. (2010) show that the Rsp5 ubiquitin ligase regulates substrate recruitment to the 26S proteasome by ubiquitinating Rpn10, the proteasome's polyubiquitin degradation signal receptor. PMID:20541994

Haas, Arthur L

2010-06-11

156

76 FR 76617 - Sudanese Sanctions Regulations  

Federal Register 2010, 2011, 2012, 2013

...Assets Control 31 CFR Part 538 Sudanese Sanctions Regulations AGENCY: Office of Foreign...OFAC'') is amending the Sudanese Sanctions Regulations by issuing two general licenses...making technical changes to the Sudanese Sanctions Regulations, including changes to...

2011-12-08

157

76 FR 31470 - Taliban (Afghanistan) Sanctions Regulations  

Federal Register 2010, 2011, 2012, 2013

...CFR Part 545 Taliban (Afghanistan) Sanctions Regulations AGENCY: Office of Foreign...Regulations the Taliban (Afghanistan) Sanctions Regulations, 31 CFR part 545, as a...Executive order on which part 545 was based. Sanctions against the Taliban pursuant to...

2011-06-01

158

Patterns of Population Regulation and Control  

E-print Network

Patterns of Population Growth Regulation and Control Population Regulation Population densities that increase and decrease population density around some limit (K) Population control: ecological mechanisms that limit population density Population Regulation Population control Can ask what combination of factors

Cochran-Stafira, D. Liane

159

Post regulation circuit with energy storage  

DOEpatents

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

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

1992-01-01

160

Drosophila Cytokine Unpaired 2 Regulates Physiological Homeostasis  

E-print Network

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

Higgins, Darren

161

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 ...

162

Wolf population regulation revisited: again  

USGS Publications Warehouse

The long-accepted conclusion that wolf density is regulated by nutrition was recently challenged, and the conclusion was reached that, at greater levels of prey biomass, social factors such as intraspecific strife and territoriality tend to regulate wolf density. We reanalyzed the data used in that study for 2 reasons: 1) we disputed the use of 2 data points, and 2) because of recognized heteroscedasticity, we used weighted-regression analysis instead of the unweighted regressions used in the original study. We concluded that the data do not support the hypothesis that wolf densities are regulated by social factors.

McRoberts, Ronald E.; Mech, L. David

2014-01-01

163

State Regulation of Private Education.  

ERIC Educational Resources Information Center

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)

Lines, Patricia M.

1982-01-01

164

State Licensing and Regulation Information  

MedlinePLUS

... Early Care and Education (EH) Oral Health in Child Care and Early Education Preventing Childhood Obesity in Early ... Checklists & Tipsheets Licensing Toolkits Videos Resources A-Z Child Care Information Links State Licensing and Regulation Information Child ...

165

Endosomal recycling regulation during cytokinesis  

PubMed Central

Successful cytokinesis is critical for cell proliferation and development. In animal cells, cytokinesis relies on temporally and spatially regulated membrane addition to the cleavage site. An important source for the new membrane is recycling endosomes. Yet how these endocytic vesicles are transported and regulated remains unclear. Several potential factors have been recently identified that regulate the trafficking of recycling endosomes during cytokinesis. Dynein and dynactin are required for the retrograde transport of recycling endosomes, while Kinesin-1 is responsible for endosome delivery to the furrow and midbody. Other regulators of recycling endosome trafficking have been identified, including RACK1, JIP3/4 and ECT2, which target recycling endosomes during the cell cycle. Here, we provide insights into the mechanisms controlling endosomal trafficking during cytokinesis. PMID:19907714

Ai, Erkang

2009-01-01

166

REGULATION SCOPING Alternative and Renewable  

E-print Network

REGULATION SCOPING PAPER Alternative and Renewable Fuel and Vehicle Technology Program, Statutes of 2007) created the Alternative and Renewable Fuel and Vehicle Technology Program (Program California's fuel and vehicle types. The Program will help meet the state's alternative fuel use

167

RAGs and regulation of autoantibodies.  

PubMed

Autoreactive antibodies are etiologic agents in a number of autoimmune diseases. Like all other antibodies these antibodies are produced in developing B cells by V(D)J recombination in the bone marrow. Three mechanisms regulate autoreactive B cells: deletion, receptor editing, and anergy. Here we review the prevalence of autoantibodies in the initial antibody repertoire, their regulation by receptor editing, and the role of the recombinase proteins (RAG1 and RAG2) in this process. PMID:15032586

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

2004-01-01

168

Analog regulation of metabolic demand  

Microsoft Academic Search

Background  The 3D structure of the chromosome of the model organism Escherichia coli is one key component of its gene regulatory machinery. This type of regulation mediated by topological transitions of the\\u000a chromosomal DNA can be thought of as an analog control, complementing the digital control, i.e. the network of regulation mediated by dedicated transcription factors. It is known that alterations

Nikolaus Sonnenschein; Marcel Geertz; Georgi Muskhelishvili; Marc-Thorsten Hütt

2011-01-01

169

Emotion regulation and sport performance.  

PubMed

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

Wagstaff, Christopher R D

2014-08-01

170

[Molecular mechanisms of circadian clock functioning].  

PubMed

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

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

2011-01-01

171

Modulation of BMAL/CLOCK/E-Box complex activity by a CT-rich cis-acting element.  

PubMed

The interaction between the BMAL1/CLOCK transcription factor and the cis-acting element known as the E-Box is a key event in the regulation of clock and clock-controlled gene expression. However, the fact that the ubiquitous E-Box element sits at the center of a presumably highly discriminating control system generates a certain level of puzzlement. Widely spread E-Boxes with a generic sequence CANNTG have been associated with expression of genes involved in a host of disparate biological processes, including the orchestration of circadian physiology. The intriguing specificity of this short DNA consensus element begs the hypothesis that its actual circadian properties might be encoded elsewhere, e.g., other factors or adjacent sequences. In a previous study, we found evidence that a short sequence in the mouse arginine vasopressin (AVP) proximal promoter has the ability to confer robust BMAL1/CLOCK responsiveness onto an adjacent E-Box. Here, we report the systematic analysis of this element. Our findings further define the determining features and sequence boundaries of this element, establish the effect of the photoperiod upon its interacting protein(s), and suggest that its cognate binding activity might be modulated by Zn2+ in a peripheral oscillator. PMID:16650525

Muñoz, Estela; Brewer, Michelle; Baler, Ruben

2006-06-27

172

Tregs in T cell vaccination: exploring the regulation of regulation  

PubMed Central

T cell vaccination (TCV) activates Tregs of 2 kinds: anti-idiotypic (anti-id) and anti-ergotypic (anti-erg). These regulators furnish a useful view of the physiology of T cell regulation of the immune response. Anti-id Tregs recognize specific effector clones by their unique TCR CDR3 peptides; anti-id networks of CD4+ and CD8+ Tregs have been described in detail. Here we shall focus on anti-erg T regulators. Anti-erg T cells, unlike anti-id T cells, do not recognize the clonal identity of effector T cells; rather, anti-erg T cells recognize the state of activation of target effector T cells, irrespective of their TCR specificity. We consider several features of anti-erg T cells: their ontogeny, subset markers, and target ergotope molecules; mechanisms by which they regulate other T cells; mechanisms by which they get regulated; and therapeutic prospects for anti-erg upregulation and downregulation. PMID:15520852

Cohen, Irun R.; Quintana, Francisco J.; Mimran, Avishai

2004-01-01

173

Adaptive Emotion Regulation among Low-Income  

Microsoft Academic Search

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

Shari L. Kidwell

2007-01-01

174

Law and regulation of benzene.  

PubMed

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

Feitshans, I L

1989-07-01

175

Vimentin regulates peripheral nerve myelination.  

PubMed

Myelination is a complex process that requires coordinated Schwann cell-axon interactions during development and regeneration. Positive and negative regulators of myelination have been recently described, and can belong either to Schwann cells or neurons. Vimentin is a fibrous component present in both Schwann cell and neuron cytoskeleton, the expression of which is timely and spatially regulated during development and regeneration. We now report that vimentin negatively regulates myelination, as loss of vimentin results in peripheral nerve hypermyelination, owing to increased myelin thickness in vivo, in transgenic mice and in vitro in a myelinating co-culture system. We also show that this is due to a neuron-autonomous increase in the levels of axonal neuregulin 1 (NRG1) type III. Accordingly, genetic reduction of NRG1 type III in vimentin-null mice rescues hypermyelination. Finally, we demonstrate that vimentin acts synergistically with TACE, a negative regulator of NRG1 type III activity, as shown by hypermyelination of double Vim/Tace heterozygous mice. Our results reveal a novel role for the intermediate filament vimentin in myelination, and indicate vimentin as a regulator of NRG1 type III function. PMID:22357929

Triolo, Daniela; Dina, Giorgia; Taveggia, Carla; Vaccari, Ilaria; Porrello, Emanuela; Rivellini, Cristina; Domi, Teuta; La Marca, Rosa; Cerri, Federica; Bolino, Alessandra; Quattrini, Angelo; Previtali, Stefano Carlo

2012-04-01

176

Bile Acids Regulate Cardiovascular Function  

PubMed Central

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

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

2011-01-01

177

How Europe regulates its genes  

SciTech Connect

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

Balter, M.

1991-06-07

178

Metabolic Mechanisms of Epigenetic Regulation  

PubMed Central

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

Meier, Jordan L.

2014-01-01

179

Regulation of ovarian follicle atresia.  

PubMed

The majority of ovarian follicles undergo atresia, a hormonally controlled apoptotic process. Monitoring apoptotic DNA fragmentation provides a quantitative and sensitive endpoint to study the hormonal regulation of atresia in ovarian follicles. During follicle development, gonadotropins, together with local ovarian growth factors (IGF-I, EGF/TGF-alpha, basic FGF) and cytokine (interleukin-1 beta), as well as estrogens, activate different intracellular pathways to rescue follicles from apoptotic demise. In contrast, TNF-alpha, Fas ligand, presumably acting through receptors with a death domain, and androgens are atretogenic factors. These diverse hormonal signals probably converge on selective intracellular pathways (including genes of the bcl-2 and ICE families) to regulate apoptosis. With a constant loss of follicles from the original stockpile, the ovary provides a unique model for studying the hormonal regulation of apoptosis. PMID:9074768

Kaipia, A; Hsueh, A J

1997-01-01

180

Signal regulation by family conspiracy.  

PubMed

The signal regulating proteins (SIRPs) are a family of ubiquitously expressed transmembrane glycoproteins composed of two subgroups: SIRP alpha and SIRP beta, containing more than ten members. SIRP alpha has been shown to inhibit signalling through a variety of receptors including receptor tyrosine kinases and cytokine receptors. This function involves protein tyrosine kinases and is dependent on immunoreceptor tyrosine-based inhibition motifs which recruit key protein tyrosine phosphatases to the membrane. Negative regulation by SIRP alpha may also involve its ligand, CD47, in a bi-directional signalling mechanism. The SIRP beta subtype has no cytoplasmic domain but instead associates with at least one other transmembrane protein (DAP-12, or KARAP). DAP-12 possesses immunoreceptor tyrosine-based activation motifs within its cytoplasmic domain that are thought to link SIRP beta to activating machinery. SIRP alpha and SIRP beta thus have complementary roles in signal regulation and may conspire to tune the response to a stimulus. PMID:11229810

Cant, C A; Ullrich, A

2001-01-01

181

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

Code of Federal Regulations, 2011 CFR

...2011-01-01 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...

2011-01-01

182

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

Code of Federal Regulations, 2010 CFR

...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...

2010-01-01

183

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

Code of Federal Regulations, 2013 CFR

...2013-01-01 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...

2013-01-01

184

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

Code of Federal Regulations, 2012 CFR

...2012-01-01 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...

2012-01-01

185

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

...2014-01-01 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...

2014-01-01

186

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

Federal Register 2010, 2011, 2012, 2013

...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...

2012-09-06

187

Positively regulated bacterial expression systems  

PubMed Central

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

Brautaset, Trygve; Lale, Rahmi; Valla, Svein

2009-01-01

188

Regulation of Ncx1 Expression  

PubMed Central

The Na+-Ca2+ exchanger (NCX1) is up-regulated in hypertrophy and is often found up-regulated in end-stage heart failure. Studies have shown that the change in its expression contributes to contractile dysfunction. We have previously shown that the 1831-bp Ncx1 H1 (1831Ncx1) promoter directs cardiac-specific expression of the exchanger in both development and in the adult, and is sufficient for the up-regulation of Ncx1 in response to pressure overload. Here, we utilized adenoviral mediated gene transfer and transgenics to identify minimal regions and response elements that mediate Ncx1 expression in the heart. We demonstrate that the proximal 184 bp of the Ncx1 H1 (184Ncx1) promoter is sufficient for expression of reporter genes in adult cardiomyocytes and for the correct spatiotemporal pattern of Ncx1 expression in development but not for up-regulation in response to pressure overload. Mutational analysis revealed that both the ?80 CArG and the ?50 GATA elements were required for expression in isolated adult cardiomyocytes. Chromatin immunoprecipitation assays in adult cardiocytes demonstrate that SRF and GATA4 are associated with the proximal region of the endogenous Ncx1 promoter. Transgenic lines were established for the 1831Ncx1 promoter-luciferase containing mutations in the ?80 CArG or ?50 GATA element. No luciferase activity was detected during development, in the adult, or after pressure overload in any of the ?80 CArG transgenic lines. The Ncx1 ?50 GATA mutant promoter was sufficient for driving the normal spatiotemporal pattern of Ncx1 expression in development and for up-regulation in response to pressure overload but importantly, expression was no longer cardiac restricted. This work is the first in vivo study that demonstrates which cis elements are important for Ncx1 regulation. PMID:16966329

Xu, Lin; Renaud, Ludivine; Müller, Joachim G.; Baicu, Catalin F.; Bonnema, D. Dirk; Zhou, Hongming; Kappler, Christiana S.; Kubalak, Steven W.; Zile, Michael R.; Conway, Simon J.; Menick, Donald R.

2011-01-01

189

Redox regulation of Janus kinase  

PubMed Central

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

Duhé, Roy J

2013-01-01

190

Regulations against the human nature  

NASA Astrophysics Data System (ADS)

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

Elizondo-Garza, Fernando J.

2001-05-01

191

Multifuel self-regulating burner  

SciTech Connect

An automatic self-regulating burner system is described. A serpentine pipe structure connected to a source of fuel has a preheating portion, an orifice pipe portion and a backpressure pipe portion. The orifice pipe portion has an orifice therethrough which exhausts vaporized fuel. The exhausted fuel vapor is burned to heat both the preheater pipe portion for vaporizing and preheating the fuel , and the backpressure pipe portion for generating an internal pressure which automatically regulates the quantity of fuel vapors which are exhausted from the orifice.

Sharp, J.

1980-11-04

192

Regulation of Francisella Tularensis Virulence  

PubMed Central

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

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

2011-01-01

193

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

Federal Register 2010, 2011, 2012, 2013

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

2011-11-10

194

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

Federal Register 2010, 2011, 2012, 2013

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

2010-01-11

195

Indiana Aquaculture Regulations and Permits  

E-print Network

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

196

Illinois Aquaculture Regulations and Permits  

E-print Network

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

197

Phytochrome-regulated Gene Expression  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

198

Regulating Collaboration in Teacher Education  

ERIC Educational Resources Information Center

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

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

2014-01-01

199

Safety Regulations of Food Enzymes  

Microsoft Academic Search

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

Armin Spök

200

Isometric Force Regulation in Children.  

ERIC Educational Resources Information Center

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

Lazarus, Jo-Anne C.; And Others

1995-01-01

201

REGULATION OF UNIVERSITY OF FLORIDA  

E-print Network

in University housing, who, in the opinion of the Director of Student Conduct and Conflict ResolutionREGULATION OF UNIVERSITY OF FLORIDA 6C1-4.0432 Student Honor Code and Student Conduct Code: Violations in University Housing. (1) The Coordinator of Residential Judicial Programs, in consultation

Pilyugin, Sergei S.

202

Regulation of cloned cardiac channels  

E-print Network

??1 integrin activation and require dual phosphorylation of a1c by PKA and c-Src. To explore common mechanisms of regulation by a5??1 integrin, whole cell patch clamp experiments were used to investigate the effects of a5??1 integrin antibody on expressed...

Balasubramanian, Bharathi

2005-11-01

203

Memory inhibition and energy regulation  

Microsoft Academic Search

At a simple behavioral level, food intake and body weight regulation depend on one's ability to balance the tendency to seek out and consume food with the ability to suppress or inhibit those responses. Accordingly, any factor that augments the tendency to engage in food seeking and eating or that interferes with the suppression of these behaviors could produce (a)

T. L. Davidson; Scott E. Kanoski; Elwood K. Walls; Leonard E. Jarrard

2005-01-01

204

Regulated Childhood: Equivalence with Variation  

ERIC Educational Resources Information Center

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

Vallberg Roth, Ann-Christine; Mansson, Annika

2009-01-01

205

Regulation of Cranial Suture Morphogenesis  

Microsoft Academic Search

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

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

2004-01-01

206

Multifuel self-regulating burner  

Microsoft Academic Search

An automatic self-regulating burner system is described. A serpentine pipe structure connected to a source of fuel has a preheating portion, an orifice pipe portion and a backpressure pipe portion. The orifice pipe portion has an orifice therethrough which exhausts vaporized fuel. The exhausted fuel vapor is burned to heat both the preheater pipe portion for vaporizing and preheating the

Sharp

1980-01-01

207

5____________________________________________________________________________ Gene Regulation in Spermatogenesis  

E-print Network

Nuclear Receptors C. HeatShock Factors D. Sox E. Plzf F. Dmrt1 G. CAF1 H. Homeobox Genes I. Perspective IV5____________________________________________________________________________ Gene Regulation. TestisSpecific Gene Expression and DNA Methylation A. Male Germ Cell­Specific Genes B. SomaticCell Testis

Wilkinson, Miles F.

208

Wood stove air flow regulating  

SciTech Connect

A wood stove has primary and secondary air regulator doors at the bottom and top, respectively, of the stove door each rotating about the axis of a tightening knob in the center of the door opposite a baffle plate that defines with the door inside an air channel open at the top and bottom.

Brefka, P.E.

1983-10-04

209

Redox Regulation of Cell Survival  

PubMed Central

Abstract Reactive oxygen species (ROS) and reactive nitrogen species (RNS) play important roles in regulation of cell survival. In general, moderate levels of ROS/RNS may function as signals to promote cell proliferation and survival, whereas severe increase of ROS/RNS can induce cell death. Under physiologic conditions, the balance between generation and elimination of ROS/RNS maintains the proper function of redox-sensitive signaling proteins. Normally, the redox homeostasis ensures that the cells respond properly to endogenous and exogenous stimuli. However, when the redox homeostasis is disturbed, oxidative stress may lead to aberrant cell death and contribute to disease development. This review focuses on the roles of key transcription factors, signal-transduction pathways, and cell-death regulators in affecting cell survival, and how the redox systems regulate the functions of these molecules. The current understanding of how disturbance in redox homeostasis may affect cell death and contribute to the development of diseases such as cancer and degenerative disorders is reviewed. We also discuss how the basic knowledge on redox regulation of cell survival can be used to develop strategies for the treatment or prevention of those diseases. Antioxid. Redox Signal. 10, 1343–1374. PMID:18522489

Trachootham, Dunyaporn; Lu, Weiqin; Ogasawara, Marcia A.; Valle, Nilsa Rivera-Del

2008-01-01

210

Temperature: Human Regulating, Ants Conforming  

ERIC Educational Resources Information Center

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

Clopton, Joe R.

2007-01-01

211

Regulating Constructed Wetlands in Scotland  

E-print Network

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

Heal, Kate

212

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

SciTech Connect

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

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

2005-07-15

213

Master thesis project: Longitudinal epigenetic regulation of aging Epigenetic regulation by hyper-or hypo  

E-print Network

Master thesis project: Longitudinal epigenetic regulation of aging Background Epigenetic regulation diseases and conditions. Epigenetic changes could be caused by environmental exposures such as smoking

Uppsala Universitet

214

B7 family checkpoint regulators in immune regulation and disease  

PubMed Central

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

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

2013-01-01

215

75 FR 55462 - Iraqi Sanctions Regulations  

Federal Register 2010, 2011, 2012, 2013

...Assets Control 31 CFR Part 575 Iraqi Sanctions Regulations AGENCY: Office of Foreign...Executive orders, by removing the Iraqi Sanctions Regulations from the Code of Federal...general information pertaining to OFAC's sanctions programs also is available via...

2010-09-13

216

76 FR 35740 - North Korea Sanctions Regulations  

Federal Register 2010, 2011, 2012, 2013

...Assets Control 31 CFR Part 510 North Korea Sanctions Regulations AGENCY: Office of Foreign...OFAC'') is amending the North Korea Sanctions Regulations to implement Executive Order...INFORMATION CONTACT: Assistant Director for Sanctions Compliance & Evaluation, tel.:...

2011-06-20

217

75 FR 73958 - Belarus Sanctions Regulations  

Federal Register 2010, 2011, 2012, 2013

...Assets Control 31 CFR Part 548 Belarus Sanctions Regulations AGENCY: Office of Foreign...OFAC'') is amending the Belarus Sanctions Regulations (``BSR'') in the Code...general information pertaining to OFAC's sanctions programs also is available via...

2010-11-30

218

Self-tuning regulators. [adaptive control research  

NASA Technical Reports Server (NTRS)

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

Astrom, K. J.

1975-01-01

219

Flexible Bureaucracies in Labor Market Regulation  

E-print Network

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

Piore, Michael J.

220

25 CFR 249.2 - Area regulations.  

...necessary to assure the conservation and wise utilization...with appropriate State conservation laws and regulations governing...incorporate such State laws or regulations, or...under the Treaty and the conservation of the fishery...

2014-04-01

221

7 CFR 932.52 - Outgoing regulations.  

Code of Federal Regulations, 2010 CFR

...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...

2010-01-01

222

7 CFR 932.52 - Outgoing regulations.  

Code of Federal Regulations, 2012 CFR

...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...

2012-01-01

223

7 CFR 932.52 - Outgoing regulations.  

Code of Federal Regulations, 2011 CFR

...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...

2011-01-01

224

7 CFR 932.52 - Outgoing regulations.  

Code of Federal Regulations, 2013 CFR

...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...

2013-01-01

225

7 CFR 932.52 - Outgoing regulations.  

...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...

2014-01-01

226

75 FR 52213 - Cold Treatment Regulations  

Federal Register 2010, 2011, 2012, 2013

...305 [Docket No. APHIS-2006-0050] Cold Treatment Regulations AGENCY: Animal and...phytosanitary treatment regulations for cold treatment enclosures and procedures, including...document requires articles destined for cold treatment to be precooled at or below...

2010-08-25

227

Is Conservation a Legitimate Goal of Regulation?  

E-print Network

a substitute for competition." There are many aispects to competitive economics which should be cons~dered in effective regulation. For purposes of ans~ering our question about the legitimacy of promoting conservation through regulation, only a...

Goble, G. L.

1984-01-01

228

15 CFR 922.185 - Emergency regulations.  

Code of Federal Regulations, 2012 CFR

...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...

2012-01-01

229

15 CFR 922.185 - Emergency regulations.  

Code of Federal Regulations, 2011 CFR

...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...

2011-01-01

230

15 CFR 922.185 - Emergency regulations.  

Code of Federal Regulations, 2013 CFR

...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...

2013-01-01

231

15 CFR 922.185 - Emergency regulations.  

...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...

2014-01-01

232

15 CFR 922.185 - Emergency regulations.  

Code of Federal Regulations, 2010 CFR

...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...

2010-01-01

233

7 CFR 948.386 - Handling regulation.  

Code of Federal Regulations, 2010 CFR

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

2010-01-01

234

32 CFR 9.7 - Regulations.  

Code of Federal Regulations, 2010 CFR

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

2010-07-01

235

Army Regulation 2550 Information Management: Records  

E-print Network

Army Regulation 25­50 Information Management: Records Management Preparing and Managing of Army Records Information Management System record numbers after the office symbol on Army Information Management: Records Management Preparing and Managing Correspondence *Army Regulation 25

US Army Corps of Engineers

236

Army Regulation 2550 Information Management: Records  

E-print Network

Army Regulation 25­50 Information Management: Records Management Preparing and Managing Information Management: Records Management Preparing and Managing Correspondence *Army Regulation 25 Agency, ATTN: Records Management Division (TAPC­PDD­RP), 6000 6th Street, Fort Belvoir, VA 22060

US Army Corps of Engineers

237

Regulation of TRP channels by PIP 2  

Microsoft Academic Search

Transient receptor potential (TRP) channels are regulated by a wide variety of physical and chemical factors. Recently, several\\u000a members of the TRP channel family were reported to be regulated by phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2, PIP2). This review will summarize the current knowledge on PIP2 regulation of TRP channels and discuss the possibility that PIP2 is a common regulator of mammalian TRP

Tibor Rohacs

2007-01-01

238

Acoustic saturation and output regulation.  

PubMed

Acoustic saturation pressures are predicted for ultrasonic beams of a range of frequencies and focal depths. Using reasonable approximations, saturation values for mechanical index (MI) and derated spatial-peak, time-average and pulse-average intensities are calculated. These are compared with thresholds set for regulatory purposes by the U. S. Food and Drug Administration (FDA), and by the International Electrotechnical Commission (IEC). It is concluded that there are many conditions for which acoustic saturation in water prevents the values of MI and regulated intensities from exceeding thresholds set by the FDA. These conditions are particularly associated with higher frequencies and deeper focal lengths. The thresholds for action set by IEC 61157 are sufficiently low that similar problems do not arise. It is concluded that present regulations are not fully effective in limiting the output from diagnostic ultrasound equipment, and that some conditions exist that are not subject to output control. PMID:10461731

Duck, F A

1999-07-01

239

p53 Regulation by Ubiquitin  

PubMed Central

The ubiquitination pathway is a highly dynamic and coordinated process that regulates degradation as well as numerous processes of proteins within a cell. The p53 tumor suppressor and several factors in the pathway are regulated by ubiquitin as well as ubiquitin-like proteins. These modifications are critical for the function of p53 and control both the degradation of the protein as well as localization and activity. Importantly, more recent studies have identified deubiquitination enzymes that can specifically remove ubiquitin moieties from p53 or other factors in the pathway, and the reversible nature of this process adds yet another layer of regulatory control of p53. This review highlights the recent advances in our knowledge of ubiquitin and the p53 pathway. PMID:21624367

Brooks, Christopher L.; Gu, Wei

2011-01-01

240

Apoptotic regulation and transfer RNA  

PubMed Central

Apoptotic regulation is critical to organismal homeostasis and protection against many human disease processes such as cancer. Significant research efforts over the past several decades have illuminated many of the signaling molecules and effecter proteins responsible for this form of programmed cell death. Recent evidence suggests that transfer RNA (tRNA) regulates apoptotic sensitivity at the level of cytochrome c-mediated apoptosome formation. This finding unexpectedly places tRNA at the nexus of cellular biosynthesis and survival. Here we review the current understanding of both the apoptotic machinery and tRNA biology. We describe the evidence linking tRNA and cytochrome c in depth, and speculate on the implications of this link in cell biology. PMID:21113408

Mei, Yide; Stonestrom, Aaron; Hou, Ya-Ming; Yang, Xiaolu

2010-01-01

241

[Environmental regulation of Citrus photosynthesis].  

PubMed

Recent researches on the mechanisms of environmental regulation of citrus photosynthesis showed that the photoinhibition of photosynthesis induced by strong light or ultraviolet radiation was related to the inactiveness of PS II reaction center, and photorespiration and xanthophyll cycle played a pivotal role in protecting photosynthetic apparatus. Under temperature stress, lower CO2 assimilation was mainly due to the decrease of RuBPCase activity and the inactiveness of PS II reaction center, and species sensitivity existed. The decline of photosynthetic CO2 assimilation under high water stress was due to non-stomatal limitation, while that under low water stress was due to stomatal limitation. The citrus growth, yield and quality could be increased by increasing photosynthesis under elevated CO2 concentration. The mechanisms of photosynthesis regulation by minerals such as nitrogen, phosphorus, sulfur and iron, as well as the effects of salt stress on photosynthesis were discussed, and the directions for future research were suggested. PMID:16724758

Hu, Meijun; Guo, Yanping; Shen, Yungang; Zhang, Liangcheng

2006-03-01

242

Peripheral Mechanisms In Appetite Regulation.  

PubMed

Peripheral mechanisms in appetite regulation include the motor functions of the stomach, such as the rate of emptying and accommodation, which convey symptoms of satiation to the brain. The rich repertoire of peripherally released peptides and hormones provides feedback from the arrival of nutrients in different regions of the gut from where they are released to exert effects on satiation, or regulate metabolism through their incretin effects. Ultimately, these peripheral factors provide input to the highly organized hypothalamic circuitry and vagal complex of nuclei to determine cessation of energy intake during meal ingestion, and the return of appetite and hunger after fasting. Understanding these mechanisms is key to the physiological control of feeding and the derangements that occur in obesity and their restoration with treatment (as demonstrated by the effects of bariatric surgery). PMID:25241326

Camilleri, Michael

2014-09-21

243

48 CFR 2501.104-2 - Arrangement of regulations.  

... Federal Acquisition Regulations System 6 2014-10-01 2014-10-01... Federal Acquisition Regulations System NATIONAL SCIENCE FOUNDATION GENERAL FEDERAL ACQUISITION REGULATIONS SYSTEM Purpose, Authority, Issuance...

2014-10-01

244

48 CFR 2501.104-2 - Arrangement of regulations.  

Code of Federal Regulations, 2011 CFR

... Federal Acquisition Regulations System 6 2011-10-01 2011-10-01... Federal Acquisition Regulations System NATIONAL SCIENCE FOUNDATION GENERAL FEDERAL ACQUISITION REGULATIONS SYSTEM Purpose, Authority, Issuance...

2011-10-01

245

Frequency regulator for synchronous generators  

DOEpatents

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

Karlicek, R.F.

1982-08-10

246

Phospholipids as Plant Growth Regulators  

Microsoft Academic Search

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

A. Keith Cowan

2006-01-01

247

Debating the benefits of regulation.  

PubMed

Franklin Square Hospital Center, Baltimore, spent nearly $1 million in 1989 on certificate-of-need and incinerator requirements alone, said Charles Mross, above, the hospital's president. Modern Healthcare asked Franklin Square and two other hospitals to estimate last year's regulatory costs (p. 40), and a broader study of regulatory costs was commissioned for this report on government regulation's merits and its impact on hospital overhead. PMID:10105809

Tokarski, C

1990-08-20

248

The regulations of Drosophila phototransduction.  

PubMed

This is the first of two reviews that include some of the studies that we, members of the Pak lab and collaborators, carried out from 1998 to 2010 on the functional and physical interactions among several Drosophila phototransduction components. The report includes our studies on the regulations and/or the functions of arrestin II (Arr2), norpA (PLC), inactivation no afterpotential D (INAD), transient receptor potential (TRP), TRP-like (TRPL), inactivation no afterpotential E (INAE), and Porin. PMID:22420370

Leung, Hung-Tat; Shino, Shikoh; Kim, Eunju

2012-06-01

249

Frequency regulator for synchronous generators  

DOEpatents

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

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

1982-01-01

250

NOTES TO ACCOMPANY FLOWCHARTS PROGRESSION REGULATIONS  

E-print Network

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

Wirosoetisno, Djoko

251

Entry regulation as a barrier to entrepreneurship  

Microsoft Academic Search

Using a comprehensive database of European firms, we study the effect of market entry regulations on the creation of new limited-liability firms, the average size of entrants, and the growth of incumbent firms. We find that costly regulations hamper the creation of new firms, especially in industries that should naturally have high entry. These regulations also force new entrants to

Leora Klapper; Luc Laeven; Raghuram Rajan

2006-01-01

252

Regulation of Hydraulic Fracturing in California  

E-print Network

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

Kammen, Daniel M.

253

Regulation of Motivation: Contextual and Social Aspects  

ERIC Educational Resources Information Center

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

Wolters, Christopher A.

2011-01-01

254

Identifying differentially regulated subnetworks from phosphoproteomic data  

Microsoft Academic Search

BACKGROUND: Various high throughput methods are available for detecting regulations at the level of transcription, translation or posttranslation (e.g. phosphorylation). Integrating these data with protein networks should make it possible to identify subnetworks that are significantly regulated. Furthermore, such integration can support identification of regulated entities from often noisy high throughput data. In particular, processing mass spectrometry-based phosphoproteomic data in

Martin Klammer; Klaus Godl; Andreas Tebbe; Christoph Schaab

2010-01-01

255

Using Plant regUlators on  

E-print Network

to pruning, which is not only costly in terms of labor, but also delays plant production for two to fourUsing Plant growth regUlators on Containerized herbaCeoUs Perennials Using Plant growth regUlators on Containerized herbaCeoUs Perennials #12;Using Plant Growth Regulators on Containerized Herbaceous Perennials

Liskiewicz, Maciej

256

Self-Regulation in Online Learning  

ERIC Educational Resources Information Center

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

Cho, Moon-Heum; Shen, Demei

2013-01-01

257

Auricular Acupuncture and Vagal Regulation  

PubMed Central

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

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

2012-01-01

258

Negative regulators of cell proliferation  

NASA Technical Reports Server (NTRS)

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

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

1994-01-01

259

Rethinking regulations for disposal criticality  

SciTech Connect

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

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

1997-08-01

260

Package warehouse upgrades and regulations  

SciTech Connect

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.

Hester, J.F.

1994-12-31

261

Hormonal Regulation of Nuclear Permeability*?  

PubMed Central

Transport into the nucleus is critical for regulation of gene transcription and other intranuclear events. Passage of molecules into the nucleus depends in part upon their size and the presence of appropriate targeting sequences. However, little is known about the effects of hormones or their second messengers on transport across the nuclear envelope. We used localized, two-photon activation of a photoactivatable green fluorescent protein to investigate whether hormones, via their second messengers, could alter nuclear permeability. Vasopressin other hormones that increase cytosolic Ca2+ and activate protein kinase C increased permeability across the nuclear membrane of SKHep1 liver cells in a rapid unidirectional manner. An increase in cytosolic Ca2+ was both necessary and sufficient for this process. Furthermore, localized photorelease of caged Ca2+ near the nuclear envelope resulted in a local increase in nuclear permeability. Neither activation nor inhibition of protein kinase C affected nuclear permeability. These findings provide evidence that hormones linking to certain G protein-coupled receptors increase nuclear permeability via cytosolic Ca2+. Short term regulation of nuclear permeability may provide a novel mechanism by which such hormones permit transcription factors and other regulatory molecules to enter the nucleus, thereby regulating gene transcription in target cells. PMID:17158097

O'Brien, Elizabeth M.; Gomes, Dawidson A.; Sehgal, Sona; Nathanson, Michael H.

2010-01-01

262

Amino acids and cell regulation.  

PubMed Central

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

Forster, R. P.; Goldstein, L.

1979-01-01

263

Compliance with Sport Fishery Regulations in Minnesota as Related to Regulation Awareness  

Microsoft Academic Search

We quantified angler party awareness of regulations for 35 Minnesota fisheries using creel surveys. On average, 14% (range = 0–48%) of angler parties were unaware a regulation was in effect for a particular fishery, while 78% (range = 27–100%) of angler parties were aware a regulation was in effect. Awareness varied within and across regulated species: black crappie (Pomoxis nigromaculatus),

Kevin S. Page; Paul Radomski

2006-01-01

264

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

E-print Network

-reported effortful emotion regulation, and an adaptive pattern of cardiovascular responding. These findings suggest on deliberate, response-focused emotion regulation, as predicted by participants' explicit reports of emotionIMPLICIT EVALUATION OF EMOTION REGULATION 1 Running Head: IMPLICIT EVALUATION OF EMOTION REGULATION

Gross, James J.

265

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

E-print Network

scientific community as necessary to validate research findings including, but not limited to, researchRegulations on the Conduct of Research 1 REGULATION ON THE CONDUCT OF RESEARCH This Regulation replaces the following: Policy on Research Ethics Regulations on Research Policy PREAMBLE Research

Fabry, Frederic

266

Evidence for Central Regulation of Glucose Metabolism*  

PubMed Central

Evidence for central regulation of glucose homeostasis is accumulating from both animal and human studies. Central nutrient and hormone sensing in the hypothalamus appears to coordinate regulation of whole body metabolism. Central signals activate ATP-sensitive potassium (KATP) channels, thereby down-regulating glucose production, likely through vagal efferent signals. Recent human studies are consistent with this hypothesis. The contributions of direct and central inputs to metabolic regulation are likely of comparable magnitude, with somewhat delayed central effects and more rapid peripheral effects. Understanding central regulation of glucose metabolism could promote the development of novel therapeutic approaches for such metabolic conditions as diabetes mellitus. PMID:24142701

Carey, Michelle; Kehlenbrink, Sylvia; Hawkins, Meredith

2013-01-01

267

77 FR 28538 - Special Local Regulations; Annual Bayview Mackinac Race  

Federal Register 2010, 2011, 2012, 2013

...within the regulated area will be operated at...These proposed Special Local Regulations shall not...participating in the event or government vessels patrolling the regulated area. In the event these proposed Special Local Regulations affect...

2012-05-15

268

77 FR 36390 - Special Local Regulations; Annual Bayview Mackinac Race  

Federal Register 2010, 2011, 2012, 2013

...within the regulated area will be operated at a...craft. These Special Local Regulations shall not...participating in the event or government vessels patrolling the regulated area. In the event these Special Local Regulations affect...

2012-06-19

269

Epigenetic regulation of polyomavirus JC  

PubMed Central

Background Polyomavirus JC (JCV) causes the CNS demyelinating disease progressive multifocal leukoencephalopathy (PML), which occurs almost exclusively in people with immune deficiencies, such as HIV-1/AIDS patients. JCV infection is very common and usually occurs early in life. After primary infection, virus is controlled by the immune system but, rarely when immune function is impaired, it can re-emerge and multiply in the astrocytes and oligodendrocytes in the brain and cause PML. Thus a central question in PML pathogenesis is the nature of the molecular mechanisms maintaining JCV in a latent state and then allowing reactivation. Methods Since transcription can be regulated by epigenetic mechanisms including DNA methylation and histone acetylation, we investigated their role in JCV regulation by employing inhibitors of epigenetic events. Results The histone deacetylase inhibitors trichostatin A (TSA) and sodium butyrate powerfully stimulated JCV early and late transcription while the DNA methylation inhibitor 5-azacytidine had no effect. Analysis of JCV mutants showed that this effect was mediated by the KB element of the JCV control region, which binds transcription factors NF-?B p65, NFAT4 and C/EBP? and mediates stimulation by TNF-?. Stimulation of transcription by p65 was additive with TSA as was cotransfection with transcriptional coactivators/acetyltransferase p300 whereas depletion of endogenous p65 by RNA interference inhibited the effect of TSA. EMSA with a KB oligonucleotide showed p65 expression, TNF-? stimulation or TSA treatment each caused a gel shift that was further shifted by antibody to p65. Conclusions We conclude that JCV is regulated epigenetically by protein acetylation events and that these involve the NF-?B p65 binding site in the JCV control region. PMID:23971673

2013-01-01

270

Redox Regulation of Plant Development  

PubMed Central

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

Considine, Michael J.

2014-01-01

271

Circadian regulation of adipose function  

PubMed Central

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

Shostak, Anton; Husse, Jana; Oster, Henrik

2013-01-01

272

Inositol pyrophosphates regulate endocytic trafficking  

PubMed Central

The high energy potential and rapid turnover of the recently discovered inositol pyrophosphates, such as diphosphoinositol-pentakisphosphate and bis-diphosphoinositol-tetrakisphosphate, suggest a dynamic cellular role, but no specific functions have yet been established. Using several yeast mutants with defects in inositol phosphate metabolism, we identify dramatic membrane defects selectively associated with deficient formation of inositol pyrophosphates. We show that this phenotype reflects specific abnormalities in endocytic pathways and not other components of membrane trafficking. Thus, inositol pyrophosphates are major regulators of endocytosis. PMID:12391334

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

2002-01-01

273

Epigenetic regulation of photoperiodic flowering  

PubMed Central

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

2010-01-01

274

Neural Regulation of Mucosal Function  

PubMed Central

Nociceptive, parasympathetic and sympathetic nerves play critical roles in regulating glandular, vascular and other processes in airway mucosa. These functions are vital for cleaning and humidifying ambient air before it is inhaled into the lungs. Recent identification of subsets of nociceptive nerves has tipped the donkey cart of dogma and led to the discovery of new receptor and ion channel families that respond to culinary odorants (“aromatherapy”), inhaled irritants, temperature and other “humors”; a new interpretation of airway nociceptive nerve axon responses; and an understanding of the neural plasticity induced by inflammation and different neurotrophic factors. PMID:17707667

Baraniuk, James N.

2009-01-01

275

QB1 - Stochastic Gene Regulation  

SciTech Connect

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

Munsky, Brian [Los Alamos National Laboratory

2012-07-23

276

Returning common sense to regulations  

SciTech Connect

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

Fox, M.R.

1995-10-01

277

Regulation possibilities of biomass combustion  

NASA Astrophysics Data System (ADS)

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.

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

2012-11-01

278

Regulation of Primary Response Genes  

PubMed Central

Primary response genes (PRGs) are a set of genes that are induced in response to both cell-extrinsic and cell-intrinsic signals and do not require de novo protein synthesis for their expression. These 'first responders' in the waves of transcription of signal responsive genes play pivotal roles in a wide rage of biological responses, including neuronal survival and plasticity, cardiac stress response, innate and adaptive immune responses, glucose metabolism and oncogeneic transformation. Here we bring together recent advances and our current understanding of the signal-induced transcriptional and epigenetic regulation of PRGs. PMID:22055182

Fowler, Trent; Sen, Ranjan; Roy, Ananda L

2011-01-01

279

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

PubMed Central

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

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

2014-01-01

280

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

PubMed

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

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

2014-09-01

281

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

282

Melatonin regulation of biliary functions  

PubMed Central

The intrahepatic biliary epithelium is a three-dimensional tubular system lined by cholangiocytes, epithelial cells that in addition to modify ductal bile are also the targets of vanishing bile duct syndromes (i.e., cholangiopathies) such as primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) that are characterized by the damage/proliferation of cholangiocytes. Cholangiocyte proliferation is critical for the maintenance of the biliary mass and secretory function during the pathogenesis of cholangiopathies. Proliferating cholangiocytes serve as a neuroendocrine compartment during the progression of cholangiopathies, and as such secrete and respond to hormones, neurotransmitters and neuropeptides contributing to the autocrine and paracrine pathways that regulate biliary homeostasis. The focus of this review is to summarize the recent findings related to the role of melatonin in the modulation of biliary functions and liver damage in response to a number of insults. We first provide a general background on the general function of cholangiocytes including their anatomic characteristics, their innervation and vascularization as well the role of these cells on secretory and proliferation events. After a background on the synthesis and regulation of melatonin and its role on the maintenance of circadian rhythm, we will describe the specific effects of melatonin on biliary functions and liver damage. After a summary of the topics discussed, we provide a paragraph on the future perspectives related to melatonin and liver functions. PMID:24696836

Glaser, Shannon; Han, Yuyan; Francis, Heather

2014-01-01

283

Microbial Regulation in Gorgonian Corals  

PubMed Central

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

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

2012-01-01

284

Opening up on ELMO regulation  

PubMed Central

GTPases are central hubs for directing cytoskeletal reorganization and cell migration. The DOCK family enforces positive regulation of certain GTPases, leading to their activation in discrete areas of the cell. ELMO, a well-known DOCK180 binding partner, has been cast with the role of potentiating DOCK180-mediated Rac activation. Exactly how ELMO contributes to Rac signaling is only beginning to be understood. Here, we discuss our most recent research investigating ELMO regulation of the DOCK180/Rac pathway. Interestingly, we found that ELMO is autoinhibited via intramolecular contacts at basal levels and we explore the novel domains that we identified at the heart of the auto-regulatory switch. We propose that the closed ELMO molecule masks protein-protein interfaces or domains with novel uncharacterized function; cell stimulation and GTPase binding to ELMO is proposed to activate (open) the protein and/or target the ELMO/DOCK180 complex to the cell membrane. In this manner, promiscuous signaling/activity downstream of ELMO/DOCK180 can be controlled for both spatially and temporally. Additionally, we report new data highlighting that DOCK proteins can form heterodimers, and we discuss possible mechanisms that could be implicated in controlling the ELMO activation state. PMID:22292130

Patel, Manishha; Pelletier, Ariane

2011-01-01

285

Regulated cell death in AKI.  

PubMed

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

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

2014-12-01

286

How cholesterol regulates endothelial biomechanics  

PubMed Central

As endothelial cells form the barrier between blood flow and surrounding tissue, many of their functions depend on mechanical integrity, in particular those of the plasma membrane. As component and organizer of the plasma membrane, cholesterol is a regulator of cellular mechanical properties. Disruption of cholesterol balance leads to impairment of endothelial functions and eventually to disease. The mechanical properties of the membrane are strongly affected by the cytoskeleton. As Phosphatidylinositol-4,5-bisphosphate (PIP2) is a key mediator between the membrane and cytoskeleton, it also affects cellular biomechanical properties. Typically, PIP2 is concentrated in cholesterol-rich microdomains, such as caveolae and lipid rafts, which are particularly abundant in the endothelial plasma membrane. We investigated the connection between cholesterol and PIP2 by extracting membrane tethers from bovine aortic endothelial cells (BAEC) at different cholesterol levels and PIP2 conditions. Our results suggest that in BAEC the role of PIP2, as a mediator of membrane-cytoskeleton adhesion, is regulated by cholesterol. Our findings confirm the specific role of cholesterol in endothelial cells and may have implications for cholesterol-dependent vascular pathologies. PMID:23162471

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

2012-01-01

287

Connexin40 regulates platelet function  

PubMed Central

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

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

2013-01-01

288

Microbial regulation in gorgonian corals.  

PubMed

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

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

2012-06-01

289

Dynamic Voltage Regulation Using Distributed Energy Resources  

SciTech Connect

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

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

2007-01-01

290

Measures of Effortful Regulation for Young Children  

PubMed Central

Emotion-related regulation is a topic of increasing interest among researchers, yet there is little agreement on ways to measure emotion regulation in young children. In this paper, we first consider important conceptual distinctions in regard to the different types of emotion-related regulation and control. Next, we describe a number of ways researchers have assessed children’s regulation. We also present data from the Toddler Emotional Development project, in which laboratory-based measures of effortful regulation were used. In this section, we highlight the measures that show promise (and those that did not work well). Future directions for research on the measurement of effortful regulation are presented. PMID:18066395

Spinrad, Tracy L.; Eisenberg, Nancy; Gaertner, Bridget M.

2005-01-01

291

Hormonal regulation of the hypothalamic melanocortin system  

PubMed Central

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

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

2014-01-01

292

Liability of Regulators New Dutch Style  

Microsoft Academic Search

Once upon a time in the world of money and greed, financial regulators saw a\\u000amajor crisis unfolding under their watch. But the regulators did not fear because\\u000athey were immune to liability. Because one day, they had got together and issued\\u000aa statement that all financial regulators be made immune. The statement also\\u000asaid that this immunity would only

C. C. van Dam

2011-01-01

293

A Simple Framework for Regulation of Biofuels  

Microsoft Academic Search

\\u000a In this chapter, we develop a framework to regulate producers of biofuel-blended fuels using GHG emissions standards, while\\u000a accounting for heterogeneity and uncertainty. To this end, we categorize the net GHG emissions caused by a regulated site\\u000a into two parts: direct and indirect emissions. Direct emissions arise both at and away from the final regulated site but are\\u000a directly attributable

Deepak Rajagopal; Gal Hochman; David Zilberman

294

Circuit Regulates Speed Of dc Motor  

NASA Technical Reports Server (NTRS)

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

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

1990-01-01

295

Focus Issue: Regulation of Lymphocyte Function  

NSDL National Science Digital Library

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

Ernesto Andrianantoandro (American Association for the Advancement of Science; Science Signaling REV)

2012-07-31

296

Mood-Regulating Strategies Used By Athletes  

Microsoft Academic Search

This study examined strategies used to self-regulate mood dimensions assessed by the Profile of Mood States (McNair, Lorr, & Droppleman, 1971) in athletes. One hundred and seven athletes completed a 29-item mood regulation questionnaire (Thayer, Newman, & McClain, 1994) assessing strategies aimed at regulating anger, confusion, depression, fatigue, tension, and vigor. Results indicated that to 'change location', 'exercise', and 'listen

Matthew J. Stevens

2001-01-01

297

Circadian Clock Proteins in Mood Regulation  

PubMed Central

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

Partonen, Timo

2015-01-01

298

MicroRNA Regulation of Cardiovascular Development  

Microsoft Academic Search

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

Eric Olson; Kimberly R. Cordes; Deepak Srivastava

2009-01-01

299

Phosphorylation Regulates SIRT1 Function  

PubMed Central

Background SIR2 is an NAD+-dependent deacetylase [1]–[3] implicated in the regulation of lifespan in species as diverse as yeast [4], worms [5], and flies [6]. We previously reported that the level of SIRT1, the mammalian homologue of SIR2 [7], [8], is coupled to the level of mitotic activity in cells both in vitro and in vivo [9]. Cells from long-lived mice maintained SIRT1 levels of young mice in tissues that undergo continuous cell replacement by proliferating stem cells. Changes in SIRT1 protein level were not associated with changes in mRNA level, suggesting that SIRT1 could be regulated post-transcriptionally. However, other than a recent report on sumoylation [10] and identification of SIRT1 as a nuclear phospho-protein by mass spectrometry [11], post-translational modifications of this important protein have not been reported. Methodology/Principal Findings We identified 13 residues in SIRT1 that are phosphorylated in vivo using mass spectrometry. Dephosphorylation by phosphatases in vitro resulted in decreased NAD+-dependent deacetylase activity. We identified cyclinB/Cdk1 as a cell cycle-dependent kinase that forms a complex with and phosphorylates SIRT1. Mutation of two residues phosphorylated by Cyclin B/Cdk1 (threonine 530 and serine 540) disturbs normal cell cycle progression and fails to rescue proliferation defects in SIRT1-deficient cells [12], [13]. Conclusions/Significance Pharmacological manipulation of SIRT1 activity is currently being tested as a means of extending lifespan in mammals. Treatment of obese mice with resveratrol, a pharmacological activator of SIRT1, modestly but significantly improved longevity and, perhaps more importantly, offered some protection against the development of type 2 diabetes mellitus and metabolic syndrome [14]–[16]. Understanding the endogenous mechanisms that regulate the level and activity of SIRT1, therefore, has obvious relevance to human health and disease. Our results identify phosphorylation by cell cycle dependent kinases as a major mechanism controlling the level and function of this sirtuin and complement recent reports of factors that inhibit [17], [18] and activate [19] SIRT1 by protein-protein interactions. PMID:19107194

Sasaki, Tsutomu; Maier, Bernhard; Koclega, Katarzyna D.; Chruszcz, Maksymilian; Gluba, Wendy; Stukenberg, P. Todd; Minor, Wladek; Scrable, Heidi

2008-01-01

300

Ultra-Low-Dropout Linear Regulator  

NASA Technical Reports Server (NTRS)

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

Thornton, Trevor; Lepkowski, William; Wilk, Seth

2011-01-01

301

Exporting licensing regulations affecting US geothermal firms  

SciTech Connect

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

Not Available

1988-08-01

302

Regulation of the photosynthetic electron transport chain.  

PubMed

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

Ott; Clarke; Birks; Johnson

1999-08-12

303

Light regulation of stomatal movement.  

PubMed

Stomatal pores, each surrounded by a pair of guard cells, regulate CO2 uptake and water loss from leaves. Stomatal opening is driven by the accumulation of K+ salts and sugars in guard cells, which is mediated by electrogenic proton pumps in the plasma membrane and/or metabolic activity. Opening responses are achieved by coordination of light signaling, light-energy conversion, membrane ion transport, and metabolic activity in guard cells. In this review, we focus on recent progress in blue- and red-light-dependent stomatal opening. Because the blue-light response of stomata appears to be strongly affected by red light, we discuss underlying mechanisms in the interaction between blue-light signaling and guard cell chloroplasts. PMID:17209798

Shimazaki, Ken-ichiro; Doi, Michio; Assmann, Sarah M; Kinoshita, Toshinori

2007-01-01

304

Metabolic regulation of immune responses.  

PubMed

The immune system defends against pathogens and maintains tissue homeostasis for the life of the organism. These diverse functions are bioenergetically expensive, requiring precise control of cellular metabolic pathways. Although initial observations in this area were made almost a century ago, studies over the past decade have elucidated the molecular basis for how extracellular signals control the uptake and catabolism of nutrients in quiescent and activated immune cells. Collectively, these studies have revealed that the metabolic pathways of oxidative metabolism, glycolysis, and glutaminolysis preferentially fuel the cell fate decisions and effector functions of immune cells. Here, we discuss these findings and provide a general framework for understanding how metabolism fuels and regulates the maturation of immune responses. A better understanding of the metabolic checkpoints that control these transitions might provide new insights for modulating immunity in infection, cancer, or inflammatory disorders. PMID:24655299

Ganeshan, Kirthana; Chawla, Ajay

2014-01-01

305

Homologous recombination and its regulation  

PubMed Central

Homologous recombination (HR) is critical both for repairing DNA lesions in mitosis and for chromosomal pairing and exchange during meiosis. However, some forms of HR can also lead to undesirable DNA rearrangements. Multiple regulatory mechanisms have evolved to ensure that HR takes place at the right time, place and manner. Several of these impinge on the control of Rad51 nucleofilaments that play a central role in HR. Some factors promote the formation of these structures while others lead to their disassembly or the use of alternative repair pathways. In this article, we review these mechanisms in both mitotic and meiotic environments and in different eukaryotic taxa, with an emphasis on yeast and mammal systems. Since mutations in several proteins that regulate Rad51 nucleofilaments are associated with cancer and cancer-prone syndromes, we discuss how understanding their functions can lead to the development of better tools for cancer diagnosis and therapy. PMID:22467216

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

2012-01-01

306

Multiple pathways regulate shoot branching  

PubMed Central

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.

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

2015-01-01

307

DNA methylation regulated nucleosome dynamics.  

PubMed

A strong correlation between nucleosome positioning and DNA methylation patterns has been reported in literature. However, the mechanistic model accounting for the correlation remains elusive. In this study, we evaluated the effects of specific DNA methylation patterns on modulating nucleosome conformation and stability using FRET and SAXS. CpG dinucleotide repeats at 10?bp intervals were found to play different roles in nucleosome stability dependent on their methylation states and their relative nucleosomal locations. An additional (CpG)5 stretch located in the nucleosomal central dyad does not alter the nucleosome conformation, but significant conformational differences were observed between the unmethylated and methylated nucleosomes. These findings suggest that the correlation between nucleosome positioning and DNA methylation patterns can arise from the variations in nucleosome stability dependent on their sequence and epigenetic content. This knowledge will help to reveal the detailed role of DNA methylation in regulating chromatin packaging and gene transcription. PMID:23817195

Jimenez-Useche, Isabel; Ke, Jiaying; Tian, Yuqing; Shim, Daphne; Howell, Steven C; Qiu, Xiangyun; Yuan, Chongli

2013-01-01

308

Molecular regulation of fruit ripening  

PubMed Central

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

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

2013-01-01

309

Taurine regulates mitochondrial calcium homeostasis.  

PubMed

We have investigated the protective role of taurine in glutamate-mediated cell death and the involvement of mitochondria in this process. In cultured cerebellar granule cells, glutamate induces a rapid and sustained elevation in cytoplasmic free calcium ([Ca2+]i), causing the collapse of the mitochondrial electrochemical gradient (MtECG) and subsequent cell death. We found that pre-treatment with taurine, did not affect the level of calcium uptake with glutamate but rather reduced its duration; the calcium increase was transient and returned to basal levels about 10 min after adding glutamate. Furthermore, taurine reduced mitochondrial calcium concentration under non-depolarizing conditions. Treatment of cerebellar granule cells with taurine enhanced mitochondrial activity as measured by rhodamine uptake, both in the presence or absence of glutamate. We conclude that taurine prevents or reduces glutamate excitotoxicity through both the enhancement of mitochondrial function and the regulation of intracellular (cytoplasmic and mitochondrial) calcium homeostasis. PMID:12908639

El Idrissi, Abdeslem; Trenkner, Ekkhart

2003-01-01

310

Metallochaperones Regulate Intracellular Copper Levels  

PubMed Central

Copper (Cu) is an important enzyme co-factor that is also extremely toxic at high intracellular concentrations, making active efflux mechanisms essential for preventing Cu accumulation. Here, we have investigated the mechanistic role of metallochaperones in regulating Cu efflux. We have constructed a computational model of Cu trafficking and efflux based on systems analysis of the Cu stress response of Halobacterium salinarum. We have validated several model predictions via assays of transcriptional dynamics and intracellular Cu levels, discovering a completely novel function for metallochaperones. We demonstrate that in addition to trafficking Cu ions, metallochaperones also function as buffers to modulate the transcriptional responsiveness and efficacy of Cu efflux. This buffering function of metallochaperones ultimately sets the upper limit for intracellular Cu levels and provides a mechanistic explanation for previously observed Cu metallochaperone mutation phenotypes. PMID:23349626

Pang, W. Lee; Kaur, Amardeep; Ratushny, Alexander V.; Cvetkovic, Aleksandar; Kumar, Sunil; Pan, Min; Arkin, Adam P.; Aitchison, John D.; Adams, Michael W. W.; Baliga, Nitin S.

2013-01-01

311

Epigenetic Regulation by Heritable RNA  

PubMed Central

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

Liebers, Reinhard; Rassoulzadegan, Minoo; Lyko, Frank

2014-01-01

312

Phosphatase regulation of intercellular junctions  

PubMed Central

Intercellular junctions represent the key contact points and sites of communication between neighboring cells. Assembly of these junctions is absolutely essential for the structural integrity of cell monolayers, tissues and organs. Disruption of junctions can have severe consequences such as diarrhea, edema and sepsis, and contribute to the development of chronic inflammatory diseases. Cell junctions are not static structures, but rather they represent highly dynamic micro-domains that respond to signals from the intracellular and extracellular environments to modify their composition and function. This review article will focus on the regulation of tight junctions and adherens junctions by phosphatase enzymes that play an essential role in preserving and modulating the properties of intercellular junction proteins. PMID:24868494

McCole, Declan F

2013-01-01

313

Mechanisms regulating epidermal stem cells  

PubMed Central

The skin epidermis contains different appendages such as the hair follicle and the sebaceous glands. Recent studies demonstrated that several types of stem cells (SCs) exist in different niches within the epidermis and maintain discrete epidermal compartments, but the exact contribution of each SC populations under physiological conditions is still unclear. In addition, the precise mechanisms controlling the balance between proliferation and differentiation of epidermal SC still remain elusive. Recent studies provide new insights into these important questions by showing the contribution of hair follicle SC to the sebaceous lineage and the importance of chromatin modifications and micro-RNAs (miRs) in regulating epidermal SCs renewal and differentiation. In this review, we will discuss the importance of these papers to our understanding of the mechanisms that control epidermal SC functions. PMID:22433839

Beck, Benjamin; Blanpain, Cédric

2012-01-01

314

HISTONE METHYLATION REGULATES MEMORY FORMATION  

PubMed Central

It has been established that regulation of chromatin structure through post-translational modification of histone proteins, primarily histone H3 phosphorylation and acetylation, is an important early step in the induction of synaptic plasticity and formation of long-term memory. In this study, we investigated the contribution of another histone modification, histone methylation, to memory formation in the adult hippocampus. We found that tri-methylation of histone H3 at lysine 4 (H3K4), an active mark for transcription, is upregulated in hippocampus one hour following contextual fear conditioning. In addition, we found that di-methylation of histone H3 at lysine 9 (H3K9), a molecular mark associated with transcriptional silencing, is increased one hour after fear conditioning and decreased twenty-four hours after context exposure alone and contextual fear conditioning. Tri-methylated H3K4 levels returned to baseline levels at twenty-four hours. We also found that mice deficient in the H3K4-specific histone methyltransferase, Mll, displayed deficits in contextual fear conditioning relative to wildtype animals. This suggests that histone methylation is required for proper long-term consolidation of contextual fear memories. Interestingly, inhibition of histone deacetylases (HDACs) with sodium butyrate (NaB) resulted in increased H3K4 tri-methylation and decreased H3K9 di-methylation in hippocampus following contextual fear conditioning. Correspondingly, we found that fear learning triggered increases in H3K4 tri-methylation at specific gene promoter regions (Zif268 and bdnf) with altered DNA methylation and MeCP2 DNA binding. Zif268 DNA methylation levels returned to baseline at twenty-four hours. Together, these data demonstrate that histone methylation is actively regulated in the hippocampus and facilitates long-term memory formation. PMID:20219993

Gupta, Swati; Kim, Se Y.; Artis, Sonja; Molfese, David L.; Schumacher, Armin; Sweatt, J. David; Paylor, Richard E.; Lubin, Farah D.

2010-01-01

315

Neural Mechanisms of Grief Regulation  

PubMed Central

Background: The death of an attachment figure triggers intrusive thoughts of the deceased, sadness, and yearning for reunion. Recovery requires reduction of symptoms. We hypothesized that symptoms might correlate with a capacity to regulate attention toward reminders of the deceased, and activity in, and functional connectivity between, prefrontal regulatory regions and the amygdala. Methods: Twenty recently bereaved subjects rated intrusive thoughts of the deceased versus a capacity to avoid thoughts (grief style). Reaction time was measured while subjects completed an Emotional Stroop (ES) task contrasting deceased-related with control words during functional magnetic resonance imaging (fMRI). Subjects subsequently visualized the death of the deceased and rated induced emotions. Results: Subjects demonstrated attentional bias toward deceased-related words. Bias magnitude correlated with amygdala, insula, dorsolateral prefrontal cortex (DLPFC) activity. Amygdala activity predicted induced sadness intensity. A double dissociation between grief style and both prefrontal and amygdala subregion activity was found. Intrusiveness correlated with activation of ventral amygdala and rostral anterior cingulate (rACC); avoidance correlated with deactivation of dorsal amygdala and DLPFC. A double dissociation between regulatory region and task-dependent functional connectivity (FC) was found. High DLPFC-amygdala FC correlated with reduced attentional bias, while low rACC-amygdala FC predicted sadness intensity. Conclusions: Results are consistent with a model in which activity in and functional connectivity between the amygdala and prefrontal regulatory regions indexes differences in mourners' regulation of attention and sadness during pangs of grief, and may be used to distinguish between clinically relevant differences in grief style. PMID:19249748

Freed, Peter J.; Yanagihara, Ted K.; Hirsch, Joy; Mann, J. John

2009-01-01

316

Environmental statistics and optimal regulation.  

PubMed

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

Sivak, David A; Thomson, Matt

2014-09-01

317

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

Code of Federal Regulations, 2010 CFR

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

2010-07-01

318

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

Code of Federal Regulations, 2013 CFR

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

2013-07-01

319

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

Code of Federal Regulations, 2011 CFR

...Federal Property Management Regulations; 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...

2011-07-01

320

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

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

2014-07-01

321

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

Code of Federal Regulations, 2012 CFR

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

2012-07-01

322

78 FR 75672 - New Jersey Regulations on Transportation of Regulated Medical Waste  

Federal Register 2010, 2011, 2012, 2013

...DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety...R)] New Jersey Regulations on Transportation of Regulated Medical Waste AGENCY...Requirements: Federal hazardous material transportation law, 49 U.S.C. 5101 et...

2013-12-12

323

Implementation Regulations MSc Chemical Engineering 2013-2014 THE IMPLEMENTATION REGULATIONS  

E-print Network

.........................................................................................4 Article 6 ­ The Process Engineering track. The programme comprises the following tracks: - Chemical Product Engineering, - Process Engineering, - NuclearImplementation Regulations MSc Chemical Engineering 2013-2014 THE IMPLEMENTATION REGULATIONS 2013

324

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

E-print Network

students with guidelines for achieving their personal academic goals; they should provide a meansACADEMIC REGULATIONS 2013-2014 #12;Page 2 Academic Regulations is an annual publication _________________________________________________________________________________ Academic Regulations 5 Academic Honesty 6 Enrollment Categories 6 Academic Status 8 Graduation Requirements

Massachusetts at Amherst, University of

325

Erratic Black Hole Regulates Itself  

NASA Astrophysics Data System (ADS)

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

2009-03-01

326

The effects of the heme precursor 5-aminolevulinic acid (ALA) on REV-ERB? activation  

PubMed Central

The nuclear receptor, REV-ERB?, has a key role in circadian rhythms and requires heme as its ligand. The present study determined whether the heme precursor, 5-aminolevulinic acid (ALA), affects REV-ERB? and its target genes. When exposed to ALA, the human lung diploid cell line, WI-38, exhibited activation of REV-ERB? and repression of the transcription of REV-ERB? target genes, including BMAL1, an essential component of the circadian oscillator. Moreover, co-incubation of sodium ferrous citrate (SFC) and ALA also activated REV-ERB? and repressed the transcription of REV-ERB? target genes. These results indicate that ALA regulates human circadian rhythms via REV-ERB?. PMID:24918048

Yamashita, Kohei; Hagiya, Yuichiro; Nakajima, Motowo; Ishizuka, Masahiro; Tanaka, Tohru; Ogura, Shun-ichiro

2014-01-01

327

The Histone Acetyltransferase CLOCK Is an Essential Component of the Herpes Simplex Virus 1 Transcriptome That Includes TFIID, ICP4, ICP27, and ICP22 ?  

PubMed Central

Studies published elsewhere have shown that the herpes simplex virus regulatory protein ICP0 interacts with BMAL1, a partner and regulator of circadian histone acetyltransferase CLOCK, that both proteins localize at ND10 bodies and are stabilized by viral proteins, that enzymatically active CLOCK partially complements ?ICP0 mutants, and that silencing of CLOCK suppresses the expression of viral genes. Here we report that CLOCK is a component of the transcriptional complex that includes TFIID, ICP4, ICP27, and ICP22. The results suggest that the CLOCK histone acetyltransferase is a component of the viral transcriptional machinery throughout the replicative cycle of the virus and that ICP27 and ICP22 initiate their involvement in viral gene expression as components of viral transcriptome. PMID:21734043

Kalamvoki, Maria; Roizman, Bernard

2011-01-01

328

Central Circadian Control of Female Reproductive Function  

PubMed Central

Over the past two decades, it has become clear just how much of our physiology is under the control of the suprachiasmatic nucleus (SCN) and the cell-intrinsic molecular clock that ticks with a periodicity of approximately 24?h. The SCN prepares our digestive system for meals, our adrenal axis for the stress of waking up in the morning, and the genes expressed in our muscles when we prepare to exercise. Long before molecular studies of genes such as Clock, Bmal1, and the Per homologs were possible, it was obvious that female reproductive function was under strict circadian control at every level of the hypothalamic-pituitary-gonadal axis, and in the establishment and successful maintenance of pregnancy. This review highlights our current understanding of the role that the SCN plays in regulating female reproductive physiology, with a special emphasis on the advances made possible through the use of circadian mutant mice. PMID:24478756

Miller, Brooke H.; Takahashi, Joseph S.

2014-01-01

329

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

PubMed Central

Summary Circadian oscillations in mammalian physiology and behavior are regulated by an endogenous biological clock. Here we show that loss of the PAS protein MOP3 (also known as BMAL1) in mice results in immediate and complete loss of circadian rhythmicity in constant darkness. Additionally, locomotor activity in light–dark (LD) cycles is impaired and activity levels are reduced in Mop3?/? mice. Analysis of Period gene expression in the suprachiasmatic nucleus (SCN) indicates that these behavioral phenotypes arise from loss of circadian function at the molecular level. These results provide genetic evidence that MOP3 is the bona fide heterodimeric partner of mCLOCK. Furthermore, these data demonstrate that MOP3 is a non-redundant and essential component of the circadian pacemaker in mammals. PMID:11163178

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

2013-01-01

330

Engineer Regulation 1110-2-1150  

E-print Network

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

US Army Corps of Engineers

331

7 CFR 984.49 - Volume regulation.  

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

2014-01-01

332

7 CFR 984.49 - Volume regulation.  

Code of Federal Regulations, 2011 CFR

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

2011-01-01

333

7 CFR 984.49 - Volume regulation.  

Code of Federal Regulations, 2013 CFR

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

2013-01-01

334

7 CFR 984.49 - Volume regulation.  

Code of Federal Regulations, 2012 CFR

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

2012-01-01

335

Measuring Generalized Expectancies for Negative Mood Regulation.  

ERIC Educational Resources Information Center

Research has suggested the utility of studying individual differences in the regulation of negative mood states. Generalized response expectancies for negative mood regulation were defined as expectancies that some overt behavior or cognition would alleviate negative mood states as they occur across situations. The Generalized Expectancy for…

Catanzaro, Salvatore J.; Mearns, Jack

336

Gun Control after Heller: Litigating against Regulation  

Microsoft Academic Search

The “core right” established in D.C. vs. Heller (2008) is to keep an operable handgun in the home for self-defense purposes. If the Court extends this right to cover state and local jurisdictions, the result is likely to include the elimination of the most stringent existing regulations – such as Chicago’s handgun ban – and could also possibly ban regulations

Philip J. Cook; Jens Ludwig; Adam Samaha

2009-01-01

337

Self-starting circuit for switching regulators  

NASA Technical Reports Server (NTRS)

Schematic is provided on a self-starting circuit for a switching regulator which uses a logic circuit to sense a change in output voltage and provides a correction signal for dc power sources. With this device, the total power consumed by the logic circuitry is held to a minimum, and the circuit receives the optimum regulated supply power.

Schraut, E. H.; Sohl, G.

1969-01-01

338

Group Regulation of Urban 4KV Feeders  

Microsoft Academic Search

The best way, theoretically, to maintain ideal voltage conditions on a given feeder is to equip each of its phases with a regulator. However, other factors in addition to voltage regulation must be considered in a practical co-ordinated design. The engineering approach toward accomplishing a purpose with the minimum physical facilities must be adhered to both in improving an old

C. L. Grim; H. B. Peck

1951-01-01

339

Epigenetic regulation of aging stem cells  

Microsoft Academic Search

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

E A Pollina; A Brunet

2011-01-01

340

PATTERNS & PHENOTYPES Piwi Regulates Vasa Accumulation During  

E-print Network

a PATTERNS & PHENOTYPES Piwi Regulates Vasa Accumulation During Embryogenesis in the Sea Urchin in epigenetic and somatic gene regulation. In the sea urchin Strongylocentrotus purpuratus, two Piwi proteins transposons, and is potentially functioning both inside and outside of the germ line during embryogenesis

Wessel, Gary M.

341

The Kidney and Acid-Base Regulation  

ERIC Educational Resources Information Center

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

Koeppen, Bruce M.

2009-01-01

342

On the Nature of Emotion Regulation  

Microsoft Academic Search

This paper presents a unitary approach to emotion and emotion regulation, building on the excellent points in the lead article by Cole, Martin, and Dennis (this issue), as well as the fine commentaries that follow it. It begins by stressing how, in the real world, the processes underlying emotion and emotion regulation appear to be largely one and the same,

Joseph J. Campos; Carl B. Frankel; Linda Camras

2004-01-01

343

Input filter compensation for switching regulators  

NASA Technical Reports Server (NTRS)

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

Lee, F. C.

1984-01-01

344

Emotion Regulation in Children with Anxiety Disorders  

ERIC Educational Resources Information Center

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

Suveg, Cynthia; Zeman, Janice

2004-01-01

345

REGULATION OF HONEY BEE HOARDING EFFICIENCY  

E-print Network

REGULATION OF HONEY BEE HOARDING EFFICIENCY Thomas E. RINDERER Bee Breeding and Stock Center.01). This supports the hypothesis that empty comb volatiles in honey bee nests regulate the acceptance of nectar sources by honey bee nectar foragers across seasonally varying conditions of nectar availability. Empty

Boyer, Edmond

346

Emotion and emotion regulation: from another perspective.  

PubMed

An overview of the content of the From Another Perspective collection on emotion and emotion regulation is provided. The lead article identifies fundamental issues of definition and the commentaries represent varying theoretical and methodological perspectives on emotion and emotion regulation. Together, the articles discuss the promises and pitfalls of emotion research and its potential for understanding child development. PMID:15056185

Langlois, Judith H

2004-01-01

347

Emotion and Emotion Regulation: From Another Perspective  

ERIC Educational Resources Information Center

An overview of the content of the From Another Perspective collection on emotion and emotion regulation is provided. The lead article identifies fundamental issues of definition and the commentaries represent varying theoretical and methodological perspectives on emotion and emotion regulation. Together, the articles discuss the promises and…

Langlois, Judith H.

2004-01-01

348

Markov process modelling of gene regulation  

Microsoft Academic Search

This paper discusses the mathematical modelling of gene regulation with emphasis on the bottom-up modelling of genetic componentry rather than the reverse-engineering of networks from gene expression data. Reflecting the stochastic nature of gene regulation, the chemical master equation is used as a tool to study Markovian models of networks of gene states between which probabilistic transitions occur. These states

Hilary S. Booth; Conrad J. Burden; Markus Hegland; Lucia Santoso

349

Stress Hormones: Their Interaction and Regulation  

Microsoft Academic Search

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

Julius Axelrod; Terry D. Reisine

1984-01-01

350

Self-Regulation: Calm, Alert, and Learning  

ERIC Educational Resources Information Center

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

Shanker, Stuart

2010-01-01

351

Regulation of mammary gland remodelling and lactation  

E-print Network

Session II Regulation of mammary gland remodelling and lactation Dr. Y. Chilliard, Prof. T. Motyl and expression of genes involved in regulation of mammary gland function, genes encoding milk proteins and mammary tissue enzymes; 2. apoptosis as a fundamental process responsible for mammary gland involution; 3

Paris-Sud XI, Université de

352

Affect Regulation in Borderline Personality Disorder  

Microsoft Academic Search

Although difficulty with affect regulation is generally considered a core component of borderline personality disorder (BPD), surprisingly little research has focused on the nature of affect regulation and dysregulation in BPD. A random national sample of 117 experienced clinicians provided data on a randomly selected patient with BPD (N 90) or dysthymic disorder (DD; N 27). Clinicians described their patients

Carolyn Zittel Conklin; Rebekah Bradley; Drew Westen

2006-01-01

353

State regulation of midwives: issues and options  

Microsoft Academic Search

In the United States, state governments play a central role in determining the extent to which midwives can provide care to women and babies. State laws and regulations establish midwives’ scope of practice, set licensure requirements, and frequently determine their ability to get paid and obtain access to health care facilities. For certified nurse-midwives (CNMs), state regulation has evolved from

Alyson Reed; Joyce E. Roberts

2000-01-01

354

Emotion Regulation and Childhood Aggression: Longitudinal Associations  

ERIC Educational Resources Information Center

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

Roll, Judith; Koglin, Ute; Petermann, Franz

2012-01-01

355

Self-Regulation and Learning Strategies  

ERIC Educational Resources Information Center

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

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

2011-01-01

356

Automatic Voltage Regulation of DC Shunt Generators  

Microsoft Academic Search

In a dc shunt generator, as the load increases the terminal voltage falls, giving a drooping characteristic. The regulation of voltage involves the adjustment of field excitation. A simple method of voltage regulation by automatic adjustment of field excitation making use of transistor circuitry is discussed. The added advantage of this method is that by the simple adjustment of circuit

Vimal Singh; S. K. Kak; Srinivasan Rangarajan

1973-01-01

357

Entrepreneurship and regulation: dynamics and political economy  

Microsoft Academic Search

Three dynamic, descriptive models of the economy are studied in which entrepreneurship and regulation are interdependent. These models, adapted from population biology, capture Baumol's observation that economic regulations are used by entrepreneurs against entrepreneurs and therefore should be made an endogenous variable in a theory of the supply of entrepreneurship. The models differ in the number of competitive processes admitted,

L. W. Lee

1991-01-01

358

Shale gas development: a smart regulation framework.  

PubMed

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

Konschnik, Katherine E; Boling, Mark K

2014-08-01

359

On the nature of emotion regulation.  

PubMed

This paper presents a unitary approach to emotion and emotion regulation, building on the excellent points in the lead article by Cole, Martin, and Dennis (this issue), as well as the fine commentaries that follow it. It begins by stressing how, in the real world, the processes underlying emotion and emotion regulation appear to be largely one and the same, rendering the value of the distinction largely for the benefit of analysis. There is an extensive discussion of how the same processes can generate emotions (i.e., are constitutive of emotion) and account for variability of manifestation of emotion in context (i.e., regulate them). Following an extensive review of many of the principles involved in emotion and emotion regulation, the paper presents implications for developmental study of infants and children, includes several methodological recommendations, and concludes with an analysis of the extent to which contemporary affective neuroscience contributes to the study of emotion and emotion regulation. PMID:15056194

Campos, Joseph J; Frankel, Carl B; Camras, Linda

2004-01-01

360

mTOR regulation of autophagy  

PubMed Central

Nutrient starvation induces autophagy in eukaryotic cells through inhibition of TOR (target of rapamycin), an evolutionarily-conserved protein kinase. TOR, as a central regulator of cell growth, plays a key role at the interface of the pathways that coordinately regulate the balance between cell growth and autophagy in response to nutritional status, growth factor and stress signals. Although TOR has been known as a key regulator of autophagy for more than a decade, the underlying regulatory mechanisms have not been clearly understood. This review discusses the recent advances in understanding of the mechanism by which TOR regulates autophagy with focus on mammalian TOR (mTOR) and its regulation of the autophagy machinery. PMID:20083114

Jung, Chang Hwa; Ro, Seung-Hyun; Cao, Jing; Otto, Neil Michael; Kim, Do-Hyung

2010-01-01

361

Differential Regulation of Cystic Fibrosis Transmembrane Conductance Regulator by Interferon   in Mast Cells and Epithelial Cells  

Microsoft Academic Search

ABSTRACT Cystic fibrosis transmembrane,conductance,regulator (CFTR) is a cAMP-dependent chloride channel in epithelial cells; recently, we,identified it in mast,cells. Previous work,that we,confirmed showed,that interferon ? (IFN?) down-regulated,CFTR expres- sion in epithelial cells (T84), but by contrast, we found that IFN? up-regulated,CFTR mRNA and,protein expression,in rat and human,mast,cells. IFN? up-regulation,of CFTR in mast,cells was,inhibited by p38 and,extracellular signal-regulated kinase (ERK) kinase,inhibitors but

Marianna Kulka

2005-01-01

362

Neural network enhanced output regulation in nonlinear systems  

Microsoft Academic Search

The solvability of the nonlinear output regulation problem relies on the existence of a feedforward function defined by a set of mixed nonlinear partial and algebraic equations called regulator equations. Previous approaches to solving the output regulation problem call for the solution of the regulator equations. However, solving the regulator equations is difficult due to the nonlinearity and complexity. This

Jin Wang; Jie Huang

2001-01-01

363

Metabolic regulation of antibiotic resistance.  

PubMed

It is generally assumed that antibiotics and resistance determinants are the task forces of a biological warfare in which each resistance determinant counteracts the activity of a specific antibiotic. According to this view, antibiotic resistance might be considered as a specific response to an injury, not necessarily linked to bacterial metabolism, except for the burden that the acquisition of resistance might impose on the bacteria (fitness costs). Nevertheless, it is known that changes in bacterial metabolism, such as those associated with dormancy or biofilm formation, modulate bacterial susceptibility to antibiotics (phenotypic resistance), indicating that there exists a linkage between bacterial metabolism and antibiotic resistance. The analyses of the intrinsic resistomes of bacterial pathogens also demonstrate that the building up of intrinsic resistance requires the concerted action of many elements, several of which play a relevant role in the bacterial metabolism. In this article, we will review the current knowledge on the linkage between bacterial metabolism and antibiotic resistance and will discuss the role of global metabolic regulators such as Crc in bacterial susceptibility to antibiotics. Given that growing into the human host requires a metabolic adaptation, we will discuss whether this adaptation might trigger resistance even in the absence of selective pressure by antibiotics. PMID:21645016

Martínez, José L; Rojo, Fernando

2011-09-01

364

Regulating ISS— An interdisciplinary essay  

NASA Astrophysics Data System (ADS)

The International Space Station (ISS) is a multifaceted international project. Several space agencies from different countries work together in the Outer Space. This paper will illustrate the exciting questions arising from such a venture and therefore the challenge to incorporate a variety of issues into a legal order. The Paper is addressed to lawyers who need not necessarily be experts in space law, and also to space experts who have no legal background. It demonstrates the three layers of the ISS regime—from the "Intergovernmental Agreement" (IGA) as a "frame" with pillars and boundaries, over the "Memoranda of Understanding" (MOU) which rules in a more specific way, to the so-called "Implementing Arrangements" regulating the overall and single aspects of ISS in detail. The paper underlines questions of applicable jurisdiction, utilization rights and the rights on intellectual property onboard of the ISS. Furthermore the problem of liability in space flight is highlighted, also with a view to the different aspects of the liability issue, for example (internal) liability caused by programme delays (e.g. US Space Shuttle delays). In conclusion, the paper illustrates the situation of astronauts by the "Code of Conduct for the International Space Station Crew" and provides an example for the actual ISS Programme—an international cooperation in a highly demanding environment which will be a basis for future space ventures in many ways.

Brünner, Christian; Soucek, Alexander

2007-02-01

365

Proteasome regulators: activators and inhibitors  

PubMed Central

This mini review covers the drug discovery aspect of both proteasome activators and inhibitors. The proteasome is involved in many essential cellular functions, such as regulation of cell cycle, cell differentiation, signal transduction pathways, antigen processing for appropriate immune responses, stress signaling, inflammatory responses, and apoptosis. Due to the importance of the proteasome in cellular functions, inhibition or activation of the proteasome could become a useful therapeutic strategy for a variety of diseases. Many proteasome inhibitors have been identified and can be classified into two groups according to their source: chemically synthesized small molecules and compounds derived from natural products. A successful case of developing a proteasome inhibitor as a clinically useful drug is that the peptide boronate, PS341 (Bortezomib), was approved for the treatment of multiple myeloma. In contrast to proteasome inhibitors, small molecules that can activate or enhance proteasome activity are rare and are not well studied. The fact that over-expression of the cellular proteasome activator PA28 exhibited beneficial effects on the Huntington’s disease neuronal model cells raised the prospect that small molecule proteasome activators could become useful therapeutics. The beneficial effect of oleuropein, a small molecule proteasome activator, on senescence of human fibroblasts also suggested that proteasome activators might have the potential to be developed into anti-aging agents. PMID:19275603

Huang, Li; Chen, Chin Ho

2013-01-01

366

Microbial regulation of intestinal radiosensitivity  

PubMed Central

We describe a method for treating germ-free (GF) mice with ?-irradiation and transplanting them with normal or genetically manipulated bone marrow while maintaining their GF status. This approach revealed that GF mice are markedly resistant to lethal radiation enteritis. Furthermore, administering lethal doses of total body irradiation to GF mice produces markedly fewer apoptotic endothelial cells and lymphocytes in the mesenchymal cores of their small intestinal villi, compared with conventionally raised animals that have acquired a microbiota from birth. Analysis of GF and conventionally raised Rag1-/- mice disclosed that mature lymphocytes are not required for the development of lethal radiation enteritis or the microbiota-associated enhancement of endothelial radiosensitivity. Studies of gnotobiotic knockout mice that lack fasting-induced adipose factor (Fiaf), a fibrinogen/angiopoietin-like protein normally secreted from the small intestinal villus epithelium and suppressed by the microbiota, showed that Fiaf deficiency results in loss of resistance of villus endothelial and lymphocyte populations to radiation-induced apoptosis. Together, these findings provide insights about the cellular and molecular targets involved in microbial regulation of intestinal radiosensitivity. PMID:16129828

Crawford, Peter A.; Gordon, Jeffrey I.

2005-01-01

367

Multiple pathways regulate shoot branching.  

PubMed

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

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

2014-01-01

368

Hormonal regulation of caveolae internalization  

PubMed Central

Caveolae undergo a cyclic transition from a flat segment of membrane to a vesicle that then returns to the cell surface. Here we present evidence that this cycle depends on a population of protein kinase C- alpha (PKC-alpha) molecules that reside in the caveolae membrane where they phosphorylate a 90-kD protein. This cycle can be interrupted by treatment of the cells with phorbol-12,13-dibutyrate or agents that raise the concentration of diacylglycerol in the cell. Each of these conditions displaces PKC-alpha from caveolae, inhibits the phosphorylation of the 90-kD protein, and prevents internalization. Caveolae also contain a protein phosphatase that dephosphorylates the 90-kD once PKC-alpha is gone. A similar dissociation of PKC-alpha from caveolae and inhibition of invagination was observed when cells were treated with histamine. This effect was blocked by pyrilamine but not cimetidine, indicating the involvement of histamine H1 receptors. These findings suggest that the caveolae internalization cycle is hormonally regulated. PMID:7490294

1995-01-01

369

Rare codons regulate KRas oncogenesis  

PubMed Central

Summary Oncogenic mutations in the small Ras GTPases KRas, HRas, or NRas render the encoded proteins constitutively GTP-bound and active, which promote cancer [1]. Ras proteins share ~85% amino acid identity [2], are activated by [3] and signal through [4] the same proteins, and can exhibit functional redundancy [5][6]. Nevertheless, manipulating expression or activation of each isoform yields different cellular responses [7–10] and tumorigenic phenotypes [11–13], even when different ras genes are expressed from the same locus [6]. We now report a novel regulatory mechanism hardwired into the very sequence of RAS genes that underlies how such similar proteins impact tumorigenesis differently. Specifically, despite their high sequence similarity, KRAS is poorly translated compared to HRAS due to enrichment in genomically underrepresented, or rare, codons. Converting rare to common codons increased KRas expression and tumorigenicity to mirror that of HRas. Furthermore, in a genome-wide survey similar gene pairs with opposing codon bias were identified that not only manifested dichotomous protein expression, but were also enriched in key signaling protein classes and pathways. Thus, synonymous nucleotide differences affecting codon usage account for differences between HRas and KRas expression and function, and may represent a broader regulation strategy in cell signaling. PMID:23246410

Lampson, Benjamin L.; Pershing, Nicole L.K.; Prinz, Joseph A.; Lacsina, Joshua R.; Marzluff, William F.; Nicchitta, Christopher V.; MacAlpine, David M.; Counter, Christopher M.

2013-01-01

370

Redox Regulation of Mitochondrial Biogenesis  

PubMed Central

Background The cell renews, adapts, or expands its mitochondrial population during episodes of cell damage or periods of intensified energy demand by the induction of mitochondrial biogenesis. This bi-genomic program is modulated by redox-sensitive signals that respond to physiological nitric oxide (NO), carbon monoxide (CO), and mitochondrial reactive oxygen species (ROS) production. Scope of Review This review summarizes our current ideas about the pathways involved in the activation of mitochondrial biogenesis by the physiological gases leading to changes in the redox milieu of the cell with an emphasis on the responses to oxidative stress and inflammation. Major Conclusions The cell’s energy supply is protected from conditions that damage mitochondria by an inducible transcriptional program of mitochondrial biogenesis that operates in large part through redox signals involving the nitric oxide synthase and the heme oxygenase-1/CO systems. These redox events stimulate the coordinated activities of several multifunctional transcription factors and co-activators also involved in the elimination of defective mitochondria and the expression of counter-inflammatory and anti-oxidant genes, such as IL10 and Sod2, as part of a unified damage-control network. General Significance The redox-regulated mechanisms of mitochondrial biogenesis schematically outlined in the graphical abstract link mitochondrial quality control to an enhanced capacity to support the cell’s metabolic needs while improving its resistance to metabolic failure and avoidance of cell death during periods of oxidative stress. PMID:23000245

Piantadosi, Claude A.; Suliman, Hagir B.

2013-01-01

371

Electronically Variable Pressure Regulator (EVPR)  

NASA Technical Reports Server (NTRS)

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.

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

1989-01-01

372

Regulation of pulpal blood flow  

SciTech Connect

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.

Kim, S.

1985-04-01

373

Circadian Mechanisms in Murine and Human Bone Marrow Mesenchymal Stem Cells Following Dexamethasone Exposure  

PubMed Central

A core group of transcriptional regulatory factors regulate circadian rhythms in mammalian cells. While the suprachiasmatic nucleus in the brain serves as the central core circadian oscillator, circadian clocks also exist within peripheral tissues and cells. A growing body of evidence has demonstrated that >20% of expressed mRNAs in bone and adipose tissues oscillate in a circadian manner. The current manuscript reports evidence of the core circadian transcriptional apparatus within primary cultures of murine and human bone marrow-derived mesenchymal stem cells (BMSCs). Exposure of confluent, quiescent BMSCs to dexamethasone synchronized the oscillating expression of the mRNAs encoding the albumin D binding protein (dbp), brain-muscle arnt-like 1 (bmal1), period 3 (per3), rev-erb ?, and rev-erb ?. The genes displayed a mean oscillatory period of 22.2 to 24.3 hours. The acrophase or peak expression of mRNAs encoding “positive” (bmal1) and “negative” (per3) transcriptional regulatory factors were out of phase with each other by ?8-12 hours, consistent with in vivo observations. In vivo, glycogen synthase kinase 3? (GSK3?) mediated phosphorylation regulates the turnover of per3 and core circadian transcriptional apparatus. In vitro addition of lithium chloride, a GSK3? inhibitor, significantly shifted the acrophase of all genes by 4.2-4.7 hours oscillation in BMSCs; however, only the male murine BMSCs displayed a significant increase in the length of the period of oscillation. We conclude that human and murine BMSCs represent a valid in vitro model for the analysis of circadian mechanisms in bone metabolism and stem cell biology. PMID:18302991

Wu, Xiying; Yu, Gang; Parks, Helen; Hebert, Teddi; Goh, Brian C.; Dietrich, Marilyn A.; Pelled, Gadi; Izadpanah, Reza; Gazit, Dan; Bunnell, Bruce A.; Gimble, Jeffrey M.

2008-01-01

374

77 FR 54843 - Integrated Mortgage Disclosures Under the Real Estate Settlement Procedure Act (Regulation X) and...  

Federal Register 2010, 2011, 2012, 2013

...Estate Settlement Procedure Act (Regulation X) and the Truth In Lending Act (Regulation...proposed rule, which would amend Regulation X (RESPA) and Regulation Z (TILA), was...The proposed rule would amend Regulation X (RESPA) and Regulation Z (TILA)....

2012-09-06

375

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

Code of Federal Regulations, 2011 CFR

...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...

2011-01-01

376

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

Code of Federal Regulations, 2012 CFR

...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...

2012-01-01

377

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

Code of Federal Regulations, 2013 CFR

...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...

2013-01-01

378

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

...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...

2014-01-01

379

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

Code of Federal Regulations, 2010 CFR

...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...

2010-01-01

380

Social regulation of emotion: messy layers.  

PubMed

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

Kappas, Arvid

2013-01-01

381

MicroRNA Regulation of SIRT1  

PubMed Central

SIRT1 is an NAD-dependent deacetylase that regulates stress response pathways. By deacetylating transcription factors and co-factors, SIRT1 modulates metabolism, inflammation, hypoxic responses, circadian rhythms, cell survival, and longevity. Since SIRT1 plays a key role in regulating pathways involved in cardiovascular diseases and metabolic diseases cancer, the regulation of SIRT1 has received intense scrutiny. The post-transcriptional regulation of SIRT1 is mediated by two classes of molecules, RNA-binding proteins (RBPs) and non-coding small RNAs. MicroRNAs (miRNAs) are short non-coding RNAs that regulate target gene expression in a post-transcriptional manner. More than 16 miRNAs modulate SIRT1 expression, including miR-34a. miR-34a induces colon cancer apoptosis through SIRT1, and miR-34a also promotes senescence in endothelial cells via SIRT1. This review describes the impact of miRNAs on SIRT1. The background of SIRT1 and miRNAs will be summarized, followed by the mechanism by which several key miRNAs alter SIRT1 levels, and how the RBP HuR regulates SIRT1. MicroRNA regulation of SIRT1 might affect a wide variety of pathways in humans, from metabolic diseases such as diabetes to cardiovascular diseases and cancer. PMID:22479251

Yamakuchi, Munekazu

2011-01-01

382

Social regulation of emotion: messy layers  

PubMed Central

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

Kappas, Arvid

2013-01-01

383

49 CFR 192.353 - Customer meters and regulators: Location.  

Code of Federal Regulations, 2012 CFR

...2012-10-01 2012-10-01 false Customer meters and regulators: Location. 192.353...MINIMUM FEDERAL SAFETY STANDARDS Customer Meters, Service Regulators, and Service Lines § 192.353 Customer meters and regulators: Location. (a)...

2012-10-01

384

49 CFR 192.357 - Customer meters and regulators: Installation.  

Code of Federal Regulations, 2012 CFR

...2012-10-01 2012-10-01 false Customer meters and regulators: Installation. 192...MINIMUM FEDERAL SAFETY STANDARDS Customer Meters, Service Regulators, and Service Lines § 192.357 Customer meters and regulators: Installation....

2012-10-01

385

49 CFR 192.357 - Customer meters and regulators: Installation.  

Code of Federal Regulations, 2013 CFR

...2013-10-01 2013-10-01 false Customer meters and regulators: Installation. 192...MINIMUM FEDERAL SAFETY STANDARDS Customer Meters, Service Regulators, and Service Lines § 192.357 Customer meters and regulators: Installation....

2013-10-01

386

49 CFR 192.357 - Customer meters and regulators: Installation.  

Code of Federal Regulations, 2011 CFR

...2011-10-01 2011-10-01 false Customer meters and regulators: Installation. 192...MINIMUM FEDERAL SAFETY STANDARDS Customer Meters, Service Regulators, and Service Lines § 192.357 Customer meters and regulators: Installation....

2011-10-01

387

49 CFR 192.353 - Customer meters and regulators: Location.  

Code of Federal Regulations, 2011 CFR

...2011-10-01 2011-10-01 false Customer meters and regulators: Location. 192.353...MINIMUM FEDERAL SAFETY STANDARDS Customer Meters, Service Regulators, and Service Lines § 192.353 Customer meters and regulators: Location. (a)...

2011-10-01

388

49 CFR 192.357 - Customer meters and regulators: Installation.  

Code of Federal Regulations, 2010 CFR

...2010-10-01 2010-10-01 false Customer meters and regulators: Installation. 192...MINIMUM FEDERAL SAFETY STANDARDS Customer Meters, Service Regulators, and Service Lines § 192.357 Customer meters and regulators: Installation....

2010-10-01

389

49 CFR 192.353 - Customer meters and regulators: Location.  

Code of Federal Regulations, 2013 CFR

...2013-10-01 2013-10-01 false Customer meters and regulators: Location. 192.353...MINIMUM FEDERAL SAFETY STANDARDS Customer Meters, Service Regulators, and Service Lines § 192.353 Customer meters and regulators: Location. (a)...

2013-10-01

390

49 CFR 192.353 - Customer meters and regulators: Location.  

Code of Federal Regulations, 2010 CFR

...2010-10-01 2010-10-01 false Customer meters and regulators: Location. 192.353...MINIMUM FEDERAL SAFETY STANDARDS Customer Meters, Service Regulators, and Service Lines § 192.353 Customer meters and regulators: Location. (a)...

2010-10-01

391

16 CFR 460.1 - What this regulation does.  

...TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.1 What this regulation does. This regulation deals with home insulation labels, fact sheets, ads, and other promotional materials in...

2014-01-01

392

16 CFR 460.1 - What this regulation does.  

Code of Federal Regulations, 2012 CFR

...TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.1 What this regulation does. This regulation deals with home insulation labels, fact sheets, ads, and other promotional materials in...

2012-01-01

393

16 CFR 460.1 - What this regulation does.  

Code of Federal Regulations, 2010 CFR

...TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.1 What this regulation does. This regulation deals with home insulation labels, fact sheets, ads, and other promotional materials in...

2010-01-01

394

16 CFR 460.1 - What this regulation does.  

Code of Federal Regulations, 2011 CFR

...TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.1 What this regulation does. This regulation deals with home insulation labels, fact sheets, ads, and other promotional materials in...

2011-01-01

395

21 CFR 870.5900 - Thermal regulating system.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Thermal regulating system. 870.5900 Section...Cardiovascular Therapeutic Devices § 870.5900 Thermal regulating system. (a) Identification. A thermal regulating system is an external...

2010-04-01

396

10 CFR 1.43 - Office of Nuclear Reactor Regulation.  

Code of Federal Regulations, 2011 CFR

...2011-01-01 2011-01-01 false Office of Nuclear Reactor Regulation. 1.43 Section 1.43... Program Offices § 1.43 Office of Nuclear Reactor Regulation. The Office of Nuclear Reactor Regulation— (a) Develops,...

2011-01-01

397

10 CFR 1.43 - Office of Nuclear Reactor Regulation.  

Code of Federal Regulations, 2013 CFR

...2013-01-01 2013-01-01 false Office of Nuclear Reactor Regulation. 1.43 Section 1.43... Program Offices § 1.43 Office of Nuclear Reactor Regulation. The Office of Nuclear Reactor Regulation— (a) Develops,...

2013-01-01

398

10 CFR 1.43 - Office of Nuclear Reactor Regulation.  

Code of Federal Regulations, 2012 CFR

...2012-01-01 2012-01-01 false Office of Nuclear Reactor Regulation. 1.43 Section 1.43... Program Offices § 1.43 Office of Nuclear Reactor Regulation. The Office of Nuclear Reactor Regulation— (a) Develops,...

2012-01-01

399

10 CFR 1.43 - Office of Nuclear Reactor Regulation.  

Code of Federal Regulations, 2010 CFR

...2010-01-01 2010-01-01 false Office of Nuclear Reactor Regulation. 1.43 Section 1.43... Program Offices § 1.43 Office of Nuclear Reactor Regulation. The Office of Nuclear Reactor Regulation— (a) Develops,...

2010-01-01

400

10 CFR 1.43 - Office of Nuclear Reactor Regulation.  

...2014-01-01 2014-01-01 false Office of Nuclear Reactor Regulation. 1.43 Section 1.43... Program Offices § 1.43 Office of Nuclear Reactor Regulation. The Office of Nuclear Reactor Regulation— (a) Develops,...

2014-01-01

401

77 FR 65477 - Repeal of Regulations on Marriages  

Federal Register 2010, 2011, 2012, 2013

...1400-AD27 Repeal of Regulations on Marriages AGENCY: Department of State. ACTION...Affairs is repealing the regulations on marriages. The current regulations are outdated...which relates to the consular role in marriages. The Department is removing Part...

2012-10-29

402

76 FR 28193 - Amendments to Material Control and Accounting Regulations  

Federal Register 2010, 2011, 2012, 2013

...Amendments to Material Control and Accounting Regulations AGENCY: Nuclear Regulatory...amendments to the material control and accounting (MC&A) regulations. These regulations...outdated term, as it does not include ``accounting,'' and thus does not fully...

2011-05-16

403

14 CFR 291.24 - Waiver of Department Economic Regulations.  

Code of Federal Regulations, 2010 CFR

...2010-01-01 false Waiver of Department Economic Regulations. 291.24 Section 291...TRANSPORTATION (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS CARGO OPERATIONS IN INTERSTATE...Transportation § 291.24 Waiver of Department Economic Regulations. Except for this...

2010-01-01

404

7 CFR 980.117 - Import regulations; onions.  

...2014-01-01 false Import regulations; onions. 980.117 Section 980.117 Agriculture...REGULATIONS § 980.117 Import regulations; onions. (a) Findings and determinations with respect to onions. (1) Under section 8e of the...

2014-01-01

405

7 CFR 980.117 - Import regulations; onions.  

Code of Federal Regulations, 2013 CFR

...2013-01-01 false Import regulations; onions. 980.117 Section 980.117 Agriculture...REGULATIONS § 980.117 Import regulations; onions. (a) Findings and determinations with respect to onions. (1) Under section 8e of the...

2013-01-01

406

7 CFR 980.117 - Import regulations; onions.  

Code of Federal Regulations, 2012 CFR

...2012-01-01 false Import regulations; onions. 980.117 Section 980.117 Agriculture...REGULATIONS § 980.117 Import regulations; onions. (a) Findings and determinations with respect to onions. (1) Under section 8e of the...

2012-01-01

407

7 CFR 980.117 - Import regulations; onions.  

Code of Federal Regulations, 2011 CFR

...2011-01-01 false Import regulations; onions. 980.117 Section 980.117 Agriculture...REGULATIONS § 980.117 Import regulations; onions. (a) Findings and determinations with respect to onions. (1) Under section 8e of the...

2011-01-01

408

40 CFR 52.345 - Stack height regulations.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 2010-07-01 false Stack height regulations. 52.345 Section...PLANS Colorado § 52.345 Stack height regulations. The State of Colorado has committed to revise its stack height regulations should EPA complete...

2010-07-01

409

40 CFR 52.2347 - Stack height regulations.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 2010-07-01 false Stack height regulations. 52.2347 Section...CONTINUED) Utah § 52.2347 Stack height regulations. The State of Utah has committed to revise its stack height regulations should EPA complete...

2010-07-01

410

12 CFR 1237.10 - Limited-life regulated entities.  

Code of Federal Regulations, 2012 CFR

...2012-01-01 2012-01-01 false Limited-life regulated entities. 1237.10 Section 1237...CONSERVATORSHIP AND RECEIVERSHIP Limited-Life Regulated Entities § 1237.10 Limited-life regulated entities. (a) Status....

2012-01-01

411

12 CFR 1237.10 - Limited-life regulated entities.  

Code of Federal Regulations, 2013 CFR

...2013-01-01 2013-01-01 false Limited-life regulated entities. 1237.10 Section 1237...CONSERVATORSHIP AND RECEIVERSHIP Limited-Life Regulated Entities § 1237.10 Limited-life regulated entities. (a) Status....

2013-01-01

412

12 CFR 1237.10 - Limited-life regulated entities.  

...2014-01-01 2014-01-01 false Limited-life regulated entities. 1237.10 Section 1237...CONSERVATORSHIP AND RECEIVERSHIP Limited-Life Regulated Entities § 1237.10 Limited-life regulated entities. (a) Status....

2014-01-01

413

50 CFR 216.1 - Purpose of regulations.  

Code of Federal Regulations, 2010 CFR

...SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS REGULATIONS GOVERNING THE TAKING AND IMPORTING OF MARINE MAMMALS Introduction § 216.1 Purpose of regulations. The regulations in this...

2010-10-01

414

29 CFR 541.1 - Terms used in regulations.  

...DEPARTMENT OF LABOR REGULATIONS DEFINING AND DELIMITING THE EXEMPTIONS FOR EXECUTIVE, ADMINISTRATIVE, PROFESSIONAL, COMPUTER AND OUTSIDE SALES EMPLOYEES General Regulations § 541.1 Terms used in regulations. Act means the Fair Labor...

2014-07-01

415

7 CFR 906.39 - Recommendations for regulations.  

Code of Federal Regulations, 2010 CFR

...Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE ORANGES AND GRAPEFRUIT GROWN IN LOWER RIO GRANDE VALLEY IN TEXAS Order Regulating Handling Regulation § 906.39 Recommendations for regulations. The committee, upon complying...

2010-01-01

416

34 CFR 472.4 - What regulations apply?  

Code of Federal Regulations, 2011 CFR

...EDUCATION, DEPARTMENT OF EDUCATION NATIONAL WORKPLACE LITERACY PROGRAM General § 472.4 What regulations apply? The following regulations apply to the National Workplace Literacy Program: (a) The regulations in this part 472....

2011-07-01

417

34 CFR 472.4 - What regulations apply?  

...EDUCATION, DEPARTMENT OF EDUCATION NATIONAL WORKPLACE LITERACY PROGRAM General § 472.4 What regulations apply? The following regulations apply to the National Workplace Literacy Program: (a) The regulations in this part 472....

2014-07-01

418

34 CFR 472.4 - What regulations apply?  

Code of Federal Regulations, 2013 CFR

...EDUCATION, DEPARTMENT OF EDUCATION NATIONAL WORKPLACE LITERACY PROGRAM General § 472.4 What regulations apply? The following regulations apply to the National Workplace Literacy Program: (a) The regulations in this part 472....

2013-07-01

419

34 CFR 472.4 - What regulations apply?  

Code of Federal Regulations, 2010 CFR

...EDUCATION, DEPARTMENT OF EDUCATION NATIONAL WORKPLACE LITERACY PROGRAM General § 472.4 What regulations apply? The following regulations apply to the National Workplace Literacy Program: (a) The regulations in this part 472....

2010-07-01

420

34 CFR 472.4 - What regulations apply?  

Code of Federal Regulations, 2012 CFR

...EDUCATION, DEPARTMENT OF EDUCATION NATIONAL WORKPLACE LITERACY PROGRAM General § 472.4 What regulations apply? The following regulations apply to the National Workplace Literacy Program: (a) The regulations in this part 472....

2012-07-01

421

7 CFR 945.51 - Recommendation for regulations.  

...AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE IRISH POTATOES GROWN IN CERTAIN DESIGNATED COUNTIES IN IDAHO, AND MALHEUR COUNTY, OREGON Order Regulating Handling Regulations § 945.51 Recommendation for regulations....

2014-01-01

422

7 CFR 958.51 - Recommendations for regulations.  

Code of Federal Regulations, 2011 CFR

...Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE ONIONS GROWN IN CERTAIN DESIGNATED COUNTIES IN IDAHO, AND MALHEUR COUNTY, OREGON Order Regulating Handling Regulation § 958.51 Recommendations for regulations....

2011-01-01

423

21 CFR 880.5560 - Temperature regulated water mattress.  

... false Temperature regulated water mattress. 880.5560 Section 880.5560...5560 Temperature regulated water mattress. (a) Identification. A temperature regulated water mattress is a device intended for medical...

2014-04-01

424

21 CFR 880.5560 - Temperature regulated water mattress.  

Code of Federal Regulations, 2012 CFR

... false Temperature regulated water mattress. 880.5560 Section 880.5560...5560 Temperature regulated water mattress. (a) Identification. A temperature regulated water mattress is a device intended for medical...

2012-04-01

425

21 CFR 880.5560 - Temperature regulated water mattress.  

Code of Federal Regulations, 2013 CFR

... false Temperature regulated water mattress. 880.5560 Section 880.5560...5560 Temperature regulated water mattress. (a) Identification. A temperature regulated water mattress is a device intended for medical...

2013-04-01

426

21 CFR 880.5560 - Temperature regulated water mattress.  

Code of Federal Regulations, 2011 CFR

... false Temperature regulated water mattress. 880.5560 Section 880.5560...5560 Temperature regulated water mattress. (a) Identification. A temperature regulated water mattress is a device intended for medical...

2011-04-01

427

21 CFR 880.5560 - Temperature regulated water mattress.  

Code of Federal Regulations, 2010 CFR

... false Temperature regulated water mattress. 880.5560 Section 880.5560...5560 Temperature regulated water mattress. (a) Identification. A temperature regulated water mattress is a device intended for medical...

2010-04-01

428

34 CFR 654.4 - What regulations apply?  

Code of Federal Regulations, 2010 CFR

...Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION ROBERT C. BYRD HONORS SCHOLARSHIP PROGRAM General § 654.4 What regulations apply? The following regulations apply to...

2010-07-01

429

7 CFR 906.120 - Fruit exempt from regulations.  

Code of Federal Regulations, 2012 CFR

...2012-01-01 2012-01-01 false Fruit exempt from regulations. 906.120...SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE... Rules and Regulations § 906.120 Fruit exempt from regulations. (a)...

2012-01-01

430

7 CFR 906.120 - Fruit exempt from regulations.  

Code of Federal Regulations, 2013 CFR

...2013-01-01 2013-01-01 false Fruit exempt from regulations. 906.120...SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE... Rules and Regulations § 906.120 Fruit exempt from regulations. (a)...

2013-01-01

431

7 CFR 906.120 - Fruit exempt from regulations.  

...2014-01-01 2014-01-01 false Fruit exempt from regulations. 906.120...SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE... Rules and Regulations § 906.120 Fruit exempt from regulations. (a)...

2014-01-01

432

34 CFR 406.4 - What regulations apply?  

Code of Federal Regulations, 2011 CFR

...ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE-ADMINISTERED TECH-PREP EDUCATION PROGRAM General § 406.4 What regulations... The following regulations apply to the State-Administered Tech-Prep Education Program: (a) The regulations in this...

2011-07-01

433

34 CFR 406.4 - What regulations apply?  

Code of Federal Regulations, 2012 CFR

...ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE-ADMINISTERED TECH-PREP EDUCATION PROGRAM General § 406.4 What regulations... The following regulations apply to the State-Administered Tech-Prep Education Program: (a) The regulations in this...

2012-07-01

434

34 CFR 406.4 - What regulations apply?  

Code of Federal Regulations, 2010 CFR

...ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE-ADMINISTERED TECH-PREP EDUCATION PROGRAM General § 406.4 What regulations... The following regulations apply to the State-Administered Tech-Prep Education Program: (a) The regulations in this...

2010-07-01

435

34 CFR 406.4 - What regulations apply?  

Code of Federal Regulations, 2013 CFR

...ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE-ADMINISTERED TECH-PREP EDUCATION PROGRAM General § 406.4 What regulations... The following regulations apply to the State-Administered Tech-Prep Education Program: (a) The regulations in this...

2013-07-01

436

34 CFR 406.4 - What regulations apply?  

...ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE-ADMINISTERED TECH-PREP EDUCATION PROGRAM General § 406.4 What regulations... The following regulations apply to the State-Administered Tech-Prep Education Program: (a) The regulations in this...

2014-07-01

437

77 FR 19079 - Removal of Regulations on Black Lung Benefits  

Federal Register 2010, 2011, 2012, 2013

...0960-AH48 Removal of Regulations on Black Lung Benefits AGENCY: Social Security Administration...final rule removes regulations on the Black Lung program from the Social Security Administration's...Federal Regulations (CFR). The Black Lung Consolidation of Administrative...

2012-03-30

438

76 FR 78121 - Fair Debt Collection Practices Act (Regulation F)  

Federal Register 2010, 2011, 2012, 2013

...Debt Collection Practices Act (Regulation F) AGENCY: Bureau of Consumer Financial Protection...final rule establishing a new Regulation F (Fair Debt Collection Practices Act...final rule establishing a new Regulation F (Fair Debt Collection Practices...

2011-12-16

439

34 CFR 365.3 - What regulations apply?  

Code of Federal Regulations, 2011 CFR

... 2010-07-01 true What regulations apply? 365.3 Section 365.3 Education Regulations of the Offices of the...EDUCATION STATE INDEPENDENT LIVING SERVICES General § 365.3 What regulations apply? The following...

2011-07-01

440

34 CFR 365.3 - What regulations apply?  

Code of Federal Regulations, 2012 CFR

... 2012-07-01 false What regulations apply? 365.3 Section 365.3 Education Regulations of the Offices of the...EDUCATION STATE INDEPENDENT LIVING SERVICES General § 365.3 What regulations apply? The following...

2012-07-01

441

34 CFR 365.3 - What regulations apply?  

Code of Federal Regulations, 2010 CFR

... 2010-07-01 false What regulations apply? 365.3 Section 365.3 Education Regulations of the Offices of the...EDUCATION STATE INDEPENDENT LIVING SERVICES General § 365.3 What regulations apply? The following...

2010-07-01

442

34 CFR 365.3 - What regulations apply?  

... 2013-07-01 true What regulations apply? 365.3 Section 365.3 Education Regulations of the Offices of the...EDUCATION STATE INDEPENDENT LIVING SERVICES General § 365.3 What regulations apply? The following...

2014-07-01

443

34 CFR 365.3 - What regulations apply?  

Code of Federal Regulations, 2013 CFR

... 2013-07-01 false What regulations apply? 365.3 Section 365.3 Education Regulations of the Offices of the...EDUCATION STATE INDEPENDENT LIVING SERVICES General § 365.3 What regulations apply? The following...

2013-07-01

444

7 CFR 966.55 - Notification of regulation.  

Code of Federal Regulations, 2010 CFR

... AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE TOMATOES GROWN IN FLORIDA Order Regulating Handling Regulation § 966.55 Notification of regulation. The Secretary...

2010-01-01

445

How to Access the Code of Federal Regulations (CFR)  

NSDL National Science Digital Library

This page explains how to use the internet to obtain the current Good Manufacturing Practices (cGMP) regulations from the Code of Federal Regulations. It describes how the regulations are organized and how they can be searched and retrieved.

Seidman, Lisa A.

446

40 CFR 52.345 - Stack height regulations.  

...2014-07-01 2014-07-01 false Stack height regulations. 52.345 Section...PLANS Colorado § 52.345 Stack height regulations. The State of Colorado has committed to revise its stack height regulations should EPA complete...

2014-07-01

447

40 CFR 52.2347 - Stack height regulations.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 2013-07-01 false Stack height regulations. 52.2347 Section...CONTINUED) Utah § 52.2347 Stack height regulations. The State of Utah has committed to revise its stack height regulations should EPA complete...

2013-07-01

448

40 CFR 52.345 - Stack height regulations.  

Code of Federal Regulations, 2011 CFR

...2011-07-01 2011-07-01 false Stack height regulations. 52.345 Section...PLANS Colorado § 52.345 Stack height regulations. The State of Colorado has committed to revise its stack height regulations should EPA complete...

2011-07-01

449

40 CFR 52.2347 - Stack height regulations.  

Code of Federal Regulations, 2011 CFR

...2011-07-01 2011-07-01 false Stack height regulations. 52.2347 Section...CONTINUED) Utah § 52.2347 Stack height regulations. The State of Utah has committed to revise its stack height regulations should EPA complete...

2011-07-01

450

40 CFR 52.345 - Stack height regulations.  

Code of Federal Regulations, 2012 CFR

...2012-07-01 2012-07-01 false Stack height regulations. 52.345 Section...PLANS Colorado § 52.345 Stack height regulations. The State of Colorado has committed to revise its stack height regulations should EPA complete...

2012-07-01

451

40 CFR 52.2347 - Stack height regulations.  

...2014-07-01 2014-07-01 false Stack height regulations. 52.2347 Section...CONTINUED) Utah § 52.2347 Stack height regulations. The State of Utah has committed to revise its stack height regulations should EPA complete...

2014-07-01

452

40 CFR 52.345 - Stack height regulations.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 2013-07-01 false Stack height regulations. 52.345 Section...PLANS Colorado § 52.345 Stack height regulations. The State of Colorado has committed to revise its stack height regulations should EPA complete...

2013-07-01

453

40 CFR 52.2347 - Stack height regulations.  

Code of Federal Regulations, 2012 CFR

...2012-07-01 2012-07-01 false Stack height regulations. 52.2347 Section...CONTINUED) Utah § 52.2347 Stack height regulations. The State of Utah has committed to revise its stack height regulations should EPA complete...

2012-07-01

454

7 CFR 944.550 - Kiwifruit import regulation.  

Code of Federal Regulations, 2011 CFR

...2011-01-01 2011-01-01 false Kiwifruit import regulation. 944.550 Section...IMPORT REGULATIONS § 944.550 Kiwifruit import regulation. (a) Pursuant...importation into the United States of any kiwifruit is prohibited unless such...

2011-01-01

455

7 CFR 944.550 - Kiwifruit import regulation.  

Code of Federal Regulations, 2012 CFR

...2012-01-01 2012-01-01 false Kiwifruit import regulation. 944.550 Section...IMPORT REGULATIONS § 944.550 Kiwifruit import regulation. (a) Pursuant...importation into the United States of any kiwifruit is prohibited unless such...

2012-01-01

456

7 CFR 944.550 - Kiwifruit import regulation.  

...2014-01-01 2014-01-01 false Kiwifruit import regulation. 944.550 Section...IMPORT REGULATIONS § 944.550 Kiwifruit import regulation. (a) Pursuant...importation into the United States of any kiwifruit is prohibited unless such...

2014-01-01

457

7 CFR 944.550 - Kiwifruit import regulation.  

Code of Federal Regulations, 2013 CFR

...2013-01-01 2013-01-01 false Kiwifruit import regulation. 944.550 Section...IMPORT REGULATIONS § 944.550 Kiwifruit import regulation. (a) Pursuant...importation into the United States of any kiwifruit is prohibited unless such...

2013-01-01

458

7 CFR 923.322 - Washington cherry handling regulation.  

Code of Federal Regulations, 2012 CFR

... 2012-01-01 false Washington cherry handling regulation. 923.322 Section...Nuts), DEPARTMENT OF AGRICULTURE SWEET CHERRIES GROWN IN DESIGNATED COUNTIES IN WASHINGTON...Regulation § 923.322 Washington cherry handling regulation. (a)...

2012-01-01

459

7 CFR 923.322 - Washington cherry handling regulation.  

Code of Federal Regulations, 2013 CFR

... 2013-01-01 false Washington cherry handling regulation. 923.322 Section...NUTS), DEPARTMENT OF AGRICULTURE SWEET CHERRIES GROWN IN DESIGNATED COUNTIES IN WASHINGTON...Regulation § 923.322 Washington cherry handling regulation. (a)...

2013-01-01

460

7 CFR 923.322 - Washington cherry handling regulation.  

Code of Federal Regulations, 2010 CFR

... 2010-01-01 false Washington cherry handling regulation. 923.322 Section...Nuts), DEPARTMENT OF AGRICULTURE SWEET CHERRIES GROWN IN DESIGNATED COUNTIES IN WASHINGTON...Regulation § 923.322 Washington cherry handling regulation. (a)...

2010-01-01

461

7 CFR 923.322 - Washington cherry handling regulation.  

... 2014-01-01 false Washington cherry handling regulation. 923.322 Section...NUTS), DEPARTMENT OF AGRICULTURE SWEET CHERRIES GROWN IN DESIGNATED COUNTIES IN WASHINGTON...Regulation § 923.322 Washington cherry handling regulation. (a)...

2014-01-01

462

7 CFR 923.322 - Washington cherry handling regulation.  

Code of Federal Regulations, 2011 CFR

... 2011-01-01 false Washington cherry handling regulation. 923.322 Section...Nuts), DEPARTMENT OF AGRICULTURE SWEET CHERRIES GROWN IN DESIGNATED COUNTIES IN WASHINGTON...Regulation § 923.322 Washington cherry handling regulation. (a)...

2011-01-01

463

JILT: Communications Regulation - New Patterns and Problems  

NSDL National Science Digital Library

The latest issue of the well-known Journal of Information, Law and Technology, provided by the CTI (Computers in Teaching Initiative) Law Technology Centre at University of Warwick (UK) and the Centre for Law, Computers and Technology at Strathclyde University (UK), contains a special section devoted to communications regulation. It features eight articles and three book reviews on the topic, including copyright issues, media regulation, telecommunications law, and the relationship between television and telecommunications policy. Articles are written from a largely European point of view. An annotated list of pointers to international communcation regulation sites is provided, as is a glossary.

1997-01-01

464

IAPs, regulators of innate immunity and inflammation.  

PubMed

As indicated by their name, members of the Inhibitor of APoptosis (IAP) family were first believed to be functionally restricted to apoptosis inhibition. It is now clear that IAPs have a much wider spectrum of action, and recent studies even suggest that some of its members primarily regulate inflammatory responses. Inflammation, the first response of the immune system to infection or tissue injury, is highly regulated by ubiquitylation - a posttranslational modification of proteins with various consequences. In this review, we focus on the recently reported functions of XIAP, cIAP1 and cIAP2 as ubiquitin ligases regulating innate immunity and inflammation. PMID:24718315

Estornes, Yann; Bertrand, Mathieu J M

2014-04-01

465

Future directions in water quality regulations  

SciTech Connect

The Safe Drinking Water Act amendments of 1996 have imposed new requirements on the US Environmental Protection Agency (USEPA) to establish drinking water regulations. The regulatory process has been revised and now requires the use of sound science. Costs, benefits, and competing risks may also be considered. Current regulations for fluoride, volatile organic chemicals, total coliforms, surface water treatment, Phase 2 and Phase 5 synthetic organic and inorganic contaminants, and lead and copper remain basically unchanged. New deadlines are established for the regulation of arsenic, sulfate, radon, disinfectants and disinfection by-products, enhanced surface water treatment, and groundwater disinfection.

Pontius, F.W. [AWWA, Denver, CO (United States)

1997-03-01

466

Mechanical regulation of secondary chondrogenesis.  

PubMed

The development of the skull is characterised by its dependence upon epigenetic influences. One of the most important of these is secondary chondrogenesis, which occurs following ossification within certain membrane bone periostea, as a result of biomechanical articulation. We have studied the genesis, character and function of the secondary chondrocytes of the quadratojugal of the chick between embryonic days 11 and 14. Analysis of gene expression revealed that secondary chondrocytes formed coincident with Sox9 upregulation from a precursor population expressing Cbfa1/Runx2: a reversal of the normal sequence. Such secondary chondrocytes rapidly acquired a phenotype that is a compound of prehypertrophic and hypertrophic chondrocytes, exited from the cell cycle and upregulated Ihh. Pulse and pulse/chase experiments with BrdU confirmed the germinal region as the highly proliferative source of the secondary chondrocytes, which formed by division of chondrocyte-committed precursors. By blocking Hh signalling in explant cultures we show that the enhanced proliferation of the germinal region surrounding the secondary chondrocytes derives from this Ihh source. Additionally, in vitro studies on membrane bone periosteal cells (nongerminal region) demonstrated that these cells can also respond to Ihh, and do so both by enhanced proliferation and precocious osteogenesis. Despite the pro-osteogenic effects of Ihh on periosteal cell differentiation, mechanical articulation of the quadratojugal/quadrate joint in explant culture revealed a negative role for articulation in the regulation of osteocalcin by germinal region descendants. Thus, the mechanical stimulus that is the spur to secondary chondrocyte formation appears able to override the osteogenic influence of Ihh on the periosteum, but does not interfere with the cell cycle-promoting component of Hh signalling. PMID:16912408

Archer, Charles W; Buxton, Paul; Hall, Brian K; Francis-West, Philippa

2006-01-01

467

Regulation of potato tuber sprouting.  

PubMed

Following tuber induction, potato tubers undergo a period of dormancy during which visible bud growth is inhibited. The length of the dormancy period is under environmental, physiological and hormonal control. Sucrose availability is one prerequisite for bud break. In the absence of sucrose, no bud break occurs. Thus, sucrose is likely to serve as nutrient and signal molecule at the same time. The mode of sucrose sensing is only vaguely understood, but most likely involves trehalose-6-phosphate and SnRK1 signalling networks. This conclusion is supported by the observation that ectopically manipulation of trehalose-6-phosphate levels influences the length of the dormancy period. Once physiological competence is achieved, sprouting is controlled by the level of phytohormones. Two phytohormones, ABA and ethylene, are supposed to suppress tuber sprouting; however, the exact role of ethylene remains to be elucidated. Cytokinins and gibberellins are required for bud break and sprout growth, respectively. The fifth classical phytohormone, auxin, seems to play a role in vascular development. During the dormancy period, buds are symplastically isolated, which changes during bud break. In parallel to the establishment of symplastic connectivity, vascular tissue develops below the growing bud most likely to support the outgrowing sprout with assimilates mobilised in parenchyma cells. Sprouting leads to major quality losses of stored potato tubers. Therefore, control of tuber sprouting is a major objective in potato breeding. Although comparative transcriptome analysis revealed a large number of genes differentially expressed in growing versus dormant buds, no master-regulator of potato tuber sprouting has been identified so far. PMID:24100410

Sonnewald, Sophia; Sonnewald, Uwe

2014-01-01

468

RETINOIDS REGULATE STEM CELL DIFFERENTIATION  

PubMed Central

Retinoids are ubiquitous signaling molecules that influence nearly every cell type, exert profound effects on development, and complement cancer chemotherapeutic regimens. All-trans retinoic acid (RA) and other active retinoids are generated from vitamin A (retinol), but key aspects of the signaling pathways required to produce active retinoids remain unclear. Retinoids generated by one cell type can affect nearby cells, so retinoids also function in intercellular communication. RA induces differentiation primarily by binding to RARs, transcription factors that associate with RXRs and bind RAREs in the nucleus. Binding of RA: (1) initiates changes in interactions of RAR/RXRs with co-repressor and co-activator proteins, activating transcription of primary target genes; (2) alters interactions with proteins that induce epigenetic changes; (3) induces transcription of genes encoding transcription factors and signaling proteins that further modify gene expression (e.g., FOX03A, Hoxa1, Sox9, TRAIL, UBE2D3); and (4) results in alterations in estrogen receptor? signaling. Proteins that bind at or near RAREs include Sin3a, N-CoR1, PRAME, Trim24, NRIP1, Ajuba, Zfp423, and MN1/TEL. Interactions among retinoids, RARs/RXRs, and these proteins explain in part the powerful effects of retinoids on stem cell differentiation. Studies of this retinol signaling cascade enhance our ability to understand and regulate stem cell differentiation for therapeutic and scientific purposes. In cancer chemotherapeutic regimens retinoids can promote tumor cell differentiation and/or induce proteins that sensitize tumors to drug combinations. Mechanistic studies of retinoid signaling continue to suggest novel drug targets and will improve therapeutic strategies for cancer and other diseases, such as immune-mediated inflammatory diseases. PMID:20836077

Gudas, Lorraine J.; Wagner, John A.

2012-01-01

469

Unity power factor switching regulator  

NASA Technical Reports Server (NTRS)

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.

Rippel, Wally E. (Inventor)

1983-01-01

470

Peripheral Leptin Regulates Bone Formation  

PubMed Central

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

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

2012-01-01

471

Bacteriophage lysis: mechanism and regulation.  

PubMed Central

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

Young, R

1992-01-01

472

A Mathematical Model of the Regulation of AMPK Activation  

E-print Network

) Regulates (if active; Hardie 2007) - Glucose uptake, glycolysis, fatty acid oxidation, mitochondrial biogenesis - Fatty acid, glycogen, protein synthesis Regulated by (Carling 2004, Xiao et al. 2007) - LKB1

Rostock, Universität

473

7 CFR 929.52 - Issuance of regulations.  

Code of Federal Regulations, 2011 CFR

...IN STATES OF MASSACHUSETTS, RHODE ISLAND, CONNECTICUT, NEW JERSEY, WISCONSIN, MICHIGAN, MINNESOTA, OREGON, WASHINGTON, AND LONG ISLAND IN THE STATE OF NEW YORK Order Regulating Handling Regulations §...

2011-01-01

474

7 CFR 929.52 - Issuance of regulations.  

...IN STATES OF MASSACHUSETTS, RHODE ISLAND, CONNECTICUT, NEW JERSEY, WISCONSIN, MICHIGAN, MINNESOTA, OREGON, WASHINGTON, AND LONG ISLAND IN THE STATE OF NEW YORK Order Regulating Handling Regulations §...

2014-01-01

475

7 CFR 929.52 - Issuance of regulations.  

Code of Federal Regulations, 2012 CFR

...IN STATES OF MASSACHUSETTS, RHODE ISLAND, CONNECTICUT, NEW JERSEY, WISCONSIN, MICHIGAN, MINNESOTA, OREGON, WASHINGTON, AND LONG ISLAND IN THE STATE OF NEW YORK Order Regulating Handling Regulations §...

2012-01-01

476

7 CFR 929.51 - Recommendations for regulation.  

Code of Federal Regulations, 2010 CFR

...IN STATES OF MASSACHUSETTS, RHODE ISLAND, CONNECTICUT, NEW JERSEY, WISCONSIN, MICHIGAN, MINNESOTA, OREGON, WASHINGTON, AND LONG ISLAND IN THE STATE OF NEW YORK Order Regulating Handling Regulations §...

2010-01-01

477

15 CFR 970.900 - Other applicable regulations.  

Code of Federal Regulations, 2012 CFR

...OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Miscellaneous § 970.900 Other applicable...

2012-01-01

478

15 CFR 970.900 - Other applicable regulations.  

Code of Federal Regulations, 2013 CFR

...OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Miscellaneous § 970.900 Other applicable...

2013-01-01

479

75 FR 77048 - Fair Credit Reporting Affiliate Marketing Regulations  

Federal Register 2010, 2011, 2012, 2013

...Supervision Fair Credit Reporting Affiliate Marketing Regulations AGENCY: Office...Proposal: Fair Credit Reporting Affiliate Marketing Regulations. OMB Number...out of their institutions' affiliate marketing practices. Respondent...

2010-12-10

480

5 CFR 2638.103 - Agency regulations.  

Code of Federal Regulations, 2013 CFR

...regulations. 2638.103 Section 2638.103 Administrative Personnel OFFICE OF GOVERNMENT ETHICS GOVERNMENT ETHICS OFFICE OF GOVERNMENT ETHICS AND EXECUTIVE AGENCY ETHICS PROGRAM RESPONSIBILITIES General Provisions § 2638.103...

2013-01-01

481

5 CFR 2638.103 - Agency regulations.  

Code of Federal Regulations, 2012 CFR

...regulations. 2638.103 Section 2638.103 Administrative Personnel OFFICE OF GOVERNMENT ETHICS GOVERNMENT ETHICS OFFICE OF GOVERNMENT ETHICS AND EXECUTIVE AGENCY ETHICS PROGRAM RESPONSIBILITIES General Provisions § 2638.103...

2012-01-01

482

5 CFR 2638.103 - Agency regulations.  

...regulations. 2638.103 Section 2638.103 Administrative Personnel OFFICE OF GOVERNMENT ETHICS GOVERNMENT ETHICS OFFICE OF GOVERNMENT ETHICS AND EXECUTIVE AGENCY ETHICS PROGRAM RESPONSIBILITIES General Provisions § 2638.103...

2014-01-01

483

21 CFR 868.2700 - Pressure regulator.  

Code of Federal Regulations, 2010 CFR

...that is intended for medical purposes and that is used to convert a medical gas pressure from a high variable pressure to a lower, more constant working pressure. This device includes mechanical oxygen regulators. (b)...

2010-04-01

484

43 CFR 431.9 - Future regulations.  

Code of Federal Regulations, 2013 CFR

...DEPARTMENT OF THE INTERIOR GENERAL REGULATIONS FOR POWER GENERATION, OPERATION, MAINTENANCE, AND REPLACEMENT AT THE...That no right under any contract made under the Hoover Power Plant Act shall be impaired or obligation...

2013-10-01

485

43 CFR 431.9 - Future regulations.  

Code of Federal Regulations, 2010 CFR

...DEPARTMENT OF THE INTERIOR GENERAL REGULATIONS FOR POWER GENERATION, OPERATION, MAINTENANCE, AND REPLACEMENT AT THE...That no right under any contract made under the Hoover Power Plant Act shall be impaired or obligation...

2010-10-01

486

43 CFR 431.9 - Future regulations.  

Code of Federal Regulations, 2011 CFR

...DEPARTMENT OF THE INTERIOR GENERAL REGULATIONS FOR POWER GENERATION, OPERATION, MAINTENANCE, AND REPLACEMENT AT THE...That no right under any contract made under the Hoover Power Plant Act shall be impaired or obligation...

2011-10-01

487

43 CFR 431.9 - Future regulations.  

...DEPARTMENT OF THE INTERIOR GENERAL REGULATIONS FOR POWER GENERATION, OPERATION, MAINTENANCE, AND REPLACEMENT AT THE...That no right under any contract made under the Hoover Power Plant Act shall be impaired or obligation...

2014-10-01

488

43 CFR 431.9 - Future regulations.  

Code of Federal Regulations, 2012 CFR

...DEPARTMENT OF THE INTERIOR GENERAL REGULATIONS FOR POWER GENERATION, OPERATION, MAINTENANCE, AND REPLACEMENT AT THE...That no right under any contract made under the Hoover Power Plant Act shall be impaired or obligation...

2012-10-01

489

Automatic Generation of Goal Models from Regulations .  

E-print Network

??Organizations in many domains such as healthcare, finances, telecommunications, educa-tion, and software development, must comply with an ever-increasing number of regula-tions, including laws and policies.… (more)

Rashidi-Tabrizi, Rouzbahan

2013-01-01

490

Student Regulations and Procedures Academic Division  

E-print Network

Student Regulations and Procedures Academic Division 2007/2008 8 Data Protection unlawfully, and the Data Protection Principles must be followed. In summary, these principles state that they follow these principles at all times. University as Data Controller In accordance

491

Gene Regulation Networks for Modeling Drosophila Development  

NASA Technical Reports Server (NTRS)

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.

Mjolsness, E.

1999-01-01

492

Regulation of crustacean molting and regeneration  

SciTech Connect

The regulation of molting and regeneration by two antagonistic hormones is discussed. The time course of ecdysteroid titers in crustacean tissues has been followed during molt and regeneration cycles. (ACR)

Skinner, D.M.; Graham, D.E.; Holland, C.A.; Soumoff, C.; Mykles, D.L.

1981-01-01

493

[Measurement of Affect Regulation Styles (MARS) expanded].  

PubMed

An expanded Spanish version of the Measure of Affect Regulation Styles (MARS), was applied to episodes of anger and sadness, in a sample of 355 graduate students from Chile, Spain, and Mexico. The study examines the association between affective regulation, adaptation to episodes and dispositional coping and emotional regulation, and psychological well-being. With regard to perceived improvement of adaptive goals, the following adaptive affect regulation strategies were confirmed: Instrumental coping, seeking social support, positive reappraisal, distraction, rumination, self-comfort, self-control, and emotional expression were functional; whereas inhibition and suppression were dysfunctional. Adaptive strategies were positively associated with psychological well-being, reappraisal and humor as a coping strategy. Negative associations were found between adaptive strategies and suppression and alexithymia. Maladaptive strategies show the opposite profile. Confrontation, instrumental coping, social support as well as social isolation were more frequently found in anger, an approach emotion. PMID:22420353

Rovira, Darío Páez; Martínez Sánchez, Francisco; Sevillano Triguero, Verónica; Mendiburo Seguel, Andrés; Campos, Miriam

2012-05-01

494

REGULATIONS ON UNDESIRABLE BEHAVIOUR RADBOUD UNIVERSITY NIJMEGEN  

E-print Network

, discrimination, sexual harassment, aggression and violence. Article 2 In these regulations, the terms given below to eliminate undesirable behaviour. To prevent and deter such behaviour, the Executive Board has adopted

van Suijlekom, Walter

495

Essays on entry regulation, institutions, and development  

E-print Network

This thesis is a collection of three essays on entry regulation, institutions, and development.Chapter 1 examines the effect of a business registration reform in Mexico on economic activity. This reform made registration ...

Bruhn, Miriam

2007-01-01

496

7 CFR 958.328 - Handling regulation.  

Code of Federal Regulations, 2013 CFR

...VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE ONIONS GROWN IN CERTAIN DESIGNATED COUNTIES IN IDAHO...regulation. No person shall handle any lot of onions, except braided red onions, unless such onions are at least...

2013-01-01

497

7 CFR 958.328 - Handling regulation.  

Code of Federal Regulations, 2011 CFR

...Vegetables, Nuts), DEPARTMENT OF AGRICULTURE ONIONS GROWN IN CERTAIN DESIGNATED COUNTIES IN IDAHO...regulation. No person shall handle any lot of onions, except braided red onions, unless such onions are at least...

2011-01-01

498

7 CFR 958.328 - Handling regulation.  

Code of Federal Regulations, 2010 CFR

...Vegetables, Nuts), DEPARTMENT OF AGRICULTURE ONIONS GROWN IN CERTAIN DESIGNATED COUNTIES IN IDAHO...regulation. No person shall handle any lot of onions, except braided red onions, unless such onions are at least...

2010-01-01

499

7 CFR 959.322 - Handling regulation.  

...VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE ONIONS GROWN IN SOUTH TEXAS Handling Regulations § 959...March 1 and ending June 4, no handler shall handle any onions, including onions for peeling, chopping, and slicing, unless...

2014-01-01

500

7 CFR 959.322 - Handling regulation.  

Code of Federal Regulations, 2010 CFR

...Vegetables, Nuts), DEPARTMENT OF AGRICULTURE ONIONS GROWN IN SOUTH TEXAS Handling Regulations § 959...March 1 and ending June 4, no handler shall handle any onions, including onions for peeling, chopping, and slicing, unless...

2010-01-01