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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; Ptacek, Louis; Fu, Ying-Hui

2014-01-01

2

Circadian gene Bmal1 regulates diurnal oscillations of Ly6Chi inflammatory monocytes  

PubMed Central

Circadian clocks have evolved to regulate physiologic and behavioral rhythms in anticipation of changes in the environment. Although the molecular clock is present in innate immune cells, its role in monocyte homeostasis remains unknown. Here, we report that Ly6Chi inflammatory monocytes exhibit diurnal variation, which controls their trafficking to sites of inflammation. This cyclic pattern of trafficking confers protection against Listeria monocytogenes and is regulated by the repressive activity of the circadian gene BMAL1. Accordingly, myeloid cell-specific deletion of BMAL1 induces expression of monocyte-attracting chemokines and disrupts rhythmic cycling of Ly6Chi monocytes, predisposing mice to development of pathologies associated with acute and chronic inflammation. These findings have unveiled a critical role for BMAL1 in controlling the diurnal rhythms in Ly6Chi monocyte numbers. PMID:23970558

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

2013-01-01

3

Brain and muscle Arnt-like protein-1 (BMAL1), a component of the molecular clock, regulates adipogenesis.  

PubMed

Brain and muscle Arnt-like protein-1 (BMAL1; also known as MOP3 or Arnt3) is a transcription factor known to regulate circadian rhythm. Here, we established its involvement in the control of adipogenesis and lipid metabolism activity in mature adipocytes. During adipose differentiation in 3T3-L1 cells, the level of BMAL1 mRNA began to increase 4 days after induction and was highly expressed in differentiated cells. In white adipose tissues isolated from C57BL/6J mice, BMAL1 was predominantly expressed in a fraction containing adipocytes, as compared with the stromal-vascular fraction. BMAL1 knockout mice embryonic fibroblast cells failed to be differentiated into adipocytes. Importantly, adding BMAL1 back by adenovirus gene transfer restored the ability of BMAL1 knockout mice embryonic fibroblast cells to differentiate. Knock-down of BMAL1 expression in 3T3-L1 cells by an RNA interference technique allowed the cells to accumulate only minimum amounts of lipid droplets in the cells. Adenovirus-mediated expression of BMAL1 in 3T3-L1 adipocytes resulted in induction of several factors involved in lipogenesis. The promoter activity of these genes was stimulated in a BMAL1-dependent manner. Interestingly, expression of these factors showed clear circadian rhythm in mice adipose tissue. Furthermore, overexpression of BMAL1 in adipocytes increased lipid synthesis activity. These results indicate that BMAL1, a master regulator of circadian rhythm, also plays important roles in the regulation of adipose differentiation and lipogenesis in mature adipocytes. PMID:16093318

Shimba, Shigeki; Ishii, Norimasa; Ohta, Yuki; Ohno, Toshiharu; Watabe, Yuichi; Hayashi, Mitsuaki; Wada, Taira; Aoyagi, Toshinori; Tezuka, Masakatsu

2005-08-23

4

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

5

Regulation of the PAI-1 promoter by circadian clock components: differential activation by BMAL1 and BMAL2.  

PubMed

Circadian variation in plasminogen activator inhibitor-1 (PAI-1) production likely contributes to increased risk of myocardial infarction and decreased efficacy of thrombolytic therapy during the morning. In this study, we characterize the abilities of fundamental molecular components of intrinsic circadian clocks to regulate the human PAI-1 promoter in transfected endothelial cells. Both CLOCK:BMAL1 and CLOCK:BMAL2 heterodimers activate the PAI-1 promoter through requisite proximal (-565 to -560 bp) and distal (-680 to -675 bp) E-box enhancers. Although the distal E-box overlaps the 4G/5G polymorphism of the PAI-1 promoter, allelic variation at this site does not influence CLOCK:BMAL1-and CLOCK:BMAL2-mediated transactivation. Together, CLOCK:BMAL1 and CLOCK:BMAL2 make additive contributions to PAI-1 gene transcription. While the abilities of these heterodimers to activate gene expression differ by twofold, the susceptibilities of these circadian activators to inhibition by period and cryptochrome proteins are equivalent and redox independent. Given that BMAL1 and BMAL2 differ in their spatiotemporal distributions, such distinctions may allow intrinsic circadian clocks to modulate the amplitudes of their oscillators, while maintaining circadian periodicity. In this way, fundamental circadian clock components may drive circadian variation in PAI-1, which in turn influences the pathogenesis, timing, and treatment of acute atherothrombotic events. PMID:12738229

Schoenhard, John A; Smith, Layton H; Painter, Corrie A; Eren, Mesut; Johnson, Carl H; Vaughan, Douglas E

2003-05-01

6

Redundant Function of REV-ERB? and ? and Non-Essential Role for Bmal1 Cycling in Transcriptional Regulation of Intracellular Circadian Rhythms  

PubMed Central

The mammalian circadian clockwork is composed of a core PER/CRY feedback loop and additional interlocking loops. In particular, the ROR/REV/Bmal1 loop, consisting of ROR activators and REV-ERB repressors that regulate Bmal1 expression, is thought to “stabilize” core clock function. However, due to functional redundancy and pleiotropic effects of gene deletions, the role of the ROR/REV/Bmal1 loop has not been accurately defined. In this study, we examined cell-autonomous circadian oscillations using combined gene knockout and RNA interference and demonstrated that REV-ERB? and ? are functionally redundant and are required for rhythmic Bmal1 expression. In contrast, the RORs contribute to Bmal1 amplitude but are dispensable for Bmal1 rhythm. We provide direct in vivo genetic evidence that the REV-ERBs also participate in combinatorial regulation of Cry1 and Rorc expression, leading to their phase-delay relative to Rev-erb?. Thus, the REV-ERBs play a more prominent role than the RORs in the basic clock mechanism. The cellular genetic approach permitted testing of the robustness of the intracellular core clock function. We showed that cells deficient in both REV-ERB? and ? function, or those expressing constitutive BMAL1, were still able to generate and maintain normal Per2 rhythmicity. Our findings thus underscore the resilience of the intracellular clock mechanism and provide important insights into the transcriptional topologies underlying the circadian clock. Since REV-ERB function and Bmal1 mRNA/protein cycling are not necessary for basic clock function, we propose that the major role of the ROR/REV/Bmal1 loop and its constituents is to control rhythmic transcription of clock output genes. PMID:18454201

Liu, Andrew C.; Tran, Hien G.; Zhang, Eric E.; Priest, Aaron A.; Welsh, David K.; Kay, Steve A.

2008-01-01

7

Opposing effects of circadian clock genes bmal1 and period2 in regulation of VEGF-dependent angiogenesis in developing zebrafish.  

PubMed

Molecular mechanisms underlying circadian-regulated physiological processes remain largely unknown. Here, we show that disruption of the circadian clock by both constant exposure to light and genetic manipulation of key genes in zebrafish led to impaired developmental angiogenesis. A bmal1-specific morpholino inhibited developmental angiogenesis in zebrafish embryos without causing obvious nonvascular phenotypes. Conversely, a period2 morpholino accelerated angiogenic vessel growth, suggesting that Bmal1 and Period2 display opposing angiogenic effects. Using a promoter-reporter system consisting of various deleted vegf-promoter mutants, we show that Bmal1 directly binds to and activates the vegf promoter via E-boxes. Additionally, we provide evidence that knockdown of Bmal1 leads to impaired Notch-inhibition-induced vascular sprouting. These results shed mechanistic insight on the role of the circadian clock in regulation of developmental angiogenesis, and our findings may be reasonably extended to other types of physiological or pathological angiogenesis. PMID:22884368

Jensen, Lasse Dahl; Cao, Ziquan; Nakamura, Masaki; Yang, Yunlong; Bräutigam, Lars; Andersson, Patrik; Zhang, Yin; Wahlberg, Eric; Länne, Toste; Hosaka, Kayoko; Cao, Yihai

2012-08-30

8

DNA binding, but not interaction with Bmal1, is responsible for DEC1-mediated transcription regulation of the circadian gene mPer1.  

PubMed

DEC1 (differentially expressed in chondrocytes 1) and DEC2 are E-box-binding transcription factors and exhibit a circadian expression pattern. Recently, both proteins were found to repress the Clock/Bmal1-activated E-box promoters (e.g. mPer1). Yeast two-hybrid assay detected interactions between Bmal1 and DECs. It was hypothesized that DEC-mediated repression on the mPer1 promoter is achieved by binding to E-box elements and interacting with Bmal1. In the present study, we report that E-box binding rather than Bmal1 interaction is responsible for the observed repression. In the absence of Clock/Bmal1, both DEC1 and DEC2 markedly repressed the mPer1 promoter reporter; however, DNA-binding mutants showed no repressive activity. Similarly, DEC1, but not its DNA-binding mutants, repressed the Clock/Bmal1-induced activation. In addition, DEC1(R58P), a DNA-binding mutant with Bmal1 interactivity, repressed neither the mPer1 reporter directly nor the Clock/Bmal1-induced activation, providing direct evidence that DNA binding, rather than Bmal1 interactions, is responsible for the repression on the mPer1 promoter. Furthermore, disruption of the Sp1 site in the proximal promoter of mPer1 increased the repression of DEC1 proteins. Previous studies with mouse DEC2 showed that this factor interacts with Sp1. These findings suggest that DEC proteins regulate the expression of mPer1 through E-box binding and Sp1 interaction. Alterations on circadian systems are increasingly recognized as important risk factors for disease initiation and progression, and the expression of Dec genes is rapidly induced by environmental stimuli and is highly increased in tumour tissues. Therefore de-regulated expression of DEC genes probably alters normal circadian rhythms and contributes significantly to the pathogenesis of many diseases including cancer. PMID:15193144

Li, Yuxin; Song, Xiulong; Ma, Yuzhong; Liu, Jirong; Yang, Dongfang; Yan, Bingfang

2004-09-15

9

Deficiency in core circadian protein Bmal1 is associated with a prothrombotic and vascular phenotype.  

PubMed

Aging is associated with both the disturbances of circadian rhythms and a prothrombotic phenotype. It remains poorly understood how the circadian system regulates thrombosis, a critical outcome of aging-related cardiovascular disease. Using multiple in vivo models, we now show that mice with genetic ablation of the core clock gene Bmal1, which display pre-mature aging, have a dramatic prothrombotic phenotype. This phenotype is mechanistically linked to changes in the regulation of key risk factors for cardiovascular disease. These include circulating vWF, fibrinogen, and PAI-1, all of which are significantly elevated in Bmal1(-/-) mice. We also show that major circadian transcriptional regulators CLOCK and Bmal1 directly regulate the activity of vWF promoter and that lack of Bmal1 results in upregulation of vWF both at mRNA and protein level. Here we report a direct regulation of vWF expression in endothelial cells by biological clock gene Bmal1. This study establishes a mechanistic connection between Bmal1 and cardiovascular phenotype. PMID:20658528

Somanath, Payaningal R; Podrez, Eugene A; Chen, Juhua; Ma, Yi; Marchant, Kandice; Antoch, Marina; Byzova, Tatiana V

2011-01-01

10

Global Loss of Bmal1 Expression Alters Adipose Tissue Hormones, Gene Expression and Glucose Metabolism  

PubMed Central

The close relationship between circadian rhythm disruption and poor metabolic status is becoming increasingly evident, but role of adipokines is poorly understood. Here we investigated adipocyte function and the metabolic status of mice with a global loss of the core clock gene Bmal1 fed either a normal or a high fat diet (22% by weight). Bmal1 null mice aged 2 months were killed across 24 hours and plasma adiponectin and leptin, and adipose tissue expression of Adipoq, Lep, Retn and Nampt mRNA measured. Glucose, insulin and pyruvate tolerance tests were conducted and the expression of liver glycolytic and gluconeogenic enzyme mRNA determined. Bmal1 null mice displayed a pattern of increased plasma adiponectin and plasma leptin concentrations on both control and high fat diets. Bmal1 null male and female mice displayed increased adiposity (1.8 fold and 2.3 fold respectively) on the normal diet, but the high fat diet did not exaggerate these differences. Despite normal glucose and insulin tolerance, Bmal1 null mice had increased production of glucose from pyruvate, implying increased liver gluconeogenesis. The Bmal1 null mice had arrhythmic clock gene expression in epigonadal fat and liver, and loss of rhythmic transcription of a range of metabolic genes. Furthermore, the expression of epigonadal fat Adipoq, Retn, Nampt, AdipoR1 and AdipoR2 and liver Pfkfb3 mRNA were down-regulated. These results show for the first time that global loss of Bmal1, and the consequent arrhythmicity, results in compensatory changes in adipokines involved in the cellular control of glucose metabolism. PMID:23750248

Kennaway, David John; Varcoe, Tamara Jayne; Voultsios, Athena; Boden, Michael James

2013-01-01

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

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

PubMed

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

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

2014-09-30

13

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

PubMed

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

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

2008-12-01

14

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

PubMed

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

15

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

PubMed Central

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

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

2013-01-01

16

Development of dilated cardiomyopathy in Bmal1-deficient mice  

PubMed Central

Circadian rhythms are approximate 24-h oscillations in physiology and behavior. Circadian rhythm disruption has been associated with increased incidence of hypertension, coronary artery disease, dyslipidemia, and other cardiovascular pathologies in both humans and animal models. Mice lacking the core circadian clock gene, brain and muscle aryl hydrocarbon receptor nuclear translocator (ARNT)-like protein (Bmal1), are behaviorally arrhythmic, die prematurely, and display a wide range of organ pathologies. However, data are lacking on the role of Bmal1 on the structural and functional integrity of cardiac muscle. In the present study, we demonstrate that Bmal1?/? mice develop dilated cardiomyopathy with age, characterized by thinning of the myocardial walls, dilation of the left ventricle, and decreased cardiac performance. Shortly after birth the Bmal1?/? mice exhibit a transient increase in myocardial weight, followed by regression and later onset of dilation and failure. Ex vivo working heart preparations revealed systolic ventricular dysfunction at the onset of dilation and failure, preceded by downregulation of both myosin heavy chain isoform mRNAs. We observed structural disorganization at the level of the sarcomere with a shift in titin isoform composition toward the stiffer N2B isoform. However, passive tension generation in single cardiomyocytes was not increased. Collectively, these findings suggest that the loss of the circadian clock gene, Bmal1, gives rise to the development of an age-associated dilated cardiomyopathy, which is associated with shifts in titin isoform composition, altered myosin heavy chain gene expression, and disruption of sarcomere structure. PMID:22707558

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

2012-01-01

17

Whole blood thrombin generation in Bmal1-deficient mice.  

PubMed

The Calibrated Automated Thrombogram (CAT) assay that measures thrombin generation (TG) in platelet-poor and -rich plasma, is increasingly being recognised as a more sensitive tool to determine the overall function of the haemostatic system. We developed a method enabling the measurement of TG in a small aliquot of blood. The objective was to validate this assay in mouse blood and to examine the rate and extent of TG in a mouse model of premature aging. TG was assayed in blood from 20- to 28-week-old brain and muscle ARNT-like protein-1 (Bmal1)-deficient (knockout, KO) mice and wild-type (WT) littermates. Bmal1-KO mice are known to display symptoms of premature aging. TG was initiated by adding calcium, tissue factor and a thrombin specific substrate. After TG, the samples were prepared for scanning electron microscopy (SEM). The intra-assay variations (%) in mouse blood of the endogenous thrombin potential (ETP), peak height, lag time, time-to-peak and velocity index were 10% or less (n=24). We found that Bmal1-KO mice have a significantly (p<0.001) higher ETP (437 ± 7 nM.min; mean ± SD, n=7) when compared with WT mice (ETP=220 ± 45 nM.min; mean ± SD, n=5). The peak heights also differed significantly (p=0.027). By applying SEM we found that Bmal1 deficient mice display a denser fibrin network with smaller pores compared to WT mice. In conclusion, the whole blood TG assay in mice revealed to be reproducible. As a proof-of-principle we have shown that the whole blood TG assay is capable of detecting a prothrombotic phenotype in Bmal1-KO mice. PMID:24740693

Ninivaggi, M; Kelchtermans, H; Kuijpers, M J; Hemmeryckx, B; Heemskerk, J W M; Lindhout, T; Hoylaerts, M F; de Laat, B

2014-08-01

18

Downregulation of core clock gene Bmal1 attenuates expression of progesterone and prostaglandin biosynthesis-related genes in rat luteinizing granulosa cells.  

PubMed

Ovarian circadian oscillators have been implicated in the reproductive processes of mammals. However, there are few reports regarding the detection of ovarian clock-controlled genes (CCGs). The present study was designed to unravel the mechanisms through which CCG ovarian circadian oscillators regulate fertility, primarily using quantitative RT-PCR and RNA interference against Bmal1 in rat granulosa cells. Mature granulosa cells were prepared from mouse Per2-destabilized luciferase (dLuc) reporter gene transgenic rats. A real-time monitoring system of Per2 promoter activity was employed to detect Per2-dLuc oscillations. The cells exposed to luteinizing hormone (LH) displayed clear Per2-dLuc oscillations and a rhythmic expression of clock genes (Bmal1, Per1, Per2, Rev-erb?, and Dbp). Meanwhile, the examined ovarian genes (Star, Cyp19a1, Cyp11a1, Ptgs2, Lhcgr, and p53) showed rhythmic transcript profiles except for Hsd3b2, indicating that these rhythmic expression genes may be CCGs. Notably, Bmal1 small interfering (si)RNA treatment significantly decreased both the amplitude of Per2-dLuc oscillations and Bmal1 mRNA levels compared with nonsilencing RNA treatment in luteinizing granulosa cells. Depletion of Bmal1 by siRNA decreased the transcript levels of clock genes (Per1, Per2, Rev-erb?, and Dbp) and examined ovarian genes (Star, Cyp19a1, Cyp11a1, Ptgs2, Hsd3b2, and Lhcgr). Accordingly, knockdown of Bmal1 also inhibited the synthesis of progesterone and prostaglandin E2, which are associated with crucial reproductive processes. Collectively, these data suggest that ovarian circadian oscillators regulate the synthesis of steroid hormones and prostaglandins through ovarian-specific CCGs in response to LH stimuli. The present study provides new insights into the physiologic significance of Bmal1 related to fertility in ovarian circadian oscillators. PMID:23596172

Chen, Huatao; Zhao, Lijia; Kumazawa, Makoto; Yamauchi, Nobuhiko; Shigeyoshi, Yasufumi; Hashimoto, Seiichi; Hattori, Masa-aki

2013-06-15

19

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-Heon, Jean-Francois; Cermakian, Nicolas; Giguere, Vincent

2011-01-01

20

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

PubMed Central

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

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

2014-01-01

21

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

22

Deficient of a Clock Gene, Brain and Muscle Arnt-Like Protein1 (BMAL1), Induces Dyslipidemia and Ectopic Fat Formation  

Microsoft Academic Search

A link between circadian rhythm and metabolism has long been discussed. Circadian rhythm is controlled by positive and negative transcriptional and translational feedback loops composed of several clock genes. Among clock genes, the brain and muscle Arnt-like protein-1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK) play important roles in the regulation of the positive rhythmic transcription. In addition to

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

2011-01-01

23

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

24

Pulses of prolactin promoter activity depend on a noncanonical E-box that can bind the circadian proteins CLOCK and BMAL1.  

PubMed

Recent findings from our laboratory and those of others demonstrated that prolactin gene expression (PRL-GE) oscillates in single living mammotropes, but little information is available on the molecular processes that contribute to this phenomenon. To elucidate the source of this activity, we generated a series of constructs containing decreasing lengths of the PRL promoter fused to a luciferase reporter gene. These constructs were injected into single cells and assayed for photonic activity. We found pulse activity with all plasmids tested, even with the smallest promoter fragment of 331 bp. Sequence analysis of this fragment identified two potential E-boxes (elements known to bind CLOCK and BMAL1 circadian proteins). Furthermore, RT-PCR of PRL cells (pituitary, MMQ, and GH(3)) revealed expression of clock and bmal1 as well as five other clock genes (per1, per2, cry1, cry2, and tim), suggesting that the circadian system may function in PRL cells. Next, we mutated the core sequences of both E-boxes within the 2.5-kb PRL promoter and found that only mutation of the E-box133 completely abolished PRL-GE pulses. EMSAs revealed that CLOCK and BMAL1 were able to bind to the E-box133 site in vitro. Our results demonstrate that PRL-GE pulses are dependent on a specific E-box binding site in the PRL promoter. Moreover, the indication that CLOCK/BMAL1 can bind to this site suggests that these circadian proteins, either alone or in conjunction with other factors, may regulate intermittent PRL promoter activity in mammotropes, perhaps by acting as a temporal switch for the on/off expression of PRL. PMID:15774559

Leclerc, Gilles M; Boockfor, Fredric R

2005-06-01

25

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

PubMed Central

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

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

2012-01-01

26

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

PubMed

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

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

2014-09-15

27

TGF? Inducible Early Gene-1 (TIEG1) and Cardiac Hypertrophy: Discovery and Characterization of a Novel Signaling Pathway  

PubMed Central

Cellular mechanisms causing cardiac hypertrophy are currently under intense investigation. We report a novel finding in the TGF? inducible early gene (TIEG) null mouse implicatingTIEG1 in cardiac hypertrophy. The TIEG?/? knock-out mouse was studied. Male mice age 4–16 months were characterized (N = 86 total) using echocardiography, transcript profiling by gene microarray, and immunohistochemistry localized upregulated genes for determination of cellular mechanism. The female mice (N =40) did not develop hypertrophy or fibrosis. The TIEG ?/? knock-out mouse developed features of cardiac hypertrophy including asymmetric septal hypertrophy, an increase in ventricular size at age 16 months, an increase (214%) in mouse heart/weight body weight ratio TIEG?/?, and an increase in wall thickness in TIEG?/? mice of (1.85 ±0.21 mm), compared to the control (1.13 ±0.15 mm, P< 0.04). Masson Trichrome staining demonstrated evidence of myocyte disarray and myofibroblast fibrosis. Microarray analysis of the left ventricles demonstrated that TIEG?/? heart tissues expressed a 13.81-fold increase in pituitary tumor-transforming gene-1 (Pttg1). An increase in Pttg1 and histone H3 protein levels were confirmed in the TIEG?/? mice hearts tissues. We present evidence implicating TIEG and possibly its target gene, Pttg1, in the development of cardiac hypertrophy in the TIEG null mouse. PMID:16888812

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

2014-01-01

28

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

29

Standards of evidence in chronobiology: critical review of a report that restoration of Bmal1 expression in the dorsomedial hypothalamus is sufficient to restore circadian food anticipatory rhythms in Bmal1-/- mice  

PubMed Central

Daily feeding schedules generate food anticipatory rhythms of behavior and physiology that exhibit canonical properties of circadian clock control. The molecular mechanisms and location of food-entrainable circadian oscillators hypothesized to control food anticipatory rhythms are unknown. In 2008, Fuller et al reported that food-entrainable circadian rhythms are absent in mice bearing a null mutation of the circadian clock gene Bmal1 and that these rhythms can be rescued by virally-mediated restoration of Bmal1 expression in the dorsomedial nucleus of the hypothalamus (DMH) but not in the suprachiasmatic nucleus (site of the master light-entrainable circadian pacemaker). These results, taken together with controversial DMH lesion results published by the same laboratory, appear to establish the DMH as the site of a Bmal1-dependent circadian mechanism necessary and sufficient for food anticipatory rhythms. However, careful examination of the manuscript reveals numerous weaknesses in the evidence as presented. These problems are grouped as follows and elaborated in detail: 1. data management issues (apparent misalignments of plotted data), 2. failure of evidence to support the major conclusions, and 3. missing data and methodological details. The Fuller et al results are therefore considered inconclusive, and fail to clarify the role of either the DMH or Bmal1 in the expression of food-entrainable circadian rhythms in rodents. PMID:19323828

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

2009-01-01

30

Age-related BMAL1 change affects mouse bone marrow stromal cell proliferation and osteo-differentiation potential  

PubMed Central

Introduction Aging people's bone regeneration potential is always impaired. Bone marrow stromal cells (MSCs) contain progenitors of osteoblasts. Donor age may affect MSCs’ proliferation and differentiation potential, but the genomic base is still unknown. Due to recent research's indication that a core circadian component, brain and muscle ARNT-like 1 protein (BMAL1), has a role in premature aging, we investigated the normal aging mechanism in mice with their MSCs and Bmal1 gene/protein level. Material and methods 1, 6 and 16 month old C57BL/6 mice were used and the bone marrow stromal cells were gained and cultured at early passage. Bmal1 gene and protein level were detected in these cells. Marrow stromal cells were also induced to differentiate to osteoblasts or adipocytes. Three groups of mice MSCs were compared on proliferation by flow cytometry, on cell senescence by SA-?-gal expression and after osteo-induction on osteogenic potential by the expression of osterix (Osx), alkaline phosphatase (ALP) and osteocalcin (OCN). Results Bmal1 gene and protein level as well as S-phase fraction of the cell cycle decreased in MSCs along with the aging process. At the same time, SA-?-gal+ levels increased, especially in the aged mice MSCs. When induced to be osteogenic, Osx gene expression and ALP activity declined in the mid-age and aged mice MSCs, while OCN protein secretion deteriorated in the aged mice MSCs. Conclusions These findings demonstrate that mouse MSCs changed with their proliferation and osteo-differentiation abilities at different aging stages, and that Bmal1 is related to the normal aging process in MSCs. PMID:22457671

Chen, Yijia; Xu, Xiaomei; Tan, Zhen; Ye, Cui; Chen, Yangxi

2012-01-01

31

Brain and muscle Arnt-like 1 is a key regulator of myogenesis  

PubMed Central

Summary The circadian clock network is an evolutionarily conserved mechanism that imparts temporal regulation to diverse biological processes. Brain and muscle Arnt-like 1 (Bmal1), an essential transcriptional activator of the clock, is highly expressed in skeletal muscle. However, whether this key clock component impacts myogenesis, a temporally regulated event that requires the sequential activation of myogenic regulatory factors, is not known. Here we report a novel function of Bmal1 in controlling myogenic differentiation through direct transcriptional activation of components of the canonical Wnt signaling cascade, a major inductive signal for embryonic and postnatal muscle growth. Genetic loss of Bmal1 in mice leads to reduced total muscle mass and Bmal1-deficient primary myoblasts exhibit significantly impaired myogenic differentiation accompanied by markedly blunted expression of key myogenic regulatory factors. Conversely, forced expression of Bmal1 enhances differentiation of C2C12 myoblasts. This cell-autonomous effect of Bmal1 is mediated by Wnt signaling as both expression and activity of Wnt components are markedly attenuated by inhibition of Bmal1, and activation of the Wnt pathway partially rescues the myogenic defect in Bmal1-deficient myoblasts. We further reveal direct association of Bmal1 with promoters of canonical Wnt pathway genes, and as a result of this transcriptional regulation, Wnt signaling components exhibit intrinsic circadian oscillation. Collectively, our study demonstrates that the core clock gene, Bmal1, is a positive regulator of myogenesis, which may represent a temporal regulatory mechanism to fine-tune myocyte differentiation. PMID:23525013

Chatterjee, Somik; Nam, Deokhwa; Guo, Bingyan; Kim, Ji M.; Winnier, Glen E.; Lee, Jeongkyung; Berdeaux, Rebecca; Yechoor, Vijay K.; Ma, Ke

2013-01-01

32

Direct regulation of CLOCK expression by REV-ERB.  

PubMed

Circadian rhythms are regulated at the cellular level by transcriptional feedback loops leading to oscillations in expression of key proteins including CLOCK, BMAL1, PERIOD (PER), and CRYPTOCHROME (CRY). The CLOCK and BMAL1 proteins are members of the bHLH class of transcription factors and form a heterodimer that regulates the expression of the PER and CRY genes. The nuclear receptor REV-ERB? plays a key role in regulation of oscillations in BMAL1 expression by directly binding to the BMAL1 promoter and suppressing its expression at certain times of day when REV-ERB? expression levels are elevated. We recently demonstrated that REV-ERB? also regulates the expression of NPAS2, a heterodimer partner of BMAL1. Here, we show that REV-ERB? also regulates the expression another heterodimer partner of BMAL1, CLOCK. We identified a REV-ERB? binding site within the 1(st) intron of the CLOCK gene using a chromatin immunoprecipitation - microarray screen. Suppression of REV-ERB? expression resulted in elevated CLOCK mRNA expression consistent with REV-ERB?'s role as a transcriptional repressor. A REV-ERB response element (RevRE) was identified within this region of the CLOCK gene and was conserved between humans and mice. Additionally, the CLOCK RevRE conferred REV-ERB responsiveness to a heterologous reporter gene. Our data suggests that REV-ERB? plays a dual role in regulation of the activity of the BMAL1/CLOCK heterodimer by regulation of expression of both the BMAL1 and CLOCK genes. PMID:21479263

Crumbley, Christine; Burris, Thomas P

2011-01-01

33

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

34

Circadian Regulation of Myocardial Sarcomeric Titin-cap (Tcap, Telethonin): Identification of Cardiac Clock-Controlled Genes Using Open Access Bioinformatics Data  

PubMed Central

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

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

2014-01-01

35

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

PubMed Central

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.

2013-01-01

36

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

PubMed

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

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

2011-12-01

37

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

PubMed

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

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

2013-03-01

38

PML regulates PER2 nuclear localization and circadian function  

PubMed Central

Studies have suggested that the clock regulator PER2 is a tumour suppressor. A cancer network involving PER2 raises the possibility that some tumour suppressors are directly involved in the mammalian clock. Here, we show that the tumour suppressor promyelocytic leukaemia (PML) protein is a circadian clock regulator and can physically interact with PER2. In the suprachiasmatic nucleus (SCN), PML expression and PML–PER2 interaction are under clock control. Loss of PML disrupts and dampens the expression of clock regulators Per2, Per1, Cry1, Bmal1 and Npas2. In the presence of PML and PER2, BMAL1/CLOCK-mediated transcription is enhanced. In Pml?/? SCN and mouse embryo fibroblast cells, the cellular distribution of PER2 is primarily perinuclear/cytoplasmic. PML is acetylated at K487 and its deacetylation by SIRT1 promotes PML control of PER2 nuclear localization. The circadian period of Pml?/? mice displays reduced precision and stability consistent with PML having a role in the mammalian clock mechanism. PMID:22274616

Miki, Takao; Xu, Zhixiang; Chen-Goodspeed, Misty; Liu, Mingguang; Van Oort-Jansen, Anita; Rea, Michael A; Zhao, Zhaoyang; Lee, Cheng Chi; Chang, Kun-Sang

2012-01-01

39

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

PubMed Central

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

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

2014-01-01

40

TGF? inducible early gene-1 plays an important role in mediating estrogen signaling in the skeleton.  

PubMed

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

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

2014-05-01

41

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

PubMed

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

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

2009-11-01

42

Regulation of CLOCK and MOP4 by nuclear hormone receptors in the vasculature: a humoral mechanism to reset a peripheral clock.  

PubMed

Circadian clock genes are expressed in the suprachiasmatic nucleus and in peripheral tissues to regulate cyclically physiological processes. Synchronization of peripheral oscillators is thought to involve humoral signals, but the mechanisms by which these are mediated and integrated are poorly understood. We report a hormone-dependent interaction of the nuclear receptors, RAR alpha and RXR alpha, with CLOCK and MOP4. These interactions negatively regulate CLOCK/MOP4:BMAL1-mediated transcriptional activation of clock gene expression in vascular cells. MOP4 exhibits a robust rhythm in the vasculature, and retinoic acid can phase shift Per2 mRNA rhythmicity in vivo and in serum-induced smooth muscle cells in vitro, providing a molecular mechanism for hormonal control of clock gene expression. We propose that circadian or periodic availability of nuclear hormones may play a critical role in resetting a peripheral vascular clock. PMID:11439184

McNamara, P; Seo, S B; Rudic, R D; Sehgal, A; Chakravarti, D; FitzGerald, G A

2001-06-29

43

Expression of the gene for Dec2, a basic helix-loop-helix transcription factor, is regulated by a molecular clock system.  

PubMed

Dec2, a member of the basic helix-loop-helix superfamily, is a recently confirmed regulatory protein for the clockwork system. Transcripts of Dec2, as well as those of its related gene Dec1, exhibit a striking circadian oscillation in the suprachiasmatic nucleus, and Dec2 inhibits transcription from the Per1 promoter induced by Clock/Bmal1 [Honma, Kawamoto, Takagi, Fujimoto, Sato, Noshiro, Kato and Honma (2002) Nature (London) 419, 841-844]. It is known that mammalian circadian rhythms are controlled by molecular clockwork systems based on negative-feedback loop(s), but the molecular mechanisms for the circadian regulation of Dec2 gene expression have not been clarified. We show here that transcription of the Dec2 gene is regulated by several clock molecules and a negative-feedback loop. Luciferase and gel retardation assays showed that expression of Dec2 was negatively regulated by binding of Dec2 or Dec1 to two CACGTG E-boxes in the Dec2 promoter. Forced expression of Clock/Bmal1 and Clock/Bmal2 markedly increased Dec2 mRNA levels, and up-regulated the transcription of the Dec2 gene through the CACGTG E-boxes. Like Dec, Cry and Per also suppressed Clock/Bmal-induced transcription from the Dec2 promoter. Moreover, the circadian expression of Dec2 transcripts was abolished in the kidney of Clock/Clock mutant mice. These findings suggest that the Clock/Bmal heterodimer enhances Dec2 transcription via the CACGTG E-boxes, whereas the induced transcription is suppressed by Dec2, which therefore must contribute to its own rhythmic expression. In addition, Cry and Per may also modulate Dec2 transcription. PMID:15147242

Hamaguchi, Hidenori; Fujimoto, Katsumi; Kawamoto, Takeshi; Noshiro, Mitsuhide; Maemura, Koji; Takeda, Norihiko; Nagai, Ryozo; Furukawa, Masae; Honma, Sato; Honma, Ken-ichi; Kurihara, Hidemi; Kato, Yukio

2004-08-15

44

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

45

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

PubMed Central

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

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

2014-01-01

46

Kruppel-like factor KLF10 targets transforming growth factor-beta1 to regulate CD4(+)CD25(-) T cells and T regulatory cells.  

PubMed

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)-beta1 and Foxp3. KLF10 overexpressing CD4(+)CD25(-) T cells induced both TGF-beta1 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-beta1, an effect completely rescued by exogenous treatment with TGF-beta1. Mechanistic studies demonstrate that in response to TGF-beta1, KLF10 can transactivate both TGF-beta1 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 approximately 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-beta1 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

2009-09-11

47

Circadian clock gene expression regulates cancer cell growth through glutaminase.  

PubMed

Glutamine is an essential amino acid for malignant tumor cells. Glutaminase that metabolizes glutamine reaches a maximum expression in tumors immediately before the maximum proliferation rate. Tumor cells grow at different rates during the day. We postulated that the activity of glutaminase in tumor cells is subject to the regulation of circadian clock gene. We measured glutaminase by western blot analysis and circadian clock gene expression by real-time polymerase chain reaction in the liver and tumor cells at six equispaced time points of the day in individual mice of a 12/12 h light/dark schedule. The results showed that the tumor-bearing mice, under normal diurnal conditions, are circadianly entrained, as reflected by the normal host locomotor activity rhythms and rhythmic liver clock gene expression. The tumors within these mice are also circadianly organized, as reflected by circadian clock gene (Bmal1) expression. What is most remarkable is that kidney-type glutaminase also showed circadian rhythms in the same pattern with tumor circadian clock gene expression in liver cancer xenograft model, indicating that conditionally inhibiting glutaminase activity may provide a new target for cancer therapy. PMID:24681885

Huang, Aixia; Bao, Bingbo; Gaskins, H Rex; Liu, Haijun; Zhang, Xueli; Lu, Liwen; Gao, Shan; Shi, Yihai; Zhang, Ming; Shan, Yuanzhou; Feng, Jing; Yao, Guoxiang

2014-05-01

48

Role of Type II Protein Arginine Methyltransferase 5 in the Regulation of Circadian Per1 Gene  

PubMed Central

Circadian clocks are the endogenous oscillators that regulate rhythmic physiological and behavioral changes to correspond to daily light-dark cycles. Molecular dissections have revealed that transcriptional feedback loops of the circadian clock genes drive the molecular oscillation, in which PER/CRY complexes inhibit the transcriptional activity of the CLOCK/BMAL1 heterodimer to constitute a negative feedback loop. In this study, we identified the type II protein arginine methyltransferase 5 (PRMT5) as an interacting molecule of CRY1. Although the Prmt5 gene was constitutively expressed, increased interaction of PRMT5 with CRY1 was observed when the Per1 gene was repressed both in synchronized mouse liver and NIH3T3 cells. Moreover, rhythmic recruitment of PRMT5 and CRY1 to the Per1 gene promoter was found to be associated with an increased level of histone H4R3 dimethylation and Per1 gene repression. Consistently, decreased histone H4R3 dimethylation and altered rhythmic Per1 gene expression were observed in Prmt5-depleted cells. Taken together, these findings provide an insight into the link between histone arginine methylation by PRMT5 and transcriptional regulation of the circadian Per1 gene. PMID:23133559

Na, Jungtae; Lee, Kwanghyun; Kim, Hwan-Gon; Shin, Jee-Yoon; Na, Wonho; Jeong, Hayan; Lee, Jong-Woo; Cho, Sehyung; Kim, Won-Sun; Ju, Bong-Gun

2012-01-01

49

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.; Moller-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

50

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

51

A molecular mechanism regulating circadian expression of vascular endothelial growth factor in tumor cells.  

PubMed

Because angiogenesis is essential for tumor growth and metastasis, inhibition of angiogenesis has emerged as a new therapy to treat cancers. Hypoxia-induced expression of vascular endothelial growth factor (VEGF) plays a central role in tumor-induced angiogenesis. In this study, we found that expression of VEGF in hypoxic tumor cells was affected by the circadian organization of molecular clockwork. The core circadian oscillator is composed of an autoregulatory transcription-translation feedback loop in which CLOCK and BMAL1 are positive regulators, and Period and Cryptochrome genes act as negative ones. The levels of VEGF mRNA in tumor cells implanted in mice rose substantially in response to hypoxia, but the levels fluctuated rhythmically in a circadian fashion. Luciferase reporter gene analysis revealed that Period2 and Cryptochrome1, whose expression in the implanted tumor cells showed a circadian oscillation, inhibited the hypoxia-induced VEGF promoter activity. These results suggest that the negative limbs of the molecular loop periodically inhibit the hypoxic induction of VEGF transcription, resulting in the circadian fluctuation of its mRNA expression. We also showed that the antitumor efficacy of antiangiogenic agents could be enhanced by administering the drugs at the time when VEGF production increased. These findings support the notion that monitoring of the circadian rhythm in VEGF production is useful for choosing the most appropriate time of day for administration of antiangiogenic agents. PMID:14612524

Koyanagi, Satoru; Kuramoto, Yukako; Nakagawa, Hiroo; Aramaki, Hironori; Ohdo, Shigehiro; Soeda, Shinji; Shimeno, Hiroshi

2003-11-01

52

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

PubMed

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

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

2012-06-01

53

TTF1, a homeodomain containing transcription factor, contributes to regulating periodic oscillations in GnRH gene expression  

PubMed Central

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

Matagne, Valerie; Kim, Jae Geun; Ryu, Byung Jun; Hur, Min Kyu; Kim, Min Sung; Kim, Kyungjin; Park, Byong Seo; Damante, Giuseppe; Smiley, Gregory; Lee, Byung Ju; Ojeda, Sergio R.

2012-01-01

54

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

PubMed Central

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

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

2014-01-01

55

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

56

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

57

Analysis and synthesis of high-amplitude Cis-elements in the mammalian circadian clock  

Microsoft Academic Search

Mammalian circadian clocks consist of regulatory loops mediated by Clock\\/Bmal1-binding elements, DBP\\/E4BP4 binding elements, and RevErbA\\/ROR binding elements. As a step toward system-level understanding of the dynamic transcriptional regulation of the oscillator, we constructed and used a mammalian promoter\\/enhancer database (http:\\/\\/promoter.cdb.riken.jp\\/) with computational models of the Clock\\/Bmal1-binding elements, DBP\\/E4BP4 binding elements, and RevErbA\\/ROR binding elements to predict new targets of

Yuichi Kumaki; Maki Ukai-Tadenuma; Ken-Ichiro D. Uno; Junko Nishio; Koh-Hei Masumoto; Mamoru Nagano; Takashi Komori; Yasufumi Shigeyoshi; John B. Hogenesch; Hiroki R. Ueda

2008-01-01

58

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

PubMed Central

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

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

2012-01-01

59

A Role for Id2 in Regulating Photic Entrainment of the Mammalian Circadian System  

PubMed Central

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

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

2009-01-01

60

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

61

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

62

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

63

Beyond Regulation  

E-print Network

customers had switched supplier. Essential Services Commission, Special Investigation: Review of Effectiveness of Retail Competition and Consumer Safety Net in Gas and Electricity, Final Report to Minister, 22 June 2004, section 2.4. Updated to December... of domestic gas and electricity competition and supply price regulation: conclusions and final proposals, 16/02 February 2002; Electricity supply competition, 83/02, December 2002; Domestic gas and electricity supply competition: recent developments, June...

Littlechild, Stephen C

2006-03-14

64

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

65

Clock controls angiogenesis.  

PubMed

Circadian rhythms control multiple physiological and pathological processes, including embryonic development in mammals and development of various human diseases. We have recently, in a developing zebrafish embryonic model, discovered that the circadian oscillation controls developmental angiogenesis. Disruption of crucial circadian regulatory genes, including Bmal1 and Period2, results in marked impairment or enhancement of vascular development in zebrafish. At the molecular level, we show that the circadian regulator Bmal1 directly targets the promoter region of the vegf gene in zebrafish, leading to an elevated expression of VEGF. These findings can reasonably be extended to developmental angiogenesis in mammals and even pathological angiogenesis in humans. Thus, our findings, for the first time, shed new light on mechanisms that underlie circadian clock-regulated angiogenesis. PMID:23324349

Jensen, Lasse Dahl; Cao, Yihai

2013-02-01

66

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

67

Taxation by Regulation  

Microsoft Academic Search

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

Richard A. Posner

1971-01-01

68

Regulation 28: Library REGULATION 28: LIBRARY  

E-print Network

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

Sussex, University of

69

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

PubMed Central

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

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

2014-01-01

70

Altered Stra13 and Dec2 circadian gene expression in hypoxic cells  

SciTech Connect

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

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

2008-05-16

71

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

PubMed Central

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

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

2014-01-01

72

Magel2, a Prader-Willi syndrome candidate gene, modulates the activities of circadian rhythm proteins in cultured cells  

PubMed Central

Background The Magel2 gene is most highly expressed in the suprachiasmatic nucleus of the hypothalamus, where its expression cycles in a circadian pattern comparable to that of clock-controlled genes. Mice lacking the Magel2 gene have hypothalamic dysfunction, including circadian defects that include reduced and fragmented total activity, excessive activity during the subjective day, but they have a normal circadian period. Magel2 is a member of the MAGE family of proteins that have various roles in cellular function, but the specific function of Magel2 is unknown. Methods We used a variety of cell-based assays to determine whether Magel2 modifies the properties of core circadian rhythm proteins. Results Magel2 represses the activity of the Clock:Bmal1 heterodimer in a Per2-luciferase assay. Magel2 interacts with Bmal1 and with Per2 as measured by co-immunoprecipitation in co-transfected cells, and exhibits a subcellular distribution consistent with these interactions when visualized by immunofluorescence. As well, Magel2 induces the redistribution of the subcellular localization of Clock towards the cytoplasm, in contrast to the nucleus-directed effect of Bmal1 on Clock subcellular localization. Conclusion Consistent with the blunted circadian rhythm observed in Magel2-null mice, these data suggest that Magel2 normally promotes negative feedback regulation of the cellular circadian cycle, through interactions with key core circadian rhythm proteins. PMID:22208286

2011-01-01

73

Resolutions and Regulations V. MEDICAL SCIENCE REGULATIONS  

E-print Network

Resolutions and Regulations Page 2.1 V. MEDICAL SCIENCE REGULATIONS A . Faculty Entrance and at least one other science. If Biology or Mathematics or Physics has not been passed at Higher grade, each Chemistry and at least one other science. If Biology or Mathematics or Physics is not offered at Advanced (A

Brierley, Andrew

74

Regulation of Hate Speech  

Microsoft Academic Search

Facing an increase of hate speech incidents on campus and in society at large, egalitarians have made great efforts to advocate (when there is no regulation) or to defend (when there is regulation) hate speech regulation. Meanwhile, civil libertarians have counter argued forcefully. This paper is designed to do an internal critique of various egalitarian arguments. Part I is introduction.

Haiping Deng

2004-01-01

75

Computer Use Regulation Introduction  

E-print Network

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

Liu, Paul

76

Emotion Regulation CONCEPTUAL FOUNDATIONS  

E-print Network

- changes that require us to regulate how emotions are experienced and expressed. But what do people do and adult literatures relevant to emotion regulation. Because a discussion of emotion regulation presupposes an understanding of what emotion is, we first consider emotion in the context of the larger family of affective pro

Gross, James J.

77

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

78

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

79

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

80

Pressure reducing regulator  

DOEpatents

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

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

1995-10-10

81

Sirtuin Catalysis and Regulation*  

PubMed Central

Sirtuins are a family of NAD+-dependent protein deacetylases/deacylases that dynamically regulate transcription, metabolism, and cellular stress response. Their general positive link with improved health span in mammals, potential regulation of pathways mediated by caloric restriction, and growing links to human disease have spurred interest in therapeutics that target their functions. Here, we review the current understanding of the chemistry of catalysis, biological targets, and endogenous regulation of sirtuin activity. We discuss recent efforts to generate small-molecule regulators of sirtuin activity. PMID:23086947

Feldman, Jessica L.; Dittenhafer-Reed, Kristin E.; Denu, John M.

2012-01-01

82

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.

83

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

84

Regulating hedge funds  

Microsoft Academic Search

Due to the ever-increasing amounts under management and their unregulated and opaque nature, hedge funds have emerged as a key concern for policymakers. While until now, hedge funds have been left essentially unregulated, we are seeing increasing calls for regulation for both microprudential and macroprudential reasons. In our view, most calls for the regulation of hedge funds are based on

J. Daníelsson; J. P. Zigrand

2007-01-01

85

Regulation of concentrated animal…  

Microsoft Academic Search

The livestock industry in the United States has experienced significant concentration and vertical integration in recent years. This change has resulted in greater observed levels of pollution attributed to concentrated animal feeding operations (CAFO) and society has attempted to use regulation to remedy these problems. Despite regulation at the federal and local level no documented improvement in water quality has

Benjamin Gramig

2004-01-01

86

Federal automobile regulations  

Microsoft Academic Search

This cost-benefit study of auto safety and emissions regulation is a major departure from the traditional methods of measuring costs and benefits. It theoreticaly derives regulation's impact on consumer demand and on production costs, and then empirically estimates these impacts with regression analysis. The study finds demand for large, expensive cars is more sensitive to price changes than small car

Langenfeld

1983-01-01

87

Pressure regulating valve controller  

Microsoft Academic Search

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

1988-01-01

88

Workshop in Regulation &  

E-print Network

Newark, NJ Continuing Problems in the Electric Utility Sector January 13, 2012 Rutgers Business School, 1Advanced Workshop in Regulation & Competition 2011-2012 Conflicting Technological and Competitive Forces in Regulated Industries November 18, 2011 Rutgers Business School, 1 Washington Park, Room 118

Lin, Xiaodong

89

The regulation of appetite  

Microsoft Academic Search

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

M Druce; S R Bloom

2006-01-01

90

Pressure regulating valve controller  

SciTech Connect

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

Goodman, R.B.

1988-04-05

91

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

92

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.

93

Self-Regulated Learning  

NSDL National Science Digital Library

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

Corsi, Gianluca

2010-10-01

94

Mercury: Laws and Regulations  

MedlinePLUS

... time EPA has ever regulated mercury emissions from coal-fired power plants. Top of page Clean Water ... use at more than half of the nation's coal-fired power plants. Read the press release | Learn ...

95

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

96

Regulation and behavior  

NSDL National Science Digital Library

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

2010-01-01

97

Regulation of university teaching  

Microsoft Academic Search

The aims of the present study are twofold: firstly, to explore dimensions in the regulation of teaching in a multidisciplinary\\u000a sample of university teachers, and secondly, to analyse factors related to the regulation of university teaching. Seventy-three\\u000a university teachers representing several disciplines participated in the study. These teachers volunteered to be interviewed.\\u000a Before the interviews, teachers were asked to fill

Sari Lindblom-YlanneAnne; Anne Nevgi; Keith Trigwell

2011-01-01

98

Regulation of Chloroplast Translation  

Microsoft Academic Search

Plastid gene expression is highly regulated in response to environmental parameters, such as light, during plant growth and development. The integrated regulation of post-transcriptional events, such as mRNA stability, mRNA processing, and translation, has been shown to play amajor role in chloroplast gene expression. Biosynthesis of many chloroplast proteins shows a requirement for nuclear-encoded proteins and hence a coordination of

Aravind Somanchi; Stephen P. Mayfield

99

In regulation we trust.  

PubMed

The role of trust has been argued to play an increasingly important role in modern, complex, and ambivalent risk societies. Trust within organizational research is anticipated to have a general strategic impact on aspects such as organizational performance, communication and knowledge exchange, and learning from accidents. Trust is also an important aspect related to regulation of risk. Diverse regulatory regimes, their contexts and risks influence regulators use of trust and distrust in regulatory practice. The aim of this paper is to discuss the relationship between risk regulation and trust across diverse risk regulation regimes. By drawing from studies of risk regulation, risk perception, and trust the purpose is to discuss how regulation and trust are linked and used in practice to control risk across system levels in socio-technical systems in high risk industries. This paper provides new knowledge on 1) how functional and dysfunctional trust and distrust are grounded in the empirical realities of high risk industries, 2) how different perspectives on trust and distrust act together and bring new knowledge on how society control risk. PMID:22317183

Wiig, Siri; Tharaldsen, Jorunn Elise

2012-01-01

100

SB 4 Well Stimulation Treatment Regulations Text of Proposed Regulations  

E-print Network

, cyclic steam injection, injection disposal, and gas storage projects. (b) Well stimulation treatments SB 4 Well Stimulation Treatment Regulations Text of Proposed Regulations Page 1 of 13 SB 4 WELL STIMULATION TREATMENT REGULATIONS TEXT OF PROPOSED REGULATIONS Added text is shown in underline

101

TOPs and their regulation.  

PubMed

Upon cell-cycle arrest or nutrient deprivation, the cellular rate of ribosome production is reduced significantly. In mammalian cells, this effect is achieved in part through a co-ordinated inhibition of RP (ribosomal protein) synthesis. More specifically, translation initiation on RP mRNAs is inhibited. Translational regulation of RP synthesis is dependent on cis-elements within the 5'-UTRs (5'-untranslated regions) of the RP mRNAs. In particular, a highly conserved 5'-TOP (5'-terminal oligopyrimidine tract) appears to play a key role in the regulation of RP mRNA translation. This article explores recent developments in our understanding of the mechanism of TOP mRNA regulation, focusing on upstream signalling pathways and trans-acting factors, and highlighting some interesting observations which have come to light following the recent development of cDNA microarray technology coupled with polysome analysis. PMID:16246169

Hamilton, T L; Stoneley, M; Spriggs, K A; Bushell, M

2006-02-01

102

Cardiac thin filament regulation  

PubMed Central

Myocardial contraction is initiated upon the release of calcium into the cytosol from the sarcoplasmic reticulum following membrane depolarization. The fundamental physiological role of the heart is to pump an amount blood that is determined by the prevailing requirements of the body. The physiological control systems employed to accomplish this task include regulation of heart rate, the amount of calcium release, and the response of the cardiac myofilaments to activator calcium ions. Thin filament activation and relaxation dynamics has emerged as a pivotal regulatory system tuning myofilament function to the beat-to-beat regulation of cardiac output. Maladaptation of thin filament dynamics, in addition to dysfunctional calcium cycling, is now recognized as an important cellular mechanism causing reduced cardiac pump function in a variety of cardiac diseases. Here, we review current knowledge regarding protein–protein interactions involved in the dynamics of thin filament activation and relaxation and the regulation of these processes by protein kinase-mediated phosphorylation. PMID:18421471

Kobayashi, Tomoyoshi; Jin, Lei; de Tombe, Pieter P.

2010-01-01

103

Sink regulation of photosynthesis.  

PubMed

The concept that photosynthetic flux is influenced by the accumulation of photo-assimilate persisted for 100 years before receiving any strong experimental support. Precise analysis of the mechanisms of photosynthetic responses to sink activity required the development of a battery of appropriate molecular techniques and has benefited from contemporary interest in the effects of elevated CO2 on photosynthesis. Photosynthesis is one of the most highly integrated and regulated metabolic processes to maximize the use of available light, to minimize the damaging effects of excess light and to optimize the use of limiting carbon and nitrogen resources. Hypotheses of feedback regulation must take account of this integration. In the short term, departure from homeostasis can lead to redox signals, which cause rapid changes in the transcription of genes encoding photosystems I and II. End-product synthesis can exert short-term metabolic feedback control through Pi recycling. Beyond this, carbohydrate accumulation in leaves when there is an imbalance between source and sink at the whole plant level can lead to decreased expression of photosynthetic genes and accelerated leaf senescence. In a high CO2 world this may become a more prevalent feature of photosynthetic regulation. However, sink regulation of photosynthesis is highly dependent on the physiology of the rest of the plant. This physiological state regulates photosynthesis through signal transduction pathways that co-ordinate the plant carbon : nitrogen balance, which match photosynthetic capacity to growth and storage capacity and underpin and can override the direct short-term controls of photosynthesis by light and CO2. Photosynthate supply and phytohormones, particularly cytokinins, interact with nitrogen supply to control the expression of photosynthesis genes, the development of leaves and the whole plant nitrogen distribution, which provides the dominant basis for sink regulation of photosynthesis. PMID:11457898

Paul, M J; Foyer, C H

2001-07-01

104

Environmentally regulated aerospace coatings  

NASA Technical Reports Server (NTRS)

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

Morris, Virginia L.

1995-01-01

105

Consolidation and translation regulation  

PubMed Central

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

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

2012-01-01

106

Nuclear regulation and safety  

SciTech Connect

Nuclear regulation and safety are discussed from the standpoint of a hypothetical country that is in the process of introducing a nuclear power industry and setting up a regulatory system. The national policy is assumed to be in favor of nuclear power. The regulators will have responsibility for economic, reliable electric production as well as for safety. Reactor safety is divided into three parts: shut it down, keep it covered, take out the afterheat. Emergency plans also have to be provided. Ways of keeping the core covered with water are discussed. (DLC)

Hendrie, J.M.

1982-01-01

107

Regulation of Smad Activities  

PubMed Central

TGF-? (Transforming Growth Factor-?) cytokines employ the Smad proteins as the intracellular mediator of signaling. Upon TGF-? stimulation, the cytoplasmic Smads become phosphorylated and consequently accumulate in the nucleus to regulate target gene expression. The cytoplasm-to-nucleus redistribution of Smads, as well as the ability of Smads to activate or repress gene transcription, is under multiple layers of regulation by factors not limited to TGF-?. With recent advance in the knowledge of regulatory factors impinged on Smads, we are beginning to understand the complexity in cellular responses to TGF-?. PMID:17182123

Xu, Lan

2007-01-01

108

Regulation of mitochondrial biogenesis  

PubMed Central

Although it is well established that physical activity increases mitochondrial content in muscle, the molecular mechanisms underlying this process have only recently been elucidated. Mitochondrial dysfunction is an important component of different diseases associated with aging, such as Type 2 diabetes and Alzheimer’s disease. PGC-1? (peroxisome-proliferator-activated receptor ? co-activator-1?) is a co-transcriptional regulation factor that induces mitochondrial biogenesis by activating different transcription factors, including nuclear respiratory factor 1 and nuclear respiratory factor 2, which activate mitochondrial transcription factor A. The latter drives transcription and replication of mitochondrial DNA. PGC-1? itself is regulated by several different key factors involved in mitochondrial biogenesis, which will be reviewed in this chapter. Of those, AMPK (AMP-activated protein kinase) is of major importance. AMPK acts as an energy sensor of the cell and works as a key regulator of mitochondrial biogenesis. AMPK activity has been shown to decrease with age, which may contribute to decreased mitochondrial biogenesis and function with aging. Given the potentially important role of mitochondrial dysfunction in the pathogenesis of numerous diseases and in the process of aging, understanding the molecular mechanisms regulating mitochondrial biogenesis and function may provide potentially important novel therapeutic targets. PMID:20533901

Jornayvaz, Francois R.; Shulman, Gerald I.

2013-01-01

109

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.

110

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.

111

Regulating Digital Power Supply.  

National Technical Information Service (NTIS)

The patent application relates to a regulating digital power supply in which an error detector compares a reference signal voltage with an unknown loop signal voltage and upon being strobed the error detector outputs a signal depending upon the relative m...

D. T. Butcher

1975-01-01

112

Regulation of Cadherin Trafficking  

PubMed Central

Cadherins are a large family of cell-cell adhesion molecules that tether cytoskeletal networks of actin and intermediate filaments to the plasma membrane. This function of cadherins promotes tissue organization and integrity, as demonstrated by numerous disease states that are characterized by the loss of cadherin-based adhesion. However, plasticity in cell adhesion is often required in cellular processes such as tissue patterning during development and epithelial migration during wound healing. Recent work has revealed a pivotal role for various membrane trafficking pathways in regulating cellular transitions between quiescent adhesive states and more dynamic phenotypes. The regulation of cadherins by membrane trafficking is emerging as a key player in this balancing act and studies are beginning to reveal how this process goes awry in the context of disease. This review summarizes the current understanding of how cadherins are routed and how the interface between cadherins and membrane trafficking pathways regulates cell surface adhesive potential. Particular emphasis is placed on the regulation of cadherin trafficking by catenins and the interplay between growth factor signaling pathways and cadherin endocytosis. PMID:19055694

Delva, Emmanuella; Kowalczyk, Andrew P.

2010-01-01

113

After the Regulated Life  

Microsoft Academic Search

Assuming that ordinary people have lacked the background, ability, and will to make prudent lifestyle decisions, Sargent and other human services professionals pursued visions of the rational, regulated life. That so many professions have entertained the same visions is not a mere coincidence. A human capital model, with its assumptions and implicit rules, unites these professions and their delivery systems.

Hal A. Lawson

1993-01-01

114

Regulation of serum phosphate.  

PubMed

The regulation of serum phosphate, an acknowledged risk factor for chronic kidney disease and cardiovascular mortality, is poorly understood. The discovery of fibroblast growth factor 23 (FGF23) as a key regulator of renal phosphate handling and activation of vitamin D has revolutionized our comprehension of phosphate homeostasis. Through as yet undetermined mechanisms, circulating and dietary phosphate appear to have a direct effect on FGF23 release by bone cells that, in turn, causes renal phosphate excretion and decreases intestinal phosphate absorption through a decrease in vitamin D production. Thus, the two major phosphaturic hormones, PTH and FGF23, have opposing effects on vitamin D production, placing vitamin D at the nexus of phosphate homeostasis. While our understanding of phosphate homeostasis has advanced, the factors determining regulation of serum phosphate level remain enigmatic. Diet, time of day, season, gender, age and genetics have all been identified as significant contributors to serum phosphate level. The effects of these factors on serum phosphate have major implications for what is understood as 'normal' and for studies of phosphate homeostasis and metabolism. Moreover, other hormonal mediators such as dopamine, insulin-like growth factor, and angiotensin II also affect renal handling of phosphate. How the major hormone effects on phosphate handling are regulated and how the effect of these other factors are integrated to yield the measurable serum phosphate are only now beginning to be studied. PMID:24973411

Lederer, Eleanor

2014-09-15

115

Migratory Bird Hunting Regulations  

NSDL National Science Digital Library

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

116

Workshop in Regulation &  

E-print Network

used to analyze major current problems of network industries. Competition, incentives for efficiency10/8/03 Advanced Workshop in Regulation & Competition 2003-2004 Who Says Network Industries@andromeda.rutgers.edu www.crri.rutgers.edu Rutgers Business School 180 University Avenue Newark, NJ 07102-1897 973

Lin, Xiaodong

117

Workshop in Regulation &  

E-print Network

used to analyze major current problems of network industries. Competition, incentives for efficiency10/1/13 Advanced Workshop in Regulation & Competition 2001-2002 COMPETITIVE CHANGE NETWORK://crri.rutgers.edu Rutgers Business School 180 University Avenue Newark, NJ 07102-1897 973-353-5761 973-353-1348 (fax) #12

Lin, Xiaodong

118

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

119

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

120

Chromatin Structure Regulates Gene  

Microsoft Academic Search

Homology-directed repair is a powerful mechanism for maintaining and altering genomic structure. We asked how chromatin structure contributes to the use of homologous sequences as donors for repair using the chicken B cell line DT40 as a model. In DT40, immunoglobulin genes undergo regulated sequence diversification by gene conversion templated by pseudogene donors. We found that the immunoglobulin Vk pseudogene

Conversion W. Jason Cummings; Munehisa Yabuki; Ellen C. Ordinario; David W. Bednarski; Simon Quay; Nancy Maizels

121

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...

122

Workshop in Regulation &  

E-print Network

Western Conference San Diego, California, June 22-24, 2005 CENTER FOR RESEARCH IN REGULATED INDUSTRIES a better understanding of competition in network industries and applying it in their company or regulatory, Principal Engineer, New England ISO, "Upstream Effects on Reliability: Effects of Natural Gas Shortages

Lin, Xiaodong

123

REGULATION OF GLUTATHIONE SYNTHESIS  

PubMed Central

Glutathione (GSH) is a ubiquitous intracellular peptide with diverse functions that include detoxification, antioxidant defense, maintenance of thiol status, and modulation of cell proliferation. GSH is synthesized in the cytosol of all mammalian cells in a tightly regulated manner. The major determinants of GSH synthesis are the availability of cysteine, the sulfur amino acid precursor, and the activity of the rate-limiting enzyme, glutamate cysteine ligase (GCL). GCL is composed for a catalytic (GCLC) and modifier (GCLM) subunit and they are regulated at multiple levels and at times differentially. The second enzyme of GSH synthesis, GSH synthase (GS) is also regulated in a coordinated manner as GCL subunits and its up-regulation can further enhance the capacity of the cell to synthesize GSH. Oxidative stress is well known to induce the expression of GSH synthetic enzymes. Key transcription factors identified thus far include Nrf2/Nrf1 via the antioxidant response element (ARE), activator protein-1 (AP-1) and nuclear factor ? B (NF?B). Dysregulation of GSH synthesis is increasingly being recognized as contributing to the pathogenesis of many pathological conditions. These include diabetes mellitus, pulmonary fibrosis, cholestatic liver injury, endotoxemia and drug-resistant tumor cells. Manipulation of the GSH synthetic capacity is an important target in the treatment of many of these disorders. PMID:18601945

Lu, Shelly C.

2009-01-01

124

Self-regulated learning and college students' regulation of motivation  

Microsoft Academic Search

This study extends current models of self-regulated learning by addressing 3 research questions, including what strategies do students use to regulate their motivation? is the use of these strategies dependent on contextual factors? how is motivational regulation related to other aspects of self-regulated learning and achievement? Self-report data were collected from 115 college students by using an open-ended questionnaire and

Christopher A. Wolters

1998-01-01

125

Self-Regulated Learning and College Students' Regulation of Motivation  

Microsoft Academic Search

This study extends current models of self-regulated learning by addressing 3 research questions, including what strategies do students use to regulate their motivation? is the use of these strategies dependent on contextual factors? how is motivational regulation related to other aspects of self-regulated learning and achievement? Self-report data were collected from 115 college students by using an open-ended questionnaire and

Christopher A. Wolters

1998-01-01

126

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

127

Iron regulation by hepcidin  

PubMed Central

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

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

2013-01-01

128

Risk and regulation  

NASA Astrophysics Data System (ADS)

Regulation of the health care industry and development of drugs, biologics and devices has developed, in part, to ensure public safety. There are numerous forces that promote regulatory efforts and those that work against formal regulatory measures. This presentation provides an overview of the following: What is risk? What is risk assessment? What drives regulatory activity to ensure public safety? What are the issue areas surrounding cost benefit analysis? How is technology helpful in assessing and managing risks? How does health care reform drive new technologies which, in turn, must be assessed for risk and cost/benefit? A force field analysis model of factors contributing to regulatory activities and those that work against the promulgation of regulations is offered.

Porter, Joan P.

1994-12-01

129

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

130

Dimensionally Regulated Pentagon Integrals  

E-print Network

We present methods for evaluating the Feynman parameter integrals associated with the pentagon diagram in 4-2 epsilon dimensions, along with explicit results for the integrals with all masses vanishing or with one non-vanishing external mass. The scalar pentagon integral can be expressed as a linear combination of box integrals, up to O(epsilon) corrections, a result which is the dimensionally-regulated version of a D=4 result of Melrose, and of van Neerven and Vermaseren. We obtain and solve differential equations for various dimensionally-regulated box integrals with massless internal lines, which appear in one-loop n-point calculations in QCD. We give a procedure for constructing the tensor pentagon integrals needed in gauge theory, again through O(epsilon^0).

Z. Bern; L. Dixon; D. A. Kosower

1993-06-07

131

Computing Borel's Regulator II.  

E-print Network

In our earlier article we described a power series formula for the Borel regulator evaluated on the odd-dimensional homology of the general linear group of a number field and, concentrating on dimension three for simplicity, described a computer algorithm which calculates the value to any chosen degree of accuracy. In this sequel we give an algorithm for the construction of the input homology classes and describe the results of one cyclotomic field computation.

Zacky Choo; Wajid Mannan; Rubén J. Sánchez-García; Victor P. Snaith

132

Advice & Regulations for parking  

E-print Network

and Display areas and car parks 7, 8a, 13, and 15 Staff permits : Staff may apply for a parking permit space Not park on yellow lines or hatched areas Not park in a disabled bay without a valid disabledAdvice & Regulations for parking 2009-2010 C A M P U S PA RK I N G P L A N PARKING ZONES Pay

Davies, Christopher

133

Regulation of Apoptosis by Caspases.  

National Technical Information Service (NTIS)

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

J. Yuan

1999-01-01

134

Domestic Regulation and International Competitiveness.  

National Technical Information Service (NTIS)

This paper analyzes two views on regulation in the United States. The first holds that the growth of regulation has seriously hindered domestic firms' competition with foreign rivals. The second argues that major economic competitors of the United States,...

C. C. DeMuth

1981-01-01

135

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 ...

136

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

137

Redox-regulated chaperones.  

PubMed

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

2009-06-01

138

Restructuring nuclear regulations.  

PubMed

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

139

Regulation of TGF-? receptor activity  

PubMed Central

TGF-? signaling regulates diverse cellular processes, including cell proliferation, differentiation, apoptosis, cell plasticity and migration. Its dysfunctions can result in various kinds of diseases, such as cancer and tissue fibrosis. TGF-? signaling is tightly regulated at different levels along the pathway, and modulation of TGF-? receptor activity is a critical step for signaling regulation. This review focuses on our recent understanding of regulation of TGF-? receptor activity. PMID:22420375

2012-01-01

140

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

PubMed Central

The circadian expression of clock and clock-controlled cognition-related genes in the hippocampus would be essential to achieve an optimal daily cognitive performance. There is some evidence that retinoid nuclear receptors (RARs and RXRs) can regulate circadian gene expression in different tissues. In this study, Holtzman male rats from control and vitamin A-deficient groups were sacrificed throughout a 24-h period and hippocampus samples were isolated every 4 or 5 h. RAR? and RXR? expression level was quantified and daily expression patterns of clock BMAL1, PER1, ROR? and REVERB genes, ROR? and REVERB proteins, as well as temporal expression of cognition-related RC3 and BDNF genes were determined in the hippocampus of the two groups of rats. Our results show significant daily variations of BMAL1, PER1, ROR? and REVERB genes, ROR? and REVERB proteins and, consequently, daily oscillating expression of RC3 and BDNF genes in the rat hippocampus. Vitamin A deficiency reduced RXR? mRNA level as well as the amplitude of PER1, REVERB gene and REVERB protein rhythms, and phase-shifted the daily peaks of BMAL1 and ROR? mRNA, ROR? protein and RC3 and BDNF mRNA levels. Thus, nutritional factors, such as vitamin A and its derivatives the retinoids, might modulate daily patterns of BDNF and RC3 expression in the hippocampus and they could be essential to maintain an optimal daily performance at molecular level in this learning-and-memory-related brain area. PMID:22434687

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

2012-01-01

141

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

PubMed Central

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

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

2014-01-01

142

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

PubMed

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

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

2014-01-01

143

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

144

[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

145

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

146

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

147

Self-regulating valve  

DOEpatents

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

Humphreys, D.A.

1982-07-20

148

Transcriptional Regulation of Osteoblasts  

PubMed Central

The differentiation of osteoblasts from mesenchymal precursors requires a series of cell fate decisions controlled by a hierarchy of transcription factors. These include RUNX2, Osterix (OSX), ATF4 and a large number of nuclear coregulators. During bone development, initial RUNX2 expression coincides with the formation of mesenchymal condensations and precedes the branching of chondrogenic and osteogenic lineages. Given its central role in bone development, it is not surprising that RUNX2 is subject to a variety of controls. These include posttranslational modification, especially phosphorylation, and interactions with accessory nuclear factors. Specific examples of RUNX2 regulation to be reviewed include phosphorylation by the ERK/MAP kinase pathway and interactions with DLX5. RUNX2 is regulated via phosphorylation of critical serine residues in the proline/serine/threonine domain. In vivo, the transgenic expression of constitutively active MAP kinase in osteoblasts accelerated skeletal development, while a dominant-negative MAPK retarded development in a RUNX2-dependent manner. DLX5-RUNX2 complexes can be detected in osteoblasts and this interaction plays a critical role in maintaining osteoblast-specific expression of the bone sialoprotein gene. These studies allow us to begin understanding the complex mechanisms necessary to fine-tune bone formation as mesenchymal progenitors progress down the osteoblast lineage. PMID:18728356

Franceschi, Renny T.; Ge, Chunxi; Xiao, Guozhi; Roca, Hernan; Jiang, Di

2008-01-01

149

Sleep and endocrine regulation.  

PubMed

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

Steiger, Axel

2003-05-01

150

7 CFR 987.48 - Container regulation.  

Code of Federal Regulations, 2010 CFR

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

2010-01-01

151

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

152

OSHA regulated hazardous substances  

SciTech Connect

This book addresses OSHA regulated hazardous substances. Included for each substance is the following information: the Chemical Abstract Service (CAS) Number; commonly used synonyms; trade names; description of the substance; common health effects caused by exposure to the substance; and toxicity/exposure limits-including the National Fire Protection Association (NFPA) Rating, Toxicity Hazard Rating, Immediate Danger to Life or Health (IDLH) quantity, the 1989 OSHA Permissible Exposure Levels (PELs), and the ACGIH Threshold Limit Value (TLV) and Time Weighted Average (TWA). Also included for each substance are a description of the most common uses of the substance in industry, the engineering controls (i.e., equipment necessary for the safe manufacture and/or use of a hazardous substance); personal protective equipment that should be worn by the employee when working with hazardous substances; and storage options (ideal location, temperature, container size).

Not Available

1990-01-01

153

[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

154

Insulin regulation of myocardial autophagy.  

PubMed

Autophagy is a conserved cellular process that plays an important role in cardiovascular homeostasis. Basal levels of autophagy are required for the maintenance of organellar quality control. Autophagy is dynamically regulated in the heart in the fasting to re-feeding transition. Insulin signaling plays an important role in the regulation of myocardial fuel metabolism, mitochondrial function and cellular growth. Recent studies have suggested an important role for insulin signaling in the regulation of myocardial autophagy. This dynamic regulation of autophagy induction during fasting may contribute to organellar homeostasis and if perturbed under conditions of hyperinsulinemia could contribute to accelerated cardiac aging. (Circ J 2014; 78: 2569-2576). PMID:25327953

Riehle, Christian; Abel, E Dale

2014-10-24

155

Regulation of Nucleoporins in Mitosis.  

E-print Network

??Nucleoporins mediate nucleocytoplasmic trafficking in interphase. In mitosis, upon nuclear envelope breakdown, the role and regulation of Nups remain to be elucidated. An important subcomplex… (more)

Chakraborty, Papia

2007-01-01

156

Post-translational regulation enables robust p53 regulation  

PubMed Central

Background The tumor suppressor protein p53 plays important roles in DNA damage repair, cell cycle arrest and apoptosis. Due to its critical functions, the level of p53 is tightly regulated by a negative feedback mechanism to increase its tolerance towards fluctuations and disturbances. Interestingly, the p53 level is controlled by post-translational regulation rather than transcriptional regulation in this feedback mechanism. Results We analyzed the dynamics of this feedback to understand whether post-translational regulation provides any advantages over transcriptional regulation in regard to disturbance rejection. When a disturbance happens, even though negative feedback reduces the steady-state error, it can cause a system to become less stable and transiently overshoots, which may erroneously trigger downstream reactions. Therefore, the system needs to balance the trade-off between steady-state and transient errors. Feedback control and adaptive estimation theories revealed that post-translational regulation achieves a better trade-off than transcriptional regulation, contributing to a more steady level of p53 under the influence of noise and disturbances. Furthermore, post-translational regulation enables cells to respond more promptly to stress conditions with consistent amplitude. However, for better disturbance rejection, the p53- Mdm2 negative feedback has to pay a price of higher stochastic noise. Conclusions Our analyses suggest that the p53-Mdm2 feedback favors regulatory mechanisms that provide the optimal trade-offs for dynamic control. PMID:23992617

2013-01-01

157

An epithelial circadian clock controls pulmonary inflammation and glucocorticoid action.  

PubMed

The circadian system is 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 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 an impaired host response to Streptococcus pneumoniae 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. The therapeutic effects of the synthetic glucocorticoid dexamethasone depend on intact clock function in the airway. We now define a regulatory mechanism that links the circadian clock and glucocorticoid hormones to control both time-of-day variation and 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

2014-08-01

158

BIOTECHNOLOGY REGULATIONS AND THE WTO  

Microsoft Academic Search

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

Ian M. Sheldon; Timothy E. Josling

2002-01-01

159

Frequency-controlled voltage regulator  

NASA Technical Reports Server (NTRS)

Converting input ac to higher frequency reduce size and weight and makes possible unique kind of regulation. Since conversion frequency is above range of human hearing, supply generated on audible noise. It also exploits highfrequency conversion features to regulate its output voltage in novel way. Circuit is inherently short-circuit proof.

Mclyman, W. T.

1980-01-01

160

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

161

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.

162

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

163

Advanced Workshop in Regulation and  

E-print Network

Advanced Workshop in Regulation and Competition 2011-2012 Conflicting Technological and Competitive Forces in Regulated Industries November 18, 2011 Continuing Problems in the Electric Utility Sector Location: Rutgers Business School 1 Washington Park, Room 118 Newark, NJ 07102 Sign In, Coffee and Tea

Lin, Xiaodong

164

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

ERIC Educational Resources Information Center

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

Saab, Nadira

2012-01-01

165

The professional nurse and regulation  

Microsoft Academic Search

The regulation of nursing began as a simple registry process to protect the nursing title and the public. Today, the primary purpose is still the protection of the public through defining nursing practice, approving nursing education, and overseeing the competence of nurses through licensing and disciplinary rules and regulations. State Boards of Nursing are legislatively given the authority to license

Denise M Flook

2003-01-01

166

NATIONAL IMMIGRATION AGENCY Regulations Governing  

E-print Network

1 NATIONAL IMMIGRATION AGENCY Regulations Governing Foreign Students' Residence Status #12 #12;14 Laws governing foreigner's visiting and residency Immigration act The enforcement rules of the immigration act Regulations governing visiting, residency and permanent residency of Aliens #12;15 Reminder(1

Wu, Yih-Min

167

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.

168

Regulation of placental angiogenesis.  

PubMed

Ample interest has been evoked in using placental angiogenesis as a target for the development of diagnosis tools and potential therapeutics for pregnancy complications based on the knowledge of placental angiogenesis in normal and aberrant pregnancies. Although these goals are still far from reach, one would expect that two complementary processes should be balanced for therapeutic angiogenesis to be successful in restoring a mature and functional vascular network in the placenta in any pregnancy complication: (i) pro-angiogenic stimulation of new vessel growth and (ii) anti-angiogenic inhibition of vessel overgrowth. As the best model of physiological angiogenesis, investigations of placental angiogenesis provide critical insights not only for better understanding of normal placental endothelial biology but also for the development of diagnosis tools for pregnancy complications. Such investigations will potentially identify novel pro-angiogenic factors for therapeutic intervention for tissue damage in various obstetric complications or heart failure or anti-angiogenic factors to target on cancer or vision loss in which circulation needs to be constrained. This review summarizes the genetic and molecular aspects of normal placental angiogenesis as well as the signaling mechanisms by which the dominant angiogenic factor vascular endothelial growth factor regulates placental angiogenesis with a focus on placental endothelial cells. PMID:23981199

Chen, Dong-Bao; Zheng, Jing

2014-01-01

169

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

170

Strategic automation of emotion regulation.  

PubMed

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

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

2009-01-01

171

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

E-print Network

Regulation 8: Responsibility for Creation and Amendment of Regulations: 36 REGULATION 8: RESPONSIBILITY FOR CREATION AND AMENDMENT OF REGULATIONS This Regulation may only be amended at a meeting of Council with the agreement of three- fourths present and voting, and having taken into account the views

Sussex, University of

172

Assessing Academic Self-Regulated Learning  

Microsoft Academic Search

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

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

173

New EU regulations in endoscopy.  

PubMed

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

Wächter, M; Diekjobst, T

1995-09-01

174

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

175

Regulation of TGF-? Signal Transduction  

PubMed Central

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

Zhao, Bing; Chen, Ye-Guang

2014-01-01

176

7 CFR 983.50 - Aflatoxin regulations.  

Code of Federal Regulations, 2010 CFR

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

2010-01-01

177

75 FR 73958 - Belarus Sanctions Regulations  

Federal Register 2010, 2011, 2012, 2013

...the Belarus Sanctions Regulations (``BSR'') in the Code of Federal Regulations...2011. In addition, OFAC is amending the BSR to make a technical correction to the authority...Sanctions Regulations, 31 CFR part 548 (``BSR''), implement Executive Order...

2010-11-30

178

47 CFR 32.14 - Regulated accounts.  

Code of Federal Regulations, 2011 CFR

...of regulated and nonregulated products and services, companies...to the provision of regulated products and services shall be accounted...and revenues related to the offering of regulated products and services which...

2011-10-01

179

47 CFR 32.14 - Regulated accounts.  

Code of Federal Regulations, 2010 CFR

...of regulated and nonregulated products and services, companies...to the provision of regulated products and services shall be accounted...and revenues related to the offering of regulated products and services which...

2010-10-01

180

47 CFR 32.14 - Regulated accounts.  

Code of Federal Regulations, 2013 CFR

...of regulated and nonregulated products and services, companies...to the provision of regulated products and services shall be accounted...and revenues related to the offering of regulated products and services which...

2013-10-01

181

47 CFR 32.14 - Regulated accounts.  

Code of Federal Regulations, 2012 CFR

...of regulated and nonregulated products and services, companies...to the provision of regulated products and services shall be accounted...and revenues related to the offering of regulated products and services which...

2012-10-01

182

18 CFR 415.30 - Regulations generally.  

Code of Federal Regulations, 2010 CFR

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

2010-04-01

183

18 CFR 415.30 - Regulations generally.  

Code of Federal Regulations, 2012 CFR

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

2012-04-01

184

18 CFR 415.30 - Regulations generally.  

Code of Federal Regulations, 2013 CFR

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

2013-04-01

185

18 CFR 415.30 - Regulations generally.  

Code of Federal Regulations, 2011 CFR

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

2011-04-01

186

18 CFR 415.30 - Regulations generally.  

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

2014-04-01

187

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 ...

188

27 CFR 25.4 - Related regulations.  

... Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL BEER Scope of Regulations § 25.4 Related regulations. Regulations relating to this part are listed below: 27 CFR...

2014-04-01

189

27 CFR 25.4 - Related regulations.  

Code of Federal Regulations, 2011 CFR

... Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS BEER Scope of Regulations § 25.4 Related regulations. Regulations relating to this part are listed below: 27 CFR...

2011-04-01

190

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

191

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

192

Feedback regulation in gene networks  

E-print Network

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

Acar, Murat

2007-01-01

193

A Regulator's View of Cogeneration  

E-print Network

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

Shanaman, S. M.

1982-01-01

194

Circadian variation of blood pressure and the vascular response to asynchronous stress.  

PubMed

The diurnal variation in the incidence of myocardial infarction and stroke may reflect an influence of the molecular clock and/or the time dependence of exposure to environmental stress. The circadian variation in blood pressure and heart rate is disrupted in mice, Bmal1(-/-), Clock(mut), and Npas2(mut), in which core clock genes are deleted or mutated. Although Bmal1 deletion abolishes the 24-h frequency in cardiovascular rhythms, a shorter ultradian rhythm remains. Sympathoadrenal function is disrupted in these mice, which reflects control of enzymes relevant to both synthesis (phenylethanolamine N-methyl transferase) and disposition (monoamine oxidase B and catechol-O-methyl transferase) of catecholamines by the clock. Both timing and disruption or mutation of clock genes modulate the magnitude of both the sympathoadrenal and pressor but not the adrenocortical response to stress. Despite diurnal variation of catecholamines and corticosteroids, they are regulated differentially by the molecular clock. Furthermore, the clock may influence the time-dependent incidence of cardiovascular events by controlling the integration of selective asynchronous stress responses with an underlying circadian rhythm in cardiovascular function. PMID:17360665

Curtis, Anne M; Cheng, Yan; Kapoor, Shiv; Reilly, Dermot; Price, Tom S; Fitzgerald, Garret A

2007-02-27

195

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

PubMed Central

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

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

2013-01-01

196

Circadian variation of blood pressure and the vascular response to asynchronous stress  

PubMed Central

The diurnal variation in the incidence of myocardial infarction and stroke may reflect an influence of the molecular clock and/or the time dependence of exposure to environmental stress. The circadian variation in blood pressure and heart rate is disrupted in mice, Bmal1?/?, Clockmut, and Npas2mut, in which core clock genes are deleted or mutated. Although Bmal1 deletion abolishes the 24-h frequency in cardiovascular rhythms, a shorter ultradian rhythm remains. Sympathoadrenal function is disrupted in these mice, which reflects control of enzymes relevant to both synthesis (phenylethanolamine N-methyl transferase) and disposition (monoamine oxidase B and catechol-O-methyl transferase) of catecholamines by the clock. Both timing and disruption or mutation of clock genes modulate the magnitude of both the sympathoadrenal and pressor but not the adrenocortical response to stress. Despite diurnal variation of catecholamines and corticosteroids, they are regulated differentially by the molecular clock. Furthermore, the clock may influence the time-dependent incidence of cardiovascular events by controlling the integration of selective asynchronous stress responses with an underlying circadian rhythm in cardiovascular function. PMID:17360665

Curtis, Anne M.; Cheng, Yan; Kapoor, Shiv; Reilly, Dermot; Price, Tom S.; FitzGerald, Garret A.

2007-01-01

197

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

PubMed Central

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

Chang, Hung-Chun; Guarente, Leonard

2013-01-01

198

Dynamic circadian protein-protein interaction networks predict temporal organization of cellular functions.  

PubMed

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

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

2013-03-01

199

Circadian rhythms of glucocorticoid hormone actions in target tissues: potential clinical implications.  

PubMed

Organisms face unforeseen short- and long-term changes in the environment (stressors). To defend against these changes, organisms have developed a stress system that includes the hypothalamic-pituitary-adrenal (HPA) axis, which employs glucocorticoids and the glucocorticoid receptor (GR) for signal transduction. In addition, organisms live under the strong influence of day-night cycles and, hence, have also developed a highly conserved circadian clock system for adjusting their activities to recurring environmental changes. This regulatory system creates and maintains internal circadian rhythmicity by employing a self-oscillating molecular pacemaker composed of the Clock-Bmal1 heterodimer and other transcription factors. The circadian clock consists of a central master clock in the suprachiasmatic nucleus of the brain hypothalamus and peripheral slave clocks in virtually all organs and tissues. The HPA axis and the circadian clock system communicate with each other at multiple levels. The central clock controls the HPA axis, creating the diurnal oscillation of circulating adrenocorticotropic hormone and cortisol, and the HPA axis adjusts the circadian rhythmicity of the peripheral clocks in response to various stressors through the GR. Further, Clock-Bmal1 regulates the response to glucocorticoids in peripheral tissues through acetylation of the GR, possibly antagonizing the biologic actions of diurnally fluctuating circulating cortisol. Importantly, dysregulation in the clock system and the HPA axis may cause similar pathologic manifestations--including obesity, metabolic syndrome, and cardiovascular disease--by uncoupling circulating cortisol concentrations from tissue sensitivity to glucocorticoids. PMID:23033538

Kino, Tomoshige

2012-10-01

200

Cytokine regulation of bone destruction  

Microsoft Academic Search

\\u000a Bone is a dynamic tissue, composed of cells, collagenous matrix and inorganic elements. Per year, it has been estimated that\\u000a 10% of the total bone mass in humans is being remodeled [1]. The growth, development and maintenance of bone is a highly regulated process [2]. Morphogenesis and remodeling of bone involve coordinate regulation of bone-forming cells (osteoblasts) and bone-resorbing\\u000a cells

Erik Lubberts; Wim B. van den Berg

201

Diacylglycerol kinase ?: Regulation and stability  

PubMed Central

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

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

2014-01-01

202

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 C, R D

2014-08-01

203

Diversification puts regulators on edge  

SciTech Connect

Recent activity at the state regulatory level shows that utilities are still seeking ways to benefit financially through diversification. They may be taking a more cautious approach by limiting investment to utility-related fields. But whether a utility seeks to diversify in areas outside of its own industry or chooses the more conservative approach, state regulators face similar problems. Statutory authority to regulate service and rates does not always provide similar broad authority to interfere in a utility's business decisionmaking. Although a utility must seek prior approval before diverting large sums of money to an unregulated affiliate, effects on service and rates are hard to discern before the fact. This leaves regulators with limited options such as imposing strict financial reporting requirements and limiting amounts invested. One option receiving increased attention from state regulators is the royalty payment, where a utility pays its captive customers for an affiliate's use of the company name. In addition, some states are sharpening cost-of-service study regulations to help detect and prevent the flow of cross-subsidies between regulated and unregulated companies and customers.

Cross, P.S.

1994-02-01

204

Precision Adjustable Liquid Regulator (ALR)  

NASA Astrophysics Data System (ADS)

A passive mechanical regulator has been developed for the control of fuel or oxidizer flow to a 450N class bipropellant engine for use on commercial and interplanetary spacecraft. There are several potential benefits to the propulsion system, depending on mission requirements and spacecraft design. This system design enables more precise control of main engine mixture ratio and inlet pressure, and simplifies the pressurization system by transferring the function of main engine flow rate control from the pressurization/propellant tank assemblies, to a single component, the ALR. This design can also reduce the thermal control requirements on the propellant tanks, avoid costly Qualification testing of biprop engines for missions with more stringent requirements, and reduce the overall propulsion system mass and power usage. In order to realize these benefits, the ALR must meet stringent design requirements. The main advantage of this regulator over other units available in the market is that it can regulate about its nominal set point to within +/-0.85%, and change its regulation set point in flight +/-4% about that nominal point. The set point change is handled actively via a stepper motor driven actuator, which converts rotary into linear motion to affect the spring preload acting on the regulator. Once adjusted to a particular set point, the actuator remains in its final position unpowered, and the regulator passively maintains outlet pressure. The very precise outlet regulation pressure is possible due to new technology developed by Moog, Inc. which reduces typical regulator mechanical hysteresis to near zero. The ALR requirements specified an outlet pressure set point range from 225 to 255 psi, and equivalent water flow rates required were in the 0.17 lb/sec range. The regulation output pressure is maintained at +/-2 psi about the set point from a P (delta or differential pressure) of 20 to over 100 psid. Maximum upstream system pressure was specified at 320 psi. The regulator is fault tolerant in that it was purposely designed with no shutoff capability, such that the minimum flow position of the poppet still allows the subsystem to provide adequate flow to the main engine for basic operation.

Meinhold, R.; Parker, M.

2004-10-01

205

Neuronal regulation of tendon homoeostasis  

PubMed Central

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

Ackermann, Paul W

2013-01-01

206

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

207

Using Plant regUlators on  

E-print Network

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

Liskiewicz, Maciej

208

ISOs: The new antitrust regulators?  

SciTech Connect

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

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

1998-04-01

209

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

210

RHUL Research Degree Regulations 2013/14 Research Degree Regulations  

E-print Network

Annual enrolment with the College Reviews of academic progress Termination of registration on Research against the outcomes of formal review and the final examination Appeals against termination Governing the Doctor of Clinical Psychology (DClinPsy) Appendix 3: Regulations Governing the Doctorate

Sheldon, Nathan D.

211

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

Duhe, Roy J

2013-01-01

212

Can Sir(2) regulate cancer?  

PubMed Central

Sirtuin activators, including small molecules such as polyphenols and resveratrol, are much desired due to their potential to ameliorate metabolic disorder and delay or prevent aging. In contrast, recent studies demonstrate that targeted silencing of sirtuin 1 (SIRT1) expression or activity by the deleted in breast cancer 1 (DBC1) may be beneficial by promoting p53-induced apoptosis in cancer cells, and by sensitizing cancerous cells to radiation therapy. Negative SIRT1 regulation also alleviates gene-repression associated with fragile X mental retardation syndrome. The targeted activation or inhibition of SIRT1 activity therefore emerges as a critical point of regulation in disease pathogenesis. PMID:19750026

Nerurkar, Vivek R.

2009-01-01

213

CNS Regulation of Glucose Homeostasis  

NSDL National Science Digital Library

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

2009-06-01

214

Transcriptional regulation in wood formation.  

PubMed

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

Demura, Taku; Fukuda, Hiroo

2007-02-01

215

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

216

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

217

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

218

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

219

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

220

FIELD CROPS 2014 Plant Regulators: Cotton Growth Regulators 6-1  

E-print Network

FIELD CROPS 2014 Plant Regulators: Cotton Growth Regulators 6-1 Cotton Growth Regulators Henry P internode (see measurement description above). #12;FIELD CROPS 2014 6-2 Plant Regulators: Cotton Growth. Wilson, Professor, Eastern Shore AREC Table 6.1 - Plant Growth Regulation Objective Chemical rate per

Liskiewicz, Maciej

221

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

222

REGULATIONS OF UNIVERSITY OF FLORIDA  

E-print Network

1 REGULATIONS OF UNIVERSITY OF FLORIDA 6C1-1.0081 Prohibition of Hazing; Procedures and Penalties. (1) Hazing Policy -- Actions which amount to hazing are prohibited. Hazing is any action or situation or organization. (2) Definition of Hazing -- In accordance with Section 1006.63, F.S., "hazing" means any action

Pilyugin, Sergei S.

223

Regulation of protein kinase C  

Microsoft Academic Search

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

Alexandra C Newton

1997-01-01

224

Promoting Floriculture Using VAT Regulation  

Microsoft Academic Search

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

225

Promoting Floriculture Using VAT Regulation  

Microsoft Academic Search

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

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

2008-01-01

226

Re-Regulating Offshore Finance?  

Microsoft Academic Search

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

B. Maurer

2008-01-01

227

Grantiau a Rheoliadau Grants & Regulations  

E-print Network

Head of Estate Management #12;Policy position on development affecting woodlands 2 | DevelopmentGrantiau a Rheoliadau Grants & Regulations Forestry Commission Wales policy position on development-forestry development proposals that might affect woodlands both on and off the Welsh Assembly Government Woodland

228

Army Regulation 690600 Civilian Personnel  

E-print Network

a t p r o h i b i t discrimination based on race, color, reli- gion, sex, national origin, age, physicalArmy Regulation 690­600 Civilian Personnel Equal Employment Opportunity Discrimination Complaints­600 Equal Employment Opportunity Discrimination Complaints This revision dated 9 February 2004--- o Contains

US Army Corps of Engineers

229

Regulation of October 6, 2009  

E-print Network

Board #12;Sediment Regulations Clean Water Act § 303 ­ Water Quality Standards (WQS) ­ List of impaired State Water Board Resolution 92-49 ­ Sediment cleanup actions #12;Sediment Regulatory Drivers Too much Likely Unimpacted Moderate Potential Possibly Impacted Possibly Impacted Likely Unimpacted Unimpacted Low

230

Army Regulation 2001 Environmental Quality  

E-print Network

of the U.S. Army Corps of Engineers (USACE). The terms "Army environmental pro- grams" and "ArmyArmy Regulation 200­1 Environmental Quality Environmental Protection and Enhancement Headquarters Department of the Army Washington, DC 13 December 2007 UNCLASSIFIED #12;SUMMARY of CHANGE AR 200

US Army Corps of Engineers

231

COVARIANCE PLASTICITY AND REGULATED CRITICALITY  

E-print Network

the two populations. We show that, under broad conditions, the system converges to a critical state lying is an everyday observation. Viewed as a dynamical system, a brain may be said to be unusually susceptible that regulated criticality may be the mechanism whereby sensitivity is maintained throughout life in the face

Lehmann, Daniel

232

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

233

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

234

High cost of government regulation  

Microsoft Academic Search

Mr. Wiedenbaum feels that the steadily growing intrusion of the public bureaucracy into the private sector, in matters ranging from environmental regulation to job safety, has inhibited the healthy growth of our economy. The majority of public policy changes affecting business-government relations in recent years has been in the direction of greater government intervention - environmental controls, job safety inspections,

Weidenbaum

1979-01-01

235

Chromatin Structure Regulates Gene Conversion  

Microsoft Academic Search

Homology-directed repair is a powerful mechanism for maintaining and altering genomic structure. We asked how chromatin structure contributes to the use of homologous sequences as donors for repair using the chicken B cell line DT40 as a model. In DT40, immunoglobulin genes undergo regulated sequence diversification by gene conversion templated by pseudogene donors. We found that the immunoglobulin V? pseudogene

W. Jason Cummings; Munehisa Yabuki; Ellen C Ordinario; David W Bednarski; Simon Quay; Nancy Maizels

2007-01-01

236

The Politics of Broadcast Regulation.  

ERIC Educational Resources Information Center

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

Krasnow, Erwin G.; Longley, Lawrence D.

237

International Trade and Domestic Regulation  

Microsoft Academic Search

Existing formal models of the relationship between trade policy and regulatory policy suggest the potential for a regulatory race to the bottom. WTO rules and disputes, however, center on complaints about excessively stringent regulations. This paper bridges the gap between the existing formal literature and the actual pattern of rules and disputes. Employing the terms-of-trade framework for the modeling of

Robert W. Staiger; Alan O. Sykes

2009-01-01

238

Coal regulations spelled out. almost  

Microsoft Academic Search

According to Energy Secretary J. P. Schlesinger, the regulations to be issued by the U.S. Department of Energy (DOE) for the conversion of existing oil-burning plants to coal may not be as strict as originally expected, due to the current glut of natural gas; conversion to gas rather than coal may be preferred in the short term for many existing

J. J. Oconnor; J. P. Schlesinger

1979-01-01

239

Molecular regulation of vessel maturation  

Microsoft Academic Search

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

Rakesh K Jain

2003-01-01

240

REGULATIONS OF UNIVERSITY OF FLORIDA  

E-print Network

1 REGULATIONS OF UNIVERSITY OF FLORIDA 6C1-4.004 Social Fraternities and Sororities. (1) Social sororities and fraternities are student organizations that are founded on the principles of brotherhood with the educational mission of the University, social sororities and fraternities promote the highest standards

Pilyugin, Sergei S.

241

Essential infrastructure: national nuclear regulation.  

PubMed

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

Paperiello, Carl J

2011-01-01

242

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

Federal Register 2010, 2011, 2012, 2013

...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 citations in...

2010-01-11

243

Regulation by light in Fusarium.  

PubMed

The genus Fusarium stands out as research model for pathogenesis and secondary metabolism. Light stimulates the production of some Fusarium metabolites, such as the carotenoids, and in many species it influences the production of asexual spores and sexual fruiting bodies. As found in other fungi with well-known photoresponses, the Fusarium genomes contain several genes for photoreceptors, among them a set of White Collar (WC) proteins, a cryptochrome, a photolyase, a phytochrome and two presumably photoactive opsins. The mutation of the opsin genes produced no apparent phenotypic alterations, but the loss of the only WC-1 orthologous protein eliminated the photoinduced expression of the photolyase and opsin genes. In contrast to other carotenogenic species, lack of the WC photoreceptor did not impede the light-induced accumulation of carotenoids, but produced alterations in conidiation, animal pathogenicity and nitrogen-regulated secondary metabolism. The regulation and functional role of other Fusarium photoreceptors is currently under investigation. PMID:20460165

Avalos, Javier; Estrada, Alejandro F

2010-11-01

244

Astrocyte regulation of synaptic behavior.  

PubMed

Astrocytes regulate multiple aspects of neuronal and synaptic function from development through to adulthood. Instead of addressing each function independently, this review provides a comprehensive overview of the different ways astrocytes modulate neuronal synaptic function throughout life, with a particular focus on recent findings in each area. It includes the emerging functions of astrocytes, such as a role in synapse formation, as well as more established roles, including the uptake and recycling of neurotransmitters. This broad approach covers the many ways astrocytes and neurons constantly interact to maintain the correct functioning of the brain. It is important to consider all of these diverse functions of astrocytes when investigating how astrocyte-neuron interactions regulate synaptic behavior to appreciate the complexity of these ongoing interactions. PMID:25288116

Allen, Nicola J

2014-10-11

245

Magnesium Regulates ADP Dissociation from  

E-print Network

Processivity in myosin V is mediated through the mechanical strain that results when both heads bind strongly to an actin filament, and this strain regulates the timing of ADP release. However, what is not known is which steps that lead to ADP release are affected by this mechanical strain. Answering this question will require determining which of the several potential pathways myosin V takes in the process of ADP release and how actin influences the kinetics of these pathways. We have addressed this issue by examining how magnesium regulates the kinetics of ADP release from myosin V and actomyosin V. Our data support a model in which actin accelerates the release of ADP from myosin V by reducing the magnesium affinity of a myosin V-MgADP intermediate. This is likely a consequence of the structural

unknown authors

246

Renewable energy and utility regulation  

SciTech Connect

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

Not Available

1991-04-10

247

Renewable energy and utility regulation  

SciTech Connect

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

Not Available

1991-04-10

248

Hyaluronan regulation of vascular integrity  

PubMed Central

Vascular integrity or the maintenance of blood vessel continuity is a fundamental process regulated, in part, by the endothelial glycocalyx and cell-cell junctions. Defects in endothelial barrier function are an initiating factor in several disease processes including atherosclerosis, ischemia/reperfusion, tumor angiogenesis, cancer metastasis, diabetes, sepsis and acute lung injury. The glycosaminoglycan, hyaluronan (HA), maintains vascular integrity through endothelial glycocalyx modulation, caveolin-enriched microdomain regulation and interaction with endothelial HA binding proteins. Certain disease states increase hyaluronidase activity and reactive oxygen species (ROS) generation which break down high molecular weight HA to low molecular weight fragments causing damage to the endothelial glycocalyx. Further, these HA fragments can activate specific HA binding proteins upregulated in vascular disease to promote actin cytoskeletal reorganization and inhibition of endothelial cell-cell contacts. This review focuses on the crucial role of HA in vascular integrity and how HA degradation promotes vascular barrier disruption. PMID:22254199

Lennon, Frances E; Singleton, Patrick A

2011-01-01

249

Molecular Mechanisms of Appetite Regulation  

PubMed Central

The prevalence of obesity has been rapidly increasing worldwide over the last several decades and has become a major health problem in developed countries. The brain, especially the hypothalamus, plays a key role in the control of food intake by sensing metabolic signals from peripheral organs and modulating feeding behaviors. To accomplish these important roles, the hypothalamus communicates with other brain areas such as the brainstem and reward-related limbic pathways. The adipocyte-derived hormone leptin and pancreatic ?-cell-derived insulin inform adiposity to the hypothalamus. Gut hormones such as cholecystokinin, peptide YY, pancreatic polypeptide, glucagon-like peptide 1, and oxyntomodulin transfer satiety signals to the brain and ghrelin relays hunger signals. The endocannabinoid system and nutrients are also involved in the physiological regulation of food intake. In this article, we briefly review physiological mechanisms of appetite regulation. PMID:23275931

Yu, Ji Hee

2012-01-01

250

Epigenetic regulation of epidermal differentiation.  

PubMed

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

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

2014-02-01

251

Redox regulation of intercellular transport  

Microsoft Academic Search

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

Yoselin Benitez-Alfonso; David Jackson; Andy Maule

2011-01-01

252

Intraovarian factors regulating ovarian function.  

PubMed

Ovarian folliculogenesis is a dynamic process marked by exponential expansion and differentiation of the granulosa cells, oocyte maturation, ovulation and corpus luteum formation. Although the central roles of gonadotropins and gonadal steroids in this explosive agenda are well accepted, the variable fate of follicles afforded comparable stimulation within the same ovary suggests the existence of an additional intraovarian system comprised of regulating species that 'fine-tune' the blood-borne hormones. PMID:7647274

Kol, S; Adashi, E Y

1995-06-01

253

Immune regulation in the retina  

Microsoft Academic Search

Immune reactivity in the retina can be critically important in inflammation and infections, but regulation of this response\\u000a is essential. The retinal pigment epithelial (RPE), a unique retinal cell, displays a number of essential functions to support\\u000a the health of the retina. In this review, we highlight how the RPE cell plays a pivotal role in immune defense. The RPE

Barbara Detrick; John J. Hooks

2010-01-01

254

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

255

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

256

Regulation of Genes by Light  

Microsoft Academic Search

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

Gabriele Klug; Shinji Masuda

257

Dimensionally-regulated pentagon integrals  

Microsoft Academic Search

We present methods for evaluating the Feynman parameter integrals associated with the pentagon diagram in 4-2? dimensions, along with explicit results for the integrals with all masses vanishing or with one non-vanishing external mass. The scalar pentagon integral can be expressed as a linear combination of box integrals, up to O(?) corrections, a result which is the dimensionally-regulated version of

Zvi Bern; Lance Dixon; David A. Kosower

1994-01-01

258

Equitable regulation of private forests  

Microsoft Academic Search

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

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

259

Tropomyosin: Regulator of Actin Filaments  

Microsoft Academic Search

Cellular movement and function have long been known to depend on the actin cytoskeleton and its regulation. The actin cytoskeleton\\u000a is the ultimate target of numerous cellular signaling pathways. The first signaling system understood in any detail was that\\u000a of vertebrate skeletal muscle. Setsuro Ebashi, celebrated by this volume, was a pioneer through his role in showing that the\\u000a calcium

Sarah E. Hitchcock-DeGregori; Norma J. Greenfield; Abhishek Singh

260

25 CFR 249.2 - Area regulations.  

Code of Federal Regulations, 2012 CFR

...regulations issued pursuant to this section shall contain provisions for invoking emergency closures or restrictions or the relaxation thereof at the field level when necessary or appropriate to meet conditions not foreseeable at the time the regulations...

2012-04-01

261

25 CFR 249.2 - Area regulations.  

Code of Federal Regulations, 2011 CFR

...regulations issued pursuant to this section shall contain provisions for invoking emergency closures or restrictions or the relaxation thereof at the field level when necessary or appropriate to meet conditions not foreseeable at the time the regulations...

2011-04-01

262

25 CFR 249.2 - Area regulations.  

Code of Federal Regulations, 2013 CFR

...regulations issued pursuant to this section shall contain provisions for invoking emergency closures or restrictions or the relaxation thereof at the field level when necessary or appropriate to meet conditions not foreseeable at the time the regulations...

2013-04-01

263

Tertium Datur: Pricing, Regulating and Intrinsic Motivation  

Microsoft Academic Search

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

Bruno S. Frey

1992-01-01

264

28 CFR 42.403 - Agency regulations.  

...2014-07-01 2014-07-01 false Agency regulations. 42.403 Section 42.403 Judicial Administration DEPARTMENT OF JUSTICE...Non-discrimination in Federally Assisted Programs § 42.403 Agency regulations. (a) Any...

2014-07-01

265

43 CFR 431.9 - Future regulations.  

Code of Federal Regulations, 2011 CFR

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

2011-10-01

266

43 CFR 431.9 - Future regulations.  

Code of Federal Regulations, 2010 CFR

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

2010-10-01

267

50 CFR 20.153 - Regulations committee.  

Code of Federal Regulations, 2012 CFR

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

2012-10-01

268

50 CFR 20.153 - Regulations committee.  

Code of Federal Regulations, 2010 CFR

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

2010-10-01

269

32 CFR 770.4 - Hunting regulations.  

Code of Federal Regulations, 2011 CFR

...2011-07-01 2011-07-01 false Hunting regulations. 770.4 Section 770...ACCESS TO PARTICULAR INSTALLATIONS Hunting and Fishing at Marine Corps Base, Quantico, Virginia § 770.4 Hunting regulations. All persons...

2011-07-01

270

32 CFR 770.4 - Hunting regulations.  

Code of Federal Regulations, 2010 CFR

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

2010-07-01

271

50 CFR 20.153 - Regulations committee.  

Code of Federal Regulations, 2013 CFR

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

2013-10-01

272

32 CFR 770.4 - Hunting regulations.  

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

2014-07-01

273

50 CFR 20.153 - Regulations committee.  

Code of Federal Regulations, 2011 CFR

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

2011-10-01

274

32 CFR 770.4 - Hunting regulations.  

Code of Federal Regulations, 2013 CFR

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

2013-07-01

275

32 CFR 770.4 - Hunting regulations.  

Code of Federal Regulations, 2012 CFR

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

2012-07-01

276

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.

277

77 FR 16784 - General Bridge Regulation; Amendment  

Federal Register 2010, 2011, 2012, 2013

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

2012-03-22

278

32 CFR 636.22 - Speed regulations.  

Code of Federal Regulations, 2011 CFR

...4 2011-07-01 2011-07-01 false Speed regulations. 636.22 Section 636.22...INSTALLATIONS) Fort Stewart, Georgia § 636.22 Speed regulations. (a) Georgia state speed limits apply unless otherwise specified by...

2011-07-01

279

32 CFR 636.22 - Speed regulations.  

Code of Federal Regulations, 2010 CFR

... 4 2010-07-01 2010-07-01 true Speed regulations. 636.22 Section 636.22...INSTALLATIONS) Fort Stewart, Georgia § 636.22 Speed regulations. (a) Georgia state speed limits apply unless otherwise specified by...

2010-07-01

280

32 CFR 770.3 - Fishing regulations.  

Code of Federal Regulations, 2012 CFR

...2012-07-01 2012-07-01 false Fishing regulations. 770.3 Section 770...PARTICULAR INSTALLATIONS Hunting and Fishing at Marine Corps Base, Quantico, Virginia § 770.3 Fishing regulations. (a) All persons...

2012-07-01

281

32 CFR 770.3 - Fishing regulations.  

Code of Federal Regulations, 2011 CFR

...2011-07-01 2011-07-01 false Fishing regulations. 770.3 Section 770...PARTICULAR INSTALLATIONS Hunting and Fishing at Marine Corps Base, Quantico, Virginia § 770.3 Fishing regulations. (a) All persons...

2011-07-01

282

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

283

Regulation of ?-adrenergic receptor function  

PubMed Central

G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors regulating multiple cellular processes. ?-adrenergic receptor (?AR) is a prototypical member of GPCR family and has been one of the most well-studied receptors in determining regulation of receptor function. Agonist activation of ?AR leads to conformational change, resulting in coupling to G protein and generating cAMP as secondary messenger. The activated ?AR is phosphorylated resulting in binding of ?-arrestin that physically interdicts further G protein coupling leading to receptor desensitization. The phosphorylated ?AR is internalized and undergoes resensitization by dephosphorylation mediated by protein phosphatase 2A in the early endosomes. Desensitization and resensitization are two sides of the same coin maintaining the homeostatic functioning of the receptor. While significant interest has revolved around understanding mechanisms of receptor desensitization little is known about resensitization. In our current review we provide an overview on regulation of ?AR function with a special emphasis on receptor resensitization and its functional relevance in the context of fine tuning receptor signaling. PMID:22041711

Vasudevan, Neelakantan T; Mohan, Maradumane L; Goswami, Shyamal K

2011-01-01

284

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

285

Cell volume regulation in chondrocytes.  

PubMed

Chondrocytes are the cells within cartilage which produce and maintain the extracellular matrix. Volume regulation in these cells is vital to their function and occurs in several different physiological and pathological contexts. Firstly, chondrocytes exist within an environment of changing osmolarity and compressive loads. Secondly, in osteoarthritic joint failure, cartilage water content changes and there is a notable increase in chondrocyte apoptosis. Thirdly, endochondral ossification requires chondrocyte swelling in association with hypertrophy. Regulatory volume decrease (RVD) and regulatory volume increase (RVI) have both been observed in articular chondrocytes and this review focuses on the mechanisms identified to account for these. There has been evidence so far to suggest TRPV4 is central to RVD; however other elements of the pathway have not yet been identified. Unlike RVD, RVI appears less robust in articular chondrocytes and there have been fewer mechanistic studies; the primary focus being on the Na(+)-K(+)-2Cl(-) co-transporter. The clinical significance of chondrocyte volume regulation remains unproven. Importantly however, transcript abundances of several ion channels implicated in volume control are changed in chondrocytes from osteoarthritic cartilage. A critical question is whether disturbances of volume regulation mechanisms lead to, result from or are simply coincidental to cartilage damage. PMID:22179000

Lewis, Rebecca; Feetham, Claire H; Barrett-Jolley, Richard

2011-01-01

286

NRC - regulator of nuclear safety  

SciTech Connect

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

NONE

1997-05-01

287

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

288

Gibberellin biosynthesis and its regulation.  

PubMed

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

Hedden, Peter; Thomas, Stephen G

2012-05-15

289

Multiplexing Regulated Traffic Streams: Design and Performance  

Microsoft Academic Search

The main network solutions for supporting QoS rely on traf- fic policing (conditioning, shaping). In particular, for IP networks the IETF has developed Intserv (individual flows regulated) and Diff serv (only ag- gregates regulated). The regulator proposed could be based on the (dual) leaky-bucket mechanism. This explains the interest in network element per- formance (loss, delay) for leaky-bucket regulated traffic.

Krishnan Kumaran; Michel Mandjes

2001-01-01

290

Environmental Regulation, Investment Timing, and Technology Choice  

Microsoft Academic Search

The authors test whether environmental regulation affects investment decisions using Census data for individual paper mills. New mills in states with strict environmental regulations choose cleaner production technologies, with differences in air and water pollution regulation also influencing technology choice. Examining investment allocation across existing plants, the authors find that abatement and productive investment tend to be scheduled together. However,

Wayne B. Gray; Ronald J. Shadbegian

1998-01-01

291

Logic-based regulation compliance-assistance  

Microsoft Academic Search

This paper focuses on the creation of a first order predicate calculus based regulation compliance-assistance system built upon an XML framework. Two areas of research that support the development of the compliance assistance system are discussed. The first is a document repository containing federal and state regulations and supplemental documents. The second is an XML framework for representing regulations and

Shawn Kerrigan; Kincho H. Law

2003-01-01

292

Mapping regulations to industry-specific taxonomies  

Microsoft Academic Search

For each industry, there exist many taxonomies that are intended for various applications. There are also multiple sources of regulations from different government agencies. Industry practitioners, unlike legal practitioners, are familiar with one or more industry-specific taxonomies but not necessarily regulatory organization systems. To help browsing of regulations by industry practitioners, we propose to map regulations to existing industry-specific taxonomies.

Chin Pang Cheng; Gloria T. Lau; Kincho H. Law

2007-01-01

293

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

294

Emotion Regulation and Depressive Symptoms in Preadolescence  

ERIC Educational Resources Information Center

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

Siener, Shannon; Kerns, Kathryn A.

2012-01-01

295

25 CFR 167.2 - General regulations.  

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

2014-04-01

296

25 CFR 167.2 - General regulations.  

Code of Federal Regulations, 2010 CFR

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

2010-04-01

297

Affect Regulation, Nicotine Addiction, and Smoking Cessation  

Microsoft Academic Search

Numerous investigators have examined the role of negative affective states and affect regulation in the initiation and development of cigarette smoking behavior, smoking cessation, and relapse prevention. Affect regulation refers to any attempt to alleviate negative mood states by means of pharmacologic-, cognitive-, behavioral-or environmental change methods. The psychological construct\\/process of affect regulation is examined in relation to (1) the

Timothy P. Carmody

1992-01-01

298

Affect Regulation, Tobacco Addiction, and Smoking Cessation  

Microsoft Academic Search

Numerous investigators have examined the role of negative affective states and affect regulation in the initiation and development of cigarette smoking behavior, smoking cessation, and relapse prevention. Affect regulation refers to any attempt to alleviate negative mood states by means of pharmacologic-, cognitive-, behavioral-or environmentalchange methods. The psychological construct\\/process of affect regulation is examined in relation to (1) the initiation,

Timothy P. Carmody

1989-01-01

299

Television Advertising Regulation and Program Quality  

Microsoft Academic Search

In many countries, including Australia and the United Kingdom, there are regulations that limit the amount of advertising content per hour of television broadcasts. This paper examines the effect this regulation has on program quality and viewer welfare. It is shown that regulation can reduce program quality and that its effect on viewer welfare is ambiguous. In some circumstances, fostering

DONALD J. WRIGHT

1994-01-01

300

The epigenetic language of circadian clocks.  

PubMed

Epigenetic control, which includes DNA methylation and histone modifications, leads to chromatin remodeling and regulated gene expression. Remodeling of chromatin constitutes a critical interface of transducing signals, such as light or nutrient availability, and how these are interpreted by the cell to generate permissive or silenced states for transcription. CLOCK-BMAL1-mediated activation of clock-controlled genes (CCGs) is coupled to circadian changes in histone modification at their promoters. Several chromatin modifiers, such as the deacetylases SIRT1 and HDAC3 or methyltransferase MLL1, have been shown to be recruited to the promoters of the CCGs in a circadian manner. Interestingly, the central element of the core clock machinery, the transcription factor CLOCK, also possesses histone acetyltransferase activity. Rhythmic expression of the CCGs is abolished in the absence of these chromatin modifiers. Here we will discuss the evidence demonstrating that chromatin remodeling is at the crossroads of circadian rhythms and regulation of metabolism and cellular proliferation. PMID:23604474

Sahar, Saurabh; Sassone-Corsi, Paolo

2013-01-01

301

Immunofluorescence analysis of circadian protein dynamics in cultured mammalian cells.  

PubMed

The timing of both entry and permanence of core-clock proteins in the nucleus is critical to maintain the correct pace of the clock mechanism. Several such proteins, namely CRYPTOCHROMEs (CRY), PERIODs (PER), and BMAL1, were recently shown to contain nuclear transport signals that facilitate their "shuttling" between the nucleus and the cytoplasm. This type of dynamic intracellular movement not only regulates protein localization, but also often affects functions by determining interactive partners and protein turnover. Because most clock genes have been identified by genetic screening in Drosophila and by gene knockdown in mammals, it is important to develop cellular techniques to study the structure-function and regulation of the corresponding proteins. Here we present working protocols for immunofluorescence studies of clock proteins in mammalian cultured cells. This technique allows the visualization in the cell of one or multiple proteins at the same time. PMID:17417041

Tamanini, Filippo

2007-01-01

302

41 CFR 109-1.102 - Federal Property Management Regulations.  

Code of Federal Regulations, 2010 CFR

...Management Federal Property Management Regulations System (Continued...DEPARTMENT OF ENERGY PROPERTY MANAGEMENT REGULATIONS GENERAL 1-INTRODUCTION 1.1-Regulation System...102 Federal Property Management...

2010-07-01

303

41 CFR 128-1.101 - Justice Property Management Regulations.  

Code of Federal Regulations, 2010 CFR

...Public Contracts and Property Management Federal Property Management Regulations System (Continued...DEPARTMENT OF JUSTICE 1-INTRODUCTION 1.1-Regulation System...101 Justice Property Management Regulations. The...

2010-07-01

304

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

Federal Register 2010, 2011, 2012, 2013

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

2011-03-11

305

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

Federal Register 2010, 2011, 2012, 2013

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

2010-12-16

306

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

307

SB 4 Interim Well Stimulation Treatment Regulations Text of Proposed Regulations  

E-print Network

injection, steamflood injection, cyclic steam injection, injection disposal, and gas storage projects. (b SB 4 Interim Well Stimulation Treatment Regulations Text of Proposed Regulations Page 1 of 12 SB 4 INTERIM WELL STIMULATION TREATMENT REGULATIONS TEXT OF PROPOSED REGULATIONS Added text is shown

308

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

ERIC Educational Resources Information Center

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

Jarvela, Sanna; Jarvenoja, Hanna

2011-01-01

309

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

E-print Network

Regulations on the Conduct of Research 1 REGULATION ON THE CONDUCT OF RESEARCH This Regulation replaces the following: Policy on Research Ethics Regulations on Research Policy PREAMBLE Research, culture, economic development and the advancement of society. Research and scholarship can flourish only

Fabry, Frederic

310

Price-cap regulation of congested airports  

Microsoft Academic Search

This paper investigates price-cap regulation of an airport where the airport facility (e.g. runway) is congested and airlines\\u000a have market power. We show that when airport congestion is not a major problem, single-till price-cap regulation dominates\\u000a dual-till price-cap regulation with respect to optimal welfare. Furthermore, we identify situations where dual-till regulation\\u000a performs better than single-till regulation when there is significant

Hangjun Yang; Anming Zhang

2011-01-01

311

Shanghai adopts family planning regulations.  

PubMed

These Regulations, adopted by the Municipal People's Congress of Shanghai on 14 March 1990, do the following: a) strictly prohibit any units and individuals from identifying the sex of a fetus without medical reasons; b) add 1 additional week to the marriage leave of couples who marry at the age set for late marriage (25 for males and 23 for females); c) add 15 days of maternity leave for women who give birth at the age set for late birth (24) and 3 days for their spouses; d) impose a fine equal to 3 to 6 times their average annual income if a couple have an unplanned birth (calculated on the basis of their income 2 years before the birth); and e) subject a couple who have an unplanned birth to disciplinary action by their working units if they work for others or by the administrative department of industry and commerce if they are self employed. Second births are allowed if a first child "can not become normal because of nonhereditary diseases," if both husband and wife are single children, or if a "remarried couple had only one child before their remarriage." The Regulations provide that "the improvement of birth quality and good upbringing of children should be promoted, advice on heredity should be provided, and premarital examinations [should] be conducted." They also stipulate that "A woman should terminate her pregnancy or undergo a sterilization operation if both husband and wife (or either of them) have [a] hereditary or other disease not medically suitable for birth." The provisions of these Regulations prohibiting prenatal sex selection were reported in Annual Review of Population Law, Vol. 17, 1990, Section 240. PMID:12348767

1990-04-01

312

Tonic regulation of vascular permeability  

PubMed Central

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

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

2014-01-01

313

Brassinosteroid-Regulated Gene Expression  

PubMed Central

Major brassinosteroid (BR) effects such as BR-induced growth are mediated through genomic pathways because RNA synthesis inhibitors and protein synthesis inhibitors interfere with these processes. A limited number of BR-regulated genes have been identified hitherto. The majority of genes (such as BRU1, CycD3, Lin6, OPR3, and TRIP-1) were identified by comparisons of BR-treated versus control-treated plants. However, altered transcript levels after BR application may not reflect normal physiological events. A complementary approach is the comparison of BR-deficient plants versus wild-type plants. No artificial treatments interfere with endogenous signaling pathways, but a subset of phenotypic alterations of phytohormone-deficient plants most probably is secondary. To identify genes that are subject to direct BR regulation, we analyzed CPD antisense and dwf1-6 (cbb1) mutant plants. Both show a mild phenotype in comparison with BR-deficient mutants such as cpd/cbb3, det2, and dwf4. Plants were grown under two different environments to filter out BR deficiency effects that occur only at certain environmental conditions. Finally, we established expression patterns after BR treatment of wild-type and dwf1-6 (cbb1) plants. Ideally, a BR-regulated gene displays a dose-response relationship in such a way that a gene with decreased transcript levels in BR-deficient plants is BR inducible and vice versa. Expression profile analysis of above ground part of plants was performed by means of Affymetrix Arabidopsis Genome Arrays. PMID:12114578

Mussig, Carsten; Fischer, Sabine; Altmann, Thomas

2002-01-01

314

Oxygen Regulates Tissue Nitrite Metabolism  

PubMed Central

Abstract Aims: Once dismissed as an inert byproduct of nitric oxide (NO) auto-oxidation, nitrite (NO2-) is now accepted as an endocrine reservoir of NO that elicits biological responses in major organs. While it is known that tissue nitrite is derived from NO oxidation and the diet, little is known about how nitrite is metabolized by tissue, particularly at intermediate oxygen tensions. We investigated the rates and mechanisms of tissue nitrite metabolism over a range of oxygen concentrations. Results: We show that the rate of nitrite consumption differs in each organ. Further, oxygen regulates the rate and products of nitrite metabolism. In anoxia, nitrite is reduced to NO, with significant formation of iron–nitrosyl proteins and S-nitrosothiols. This hypoxic nitrite metabolism is mediated by different nitrite reductases in each tissue. In contrast, low concentrations (?3.5??M) of oxygen increase the rate of nitrite consumption by shifting nitrite metabolism to oxidative pathways, yielding nitrate. While cytochrome P450 and myoglobin contribute in the liver and heart, respectively, mitochondrial cytochrome c oxidase plays a significant role in nitrite oxidation, which is inhibited by cyanide. Using cyanide to prevent artifactual nitrite decay, we measure metabolism of oral and intraperitoneally administered nitrite in mice. Innovation: These data provide insight into the fate of nitrite in tissue, the enzymes involved in nitrite metabolism, and the role of oxygen in regulating these processes. Conclusion: We demonstrate that even at low concentrations, oxygen is a potent regulator of the rate and products of tissue nitrite metabolism. Antioxid. Redox Signal. 17, 951–961. PMID:22098300

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

2012-01-01

315

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

316

Metabolic regulation of stem cell function.  

PubMed

Stem cell function is regulated by intrinsic mechanisms, such as transcriptional and epigenetic regulators, as well as extrinsic mechanisms, such as short-range signals from the niche and long-range humoral signals. Interactions between these regulatory mechanisms and cellular metabolism are just beginning to be identified. In multiple systems, differentiation is accompanied by changes in glycolysis, oxidative phosphorylation and the levels of reactive oxygen species. Indeed, metabolic pathways regulate proliferation and differentiation by regulating energy production and the generation of substrates for biosynthetic pathways. Some metabolic pathways appear to function differently in stem cells as compared with restricted progenitors and differentiated cells. They also appear to influence stem cell function by regulating signal transduction, epigenetic marks and oxidative stress. Studies to date illustrate the importance of metabolism in the regulation of stem cell function and suggest complex cross-regulation likely exists between metabolism and other stem cell regulatory mechanisms. PMID:24697828

Burgess, R J; Agathocleous, M; Morrison, S J

2014-07-01

317

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

318

Safe harbor regulations for GPOs.  

PubMed

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

Thomas, H

1992-05-01

319

Regulation of aquaporin-2 trafficking.  

PubMed

Principal cells lining renal collecting ducts control the fine-tuning of body water homeostasis by regulating water reabsorption through the water channels aquaporin-2 (AQP2), aquaporin-3 (AQP3), and aquaporin-4 (AQP4). While the localization of AQP2 is subject to regulation by arginine-vasopressin (AVP), AQP3 and AQP4 are constitutively expressed in the basolateral plasma membrane. AVP adjusts the amount of AQP2 in the plasma membrane by triggering its redistribution from intracellular vesicles into the plasma membrane. This permits water entry into the cells and water exit through AQP3 and AQP4. The translocation of AQP2 is initiated by an increase in cAMP following V2R activation through AVP. The AVP-induced rise in cAMP activates protein kinase A (PKA), which in turn phosphorylates AQP2, and thereby triggers the redistribution of AQP2. Several proteins participating in the control of cAMP-dependent AQP2 trafficking have been identified; for example, A kinase anchoring proteins (AKAPs) tethering PKA to cellular compartments; phosphodiesterases (PDEs) regulating the local cAMP level; cytoskeletal components such as F-actin and microtubules; small GTPases of the Rho family controlling cytoskeletal dynamics; motor proteins transporting AQP2-bearing vesicles to and from the plasma membrane for exocytic insertion and endocytic retrieval; SNAREs inducing membrane fusions, hsc70, a chaperone, important for endocytic retrieval. In addition, cAMP-independent mechanisms of translocation mainly involving the F-actin cytoskeleton have been uncovered. Defects of AQP2 trafficking cause diseases such as nephrogenic diabetes insipidus (NDI), a disorder characterized by a massive loss of hypoosmotic urine.This review summarizes recent data elucidating molecular mechanisms underlying the trafficking of AQP2. In particular, we focus on proteins involved in the regulation of trafficking, and physiological and pathophysiological stimuli determining the cellular localization of AQP2. The identification of proteins and protein-protein interactions may lead to the development of drugs targeting AQP2 trafficking. Such drugs may be suitable for the treatment of diseases associated with dysregulation of body water homeostasis, including NDI or cardiovascular diseases (e.g., chronic heart failure) where the AVP level is elevated, inducing excessive water retention. PMID:19096775

Nedvetsky, Pavel I; Tamma, Grazia; Beulshausen, Sven; Valenti, Giovanna; Rosenthal, Walter; Klussmann, Enno

2009-01-01

320

Hypoxia-regulated angiogenic inhibitors  

PubMed Central

The regulation of angiogenesis by hypoxia is an essential homeostatic mechanism that depends on a precise balance between positive and negative angiogenic regulatory molecules. Pro-angiogenic factors are well characterized; however, several in vivo and in vitro studies indicate that there are feedback mechanisms in place to inhibit angiogenesis during hypoxia. Understanding the signaling pathways leading to the negative feedback of angiogenesis will undoubtedly provide important tools to develop novel therapeutic strategies not only to enhance the angiogenic response in coronary artery disease but also to hinder deregulated angiogenesis in tumorigenesis. PMID:20447566

Messmer-Blust, Angela; An, Xiaojin; Li, Jian

2010-01-01

321

Regulation of xylem cell fate.  

PubMed

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

Kondo, Yuki; Tamaki, Takayuki; Fukuda, Hiroo

2014-01-01

322

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

323

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

Microsoft Academic Search

In this commentary on the special issue, I join the authors in searching for a conceptual framework that would clarify the\\u000a concepts of metacognition, self-regulation, and self-regulated learning. Building on the insights of the different articles,\\u000a I suggest that metacognition, self-regulation, and self-regulated learning should be considered as subtypes of the general,\\u000a abstract, phenomenon of self-regulated action. I continue by

Avi Kaplan

2008-01-01

324

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

Microsoft Academic Search

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

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

2006-01-01

325

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.

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

2014-01-01

326

Stoichiometric regulation of phytoplankton toxins.  

PubMed

Ecological Stoichiometry theory predicts that the production, elemental structure and cellular content of biomolecules should depend on the relative availability of resources and the elemental composition of their producer organism. We review the extent to which carbon- and nitrogen-rich phytoplankton toxins are regulated by nutrient limitation and cellular stoichiometry. Consistent with theory, we show that nitrogen limitation causes a reduction in the cellular quota of nitrogen-rich toxins, while phosphorus limitation causes an increase in the most nitrogen-rich paralytic shellfish poisoning toxin. In addition, we show that the cellular content of nitrogen-rich toxins increases with increasing cellular N : P ratios. Also consistent with theory, limitation by either nitrogen or phosphorus promotes the C-rich toxin cell quota or toxicity of phytoplankton cells. These observed relationships may assist in predicting and managing toxin-producing phytoplankton blooms. Such a stoichiometric regulation of toxins is likely not restricted to phytoplankton, and may well apply to carbon- and nitrogen-rich secondary metabolites produced by bacteria, fungi and plants. PMID:24712512

Van de Waal, Dedmer B; Smith, Val H; Declerck, Steven A J; Stam, Eva C M; Elser, James J

2014-06-01

327

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

328

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

329

Phosphorylation regulates human OCT4.  

PubMed

The transcription factor OCT4 is fundamental to maintaining pluripotency and self-renewal. To better understand protein-level regulation of OCT4, we applied liquid chromatography-MS to identify 14 localized sites of phosphorylation, 11 of which were previously unknown. Functional analysis of two sites, T234 and S235, suggested that phosphorylation within the homeobox region of OCT4 negatively regulates its activity by interrupting sequence-specific DNA binding. Mutating T234 and S235 to mimic constitutive phosphorylation at these sites reduces transcriptional activation from an OCT4-responsive reporter and decreases reprogramming efficiency. We also cataloged 144 unique phosphopeptides on known OCT4 interacting partners, including SOX2 and SALL4, that copurified during immunoprecipitation. These proteins were enriched for phosphorylation at motifs associated with ERK signaling. Likewise, OCT4 harbored several putative ERK phosphorylation sites. Kinase assays confirmed that ERK2 phosphorylated these sites in vitro, providing a direct link between ERK signaling and the transcriptional machinery that governs pluripotency. PMID:22474382

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

2012-05-01

330

Regulating dynamin dynamics during endocytosis  

PubMed Central

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

Sundborger, Anna C.

2014-01-01

331

Forms Supplement page -1 Export Administration Regulations January 2001  

E-print Network

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

Bernstein, Daniel

332

7 CFR 915.305 - Florida Avocado Container Regulation 5.  

Code of Federal Regulations, 2010 CFR

...false Florida Avocado Container Regulation 5. 915.305 Section 915.305 Agriculture Regulations of the Department of Agriculture...SOUTH FLORIDA Container and Pack Regulations § 915.305 Florida Avocado Container Regulation 5....

2010-01-01

333

7 CFR 905.52 - Issuance of regulations.  

Code of Federal Regulations, 2010 CFR

...2010-01-01 false Issuance of regulations. 905.52 Section 905.52 Agriculture Regulations of the Department of Agriculture (Continued...FLORIDA Order Regulating Handling Regulations § 905.52 Issuance of...

2010-01-01

334

7 CFR 923.51 - Recommendations for regulation.  

Code of Federal Regulations, 2010 CFR

...2010-01-01 false Recommendations for regulation. 923.51 Section 923.51 Agriculture Regulations of the Department of Agriculture (Continued...WASHINGTON Order Regulating Handling Regulations § 923.51 Recommendations for...

2010-01-01

335

7 CFR 999.300 - Regulation governing importation of raisins.  

Code of Federal Regulations, 2010 CFR

...2010-01-01 2010-01-01 false Regulation governing importation of raisins... Section 999.300 Agriculture Regulations of the Department of Agriculture (Continued...AGRICULTURE SPECIALTY CROPS; IMPORT REGULATIONS § 999.300 Regulation...

2010-01-01

336

7 CFR 958.52 - Issuance of regulations.  

Code of Federal Regulations, 2010 CFR

...2010-01-01 false Issuance of regulations. 958.52 Section 958.52 Agriculture Regulations of the Department of Agriculture (Continued...OREGON Order Regulating Handling Regulation § 958.52 Issuance of...

2010-01-01

337

7 CFR 987.40 - Additional grade or size regulations.  

Code of Federal Regulations, 2010 CFR

...2010-01-01 false Additional grade or size regulations. 987.40 Section 987.40 Agriculture Regulations of the Department of Agriculture (Continued... Order Regulating Handling Grade Regulation § 987.40 Additional grade or...

2010-01-01

338

7 CFR 948.22 - Issuance of regulations.  

Code of Federal Regulations, 2010 CFR

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

2010-01-01

339

7 CFR 959.52 - Issuance of regulations.  

Code of Federal Regulations, 2010 CFR

...2010-01-01 false Issuance of regulations. 959.52 Section 959.52 Agriculture Regulations of the Department of Agriculture (Continued...TEXAS Order Regulating Handling Regulations § 959.52 Issuance of...

2010-01-01

340

7 CFR 917.40 - Recommendations for regulations.  

Code of Federal Regulations, 2010 CFR

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

2010-01-01

341

48 CFR 22.403-4 - Department of Labor regulations.  

Code of Federal Regulations, 2010 CFR

48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Department of Labor regulations. 22.403-4 Section 22.403-4 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION...

2010-10-01

342

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

PubMed

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

Troxell, Bryan; Hassan, Hosni M

2013-01-01

343

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

344

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

345

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

346

Transcriptional regulation by STAT6  

PubMed Central

Signal transducer and activator of transcription (STAT) proteins are critical mediators of cytokine signaling. Among the seven STAT proteins, STAT6 is activated by IL-4 and IL-13 and plays a predominant role in the immune system. However, there is increasing evidence that STAT6 may function in other tissues and organ systems. IL-4, IL-13, and STAT6 promote humoral immunity, clearance of helminthic parasites as well as the pathogenesis of allergic disorders like asthma, food allergies, and atopic dermatitis. In this review, we will describe our current understanding of the biological functions of STAT6 and summarize recent advances in understanding the molecular mechanisms by which STAT6 regulates transcription. PMID:21442426

Kaplan, Mark H.

2011-01-01

347

Metallochaperones regulate intracellular copper levels.  

PubMed

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

348

Implementing CITES regulations for timber.  

PubMed

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

Blundell, Arthur G

2007-03-01

349

Dynamics of bacterial gene regulation  

NASA Astrophysics Data System (ADS)

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

Narang, Atul

2009-03-01

350

Extracellular Matrix Regulation of Autophagy  

PubMed Central

Summary Integrin-mediated attachment of epithelial cells to extracellular matrix (ECM) is critical for proper growth and survival. Although detachment leads to apoptosis, termed anoikis, recent work demonstrates that ECM detachment also robustly induces autophagy, a tightly regulated lysosomal self-digestion process that actually promotes survival. Autophagy presumably protects epithelial cells from the stresses of ECM detachment, allowing them to survive provided they reattach in a timely manner. Currently, the intracellular signals linking integrin engagement to autophagy remain unclear, but certain growth factor, energy-sensing, and stress response pathways represent attractive candidates. Moreover, autophagy may be a previously unrecognized mechanism utilized by detached cancer cells to survive anoikis, which may facilitate tumor cell dormancy, dissemination, and metastasis. PMID:18573652

Lock, Rebecca; Debnath, Jayanta

2008-01-01

351

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

352

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

353

Gene regulation by growth hormone  

PubMed Central

Since the somatomedin hypothesis of growth hormone (GH) action was first formulated more than 50 years ago, the key roles of both GH and insulin-like growth factor-I (IGF-I) in human growth have been extended to include important effects on tissue maintenance and repair. More recent observations have revealed that this pathway has a negative side, as it has been implicated as a potential contributor to the development of several human cancers and has been linked to diminished lifespan in experimental animals. This brief review focuses on fundamental aspects of gene regulation by GH, as long-term hormonal effects all require changes in gene expression. Topics to be discussed include GH-stimulated signal transduction pathways, mechanisms of gene activation and gene repression by GH, and an analysis of control of IGF-I gene transcription by the GH-stimulated transcription factor, signal transducer and activator of transcription (Stat)5b. PMID:19626342

Chia, Dennis J.

2014-01-01

354

[Medication, athletes and doping regulations].  

PubMed

Doping is defined as an offence of the antidopingcode of the World Anti-Doping Agency (WADA). To uphold the code WADA has composed a list of prohibited substances and methods. The composition of the list is based on three mainstays: fair play, health risks and spirit of the sport. Among the prohibited substances are anabolic agents, erythropoietin, beta2-sympathicomimetics, growth hormone and masking agents. For some medications athletes may receive a therapeutic use exemption. Enforcement of the antidoping-code is performed by doping controls. For this purpose, blood and urine samples of athletes are collected and analysed. In 2006 approximately 200,000 samples were analysed worldwide, with 1.96% being tested positive. All physicians should be aware of the possibility that athletes use medication subjected to the doping regulations. There are guidelines for physicians on doping-related issues in medical practice. PMID:18783164

Hartgens, F

2008-08-16

355

Air/fuel ratio regulator  

SciTech Connect

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

Simko, A.

1980-07-22

356

Fibronectin regulates calvarial osteoblast differentiation  

NASA Technical Reports Server (NTRS)

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

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

1996-01-01

357

CELLULAR ADMA: REGULATION AND ACTION  

PubMed Central

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

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

2009-01-01

358

Environmental Statistics and Optimal Regulation  

PubMed Central

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

2014-01-01

359

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

360

Focus Issue: Regulation of Lymphocyte Function  

NSDL National Science Digital Library

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

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

2012-07-31

361

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

362

Self-regulated profiles and academic achievement  

Microsoft Academic Search

To date, research on the relation between learning self-regulation and academic achievement has generally show disparate results. This work intends to look into this relation from a new perspective, which consists in classifying the students as more or less self-regulated depending on diverse indicators and using cluster analysis. The aim of this work was to identify the possible self-regulated learning

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

2008-01-01

363

Performance and learning goals for emotion regulation  

Microsoft Academic Search

Goal orientation theory is concerned with performance and learning goals in academic, athletic, and other ability areas. Here\\u000a we examine performance and learning goals for emotion regulation. We define performance goals for emotion regulation as seeking\\u000a to prove one’s ability to manage emotions; learning goals for emotion regulation are defined as seeking to improve one’s ability to manage emotions. In

Natalie RuskMaya TamirFred Rothbaum; Maya Tamir; Fred Rothbaum

364

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

365

Cognitive emotion regulation fails the stress test  

PubMed Central

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

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

2013-01-01

366

An Economic Evaluation of Plastic Bag Regulation.  

E-print Network

??In recent years, several jurisdictions worldwide have implemented plastic bag regulations to curb environmentally deleterious effects of plastic bag production and consumption. The problems that… (more)

Nilsen, Anders

2010-01-01

367

76 FR 9988 - Improving EPA Regulations  

Federal Register 2010, 2011, 2012, 2013

...Environmental Justice/Children's Health/Elderly Submit a comment related to environmental justice, children's health, or the elderly to the ``Improving Regulations: EJ, Children & Elderly'' docket...

2011-02-23

368

RESIDENCE REGULATIONS 2012/2013 APPLICABLE TO  

E-print Network

1 RESIDENCE REGULATIONS 2012/2013 APPLICABLE TO STUDENT ACCOMMODATION SERVICES (SAS) PROPERTIES.................................................................... 11 Residential Services' Debt Management Policy and Procedure ......................................................................... 30 Residential Services' Student Charter

Martin, Ralph R.

369

Mechanotransduction: a major regulator of homeostasis and  

E-print Network

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

Mofrad, Mohammad R. K.

370

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

371

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

372

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

373

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

374

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

375

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

376

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

377

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

PubMed Central

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

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

2013-01-01

378

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

Federal Register 2010, 2011, 2012, 2013

...Flowers/IC 9000-0095, Commerce Patent Regulations. Instructions...Information Collection 9000-0095, Commerce Patent Regulations, in all...implements the Department of Commerce regulation (37 CFR 401) based...contracting officer may insert clauses 52.227-11, Patent...

2012-07-23

379

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

Federal Register 2010, 2011, 2012, 2013

...Flowers/IC 9000-0095, Commerce Patent Regulations. Instructions...Information Collection 9000-0095, Commerce Patent Regulations, in all...implements the Department of Commerce regulation (37 CFR 401) based...contracting officer may insert clauses 52.227-11, Patent...

2013-05-24

380

Do Environmental Regulations Cause Firms to Exit the Market? Evidence from Underground Storage Tank (UST) Regulations  

Microsoft Academic Search

This paper examines whether Underground Storage Tank (UST) regulations had uneven impacts on petroleum retail outlets, and explores the reasons why some outlets are more likely to exit the market than others under UST regulations. The analyses suggest that both the economies of scale and liquidity constraints can explain the uneven impact UST regulations had on different petroleum retail outlets.

Haitao Yin; Howard Kunreuther; Matthew White

381

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

E-print Network

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

Stuart, Steven J.

382

Assessing Emotion Regulation in Social Anxiety Disorder: The Emotion Regulation Interview  

E-print Network

specified by Gross's (Review of General Psychology 2: 271­299, 1998) process model of emotion regulationAssessing Emotion Regulation in Social Anxiety Disorder: The Emotion Regulation Interview Kelly H to involve emotional hyper-reactivity and emotion dysregulation. How- ever, the precise nature of the emotion

Gross, James J.

383

Analyzing the Laws, Regulations, and Policies Affecting FDA-Regulated Products  

E-print Network

Analyzing the Laws, Regulations, and Policies Affecting FDA-Regulated Products FDLI FOOD AND DRUG additional regulation. As part of the National Nanotechnol- ogy Initiative (NNI) in the United States, 26 federal agencies, including the Food and Drug Administration (FDA), contributed to the development

Kokkoli, Efie

384

Developmental regulation and overexpression of the transcription factor AP-2, a potential regulator of  

E-print Network

Developmental regulation and overexpression of the transcription factor AP-2, a potential regulator, rat, Schwann cell precursors, transcription factors Abstract There is now evidence from in vivo and in vitro studies that the rate of Schwann cell generation is regulated by the balance of two opposing

Jessen, Kristjan R

385

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

386

Teachers as Self-Regulated Learners  

ERIC Educational Resources Information Center

This article describes how preservice teachers are afforded opportunities for developing self-regulation as they learn to transition to the other side of the desk in their teacher education program. The article focuses on self-regulated learning as it applies to teachers' work in the classroom and distinguishes volitional work styles and student…

Randi, Judi

2004-01-01

387

Transcriptional Regulation and its Misregulation in Disease  

PubMed Central

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

Lee, Tong Ihn; Young, Richard A.

2013-01-01

388

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

389

Regulation of Blood Pressure by Dopamine Receptors  

Microsoft Academic Search

Dopamine is an important regulator of blood pressure. Its actions on renal hemodynamics, epithelial transport and humoral agents such as aldosterone, catecholamines, endothelin, prolactin, pro-opiomelanocortin, renin and vasopressin place it in central homeostatic position for regulation of extracellular fluid volume and blood pressure. Dopamine also modulates fluid and sodium intake via actions in the central nervous system and gastrointestinal tract,

Pedro A. Jose; Gilbert M. Eisner; Robin A. Felder

2003-01-01

390

Improved Two-Phase Switching Regulator  

NASA Technical Reports Server (NTRS)

Coupled-inductor polyphase regulator has better efficiency and lower inductor losses. Improved two-phase switching regulator employs negative coupling between inductors to achieve better power-to-weight ratio while reducing peak switching currents and inductor losses. Improvement of about 35 percent using new technique.

Rippel, W. E.

1984-01-01

391

Conserved mechanisms regulate outgrowth in zebrafish fins  

E-print Network

to identify pathways regulating overall limb growth and morphology, experiments have evaluated gene expression, transplanted and removed tissues, and knocked out genes. This work has provided a vast amount of information identifying molecular mechanisms regulating limb axis formation, outgrowth, and pattern formation. Using

Behe, Michael J.

392

50 CFR 665.934 - Regulated activities.  

Code of Federal Regulations, 2013 CFR

...Fisheries 13 2013-10-01 2013-10-01 false Regulated activities. 665.934 Section 665.934 Wildlife...Pacific Remote Islands Marine National Monument § 665.934 Regulated activities. (a) Commercial fishing is prohibited in...pursuant to § 665.934(d). (c) Commercial fishing outside the Monument and non-commercial fishing within the...

2013-10-01

393

50 CFR 404.7 - Regulated activities.  

Code of Federal Regulations, 2010 CFR

...Fisheries 7 2010-10-01 2010-10-01 false Regulated activities. 404.7 Section 404.7 Wildlife and...NORTHWESTERN HAWAIIAN ISLANDS MARINE NATIONAL MONUMENT § 404.7 Regulated activities. Except as provided in §§ 404.8, 404...or discharging or depositing any material or other matter outside the Monument that subsequently enters the Monument...

2010-10-01

394

50 CFR 404.7 - Regulated activities.  

Code of Federal Regulations, 2012 CFR

...Fisheries 11 2012-10-01 2012-10-01 false Regulated activities. 404.7 Section 404.7 Wildlife and...NORTHWESTERN HAWAIIAN ISLANDS MARINE NATIONAL MONUMENT § 404.7 Regulated activities. Except as provided in §§ 404.8, 404...or discharging or depositing any material or other matter outside the Monument that subsequently enters the Monument...

2012-10-01

395

50 CFR 404.7 - Regulated activities.  

Code of Federal Regulations, 2011 CFR

...Fisheries 9 2011-10-01 2011-10-01 false Regulated activities. 404.7 Section 404.7 Wildlife and...NORTHWESTERN HAWAIIAN ISLANDS MARINE NATIONAL MONUMENT § 404.7 Regulated activities. Except as provided in §§ 404.8, 404...or discharging or depositing any material or other matter outside the Monument that subsequently enters the Monument...

2011-10-01

396

50 CFR 665.904 - Regulated activities.  

Code of Federal Regulations, 2013 CFR

...Fisheries 13 2013-10-01 2013-10-01 false Regulated activities. 665.904 Section 665.904 Wildlife...Marianas Trench Marine National Monument § 665.904 Regulated activities. (a) Commercial fishing is prohibited in...established in § 665.905. (c) Commercial fishing outside the Islands Unit and non-commercial fishing within...

2013-10-01

397

50 CFR 665.964 - Regulated activities.  

Code of Federal Regulations, 2013 CFR

...Fisheries 13 2013-10-01 2013-10-01 false Regulated activities. 665.964 Section 665.964 Wildlife...PACIFIC Rose Atoll Marine National Monument § 665.964 Regulated activities. (a) Commercial fishing is prohibited in...established in § 665.965. (c) Commercial fishing outside the Monument and non-commercial fishing within the...

2013-10-01

398

50 CFR 404.7 - Regulated activities.  

Code of Federal Regulations, 2013 CFR

...Fisheries 11 2013-10-01 2013-10-01 false Regulated activities. 404.7 Section 404.7 Wildlife and...NORTHWESTERN HAWAIIAN ISLANDS MARINE NATIONAL MONUMENT § 404.7 Regulated activities. Except as provided in §§ 404.8, 404...or discharging or depositing any material or other matter outside the Monument that subsequently enters the Monument...

2013-10-01

399

Regulations and Universities: An Argument for Compliance.  

ERIC Educational Resources Information Center

The president of Towson State University (Maryland) encourages college administrators to comply with both the spirit and the letter of federal regulations, because (1) universities are similar to business corporations; (2) the university community has been an active supporter of many regulations; and (3) universities should model responsible…

Smith, Hoke L.

1992-01-01

400

Emotion Regulation in Children with Down Syndrome.  

ERIC Educational Resources Information Center

This study presents a preliminary exploration of emotion regulation in a sample of 20 children (ages 3-18 years) with Down Syndrome. Three aspects of emotion regulation (modulation, organization, flexibility) were predicted from emotion variables (affect intensity, affective expression, and autonomy-curiosity and motivation) in backward regression…

Smith, Maureen C.; Walden, Tedra A.

401

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

402

Regulation of Competence Development in Haemophilus influenzae  

Microsoft Academic Search

Development of competence for DNA uptake by the bacterium Haemophilus influenzae is tightly regulated, and expression of the cell's complement of competence genes is absolutely dependent on the cAMP–CRP complex. A second regulator of competence may maximize competence under starvation conditions. Several investigators have recently identified a consensus sequence (competence regulatory element, CRE) in the promoter regions of some competence

LEAH P. MACFADYEN

2000-01-01

403

Aesthetic medicine: a health regulator's perspective  

Microsoft Academic Search

Purpose – The purpose of this paper is to help understand the extent of regulation of aesthetic medicine in various developed countries and to discuss the current pitfalls and potential strategies in regulating this area of healthcare. Design\\/methodology\\/approach – A range of published articles and press reports from bound and internet sources on aesthetic medicine in the recent five to

Keng Boon Harold Tan

2007-01-01

404

Test Review: Anger Regulation and Expression Scale  

ERIC Educational Resources Information Center

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

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

2013-01-01

405

Regulation of transcription factors by neuronal activity  

Microsoft Academic Search

Synaptic activity regulates the expression of a set of neuronal gene products that are important for neuronal survival and differentiation, synaptogenesis and, ultimately, complex behaviour. Activity-dependent signalling pathways induce neuronal gene transcription by modulating the function of both transcriptional activators and repressors, and recent studies have revealed significant diversity in the mechanisms that control the activity of these transcriptional regulators.

Anne E. West; Eric C. Griffith; Michael E. Greenberg

2002-01-01

406

MAPPING GASOLINE REQUIREMENTS, APPLICABLE REGULATIONS AND BANS  

EPA Science Inventory

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

407

Food Safety Regulations for Farmers'Markets  

E-print Network

Food Safety Regulations for Farmers'Markets Christa Hofmann and Jennifer Dennis Department of the product offerings at farmers'markets,health departments have become more involved in ensuring food safety safety regulations. Classification of a Farmers'Market Food safety issues are governed by the retail food

408

Benefits and costs of food safety regulation  

Microsoft Academic Search

This paper begins with a review of the concepts and methods that can be used to quantify the benefits and costs of food safety regulations. On the cost side, where research is only beginning to emerge, this paper also provides an analytical framework for measurement of the costs of statutory regulations in the form of design and performance standards. This

John M. Antle

1999-01-01

409

Hair cycle regulation of Hedgehog signal reception  

Microsoft Academic Search

Proper patterning of self-renewing organs, like the hair follicle, requires exquisite regulation of growth signals. Sonic hedgehog (Shh) signaling in skin controls the growth and morphogenesis of hair follicle epithelium in part through regulating the Gli transcription factors. While ectopic induction of Shh target genes leads to hair follicle tumors, such as basal cell carcinomas, how Shh signaling normally functions

Anthony E Oro; Kay Higgins

2003-01-01

410

Regulation of Dendritic Development by Neuronal Activity  

E-print Network

of the dendritic tree is a highly dynamic and regulated process, which involves the formation of new branchesRegulation of Dendritic Development by Neuronal Activity Yachi Chen,1 Anirvan Ghosh2 1 Department development of dendrites is essential for the establishment of neuronal circuitry. The elaboration

Ghosh, Anirvan

411

A Computational Model for Adaptive Emotion Regulation  

E-print Network

Vrije Universiteit Amsterdam, Department of Artificial Intelligence, De Boelelaan 1081a, 1081 HVA Computational Model for Adaptive Emotion Regulation Tibor Bosse, Matthijs Pontier, and Jan Treur} Abstract. Emotion regulation describes how a subject can use certain strategies to affect emotion response

Treur, Jan

412

Implementing electrical safety regulations and standards  

Microsoft Academic Search

Since the creation of OSHA in 1912, there have been continuing changes in regulations, codes and standards impacting work practices and exposure to hazardous electrical energy. These include, but are not limited to, various OSHA regulations, NFPA 70E (1988 & 1995), National Electrical Code and National Electrical Safety Code. These consensus documents are written with the intention to establish lower

S. Jamil; H. Landis Floyd; D. A. Pace

1999-01-01

413

Higher Education Regulations Study: Final Report  

ERIC Educational Resources Information Center

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

Advisory Committee on Student Financial Assistance, 2011

2011-01-01

414

How to Influence the IDEA Regulations  

ERIC Educational Resources Information Center

Teachers of children with disabilities know how greatly the Individuals With Disabilities Education Act (IDEA) regulations influence their daily practices; and they no doubt have strong opinions about regulations that go too far or not far enough to allow them to help their students succeed. This article offers practical, nuts-and-bolts help for…

Dale, Richard E.

2011-01-01

415

The Economics and Politics of Regulation  

Microsoft Academic Search

This article provides a critical survey of the literature on the economics and politics of regulation. After some conceptual clarifications, the article surveys the evolution of perspectives on regulation during the post-Second World War period, emphasizing especially the interactions between intellectual changes and real world economic and political developments. It then looks at some themes that are neglected in the

Ha-Joon Chang

1997-01-01

416

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

417

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

418

EMERGING ISSUE OF REGULATION FOR ONLINE EDUCATION  

Microsoft Academic Search

The issue of laws and regulations lead to the quality of online education. Frydenberg (4) contends that a major source of regulation in the United States is the regional accreditation agencies for higher education. The regional accreditation agencies are charged with setting standards of quality practice and to guide toward achieving those standards. These standards must meet the state and

Deanna Klein

419

REGULATIONS OF THE UNIVERSITY OF FLORIDA  

E-print Network

1 REGULATIONS OF THE UNIVERSITY OF FLORIDA 3.0421 Employee Debt Collection. (1) Purpose to the collection of delinquent accounts of a student while the student is enrolled at the University but will apply if the student thereafter becomes an employee of the University. (2) For purposes of this regulation, employee

Pilyugin, Sergei S.

420

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

421

New HCFA regulations clarify PSO requirements.  

PubMed

In March and April of 1998, HCFA promulgated regulations regarding various requirements for provider-sponsored organizations (PSOs). These regulations define what constitutes an affiliated provider to a PSO, identify what percentage of services must be provided directly to beneficiaries by PSO affiliated providers, define what constitutes provider ownership in a PSO, and set minimum capitalization and liquidity standards for PSOs. PMID:10179971

Brock, T H

1998-06-01

422

A Guide to Federal Reserve Regulations.  

ERIC Educational Resources Information Center

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

Federal Reserve Bank of New York, NY.

423

Drosophila Cytokine Unpaired 2 Regulates Physiological Homeostasis  

E-print Network

). The production of insulin by pancreatic beta cells is tightly regulated to ensure that appropriate amountsDrosophila Cytokine Unpaired 2 Regulates Physiological Homeostasis by Remotely Controlling Insulin that conveys the nutrient status to the insulin-producing cells (IPCs) in the fly brain to release Drosophila

Perrimon, Norbert

424

Engineer Regulation Department of the Army  

E-print Network

CECW-P Engineer Regulation 1105-2-100 Department of the Army U.S. Army Corps of Engineers-2-100 U. S. Army Corps of Engineers CECW-P Washington, D.C. 20314-1000 Regulation No. 1105-2-100 22 April...................................................................................................................3-1 3-3. Flood Damage Reduction

US Army Corps of Engineers

425

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

426

Cell Metabolism Regulation of Ceramide Biosynthesis  

E-print Network

Cell Metabolism Article Regulation of Ceramide Biosynthesis by TOR Complex 2 Sofia Aronova,1 Karen.11.015 SUMMARY Ceramides and sphingoid long-chain bases (LCBs) are precursors to more complex sphingolipids. cerevisiae; however, the precise step regulated by this complex remains unknown. Here we demon- strate

Hammock, Bruce D.

427

Nonprescription Drug Regulation in the United States  

Microsoft Academic Search

In the United States, nonprescription drug products are regulated through implementation of laws enacted by Congress. The Food and Drug Administration (FDA) follows specific procedures that allow for public notice and comment when promulgating implementing regulations. Drug products may be marketed directly to consumers, unless they are limited to prescription use only because they meet certain criteria. Nonprescription drug products

Debra Bowen

2000-01-01

428

Regulations which require employee training: An overview  

SciTech Connect

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

Gilfus, L.J.

1995-11-01

429

Book review Photosynthesis: Regulation under Varying Light  

E-print Network

Book review Photosynthesis: Regulation under Varying Light Regimes, by V.S. Rama Das. Science of the research in the area of regulation of photosynthesis under varying light regimes. As stated in the Preface, he has provided a frame- work, rather than an exhaustive description, of the field. His goal

Govindjee "Gov"

430

Essays on electricity regulation and restructuring  

NASA Astrophysics Data System (ADS)

The study of the regulation of the electric power industry is important to understanding the role of the industry in the economic development of this country. These essays attempt to clarify the analysis and emphasize the salient features of regulation and the restructuring of the electric power industry and the organization of the firms that make up the industry.

Davis, Earl Hansford, III

431

Advanced Clean Cars Zero Emission Vehicle Regulation  

E-print Network

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

California at Davis, University of

432

Voltage regulators for self excited induction generator  

Microsoft Academic Search

When an induction machine is driven from external prime mover at a speed greater than synchronous speed, it acts as induction generator provided reactive power is supplied. This reactive current generates required magnetic field for self-excitation of induction generator (seig). The induction generator thus produced has poor voltage regulation. To get better voltage regulation the reactive current need to be

T. Chandra Sekhar; Bishnu P. Muni

2004-01-01

433

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

434

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

435

ENVIRONMENTAL REGULATIONS AND TECHNOLOGY - THE ELECTROPLATING INDUSTRY  

EPA Science Inventory

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

436

[Cosmetic colorants. Toxicology and regulation].  

PubMed

Some recent publications raised concern over a possible link between hair dye use and the incidence of bladder tumours in a Californian population. The Scientific Committee for Cosmetic Products and Non-Food Products intended for Consumers (SCCNFP) demanded the toxicological testing of all hair dyes used in Europe to exclude any risk. The EU commission initiated corresponding measures. Only safe hair dyes will be included on a positive list while all other hair dyes will be banned. The hair dye lawsone--the dyeing ingredient of henna--was evaluated by the SCCNFP as genotoxic but the BfR came to another conclusion. The regulation of both lawsone and henna remains an open question. Furthermore, some cosmetic colorants were critically discussed. The azo dyes CI 12150, CI 26100, CI 27290 and CI 20170 are allowed for use in cosmetics. On cleavage they form the carcinogenic aromatic amines o-anisidine, 4-aminoazobenzene and 2,4-xylidine, respectively. For three of these dyes the cleavage by human skin bacteria in vitro to the respective arylamine was shown experimentally. Further problems may arise from colorants used for tattoos and permanent makeup. These products up to now are not subject to legislation and there are no regulatory stipulations with respect to health safety and purity for colorants used for these purposes. PMID:15650909

Platzek, T; Krätke, R; Klein, G; Schulz, C

2005-01-01

437

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

438

Asbestos products, hazards, and regulation.  

PubMed

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

Castleman, Barry

2006-01-01

439

Regulation of immunity in bronchiectasis.  

PubMed

Bronchiectasis is a chronic, progressive lung disease where there is irreversible, abnormal dilatation of one or more bronchi, with chronic airway inflammation, associated chronic cough and sputum production, recurrent chest infections, and airflow obstruction. As such it is essentially a pathological endpoint with several underlying causes. Allergic bronchopulmonary aspergillosis (ABPA) is an important cause of bronchiectasis and aspergillus related lung disease sometimes complicates established bronchiectasis. A diagnosis of bronchiectasis is made clinically and confirmed with high-resolution computed tomography (HRCT) of the thorax. Progressive lung damage results from a 'vicious cycle' of recurrent bacterial infection and a poorly regulated inflammatory response. There appear to be two stages to the disease process: the initial insult that sets off the disease and then the ongoing, inflammatory process encompassing recurrent infection and progressive lung damage. Abnormalities in innate and adaptive immunity may predispose to bronchiectasis at both stages. Recent immunogenetic evidence suggests that there may be a link between the level of natural killer (NK) cell activation and disease susceptibility, implicating a predisposing role for innate immune mechanisms. A role for adaptive immune mechanisms is suggested by the genetic association of HLA-DR1, DQ5 with increased susceptibility to idiopathic bronchiectasis. PMID:18608925

Boyton, R J

2009-01-01

440

Regulation of Eukaryotic Flagellar Motility  

NASA Astrophysics Data System (ADS)

The central apparatus is essential for normal eukaryotic flagellar bend propagation as evidenced by the paralysis associated with mutations that prevent central pair (CP) assembly. Interactions between doublet-associated radial spokes and CP projections are thought to modulate spoke-regulated protein kinases and phosphatases on outer doublets, and these enzymes in turn modulate dynein activity. To better understand CP control mechanisms, we determined the three-dimensional structure of the Chlamydomonas reinhardtii CP complex and analyzed CP orientation during formation and propagation of flagellar bending waves. We show that a single CP microtubule, C1, is near the outermost doublet in curved regions of the flagellum, and this orientation is maintained by twists between successive principal and reverse bends. The Chlamydomonas CP is inherently twisted; twists are not induced by bend formation, and do not depend on forces or signals transmitted through spoke-central pair interactions. We hypothesize that CP orientation passively responds to bend formation, and that bend propagation drives rotation of the CP and maintains a constant CP orientation in bends, which in turn permits signal transduction between specific CP projections and specific doublet-associated dyneins through radial spokes. The central pair kinesin, Klp1, although essential for normal motility, is therefore not the motor that drives CP rotation. The CP also acts as a scaffold for enzymes that maintain normal intraflagellar ATP concentration.

Mitchell, David R.

2005-03-01

441

Regulated cell death: signaling and mechanisms.  

PubMed

Cell turnover is a fundamental feature in metazoans. Cells can die passively, as a consequence of severe damage to their structural integrity, or actively, owing to a more confined biological disruption such as DNA damage. Passive cell death is uncontrolled and often harmful to the organism. In contrast, active cell death is tightly regulated and serves to support the organism's life. Apoptosis-the primary form of regulated cell death-is relatively well defined. Necroptosis-an alternative, distinct kind of regulated cell death discovered more recently-is less well understood. Apoptosis and necroptosis can be triggered either from within the cell or by extracellular stimuli. Certain signaling components, including several death ligands and receptors, can regulate both processes. Whereas apoptosis is triggered and executed via intracellular proteases called caspases, necroptosis is suppressed by caspase activity. Here we highlight current understanding of the key signaling mechanisms that control regulated cell death. PMID:25150011

Ashkenazi, Avi; Salvesen, Guy

2014-10-11

442

Daily patterns and adaptation of the ghrelin, growth hormone and insulin-like growth factor-1 system under daytime food synchronisation in rats.  

PubMed

Daytime restricted feeding promotes the re-alignment of the food entrained oscillator (FEO). Endocrine cues which secretion is regulated by the transition of fasting and feeding cycles converge in the FEO. The present study aimed to investigate the ghrelin, growth hormone (GH) and insulin-like growth factor (IGF)-1 system because their release depends on rhythmic and nutritional factors, and the output from the system influences feeding and biochemical status. In a daily sampling approach, rats that were fed ad lib. were compared with rats on a reversed (daytime) and restricted feeding schedule by 3 weeks (dRF; food access for 2 h), also assessing the effect of acute fasting and refeeding. We undertook measurements of clock protein BMAL1 and performed somatometry of peripheral organs and determined the concentration of total, acylated and unacylated ghrelin, GH and IGF-1 in both serum and in its main synthesising organs. During dRF, BMAL1 expression was synchronised to mealtime in hypophysis and liver; rats exhibited acute hyperphagia, stomach distension with a slow emptying, a phase shift in liver mass towards the dark period and decrease in mass perigonadal white adipose tissue. Total ghrelin secretion during the 24-h period increased in the dRF group as a result of elevation of the unacylated form. By contrast, GH and IGF-1 serum concentration fell, with a modification of GH daily pattern after mealtime. In the dRF group, ghrelin content in the stomach and pituitary GH content decreased, whereas hepatic IGF-1 remained equal. The daily patterns and synthesis of these hormones had a rheostatic adaptation. The endocrine adaptive response elicited suggests that it may be associated with the regulation of metabolic, behavioural and physiological processes during the paradigm of daytime restricted feeding and associated FEO activity. PMID:24617825

Arellanes-Licea, E del C; Báez-Ruiz, A; Carranza, M E; Arámburo, C; Luna, M; Díaz-Muñoz, M

2014-05-01

443

Fetal alcohol exposure disrupts metabolic signaling in hypothalamic proopiomelanocortin neurons via a circadian mechanism in male mice.  

PubMed

Early-life ethanol feeding (ELAF) alters the metabolic function of proopiomelanocortin (POMC)-producing neurons and the circadian expression of clock regulatory genes in the hypothalamus. We investigated whether the circadian mechanisms control the action of ELAF on metabolic signaling genes in POMC neurons. Gene expression measurements of Pomc and a selected group of metabolic signaling genes, Stat3, Sirt1, Pgc1-?, and Asb4 in laser-captured microdissected POMC neurons in the hypothalamus of POMC-enhanced green fluorescent protein mice showed circadian oscillations under light/dark and constant darkness conditions. Ethanol programmed these neurons such that the adult expression of Pomc, Stat3, Sirt, and Asb4 gene transcripts became arrhythmic. In addition, ELAF dampened the circadian peak of gene expression of Bmal1, Per1, and Per2 in POMC neurons. We crossed Per2 mutant mice with transgenic POMC-enhanced green fluorescent protein mice to determine the role of circadian mechanism in ELAF-altered metabolic signaling in POMC neurons. We found that ELAF failed to alter arrhythmic expression of most circadian genes, with the exception of the Bmal1 gene and metabolic signaling regulating genes in Per2 mutant mice. Comparison of the ELAF effects on the circadian blood glucose in wild-type and Per2 mutant mice revealed that ELAF dampened the circadian peak of glucose, whereas the Per2 mutation shifted the circadian cycle and prevented the ELAF dampening of the glucose peak. These data suggest the possibility that the Per2 gene mutation may regulate the ethanol actions on Pomc and the metabolic signaling genes in POMC neurons in the hypothalamus by blocking circadian mechanisms. PMID:24797626

Agapito, Maria A; Zhang, Changqing; Murugan, Sengottuvelan; Sarkar, Dipak K

2014-07-01

444

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

445

Neurotrophin-regulated signalling pathways  

PubMed Central

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

Reichardt, Louis F

2006-01-01

446

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

447

Scyl1 Regulates Golgi Morphology  

PubMed Central

Background Membrane trafficking is a defining feature of eukaryotic cells, and is essential for the maintenance of organelle homeostasis and identity. We previously identified Scy1-like 1 (Scyl1), a member of the Scy1-like family of catalytically inactive protein kinases, as a high-affinity binding partner of COPI coats. COPI-coated vesicles control Golgi to endoplasmic reticulum trafficking and we observed that disruption of Scyl1 function leads to a decrease in trafficking of the KDEL receptor via the COPI pathway. We reasoned that if Scyl1 plays a major role in COPI trafficking its disruption could influence Golgi homeostasis. Methodology/Principal Findings We performed Scyl1 knock down in cultured cells using previously established methods and observed an alteration in Golgi morphology. Both the surface area and volume of the Golgi is increased in Scyl1-depleted cells, but the continuity and polarity of the organelle is unperturbed. At the ultrastructural level we observe a decrease in the orderly structure of the Golgi with an increase in cisternal luminal width, while the number of Golgi cisternae remains unchanged. The golgin family of proteins forms a detergent resistant network that controls Golgi homeostasis. Disruption of this protein network by knock down of the golgin p115 disrupts the Golgi localization of Scyl1. Moreover, we find that Scyl1 interacts with 58K/formiminotransferase cyclodeaminase (FTCD), a protein that is tightly associated with the cis face of the Golgi. Conclusions/Significance Our results place Scyl1 at an interface between the golgin network and COPI trafficking and demonstrate that Scyl1 is required for the maintenance of Golgi morphology. Coupled with the observation from others that Scyl1 is the gene product responsible for the neurodegenerative mouse model mdf, our results additionally implicate the regulation of COPI trafficking and Golgi homeostasis in neurodegeneration. PMID:20209057

Burman, Jonathon L.; Hamlin, Jason N. R.; McPherson, Peter S.

2010-01-01

448

Steroid regulation of sexual behavior.  

PubMed

Investigation into the hormonal control of sexual behavior has a rich and extensive history. For many researchers currently active in the field, the physiological psychologist Frank A. Beach is recognized as the modern father of the study of hormones and behavior. His publication of the seminal book Hormones and Behavior-A Survey of Interrelationships Between Endocrine Secretions and Patterns of Overt Response, published in 1948, was a compilation of the previous 20 years of research establishing that gonadal secretions acted in the brain and modulated behavior. The question of precisely how hormones can alter brain functioning in a coordinated fashion and profoundly influence the patterns of behavioral responsiveness remains unanswered. As with many research areas, application of new techniques and approaches to the problem reveals additional layers of complexity and previously unimagined relationships between hormones, brain, and behavior. In addition, with the increasing understanding that the brain is a target organ for steroids, the implications of the ramifications of this steroid sensitivity have broadened. The hormonal regulation of sexual behavior is not an isolated aspect of steroid action in the brain; rather, it is one component of a host of physiological responses influenced by steroids. These include such diverse responses as anxiety, aggression, feeding, and learning and memory. An appreciation of the diverse effects of steroids has emerged from studies on sexual behavior, and a mutually beneficial relationship between this and other aspects of behavioral neuroscience has flourished and endured. As with all of neuroscience, this research area has been dynamic and progressive and has additionally benefited from a long history of comparative and integrative approaches to animal behavior. PMID:18406766

McCarthy, M M; Albrecht, E D

1996-11-01

449

Neurovegetative regulation and cardiovascular diseases.  

PubMed

Heart period and arterial pressure short term variabilities contain rhythmic oscillations which might provide information on neural mechanisms regulating cardiovascular function. Continuous electrocardiographic and/or arterial pressure signals, after appropriate analogue to digital conversion, furnish the time series which constitute the basis for spectral analysis of their variabilities. Under stationary conditions, this methodology can be utilized to assess both total variability and the power and center frequency of each rhythmic component. Human physiological and animal studies support the hypothesis that the low frequency (LF) component, around 0.1 Hz, is a marker of sympathetic modulation of both R-R and arterial pressure variabilities, while the high frequency (HF) component, around 0.25 Hz, is a marker of vagal modulation of R-R variability. LF/HF ratio of R-R variability is a marker of sympatho-vagal balance. Spectral components when assessed for a 24-hour period evidence marked circadian rhythmicity with sympathetic predominance during the day and vagal predominance at night. Various pathophysiological conditions including arterial hypertension, ischemic heart disease, cardiac transplantation, congestive heart failure, Chagas' disease and diabetic neuropathy have been explored with this methodology, and a new quantitative evaluation of the alterations in sympatho-vagal balance which seem to characterize these abnormal states has been obtained. The study of cardiovascular rhythmicity, i.e. an analysis performed in the frequency domain, although based on indirect spectral markers, seems to offer a new clinical tool for the exploration of cardiovascular neural control in health and disease. PMID:1840813

Malliani, A; Pagani, M; Lombardi, F

1991-01-01

450

Heregulin regulates Prolactinoma Gene Expression  

PubMed Central

To investigate the role of p185her2/neu / ErbB3 signaling in pituitary tumor function we examined these receptors in human prolactinomas. Immunofluorescent p185her2/neu was detected in almost all (7/8), and ErbB3 expression in a subset (4/8) of tumors (7 adenomas and one carcinoma). Quantitative PCR also showed abundant ErbB3 mRNA in tumor specimens derived from a rarely encountered prolactin-cell carcinoma. Activation of p185c-neu / ErbB3 signaling with heregulin, the ErbB3 ligand, in rat lactosomatotroph (GH4C1) tumor cells specifically induced prolactin (PRL) mRNA expression ~ 5-fold and PRL secretion ~ 4-fold, while growth hormone (GH) expression was unchanged. Heregulin (6 nM) induced tyrosine phosphorylation and ErbB3 and p185c-neu heterodimerization, with subsequent activation of intracellular ERK and Akt. The Akt signal was specific to ErbB3 activation by heregulin, and was not observed in response to EGF activation of EGFR. Gefitinib, the tyrosine kinase inhibitor, suppressed heregulin-mediated p185c-neu / ErbB3 signaling to PRL. Heregulin induction of PRL was also abrogated by transfecting cells with siRNA directed against ErbB3. Pharmacological inhibition of heregulin-induced PI3K / Akt (with LY294002) and ERK (with U0126) signaling, as well as siRNA-mediated MAPK1 downregulation showed ERK signaling as the primary transducer of heregulin signaling to PRL. These results demonstrate ErbB3 expression in human prolactinomas and a novel ErbB3-mediated mechanism for PRL regulation in experimental lactotroph tumors. Targeted inhibition of upregulated p185c-neu / ErbB3 activity could be useful for the treatment of aggressive prolactinomas resistant to conventional therapy. PMID:19401448

Vlotides, George; Cooper, Odelia; Chen, Yen-Hao; Ren, Song-Guang; Greenman, Yona; Melmed, Shlomo

2009-01-01

451

Harnessing science for environmental regulation  

SciTech Connect

An introductory chapter by Graham frames the issues to be discussed; then the following three chapters describe the formation and character of three organizations. These chapters are written by authors who have each had an active management role in the organization they are writing about: Terry F. Yosie, now at the American Petroleum Institute, who staffed the SAB (Science Advisory Board) while he was at EPA; Robert A. Neal, who headed CIIT (Chemical Industry Institute of Toxicology) before leaving for a position at Vanderbilt University; and Thomas P. Grumbly, former executive director of HEI (Health Effects Institute) now president of Clean Sites, Inc. While these chapters are well written and make a vital contribution to the overall development of the book's themes, the most valuable and enjoyable parts of the book are the succeeding five chapters, which present case studies dealing with EPA's regulatory efforts on unleaded gasoline, perchloroethylene, formaldehyde, nitrates in drinking water, and carbon monoxide. Each of these case studies, nominally historical accounts of how one or more of these (three) organizations participated in the regulatory controversy, offer insight into the broader issues of dealing with, and incorporating into regulations scientific information that has high uncertainty. One of the richest aspects of the five case studies is the extensive use of referenced interviews with identified participants from all aspects of the regulatory process. This material illuminates the motivation, emotions, and goals of the different players, helping the reader to understand their positions and other issues, such as why industry pursues, and EPA and the environmental movement appear to resist, good science; what underlies EPA's preferences for one regulatory option over another; and why scientists are histant to give yes-or-no answers in accord with the real time needs of the regulatory agency.

Graham, J.D. (ed.)

1991-01-01

452

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

453

77 FR 4714 - Self-Regulation of Class II Gaming  

Federal Register 2010, 2011, 2012, 2013

...to a tribe's regulation of class II gaming activity and more...518--Self-Regulation of Class II Gaming. Tribal consultations...to a tribe's regulation of class II gaming activity; and...self-regulation regulation discourages participation because the burdens...

2012-01-31

454

The psychology of emotion regulation: An integrative review  

Microsoft Academic Search

The present article reviews modern research on the psychology of emotion regulation. Emotion regulation determines the offset of emotional responding and is thus distinct from emotional sensitivity, which determines the onset of emotional responding. Among the most viable categories for classifying emotion-regulation strategies are the targets and functions of emotion regulation. The emotion-generating systems that are targeted in emotion regulation

Sander L. Koole

2009-01-01

455

Saccharomyces genome database provides new regulation data.  

PubMed

The Saccharomyces Genome Database (SGD; http://www.yeastgenome.org) is the community resource for genomic, gene and protein information about the budding yeast Saccharomyces cerevisiae, containing a variety of functional information about each yeast gene and gene product. We have recently added regulatory information to SGD and present it on a new tabbed section of the Locus Summary entitled 'Regulation'. We are compiling transcriptional regulator-target gene relationships, which are curated from the literature at SGD or imported, with permission, from the YEASTRACT database. For nearly every S. cerevisiae gene, the Regulation page displays a table of annotations showing the regulators of that gene, and a graphical visualization of its regulatory network. For genes whose products act as transcription factors, the Regulation page also shows a table of their target genes, accompanied by a Gene Ontology enrichment analysis of the biological processes in which those genes participate. We additionally synthesize information from the literature for each transcription factor in a free-text Regulation Summary, and provide other information relevant to its regulatory function, such as DNA binding site motifs and protein domains. All of the regulation data are available for querying, analysis and download via YeastMine, the InterMine-based data warehouse system in use at SGD. PMID:24265222

Costanzo, Maria C; Engel, Stacia R; Wong, Edith D; Lloyd, Paul; Karra, Kalpana; Chan, Esther T; Weng, Shuai; Paskov, Kelley M; Roe, Greg R; Binkley, Gail; Hitz, Benjamin C; Cherry, J Michael

2014-01-01

456

Patterns of emotion regulation and psychopathology  

PubMed Central

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

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

2011-01-01

457

Saccharomyces genome database provides new regulation data  

PubMed Central

The Saccharomyces Genome Database (SGD; http://www.yeastgenome.org) is the community resource for genomic, gene and protein information about the budding yeast Saccharomyces cerevisiae, containing a variety of functional information about each yeast gene and gene product. We have recently added regulatory information to SGD and present it on a new tabbed section of the Locus Summary entitled ‘Regulation’. We are compiling transcriptional regulator–target gene relationships, which are curated from the literature at SGD or imported, with permission, from the YEASTRACT database. For nearly every S. cerevisiae gene, the Regulation page displays a table of annotations showing the regulators of that gene, and a graphical visualization of its regulatory network. For genes whose products act as transcription factors, the Regulation page also shows a table of their target genes, accompanied by a Gene Ontology enrichment analysis of the biological processes in which those genes participate. We additionally synthesize information from the literature for each transcription factor in a free-text Regulation Summary, and provide other information relevant to its regulatory function, such as DNA binding site motifs and protein domains. All of the regulation data are available for querying, analysis and download via YeastMine, the InterMine-based data warehouse system in use at SGD. PMID:24265222

Costanzo, Maria C.; Engel, Stacia R.; Wong, Edith D.; Lloyd, Paul; Karra, Kalpana; Chan, Esther T.; Weng, Shuai; Paskov, Kelley M.; Roe, Greg R.; Binkley, Gail; Hitz, Benjamin C.; Cherry, J. Michael

2014-01-01

458

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

459

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

460

Dental hygiene regulation: a global perspective.  

PubMed

Occupational regulation of health personnel is important to professional associations and their members, the public that relies on their services and the regulatory agencies responsible for their conduct. There is increasing interest in ensuring that dental hygiene regulation fosters the continuing evolution of the profession and its contribution to oral health. The keynote address for the 2007 Regulatory Forum on Dental Hygiene, this paper discusses the rationale for and issues pertaining to occupational regulation, outlines the evolvement of dental hygiene and identifies regulatory options for the profession. Professional regulation exists to ensure public safety, health and welfare. However, negative political-economic side effects coupled with environmental pressures have resulted in increased scrutiny for health professionals. One such profession is dental hygiene. Its evolution has been dramatic, in particular over the past few decades, as illustrated by its rapidly increasing numbers and broader distribution globally, gradual shift to the baccalaureate as the entry-level educational requirement and increase in postgraduate programs and expanding scope of practice and increased professional autonomy. Regulatory changes have been more gradual. Regulation is mandatory for the vast majority of dental hygienists. Of the options available, the practice act - the most rigorous type, is predominant. Globally, regulation tends to be administered directly by the government (n = 9 countries) more so than indirectly through a dental board (n = 4) or self-regulation (n = 3). Whether regulated directly or indirectly, dental hygienists increasingly are seeking a greater role in shaping their professional future. Self-regulation, its responsibilities, misperceptions and challenges, is examined as an option. PMID:18768027

Johnson, P M

2008-08-01

461

Ubiquitin makes its mark on immune regulation  

PubMed Central

Ubiquitination, the covalent attachment of ubiquitin molecules to proteins, is emerging as a widely utilized mechanism for rapidly regulating cell signaling. Recent studies indicate that ubiquitination plays potent roles in regulating a variety of signals in both innate and adaptive immune cells. Here, we will review recent studies of ubiquitin ligases, ubiquitin chain linkages and ubiquitin binding proteins that highlight the diversity and specificity of ubiquitin dependent functions in immune cells. We will also review studies that shed light on how ubiquitination signals are integrated in cell-type specific fashion to regulate the immune system in vivo. PMID:21168777

Malynn, Barbara A.; Ma, Averil

2011-01-01

462

Emotion regulation strategies in preschool children.  

PubMed

This study investigated the development of emotion regulation strategies as reflected in the narratives of children between the ages of 3 and 6 years. An experimental procedure based on story completion tasks was devised to elicit the emotion-related narratives of 69 preschool children. Coding of the narratives led to the observation of different emotion regulation strategies: Behavioural strategies, social support, and cognitive reappraisal. Several significant gender and age differences were identified in the use of these strategies. In addition, verbal skills, non-verbal intelligence, and emotion comprehension were found to be associated with use of the observed emotion regulation strategies, although only at specific ages. PMID:25040163

Sala, Maria Nives; Pons, Francisco; Molina, Paola

2014-11-01

463

Fluorescent probes for monitoring regulated secretion  

PubMed Central

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

Li, Wen-hong; Li, Daliang

2013-01-01

464

Emotion regulation: influences of attachment relationships.  

PubMed

Emotion regulation and quality of attachment are closely linked. It has been proposed here that one influence on individual differences in emotion regulation may be a child's attachment history. Individuals characterized by the flexible ability to accept and integrate both positive and negative emotions are generally securely attached; on the other hand, individuals characterized by either limited or heightened negative affect are more likely to be insecurely attached. While acknowledging the role of infant temperament, I have focused on the role of social factors in examining the link between emotion regulation and attachment. The approach to emotion regulation taken here--that emotion regulation is adaptive in helping a child attain her goals--is esentially a functionalist approach (Bretherton et al., 1986; Campos et al., 1983), consistent with earlier views of emotions as important regulators of interpersonal relationships (Charlesworth, 1982; Izard, 1977). It has been proposed that patterns of emotion regulation serve an important function for the infant: the function of maintaining the relationship with the attachment figure. Emotion regulation has been described as serving this function in two ways. First, the function of maintaining the relationship is thought to be served when infant emotion regulation contributes to the infant's more generalized regulation of the attachment system in response to experiences with the caregiver. Infants who have experienced rejection (insecure/avoidant infants) are thought to minimize negative affect in order to avoid the risk of further rejection. Infants whose mothers have been relatively unavailable or inconsistently available (insecure/ambivalent infants) are thought to maximize negative affect in order to increase the likelihood of gaining the attention of a frequently unavailable caregiver. Both these patterns of emotion regulation help ensure that the child will remain close to the parent and thereby be protected. Second, the function of maintaining the attachment relationship is thought to be served when the infant signals to the parent that she will cooperate in helping maintain the parent's own state of mind in relation to attachment. The minimizing of negative affect of the avoidant infant signals that the infant will not seek caregiving that would interfere with the parent's dismissal of attachment. The heightened negative emotionality of the ambivalent infant signals to the parent that the infant needs her and thus helps maintain a state of mind in which attachment is emphasized. The approach to emotion regulation presented here is congruent with much work examining the socialization of emotions (Lewis & Saarni, 1985; Thompson, 1990). PMID:7984163

Cassidy, J

1994-01-01

465

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

466

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

467

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