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Sample records for level isovolumetric regulation

  1. Vena Cava Responsiveness to Controlled Isovolumetric Respiratory Efforts.

    Science.gov (United States)

    Folino, Anna; Benzo, Marco; Pasquero, Paolo; Laguzzi, Andrea; Mesin, Luca; Messere, Alessandro; Porta, Massimo; Roatta, Silvestro

    2017-10-01

    Respirophasic variation of inferior vena cava (IVC) size is affected by large variability with spontaneous breathing. This study aims at characterizing the dependence of IVC size on controlled changes in intrathoracic pressure. Ten healthy subjects, in supine position, performed controlled isovolumetric respiratory efforts at functional residual capacity, attaining positive (5, 10, and 15 mmHg) and negative (-5, -10, and -15 mmHg) alveolar pressure levels. The isovolumetric constraint implies that equivalent changes are exhibited by alveolar and intrathoracic pressures during respiratory tasks. The IVC cross-sectional area equal to 2.88 ± 0.43 cm 2 at baseline (alveolar pressure = 0 mmHg) was progressively decreased by both expiratory and inspiratory efforts of increasing strength, with diaphragmatic efforts producing larger effects than thoracic ones: -55 ± 15% decrease, at +15 mmHg of alveolar pressure (P < .01), -80 ± 33 ± 12% at -15 mmHg diaphragmatic (P < .01), -33 ± 12% at -15 mmHg thoracic. Significant IVC changes in size (P < .01) and pulsatility (P < .05), along with non significant reduction in the response to respiratory efforts, were also observed during the first 30 minutes of supine rest, detecting an increase in vascular filling, and taking place after switching from the standing to the supine position. This study quantified the dependence of the IVC cross-sectional area on controlled intrathoracic pressure changes and evidenced the stronger influence of diaphragmatic over thoracic activity. Individual variability in thoracic/diaphragmatic respiratory pattern should be considered in the interpretation of the respirophasic modulations of IVC size. © 2017 by the American Institute of Ultrasound in Medicine.

  2. Elasticity-based determination of isovolumetric phases in the human heart

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    Braun Jürgen

    2010-10-01

    Full Text Available Abstract Background/Motivation To directly determine isovolumetric cardiac time intervals by magnetic resonance elastography (MRE using the magnitude of the complex signal for deducing morphological information combined with the phase of the complex signal for tension-relaxation measurements. Methods Thirty-five healthy volunteers and 11 patients with relaxation abnormalities were subjected to transthoracic wave stimulation using vibrations of approximately 25 Hz. A k-space-segmented, ECG-gated gradient-recalled echo steady-state sequence with a 500-Hz bipolar motion-encoding gradient was used for acquiring a series of 360 complex images of a short-axis view of the heart at a frame rate of less than 5.2 ms. Magnitude images were employed for measuring the cross-sectional area of the left ventricle, while phase images were used for analyzing the amplitudes of the externally induced waves. The delay between the decrease in amplitude and onset of ventricular contraction was determined in all subjects and assigned to the time of isovolumetric tension. Conversely, the delay between the increase in wave amplitude and ventricular dilatation was used for measuring the time of isovolumetric elasticity relaxation. Results Wave amplitudes decreased during systole and increased during diastole. The variation in wave amplitude occurred ahead of morphological changes. In healthy volunteers the time of isovolumetric elasticity relaxation was 75 ± 31 ms, which is significantly shorter than the time of isovolumetric tension of 136 ± 36 ms (P n = 11 isovolumetric elasticity relaxation was significantly prolonged, with 133 ± 57 ms (P P = 0.053. Conclusion The complex MRE signal conveys complementary information on cardiac morphology and elasticity, which can be combined for directly measuring isovolumetric tension and elasticity relaxation in the human heart.

  3. Low-level radioactive waste management: French and foreign regulations

    International Nuclear Information System (INIS)

    Coulon, R.

    1991-01-01

    This paper describes radioactive waste management regulations applied in USA, CANADA, SCANDINAVIA and FRANCE. For low level radioactive wastes, it is necessary to adapt waste management regulations which were firt definite for high level radioactive wastes. So the exemption concept is a simplification method of regulations applied to low radiation sources

  4. Climatic impact on isovolumetric weathering of a coarse-grained schist in the northern Piedmont Province of the central Atlantic states

    Science.gov (United States)

    Cleaves, E.T.

    1993-01-01

    The possible impact of periglacial climates on the rate of chemical weathering of a coarse-grained plagioclase-muscovite-quartz schist has been determined for a small watershed near Baltimore, Maryland. The isovolumetric chemical weathering model formulated from the geochemical mass balance study of the watershed shows that the weathering front advances at a velocity of 9.1 m/m.y., if the modern environmental parameters remain the same back through time. However, recent surficial geological mapping demonstrates that periglacial climates have impacted the area. Such an impact significantly affects two key chemical weathering parameters, the concentration of CO2 in the soil and groundwater moving past the weathering front. Depending upon the assumptions used in the model, the rate of saprolitization varies from 2.2 to 5.3 m/m.y. The possible impact of periglacial processes suggested by the chemical weathering rates indicates a need to reconsider theories of landscape evolution as they apply to the northern Piedmont Province of the mid-Atlantic states. I suggest that from the Late Miocene to the present that the major rivers have become incised in their present locations; this incision has enhanced groundwater circulation and chemical weathering such that crystalline rocks beneath interfluvial areas remain mantled by saprolite; and the saprolite mantle has been partially stripped as periglacial conditions alternate with humid-temperate conditions. ?? 1993.

  5. Liquid hydrogen transfer pipes and level regulation systems

    International Nuclear Information System (INIS)

    Marquet, M.; Prugne, P.; Roubeau, P.

    1961-01-01

    Describes: 1) Transfer pipes - Plunging rods in liquid hydrogen Dewars; transfer pipes: knee-joint system for quick and accurate positioning of plunging Dewar rods; system's rods: combined valve and rod; valves are activated either by a bulb pressure or by a solenoid automatically or hand controlled. The latter allows intermittent filling. 2) Level regulating systems: Level bulbs: accurate to 1 or 4 m; maximum and minimum level bulbs: automatic control of the liquid hydrogen valve. (author) [fr

  6. Calcium regulates caveolin-1 expression at the transcriptional level

    International Nuclear Information System (INIS)

    Yang, Xiao-Yan; Huang, Cheng-Cheng; Kan, Qi-Ming; Li, Yan; Liu, Dan; Zhang, Xue-Cheng; Sato, Toshinori; Yamagata, Sadako; Yamagata, Tatsuya

    2012-01-01

    Highlights: ► Caveolin-1 expression is regulated by calcium signaling at the transcriptional level. ► An inhibitor of or siRNA to L-type calcium channel suppressed caveolin-1 expression. ► Cyclosporine A or an NFAT inhibitor markedly reduced caveolin-1 expression. ► Caveolin-1 regulation by calcium signaling is observed in several mouse cell lines. -- Abstract: Caveolin-1, an indispensable component of caveolae serving as a transformation suppressor protein, is highly expressed in poorly metastatic mouse osteosarcoma FBJ-S1 cells while highly metastatic FBJ-LL cells express low levels of caveolin-1. Calcium concentration is higher in FBJ-S1 cells than in FBJ-LL cells; therefore, we investigated the possibility that calcium signaling positively regulates caveolin-1 in mouse FBJ-S1 cells. When cells were treated with the calcium channel blocker nifedipine, cyclosporin A (a calcineurin inhibitor), or INCA-6 (a nuclear factor of activated T-cells [NFAT] inhibitor), caveolin-1 expression at the mRNA and protein levels decreased. RNA silencing of voltage-dependent L-type calcium channel subunit alpha-1C resulted in suppression of caveolin-1 expression. This novel caveolin-1 regulation pathway was also identified in mouse NIH 3T3 cells and Lewis lung carcinoma cells. These results indicate that caveolin-1 is positively regulated at the transcriptional level through a novel calcium signaling pathway mediated by L-type calcium channel/Ca 2+ /calcineurin/NFAT.

  7. Regulation of glycolysis and level of the Crassulacean acid metabolism.

    Science.gov (United States)

    Pierre, J N; Queiroz, O

    1979-01-01

    Glycolysis shows different patterns of operation and different control steps, depending on whether the level of Crassulacean acid metabolism (CAM) is low or high in the leaves of Kalanchoe blossfeldiana v.Poelln., when subjected to appropriate photoperiodic treatments: at a low level of CAM operation all the enzymes of glycolysis and phosphoenol pyruvate (PEP) carboxylase present a 12 h rhythm of capacity, resulting from the superposition of two 24h rhythms out of phase; phosphofructokinase appears to be the main regulation step; attainment of high CAM level involves (1) an increase in the peak of capacity occurring during the night of all the glycolytic enzymes, thus achieving an over-all 24h rhythm, in strict allometric coherence with the increase in PEP carboxylase capacity, (2) the establishment of different phase relationships between the rhythms of enzyme capacity, and (3) the control of three enzymic steps (phosphofructokinase, the group 3-P-glyceraldehyde dehydrogenase - 3-P-glycerate kinase, and PEP carboxylase). Results show that the hypothesis of allosteric regulation of phosphofructokinase (by PEP) and PEP carboxylase (by malate and glucose-6-P) cannot provide a complete explanation for the temporal organization of glycolysis and that changes in the phase relationships between the rhythms of enzyme capacity along the pathway and a strict correlation between the level of PEP carboxylase capacity and the levels of capacity of the glycolytic enzymes are important components of the regulation of glycolysis in relation to CAM.

  8. Regulation Concepts for Clearance Level of Radionuclide in Solid Materials

    International Nuclear Information System (INIS)

    Nanang Triagung Edi Hermawan

    2008-01-01

    Practices of nuclear energy have expanded in some fields such as researches and development, educations, agricultures, medicines and industries. Every practice beside give much benefit, could generate residue or waste. Radioactive waste needs management to ensure the safety of workers, member of the public, and for the eternal of environment. The product of radioactive waste management, in generally, is some containment of radionuclide concentration in solid matrix material after immobilization or conditioning process. Some kind of processed radioactive wastes with short half live then decay faster to stabile condition. The decay will reach clearance level in sometimes, so from the radiation protection views is harmless. This materials above didn’t need control and must be cleared from all determinate and regulation aspects of radioactive material practices. There is clearance for harmless material off course will be simplify management task and efficiency of money. So the regulation about clearance levels will be important as law basic for technical practices in field. (author)

  9. Application of EPA regulations to low-level radioactive waste

    International Nuclear Information System (INIS)

    Bowerman, B.S.; Piciulo, P.L.

    1985-01-01

    The survey reported here was conducted with the intent of identifying categories of low-level radioactive wastes which would be classified under EPA regulations 40 CFR Part 261 as hazardous due to the chemical properties of the waste. Three waste types are identified under these criteria as potential radioactive mixed wastes: wastes containing organic liquids; wastes containing lead metal; and wastes containing chromium. The survey also indicated that certain wastes, specific to particular generators, may also be radioactive mixed wastes. Ultimately, the responsibility for determining whether a facility's wastes are mixed wastes rest with the generator. However, the uncertainties as to which regulations are applicable, and the fact that no legal definition of mixed wastes exists, make such a determination difficult. In addition to identifying mixed wastes, appropriate methods for the management of mixed wastes must be defined. In an ongoing study, BNL is evaluating options for the management of mixed wastes. These options will include segregation, substitution, and treatments to reduce or eliminate chemical hazards associated with the wastes listed above. The impacts of the EPA regulations governing hazardous wastes on radioactive mixed waste cannot be assessed in detail until the applicability of these regulations is agreed upon. This issue is still being discussed by EPA and NRC and should be resolved in the near future. Areas of waste management which may affect generators of mixed wastes include: monitoring/tracking of wastes before shipment; chemical testing of wastes; permits for treatment of storage of wastes; and additional packaging requirements. 3 refs., 1 fig., 2 tabs

  10. Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels.

    Science.gov (United States)

    Zhang, Ren

    2012-08-10

    The metabolic syndrome, a common disorder including glucose intolerance and dyslipidemia, poses a major public health issue. Patients with high blood lipids, such as triglycerides, are at high risk in developing atherosclerotic cardiovascular diseases. To identify genes involved in metabolism, we performed RNA-seq experiments on the liver and fat in mice treated with a high-fat diet or fasting, and identified Gm6484 (named Lipasin) as a novel nutritionally regulated gene. Human LIPASIN is liver specific, while the mouse one is enriched in the liver and fat, including both brown and white adipose tissues. Obesity increases liver Lipasin, whereas fasting reduces its expression in fat. ANGPTL3 (Angiopoietin-like 3) and ANGPTL4 are critical regulators of blood lipids. LIPASIN shares homology with ANGPTL3's N-terminal domain that is needed for lipid regulation, and with ANGPTL4's N-terminal segment that mediates lipoprotein lipase (LPL) binding. Lipasin overexpression by adenoviruses in mice increases serum triglyceride levels, and a recombinant Lipasin inhibits LPL activity. Therefore, a potential mechanism for Lipasin-mediated triglyceride elevation is through reduced triglyceride clearance by LPL inhibition. Lipasin is thus a novel nutritionally-regulated liver-enriched factor that plays a role in lipid metabolism. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Study on the development of safety regulations for geological disposal of high-level radioactive waste

    International Nuclear Information System (INIS)

    Wei Fangxin

    2012-01-01

    The development of regulations under Regulations on Safety Management of Radioactive Waste has become necessary as the issuance of it. The regulations related to geological disposal of high-level radioactive waste can promote the progress of research and development on geological disposal of high-level radioactive waste in China. This paper has present suggestions on development of regulations on geological disposal of high-level radioactive waste by analyzing development of safety regulations on geological disposal of high-level radioactive waste in foreign countries and problems occurred in China and discussed important issues related to the development of safety regulations on geological disposal of high-level radioactive waste. (author)

  12. Circulating Irisin Levels Are Not Regulated by Nutritional Status, Obesity, or Leptin Levels in Rodents.

    Science.gov (United States)

    Quiñones, Mar; Folgueira, Cintia; Sánchez-Rebordelo, Estrella; Al-Massadi, Omar

    2015-01-01

    Irisin is a cleaved and secreted fragment of fibronectin type III domain containing 5 (FNDC5) that is mainly released by skeletal muscle and was proposed to mediate the beneficial effects of exercise on metabolism. In the present study we aim to investigate the regulation of the circulating levels of irisin in obese animal models (diet-induced obese (DIO) rats and leptin-deficient (ob/ob) mice), as well as the influence of nutritional status and leptin. Irisin levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA) and Radioimmunoassay (RIA). Serum irisin levels remained unaltered in DIO rats and ob/ob mice. Moreover, its circulating levels were also unaffected by fasting, leptin deficiency, and exogenous leptin administration in rodents. In spite of these negative results we find a negative correlation between irisin and insulin in DIO animals and a positive correlation between irisin and glucose under short-term changes in nutritional status. Our findings indicate that serum irisin levels are not modulated by different physiological settings associated to alterations in energy homeostasis. These results suggest that in rodents circulating levels of irisin are not involved in the pathophysiology of obesity and could be unrelated to metabolic status; however, further studies should clarify its precise role in states of glucose homeostasis imbalance.

  13. Circulating Irisin Levels Are Not Regulated by Nutritional Status, Obesity, or Leptin Levels in Rodents

    Directory of Open Access Journals (Sweden)

    Mar Quiñones

    2015-01-01

    Full Text Available Irisin is a cleaved and secreted fragment of fibronectin type III domain containing 5 (FNDC5 that is mainly released by skeletal muscle and was proposed to mediate the beneficial effects of exercise on metabolism. In the present study we aim to investigate the regulation of the circulating levels of irisin in obese animal models (diet-induced obese (DIO rats and leptin-deficient (ob/ob mice, as well as the influence of nutritional status and leptin. Irisin levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA and Radioimmunoassay (RIA. Serum irisin levels remained unaltered in DIO rats and ob/ob mice. Moreover, its circulating levels were also unaffected by fasting, leptin deficiency, and exogenous leptin administration in rodents. In spite of these negative results we find a negative correlation between irisin and insulin in DIO animals and a positive correlation between irisin and glucose under short-term changes in nutritional status. Our findings indicate that serum irisin levels are not modulated by different physiological settings associated to alterations in energy homeostasis. These results suggest that in rodents circulating levels of irisin are not involved in the pathophysiology of obesity and could be unrelated to metabolic status; however, further studies should clarify its precise role in states of glucose homeostasis imbalance.

  14. A NEW APPROACH TO FINANCIAL REGULATION AT THE EUROPEAN LEVEL

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    Ioana Laura VALEANU

    2015-12-01

    Full Text Available With the recent financial and economic crisis onset, a fragility of the financial system became apparent, under the form of a series of vulnerabilities and failures with a strong destabilizing impact on the economy. In this context, a new approach to financial stability has outlined itself, pleading for a more extensive financial regulation and macro-prudential supervision, complementary to the micro-prudential one. The objectives of this article are to highlight the context and need for a new financial regulatory framework and underline the main problems of the banking system the new European regulations addresses.

  15. Design of an optimal automatic regulator for regulating the power levels of a nuclear reactor in a wind power range

    International Nuclear Information System (INIS)

    Noori Khajavi, M.; Menhaj, M.B.; Ghofrani, M.B.

    2000-01-01

    Nuclear power reactors are, in nature nonlinear and time varying. These characteristics must be considered, if large power variations occur in their working regime. In this paper a robust optimal self-tuning regulator for regulating the power of a nuclear reactor has been designed and simulated. The proposed controller is capable of regulating power levels in a wide power range (10% to 100% power levels). The controller achieves a fast and good transient response. The simulation results show that the proposed controller outperforms the fixed optimal control recently cited in the literature for nuclear power plants

  16. Leucine supplementation protects from insulin resistance by regulating adiposity levels.

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    Elke Binder

    Full Text Available BACKGROUND: Leucine supplementation might have therapeutic potential in preventing diet-induced obesity and improving insulin sensitivity. However, the underlying mechanisms are at present unclear. Additionally, it is unclear whether leucine supplementation might be equally efficacious once obesity has developed. METHODOLOGY/PRINCIPAL FINDINGS: Male C57BL/6J mice were fed chow or a high-fat diet (HFD, supplemented or not with leucine for 17 weeks. Another group of HFD-fed mice (HFD-pairfat group was food restricted in order to reach an adiposity level comparable to that of HFD-Leu mice. Finally, a third group of mice was exposed to HFD for 12 weeks before being chronically supplemented with leucine. Leucine supplementation in HFD-fed mice decreased body weight and fat mass by increasing energy expenditure, fatty acid oxidation and locomotor activity in vivo. The decreased adiposity in HFD-Leu mice was associated with increased expression of uncoupling protein 3 (UCP-3 in the brown adipose tissue, better insulin sensitivity, increased intestinal gluconeogenesis and preservation of islets of Langerhans histomorphology and function. HFD-pairfat mice had a comparable improvement in insulin sensitivity, without changes in islets physiology or intestinal gluconeogenesis. Remarkably, both HFD-Leu and HFD-pairfat mice had decreased hepatic lipid content, which likely helped improve insulin sensitivity. In contrast, when leucine was supplemented to already obese animals, no changes in body weight, body composition or glucose metabolism were observed. CONCLUSIONS/SIGNIFICANCE: These findings suggest that leucine improves insulin sensitivity in HFD-fed mice by primarily decreasing adiposity, rather than directly acting on peripheral target organs. However, beneficial effects of leucine on intestinal gluconeogenesis and islets of Langerhans's physiology might help prevent type 2 diabetes development. Differently, metabolic benefit of leucine supplementation

  17. Insulin signaling regulates fatty acid catabolism at the level of CoA activation.

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    Xiaojun Xu

    2012-01-01

    Full Text Available The insulin/IGF signaling pathway is a highly conserved regulator of metabolism in flies and mammals, regulating multiple physiological functions including lipid metabolism. Although insulin signaling is known to regulate the activity of a number of enzymes in metabolic pathways, a comprehensive understanding of how the insulin signaling pathway regulates metabolic pathways is still lacking. Accepted knowledge suggests the key regulated step in triglyceride (TAG catabolism is the release of fatty acids from TAG via the action of lipases. We show here that an additional, important regulated step is the activation of fatty acids for beta-oxidation via Acyl Co-A synthetases (ACS. We identify pudgy as an ACS that is transcriptionally regulated by direct FOXO action in Drosophila. Increasing or reducing pudgy expression in vivo causes a decrease or increase in organismal TAG levels respectively, indicating that pudgy expression levels are important for proper lipid homeostasis. We show that multiple ACSs are also transcriptionally regulated by insulin signaling in mammalian cells. In sum, we identify fatty acid activation onto CoA as an important, regulated step in triglyceride catabolism, and we identify a mechanistic link through which insulin regulates lipid homeostasis.

  18. Self-regulation of learning and performance level of elite youth soccer players

    NARCIS (Netherlands)

    Marije Elferink-Gemser; G. Pepping; G. Jordet; C. Visscher; T. Toering

    2012-01-01

    In learning and development, self-regulation can be described as the extent to which individuals are metacognitively, motivationally, and behaviourally proactive participants in their learning process (Zimmerman, 1989, 2006). We examined the relationship between self-regulation and performance level

  19. Self-regulation and performance level of elite and non-elite youth soccer players

    NARCIS (Netherlands)

    Toering, T. T.; Elferink-Gemser, M. T.; Jordet, G.; Visscher, C.

    2009-01-01

    In learning and development, self-regulation can be described as the extent to which individuals are metacognitively, motivationally, and behaviourally proactive participants in their learning process (Zimmerman, 1989, 2006). We examined the relationship between self-regulation and performance level

  20. Grass Carp Follisatin: Molecular Cloning, Functional Characterization, Dopamine D1 Regulation at Pituitary Level, and Implication in Growth Hormone Regulation

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    Roger S. K. Fung

    2017-08-01

    Full Text Available Activin is involved in pituitary hormone regulation and its pituitary actions can be nullified by local production of its binding protein follistatin. In our recent study with grass carp, local release of growth hormone (GH was shown to induce activin expression at pituitary level, which in turn could exert an intrapituitary feedback to inhibit GH synthesis and secretion. To further examine the activin/follistatin system in the carp pituitary, grass carp follistatin was cloned and confirmed to be single-copy gene widely expressed at tissue level. At the pituitary level, follistatin signals could be located in carp somatotrophs, gonadotrophs, and lactotrophs. Functional expression also revealed that carp follistatin was effective in neutralizing activin’s action in stimulating target promoter with activin-responsive elements. In grass carp pituitary cells, follistatin co-treatment was found to revert activin inhibition on GH mRNA expression. Meanwhile, follistatin mRNA levels could be up-regulated by local production of activin but the opposite was true for dopaminergic activation with dopamine (DA or its agonist apomorphine. Since GH stimulation by DA via pituitary D1 receptor is well-documented in fish models, the receptor specificity for follistatin regulation by DA was also investigated. Using a pharmacological approach, the inhibitory effect of DA on follistatin gene expression was confirmed to be mediated by pituitary D1 but not D2 receptor. Furthermore, activation of D1 receptor by the D1-specific agonist SKF77434 was also effective in blocking follistatin mRNA expression induced by activin and GH treatment both in carp pituitary cells as well as in carp somatotrophs enriched by density gradient centrifugation. These results, as a whole, suggest that activin can interact with dopaminergic input from the hypothalamus to regulate follistatin expression in carp pituitary, which may contribute to GH regulation by activin/follistatin system

  1. Project NOAH: Regulating modern sea-level rise. Phase II: Jerusalem Underground

    Science.gov (United States)

    Newman, Walter S.; Fairbridge, Rhodes W.

    This proposal builds a high-speed inter-urban express between Jerusalem and Tel Aviv, generates 1500 megawatts of hydroelectric energy, curtails littoral erosion, builds a port along the Israeli Mediterranean coast and demands peaceful cooperation on both sides of the Jordan River. Phase II represents a pilot project demonstrating the feasibility of continuing to regulate world sea-level by a new series of water regulation schemes. Phase I previously described all those projects already completed or underway which have inadvertently and/or unintentionally served the purpose of sea-level regulation. These forms of Phase I sea-level regulation include large and small reservoirs, irrigation projects, water infiltration schemes, farm ponds, and swimming and reflecting pools. All these water storage projects have already exercised a very appreciable brake on 20th century sea-level rise. Phase II outlines a high-visibility proposal which will serve to illustrate the viability of “Project NOAH”.

  2. Meeting the International Health Regulations (2005) surveillance core capacity requirements at the subnational level in Europe

    DEFF Research Database (Denmark)

    Ziemann, Alexandra; Rosenkötter, Nicole; Riesgo, Luis Garcia-Castrillo

    2015-01-01

    BACKGROUND: The revised World Health Organization's International Health Regulations (2005) request a timely and all-hazard approach towards surveillance, especially at the subnational level. We discuss three questions of syndromic surveillance application in the European context for assessing...... public health emergencies of international concern: (i) can syndromic surveillance support countries, especially the subnational level, to meet the International Health Regulations (2005) core surveillance capacity requirements, (ii) are European syndromic surveillance systems comparable to enable cross...... effect of different types of public health emergencies in a timely manner as required by the International Health Regulations (2005)....

  3. Who regulates the disposal of low-level radioactive waste under the Low-Level Radioactive Waste Policy Act

    International Nuclear Information System (INIS)

    Mostaghel, D.M.

    1988-01-01

    The present existence of immense quantities of low-level nuclear waste, a federal law providing for state or regional control of such waste disposal, and a number of state disposal laws challenged on a variety of constitutional grounds underscore what currently may be the most serious problem in nuclear waste disposal: who is to regulate the disposal of low-level nuclear wastes. This problem's origin may be traced to crucial omissions in the Atomic Energy Act of 1946 and its 1954 amendments (AEA) that concern radioactive waste disposal. Although the AEA states that nuclear materials and facilities are affected with the public interest and should be regulated to provide for the public health and safety, the statute fails to prescribe specific guidelines for any nuclear waste disposal. The Low-Level Radioactive Waste Policy Act of 1980 (LLRWPA) grants states some control over radioactive waste disposal, an area from which they were previously excluded by the doctrine of federal preemption. This Comment discusses the question of who regulates low-level radioactive waste disposal facilities by examining the following: the constitutional doctrines safeguarding federal government authority; area of state authority; grants of specific authority delegations under the LLRWPA and its amendment; and finally, potential problems that may arise depending on whether ultimate regulatory authority is deemed to rest with single states, regional compacts, or the federal government

  4. Self-regulation of learning and performance level of elite youth soccer players

    NARCIS (Netherlands)

    Toering, Tynke; Elferink-Gemser, Marije T.; Jordet, Geir; Pepping, Gert-Jan; Visscher, Chris

    2012-01-01

    This study examined the relationship between self-regulated learning and performance level of 256 elite youth soccer players aged 12 to 17 years (M-age = 14.2; SD = 1.2). As relative age may affect this relationship through its association with maturation, experience, and performance level, we

  5. Regulation of the water level in the steam generator using modal control

    International Nuclear Information System (INIS)

    Benoit, Guy.

    1981-11-01

    The nuclear power reactors type P.W.R. (900 MWe) have three steam generators (S.G.). The problem of the water level in the S.G. is analogous to that for a system with non-minimum phase. This causes a serious trouble for the stability of the regulation, which is actually realized by using the PID regulator. The first part of this study is devoted to construct a mathematical model which represents the S.G. This model is simulated on a digital computer, which order is six. The validity of this model is checked using actual measured signals which have been collected from the BUGEY III power reactor. In the second part, the mathematical representation for simulating the regulation of the level in the S.G. using the modal control is given. The simulation of the actual system is given in the third part. This actual system is composed from the S.G. as well as the PI and PID for regulating the water level. As results from this study, it can be concluded that, the modal control improves the regulation of the water level. The accuracy of the steam flow measurement at low rate is poor. So, the actual regulating system using the measurements has a reduced performance performance. The control modal which is represented in this study overcome this problem [fr

  6. Differences in academic achievement according to the levels of cognitive and of self-regulation strategies

    Directory of Open Access Journals (Sweden)

    Antonio Valle

    2013-08-01

    Full Text Available Understanding study as a strategic and self-regulated activity and having in mind the distinction between cognitive and self-regulated learning strategies suggested in the literature, this paper analyses whether the differences in the use of this kind of strategies leads to different levels of academic achievement. Data were collected using a sample of 447 (12 to 16 years-old students from Spanish Secondary Compulsive Education. Various instruments were applied to assess students’ cognitive and self-regulated learning strategies. Students’ marks in Maths, Spanish, English (Foreign language, Science, Social studies and Music were taken as indicators of academic achievement. Data suggest that the more students use cognitive and self-regulated learning strategies in a specifi c subject the better their level of achievement in that same subject.

  7. Protein Phosphatase 1 Down Regulates ZYG-1 Levels to Limit Centriole Duplication.

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    Nina Peel

    2017-01-01

    Full Text Available In humans perturbations of centriole number are associated with tumorigenesis and microcephaly, therefore appropriate regulation of centriole duplication is critical. The C. elegans homolog of Plk4, ZYG-1, is required for centriole duplication, but our understanding of how ZYG-1 levels are regulated remains incomplete. We have identified the two PP1 orthologs, GSP-1 and GSP-2, and their regulators I-2SZY-2 and SDS-22 as key regulators of ZYG-1 protein levels. We find that down-regulation of PP1 activity either directly, or by mutation of szy-2 or sds-22 can rescue the loss of centriole duplication associated with a zyg-1 hypomorphic allele. Suppression is achieved through an increase in ZYG-1 levels, and our data indicate that PP1 normally regulates ZYG-1 through a post-translational mechanism. While moderate inhibition of PP1 activity can restore centriole duplication to a zyg-1 mutant, strong inhibition of PP1 in a wild-type background leads to centriole amplification via the production of more than one daughter centriole. Our results thus define a new pathway that limits the number of daughter centrioles produced each cycle.

  8. State-Level Community Benefit Regulation and Nonprofit Hospitals' Provision of Community Benefits.

    Science.gov (United States)

    Singh, Simone R; Young, Gary J; Loomer, Lacey; Madison, Kristin

    2018-04-01

    Do nonprofit hospitals provide enough community benefits to justify their tax exemptions? States have sought to enhance nonprofit hospitals' accountability and oversight through regulation, including requirements to report community benefits, conduct community health needs assessments, provide minimum levels of community benefits, and adhere to minimum income eligibility standards for charity care. However, little research has assessed these regulations' impact on community benefits. Using 2009-11 Internal Revenue Service data on community benefit spending for more than eighteen hundred hospitals and the Hilltop Institute's data on community benefit regulation, we investigated the relationship between these four types of regulation and the level and types of hospital-provided community benefits. Our multivariate regression analyses showed that only community health needs assessments were consistently associated with greater community benefit spending. The results for reporting and minimum spending requirements were mixed, while minimum income eligibility standards for charity care were unrelated to community benefit spending. State adoption of multiple types of regulation was consistently associated with higher levels of hospital-provided community benefits, possibly because regulatory intensity conveys a strong signal to the hospital community that more spending is expected. This study can inform efforts to design regulations that will encourage hospitals to provide community benefits consistent with policy makers' goals. Copyright © 2018 by Duke University Press.

  9. Biological/Genetic Regulation of Physical Activity Level: Consensus from GenBioPAC.

    Science.gov (United States)

    Lightfoot, J Timothy; DE Geus, Eco J C; Booth, Frank W; Bray, Molly S; DEN Hoed, Marcel; Kaprio, Jaakko; Kelly, Scott A; Pomp, Daniel; Saul, Michael C; Thomis, Martine A; Garland, Theodore; Bouchard, Claude

    2018-04-01

    Physical activity unquestionably maintains and improves health; however, physical activity levels globally are low and not rising despite all the resources devoted to this goal. Attention in both the research literature and the public policy domain has focused on social-behavioral factors; however, a growing body of literature suggests that biological determinants play a significant role in regulating physical activity levels. For instance, physical activity level, measured in various manners, has a genetic component in both humans and nonhuman animal models. This consensus article, developed as a result of an American College of Sports Medicine-sponsored round table, provides a brief review of the theoretical concepts and existing literature that supports a significant role of genetic and other biological factors in the regulation of physical activity. Future research on physical activity regulation should incorporate genetics and other biological determinants of physical activity instead of a sole reliance on social and other environmental determinants.

  10. Transcriptional feedback regulation of YUCCA genes in response to auxin levels in Arabidopsis.

    Science.gov (United States)

    Suzuki, Masashi; Yamazaki, Chiaki; Mitsui, Marie; Kakei, Yusuke; Mitani, Yuka; Nakamura, Ayako; Ishii, Takahiro; Soeno, Kazuo; Shimada, Yukihisa

    2015-08-01

    The IPyA pathway, the major auxin biosynthesis pathway, is transcriptionally regulated through a negative feedback mechanism in response to active auxin levels. The phytohormone auxin plays an important role in plant growth and development, and levels of active free auxin are determined by biosynthesis, conjugation, and polar transport. Unlike conjugation and polar transport, little is known regarding the regulatory mechanism of auxin biosynthesis. We discovered that expression of genes encoding indole-3-pyruvic acid (IPyA) pathway enzymes is regulated by elevated or reduced active auxin levels. Expression levels of TAR2, YUC1, YUC2, YUC4, and YUC6 were downregulated in response to synthetic auxins [1-naphthaleneacetic acid (NAA) and 2,4-dichlorophenoxyacetic acid (2,4-D)] exogenously applied to Arabidopsis thaliana L. seedlings. Concomitantly, reduced levels of endogenous indole-3-acetic acid (IAA) were observed. Alternatively, expression of these YUCCA genes was upregulated by the auxin biosynthetic inhibitor kynurenine in Arabidopsis seedlings, accompanied by reduced IAA levels. These results indicate that expression of YUCCA genes is regulated by active auxin levels. Similar results were also observed in auxin-overproduction and auxin-deficient mutants. Exogenous application of IPyA to Arabidopsis seedlings preincubated with kynurenine increased endogenous IAA levels, while preincubation with 2,4-D reduced endogenous IAA levels compared to seedlings exposed only to IPyA. These results suggest that in vivo conversion of IPyA to IAA was enhanced under reduced auxin levels, while IPyA to IAA conversion was depressed in the presence of excess auxin. Based on these results, we propose that the IPyA pathway is transcriptionally regulated through a negative feedback mechanism in response to active auxin levels.

  11. Experience in adjusting of the level regulation system of steam generators of the Rovno NPP

    International Nuclear Information System (INIS)

    Patselyuk, S.N.; Sokolov, A.G.; Kazakov, V.I.; Dorosh, Yu.A.

    1984-01-01

    A system of feed water level control in steam generators at the Rovno NPP with WWER-440 reactors which comprises start-up as well as main regulators is described. The start-up regulator (single-pulsed with a signal by the level) keeps the level in the steam generator at loadings up to 30% of the nominal reactor power Nsub(nom.) The main regulator is connected in the three-pulsed circuit and it receives signals by steam and water flow rate and by the level in the steam generator. The main regulator has been started only at loadings above 40% Nsub(nom.). After reconstruction it was used in the 15-100% Nsub(nom.) range. Characteristics of the level control system in the steam generator at perturbations intoduced by the main circulating pump (MCP) and turbine disconnection as well as change in feed water flow rate have been studied. The studies have revealed that the system ensures necessary quality of control in stationary modes. The system operates stably at perturbations of feed water flow rate up to 50% Nsub(nom.). Perturbations by MCP connections and disconnections is most difficult for control system

  12. Basic concept on safety regulation for land disposal of low level radioactive solid wastes

    International Nuclear Information System (INIS)

    1985-01-01

    As to the land disposal of low level radioactive solid wastes, to which the countermeasures have become the urgent problem at present, it is considered to be a realistic method to finally store the solid wastes concentratedly outside the sites of nuclear power stations and others, and effort has been exerted by those concerned to realize it. Besides, as for extremely low level radioactive solid wastes, the measures of disposing them corresponding to the radioactivity level are necessary, and the concrete method has been examined. The Committee on Safety Regulation for Radioactive Wastes has discussed the safety regulation for those since April, 1984, and the basic concept on the safety regulation was worked up. It is expected that the safety of the land disposal of low level radioactive solid wastes can be ensured when the safety regulation is carried out in conformity with this basic concept. The present status of the countermeasures to the land disposal of low level radioactive solid wastes is shown. As the concrete method, the disposal in shallow strate has been generally adopted. At present, the plan for the final storage in Aomori Prefecture is considered, and it will be started with the first stage of four-stage control. (Kako, I.)

  13. Autism and increased paternal age related changes in global levels of gene expression regulation.

    Directory of Open Access Journals (Sweden)

    Mark D Alter

    2011-02-01

    Full Text Available A causal role of mutations in multiple general transcription factors in neurodevelopmental disorders including autism suggested that alterations in global levels of gene expression regulation might also relate to disease risk in sporadic cases of autism. This premise can be tested by evaluating for changes in the overall distribution of gene expression levels. For instance, in mice, variability in hippocampal-dependent behaviors was associated with variability in the pattern of the overall distribution of gene expression levels, as assessed by variance in the distribution of gene expression levels in the hippocampus. We hypothesized that a similar change in variance might be found in children with autism. Gene expression microarrays covering greater than 47,000 unique RNA transcripts were done on RNA from peripheral blood lymphocytes (PBL of children with autism (n = 82 and controls (n = 64. Variance in the distribution of gene expression levels from each microarray was compared between groups of children. Also tested was whether a risk factor for autism, increased paternal age, was associated with variance. A decrease in the variance in the distribution of gene expression levels in PBL was associated with the diagnosis of autism and a risk factor for autism, increased paternal age. Traditional approaches to microarray analysis of gene expression suggested a possible mechanism for decreased variance in gene expression. Gene expression pathways involved in transcriptional regulation were down-regulated in the blood of children with autism and children of older fathers. Thus, results from global and gene specific approaches to studying microarray data were complimentary and supported the hypothesis that alterations at the global level of gene expression regulation are related to autism and increased paternal age. Global regulation of transcription, thus, represents a possible point of convergence for multiple etiologies of autism and other

  14. Harmonization of nuclear and radiation safety regulations for nuclear power plants with reference levels of Western European Nuclear Regulators Association (WENRA)

    International Nuclear Information System (INIS)

    Bojchuk, V.S.; Mikolajchuk, O.A.; Gromov, G.V.; Dibach, O.M.; Godovanyuk, G.M.; Nosovs'kij, A.V.

    2014-01-01

    Self-evaluation of the Ukrainian regulations on nuclear and radiation safety that apply to nuclear power plants for compliance with the reference levels of the Western European Nuclear Regulators Association (WENRA) is presented. Proposals on improvement of the regulations upon self-evaluation are provided

  15. "SAFE" LEVEL OF SOMATIC HEALTH IN INDICATORS REGULATION OF CARDIORESPIRATORY SYSTEM AT YOUNG MEN

    Directory of Open Access Journals (Sweden)

    Alexander P Romanchuk

    2015-12-01

    2Lviv State University Physical Culture The aim of this study was to determine the functional state cardiorespiratory system in males younger with "safe" level of somatic health (LSH. Were examined 104 males aged 20,6 ± 0,9 years, engaged in various sports, and had no existing acute and chronic diseases. The survey was conducted using spiroarteriocardiorhythmography (SACR. It is shown that in all studied systems of regulation, regulation except SBP probably marked differences between persons with "safe" and "low" LSH. At the same time, the comparison of "safe" and "medium" LSH differences relate only to the predominance of sympathetic influences on heart rate, decrease suprasegmental effects on DBP, reducing regulatory influences on spontaneous breath and their high-frequency components, reducing of baroreflex sensitivity and cardiac output. Key words: "safe" level of somatic health, regulation of the cardiorespiratory system.

  16. Genetic regulation ofmethylation and IL1RL1-a protein levels in asthma

    NARCIS (Netherlands)

    Dijk, F Nicole; Xu, Chengjian; Melén, Erik; Carsin, Anne-Elie; Kumar, Asish; Nolte, Ilja M; Gruzieva, Olena; Pershagen, Goran; Grotenboer, Neomi S; Savenije, Olga E M; Antó, Josep Maria; Lavi, Iris; Dobaño, Carlota; Bousquet, Jean; van der Vlies, Pieter; van der Valk, Ralf J P; de Jongste, Johan C; Nawijn, Martijn C; Guerra, Stefano; Postma, Dirkje S; Koppelman, Gerard H

    2018-01-01

    Interleukin-1 receptor-like 1 (IL1RL1) is an important asthma gene. (Epi)genetic regulation ofIL1RL1protein expression has not been established. We assessed the association betweenIL1RL1single nucleotide polymorphisms (SNPs),IL1RL1methylation and serum IL1RL1-a protein levels, and aimed to identify

  17. The Relationship between Maternal Acceptance-Rejection Levels and Preschoolers' Social Competence and Emotion Regulation Skills

    Science.gov (United States)

    Bayindir, Dilan; Güven, Gülçin; Sezer, Türker; Aksin-Yavuz, Ezgi; Yilmaz, Elif

    2017-01-01

    The purpose of this research was to examine the relationship between maternal acceptance-rejection levels and preschool children's social competence and emotion regulation skills. The study group of the research, which was designed in survey method, consisted of 303 voluntary mother-child dyad. The participant children were attending a preschool…

  18. High levels of Notch signaling down-regulate Numb and Numblike

    NARCIS (Netherlands)

    Chapman, G.; Liu, L.; Sahlgren, C.; Dahlqvist, C.; Lendahl, U.

    2006-01-01

    Inhibition of Notch signaling by Numb is critical for many cell fate decisions. In this study, we demonstrate a more complex relationship between Notch and the two vertebrate Numb homologues Numb and Numblike. Although Numb and Numblike at low levels of Notch signaling negatively regulated Notch,

  19. Regulation of myogenesis and skeletal muscle regeneration: effects of oxygen levels on satellite cell activity.

    Science.gov (United States)

    Chaillou, Thomas; Lanner, Johanna T

    2016-12-01

    Reduced oxygen (O 2 ) levels (hypoxia) are present during embryogenesis and exposure to altitude and in pathologic conditions. During embryogenesis, myogenic progenitor cells reside in a hypoxic microenvironment, which may regulate their activity. Satellite cells are myogenic progenitor cells localized in a local environment, suggesting that the O 2 level could affect their activity during muscle regeneration. In this review, we present the idea that O 2 levels regulate myogenesis and muscle regeneration, we elucidate the molecular mechanisms underlying myogenesis and muscle regeneration in hypoxia and depict therapeutic strategies using changes in O 2 levels to promote muscle regeneration. Severe hypoxia (≤1% O 2 ) appears detrimental for myogenic differentiation in vitro, whereas a 3-6% O 2 level could promote myogenesis. Hypoxia impairs the regenerative capacity of injured muscles. Although it remains to be explored, hypoxia may contribute to the muscle damage observed in patients with pathologies associated with hypoxia (chronic obstructive pulmonary disease, and peripheral arterial disease). Hypoxia affects satellite cell activity and myogenesis through mechanisms dependent and independent of hypoxia-inducible factor-1α. Finally, hyperbaric oxygen therapy and transplantation of hypoxia-conditioned myoblasts are beneficial procedures to enhance muscle regeneration in animals. These therapies may be clinically relevant to treatment of patients with severe muscle damage.-Chaillou, T. Lanner, J. T. Regulation of myogenesis and skeletal muscle regeneration: effects of oxygen levels on satellite cell activity. © FASEB.

  20. Environmental factors related to water level regulation - a comparative study in northern Finland

    International Nuclear Information System (INIS)

    Hellsten, S.K.

    1997-01-01

    The environmental conditions of the littoral zone were studied in the regulated Lake Ontojaervi and the unregulated Lake Lentua in northern Finland. The general aims of the study were to analyse the environmental factors related to water level regulation in the littoral zone and to produce information for assessing the effects of hydroelectric development in northern lakes. The study was basically carried out by comparing the littoral environments of the two study lakes. The most visible effects of water level regulation were related to the raised water level, which yielded erosion of sandy shores at the beginning of the regulation. Another effect of lake regulation was the altered fluctuation of the water level, which led to bottom instability and increased the size of the frozen and ice penetration zones. The effect of ice penetration was also easy to recognize on the shores of Lake Ontojaervi, where the surface sediment was frozen to a greater depth and across wider areas than in Lake Lentua. Below the freezing zone, the ice just pressed down on the sediment. The shores of Lake Ontojaervi were steeper than those of Lake Lentua, which affected the distribution of bottom types, with sandy bottoms being more common in Lake Lentua than in Lake Ontojaervi. The factors related to site exposure included effective fetch and the shape of the shoreline. The sedimentation level correlated only with the slope and was not predicted by the fetch or shape. The vertical reduction of light was estimated on the basis of water colour. The main environmental factors from the two lakes were used in a discriminant analysis to predict the bottom type distribution of the littoral (r 2 = 0.41). (orig.) 66 refs

  1. Environmental factors related to water level regulation - a comparative study in northern Finland

    Energy Technology Data Exchange (ETDEWEB)

    Hellsten, S K [VTT Communities and Infrastructure. Water Engineering and Ecotechnology, Oulu (Finland)

    1998-12-31

    The environmental conditions of the littoral zone were studied in the regulated Lake Ontojaervi and the unregulated Lake Lentua in northern Finland. The general aims of the study were to analyse the environmental factors related to water level regulation in the littoral zone and to produce information for assessing the effects of hydroelectric development in northern lakes. The study was basically carried out by comparing the littoral environments of the two study lakes. The most visible effects of water level regulation were related to the raised water level, which yielded erosion of sandy shores at the beginning of the regulation. Another effect of lake regulation was the altered fluctuation of the water level, which led to bottom instability and increased the size of the frozen and ice penetration zones. The effect of ice penetration was also easy to recognize on the shores of Lake Ontojaervi, where the surface sediment was frozen to a greater depth and across wider areas than in Lake Lentua. Below the freezing zone, the ice just pressed down on the sediment. The shores of Lake Ontojaervi were steeper than those of Lake Lentua, which affected the distribution of bottom types, with sandy bottoms being more common in Lake Lentua than in Lake Ontojaervi. The factors related to site exposure included effective fetch and the shape of the shoreline. The sedimentation level correlated only with the slope and was not predicted by the fetch or shape. The vertical reduction of light was estimated on the basis of water colour. The main environmental factors from the two lakes were used in a discriminant analysis to predict the bottom type distribution of the littoral (r{sup 2} = 0.41). (orig.) 66 refs.

  2. Uridine 5'-Monophosphate Synthase Is Transcriptionally Regulated by Pyrimidine Levels in Nicotiana plumbaginifolia

    Science.gov (United States)

    Santoso; Thornburg

    1998-02-01

    To understand the regulation and expression of pyrimidine biosynthesis in plants, we have examined the effect of the metabolic inhibitor 5-fluoroorotic acid (FOA) on uridine-5'-monophosphate synthase (UMPSase) expression in cell cultures of Nicotiana plumbaginifolia. UMPSase is the rate-limiting step of pyrimidine biosynthesis in plants. Addition of FOA causes an up-regulation of UMPSase enzyme activity in cell cultures after a lag phase of several days. Western-blot analysis demonstrated that the up-regulation in enzyme activity was caused by increased expression of the UMPSase protein. Northern-blot analysis demonstrated a higher level of UMPSase mRNA in the FOA-induced tissues than in control tissues. Run-on transcriptional assays showed that the UMPSase gene was transcriptionally activated after FOA treatment. The mechanism of toxicity of FOA is through thymine starvation. We found that addition of thymine abrogated the FOA-mediated up-regulation of UMPSase. In addition, methotrexate and aminopterin, which affect thymine levels by inhibiting dihydrofolate reductase, also up-regulate UMPSase in N. plumbaginifolia cells.

  3. Uridine 5′-Monophosphate Synthase Is Transcriptionally Regulated by Pyrimidine Levels in Nicotiana plumbaginifolia1

    Science.gov (United States)

    Santoso, Djoko; Thornburg, Robert

    1998-01-01

    To understand the regulation and expression of pyrimidine biosynthesis in plants, we have examined the effect of the metabolic inhibitor 5-fluoroorotic acid (FOA) on uridine-5′-monophosphate synthase (UMPSase) expression in cell cultures of Nicotiana plumbaginifolia. UMPSase is the rate-limiting step of pyrimidine biosynthesis in plants. Addition of FOA causes an up-regulation of UMPSase enzyme activity in cell cultures after a lag phase of several days. Western-blot analysis demonstrated that the up-regulation in enzyme activity was caused by increased expression of the UMPSase protein. Northern-blot analysis demonstrated a higher level of UMPSase mRNA in the FOA-induced tissues than in control tissues. Run-on transcriptional assays showed that the UMPSase gene was transcriptionally activated after FOA treatment. The mechanism of toxicity of FOA is through thymine starvation. We found that addition of thymine abrogated the FOA-mediated up-regulation of UMPSase. In addition, methotrexate and aminopterin, which affect thymine levels by inhibiting dihydrofolate reductase, also up-regulate UMPSase in N. plumbaginifolia cells. PMID:9490773

  4. Effects of the lipid regulating drug clofibric acid on PPARα-regulated gene transcript levels in common carp (Cyprinus carpio) at pharmacological and environmental exposure levels

    Energy Technology Data Exchange (ETDEWEB)

    Corcoran, Jenna, E-mail: J.F.Corcoran@exeter.ac.uk [University of Exeter, Biosciences, College of Life & Environmental Sciences, Exeter EX4 4QD (United Kingdom); Winter, Matthew J., E-mail: M.Winter@exeter.ac.uk [AstraZeneca Global Environment, Brixham Laboratory, Freshwater Quarry, Brixham TQ5 8BA (United Kingdom); Lange, Anke, E-mail: A.Lange@exeter.ac.uk [University of Exeter, Biosciences, College of Life & Environmental Sciences, Exeter EX4 4QD (United Kingdom); Cumming, Rob, E-mail: Rob.Cumming@astrazeneca.com [AstraZeneca Global Environment, Brixham Laboratory, Freshwater Quarry, Brixham TQ5 8BA (United Kingdom); Owen, Stewart F., E-mail: Stewart.Owen@astrazeneca.com [AstraZeneca Global Environment, Brixham Laboratory, Freshwater Quarry, Brixham TQ5 8BA (United Kingdom); Tyler, Charles R., E-mail: C.R.Tyler@exeter.ac.uk [University of Exeter, Biosciences, College of Life & Environmental Sciences, Exeter EX4 4QD (United Kingdom)

    2015-04-15

    Highlights: • CFA appears to have a low propensity to bioconcentrate and has a plasma half-life of <4 days in carp. • CFA increases levels of mRNA of a number of genes known to be regulated by PPARα in mammals. • PPARα activation changes levels of mRNA of genes involved with several detoxification/ biotransformation system components in carp. • CFA alters levels of mRNA and activity of the inducible β-oxidation pathway enzyme Acox1, a known indicator of peroxisome proliferator exposure. - Abstract: In mammals, the peroxisome proliferator-activated receptor α (PPARα) plays a key role in regulating various genes involved in lipid metabolism, bile acid synthesis and cholesterol homeostasis, and is activated by a diverse group of compounds collectively termed peroxisome proliferators (PPs). Specific PPs have been detected in the aquatic environment; however little is known on their pharmacological activity in fish. We investigated the bioavailability and persistence of the human PPARα ligand clofibric acid (CFA) in carp, together with various relevant endpoints, at a concentration similar to therapeutic levels in humans (20 mg/L) and for an environmentally relevant concentration (4 μg/L). Exposure to pharmacologically-relevant concentrations of CFA resulted in increased transcript levels of a number of known PPARα target genes together with increased acyl-coA oxidase (Acox1) activity, supporting stimulation of lipid metabolism pathways in carp which are known to be similarly activated in mammals. Although Cu,Zn-superoxide dismutase (Sod1) activity was not affected, mRNA levels of several biotransformation genes were also increased, paralleling previous reports in mammals and indicating a potential role in hepatic detoxification for PPARα in carp. Importantly, transcription of some of these genes (and Acox1 activity) were affected at exposure concentrations comparable with those reported in effluent discharges. Collectively, these data suggest that CFA

  5. Effects of the lipid regulating drug clofibric acid on PPARα-regulated gene transcript levels in common carp (Cyprinus carpio) at pharmacological and environmental exposure levels

    International Nuclear Information System (INIS)

    Corcoran, Jenna; Winter, Matthew J.; Lange, Anke; Cumming, Rob; Owen, Stewart F.; Tyler, Charles R.

    2015-01-01

    Highlights: • CFA appears to have a low propensity to bioconcentrate and has a plasma half-life of <4 days in carp. • CFA increases levels of mRNA of a number of genes known to be regulated by PPARα in mammals. • PPARα activation changes levels of mRNA of genes involved with several detoxification/ biotransformation system components in carp. • CFA alters levels of mRNA and activity of the inducible β-oxidation pathway enzyme Acox1, a known indicator of peroxisome proliferator exposure. - Abstract: In mammals, the peroxisome proliferator-activated receptor α (PPARα) plays a key role in regulating various genes involved in lipid metabolism, bile acid synthesis and cholesterol homeostasis, and is activated by a diverse group of compounds collectively termed peroxisome proliferators (PPs). Specific PPs have been detected in the aquatic environment; however little is known on their pharmacological activity in fish. We investigated the bioavailability and persistence of the human PPARα ligand clofibric acid (CFA) in carp, together with various relevant endpoints, at a concentration similar to therapeutic levels in humans (20 mg/L) and for an environmentally relevant concentration (4 μg/L). Exposure to pharmacologically-relevant concentrations of CFA resulted in increased transcript levels of a number of known PPARα target genes together with increased acyl-coA oxidase (Acox1) activity, supporting stimulation of lipid metabolism pathways in carp which are known to be similarly activated in mammals. Although Cu,Zn-superoxide dismutase (Sod1) activity was not affected, mRNA levels of several biotransformation genes were also increased, paralleling previous reports in mammals and indicating a potential role in hepatic detoxification for PPARα in carp. Importantly, transcription of some of these genes (and Acox1 activity) were affected at exposure concentrations comparable with those reported in effluent discharges. Collectively, these data suggest that CFA

  6. Greater-than-Class C low-level radioactive waste transportation regulations and requirements study

    International Nuclear Information System (INIS)

    Tyacke, M.; Schmitt, R.

    1993-07-01

    The purpose of this report is to identify the regulations and requirements for transporting greater-than-Class C (GTCC) low-level radioactive waste (LLW) and to identify planning activities that need to be accomplished in preparation for transporting GTCC LLW. The regulations and requirements for transporting hazardous materials, of which GTCC LLW is included, are complex and include several Federal agencies, state and local governments, and Indian tribes. This report is divided into five sections and three appendices. Section 1 introduces the report. Section 2 identifies and discusses the transportation regulations and requirements. The regulations and requirements are divided into Federal, state, local government, and Indian tribes subsections. This report does not identify the regulations or requirements of specific state, local government, and Indian tribes, since the storage, treatment, and disposal facility locations and transportation routes have not been specifically identified. Section 3 identifies the planning needed to ensure that all transportation activities are in compliance with the regulations and requirements. It is divided into (a) transportation packaging; (b) transportation operations; (c) system safety and risk analysis, (d) route selection; (e) emergency preparedness and response; and (f) safeguards and security. This section does not provide actual planning since the details of the Department of Energy (DOE) GTCC LLW Program have not been finalized, e.g., waste characterization and quantity, storage, treatment and disposal facility locations, and acceptance criteria. Sections 4 and 5 provide conclusions and referenced documents, respectively

  7. Modulation of ROS levels in fibroblasts by altering mitochondria regulates the process of wound healing.

    Science.gov (United States)

    Janda, Jaroslav; Nfonsam, Valentine; Calienes, Fernanda; Sligh, James E; Jandova, Jana

    2016-05-01

    Mitochondria are the major source of reactive oxygen species (ROS) in fibroblasts which are thought to be crucial regulators of wound healing with a potential to affect the expression of nuclear genes involved in this process. ROS generated by mitochondria are involved in all stages of tissue repair process but the regulation of ROS-generating system in fibroblasts still remains poorly understood. The purpose of this study was to better understand molecular mechanisms of how the regulation of ROS levels generated by mitochondria may influence the process of wound repair. Cybrid model system of mtDNA variations was used to study the functional consequences of altered ROS levels on wound healing responses in a uniform nuclear background of cultured ρ(0) fibroblasts. Mitochondrial ROS in cybrids were modulated by antioxidants that quench ROS to examine their ability to close the wound. Real-time PCR arrays were used to investigate whether ROS generated by specific mtDNA variants have the ability to alter expression of some key nuclear-encoded genes central to the wound healing response and oxidative stress. Our data suggest levels of mitochondrial ROS affect expression of some nuclear encoded genes central to wound healing response and oxidative stress and modulation of mitochondrial ROS by antioxidants positively affects in vitro process of wound closure. Thus, regulation of mitochondrial ROS-generating system in fibroblasts can be used as effective natural redox-based strategy to help treat non-healing wounds.

  8. United States regulations for institutional controls at high-level waste repositories

    International Nuclear Information System (INIS)

    Piccone, Josephine

    2015-01-01

    The United States regulations for disposal of spent nuclear fuel and high-level radioactive waste are found at Title 10 of the Code of Federal Regulations (10 CFR) Parts 60 and 63, which cover deep geologic disposal at a generic site and at Yucca Mountain, Nevada, respectively. As an independent regulator, the US Nuclear Regulatory Commission (NRC) is responsible for licensing and oversight of a high-level waste repository in the United States. The licensing approach for disposal has discreet decisions, made by the NRC, that include approval of construction authorisation, approval to receive and possess high-level radioactive waste, and approval for permanent closure. For construction authorisation approval, the applicant must provide a description of the programme to be used to maintain the records. The NRC will have an active oversight role during the construction and operation period, which can be on the order of 100 years for the facility before permanent closure. The oversight activities are part of the active institutional controls, and serve as a means of conveying knowledge for that initial period, given that this will likely involve multiple generations of workers for both the implementer and the regulator. Additionally, the NRC provides requirements for the physical protection of stored spent nuclear fuel and high-level radioactive waste at 10 CFR Chap. 73.51. For permanent closure approval, the applicant must provide a detailed description of the measures to be employed-such as land use controls, construction of monuments, and preservation of records. The NRC's regulatory role in any licensing action is to apply the applicable regulations and guidance, and to review applications for proposed actions to determine if compliance with regulations has been achieved. The burden of proof is on the applicant or licensee to show that the proposed action is safe, to demonstrate that regulations are met, and to ensure continued compliance with the regulations

  9. Impacts of hazardous waste regulation on low-level waste management

    International Nuclear Information System (INIS)

    Sharples, F.E.; Eyman, L.D.

    1987-01-01

    Since passage of the 1984 amendments to the Resource Conservation and Recovery Act (RCRA), major changes have occurred in the regulation of hazardous waste. The US Environmental Protection Agency (EPA) has also greatly modified its interpretation of how these regulations apply to wastes from federal facilities, including defense wastes from US Department of Energy (DOE) sites. As a result, the regulatory distinctions between low-level radioactive waste (LLW) and hazardous waste are becoming blurred. This paper discusses recent statutory and regulatory changes and how they might affect the management of LLW at DOE facilities. 6 references

  10. Theorizing and researching levels of processing in self-regulated learning.

    Science.gov (United States)

    Winne, Philip H

    2018-03-01

    Deep versus surface knowledge is widely discussed by educational practitioners. A corresponding construct, levels of processing, has received extensive theoretical and empirical attention in learning science and psychology. In both arenas, lower levels of information and shallower levels of processing are predicted and generally empirically demonstrated to limit knowledge learners gain, curtail what they can do with newly acquired knowledge, and shorten the life span of recently acquired knowledge. I recapitulate major accounts of levels or depth of information and information processing to set a stage for conceptualizing, first, self-regulated learning (SRL) from this perspective and, second, how a "levels-sensitive" approach might be implemented in research about SRL. I merge the levels construct into a model of SRL (Winne, 2011, Handbook of self-regulation of learning and performance (pp. 15-32), New York: Routledge; Winne, 2017b, Handbook of self-regulation of learning and performance (2 nd ed.), New York: Routledge; Winne & Hadwin, 1998, Metacognition in educational theory and practice (pp. 277-304). Mahwah, NJ: Lawrence Erlbaum) conceptually and with respect to operationally defining the levels construct in the context of SRL in relation to each of the model's four phases - surveying task conditions, setting goals and planning, engaging the task, and composing major adaptations for future tasks. Select illustrations are provided for each phase of SRL. Regarding phase 3, a software system called nStudy is introduced as state-of-the-art instrumentation for gathering fine-grained, time-stamped trace data about information learners select for processing and operations they use to process that information. Self-regulated learning can be viewed through a lens of the levels construct, and operational definitions can be designed to research SRL with respect to levels. While information can be organized arbitrarily deeply, the levels construct may not be particularly

  11. Nucleolin is regulated both at the level of transcription and translation

    International Nuclear Information System (INIS)

    Bicknell, Katrina; Brooks, Gavin; Kaiser, Pete; Chen Hongying; Dove, Brian K.; Hiscox, Julian A.

    2005-01-01

    Nucleolin is a multi-functional protein that is located to the nucleolus. In tissue culture cells, the stability of nucleolin is related to the proliferation status of the cell. During development, rat cardiomyocytes proliferate actively with increases in the mass of the heart being due to both hyperplasia and hypertrophy. The timing of this shift in the phenotype of the myocyte from one capable of undergoing hyperplasia to one that can grow only by hypertrophy occurs within 4 days of post-natal development. Thus, cardiomyocytes are an ideal model system in which to study the regulation of nucleolin during growth in vivo. Using Western blot and quantitative RT-PCR (TaqMan) we found that the amount of nucleolin is regulated both at the level of transcription and translation during the development of the cardiomyocyte. However, in cells which had exited the cell cycle and were subsequently given a hypertrophic stimulus, nucleolin was regulated post-transcriptionally

  12. A gene expression system offering multiple levels of regulation: the Dual Drug Control (DDC) system.

    Science.gov (United States)

    Sudomoina, Marina; Latypova, Ekaterina; Favorova, Olga O; Golemis, Erica A; Serebriiskii, Ilya G

    2004-04-29

    Whether for cell culture studies of protein function, construction of mouse models to enable in vivo analysis of disease epidemiology, or ultimately gene therapy of human diseases, a critical enabling step is the ability to achieve finely controlled regulation of gene expression. Previous efforts to achieve this goal have explored inducible drug regulation of gene expression, and construction of synthetic promoters based on two-hybrid paradigms, among others. In this report, we describe the combination of dimerizer-regulated two-hybrid and tetracycline regulatory elements in an ordered cascade, placing expression of endpoint reporters under the control of two distinct drugs. In this Dual Drug Control (DDC) system, a first plasmid expresses fusion proteins to DBD and AD, which interact only in the presence of a small molecule dimerizer; a second plasmid encodes a cassette transcriptionally responsive to the first DBD, directing expression of the Tet-OFF protein; and a third plasmid encodes a reporter gene transcriptionally responsive to binding by Tet-OFF. We evaluate the dynamic range and specificity of this system in comparison to other available systems. This study demonstrates the feasibility of combining two discrete drug-regulated expression systems in a temporally sequential cascade, without loss of dynamic range of signal induction. The efficient layering of control levels allowed by this combination of elements provides the potential for the generation of complex control circuitry that may advance ability to regulate gene expression in vivo.

  13. A gene expression system offering multiple levels of regulation: the Dual Drug Control (DDC system

    Directory of Open Access Journals (Sweden)

    Golemis Erica A

    2004-04-01

    Full Text Available Abstract Background Whether for cell culture studies of protein function, construction of mouse models to enable in vivo analysis of disease epidemiology, or ultimately gene therapy of human diseases, a critical enabling step is the ability to achieve finely controlled regulation of gene expression. Previous efforts to achieve this goal have explored inducible drug regulation of gene expression, and construction of synthetic promoters based on two-hybrid paradigms, among others. Results In this report, we describe the combination of dimerizer-regulated two-hybrid and tetracycline regulatory elements in an ordered cascade, placing expression of endpoint reporters under the control of two distinct drugs. In this Dual Drug Control (DDC system, a first plasmid expresses fusion proteins to DBD and AD, which interact only in the presence of a small molecule dimerizer; a second plasmid encodes a cassette transcriptionally responsive to the first DBD, directing expression of the Tet-OFF protein; and a third plasmid encodes a reporter gene transcriptionally responsive to binding by Tet-OFF. We evaluate the dynamic range and specificity of this system in comparison to other available systems. Conclusion This study demonstrates the feasibility of combining two discrete drug-regulated expression systems in a temporally sequential cascade, without loss of dynamic range of signal induction. The efficient layering of control levels allowed by this combination of elements provides the potential for the generation of complex control circuitry that may advance ability to regulate gene expression in vivo.

  14. A biomolecular proportional integral controller based on feedback regulations of protein level and activity.

    Science.gov (United States)

    Mairet, Francis

    2018-02-01

    Homeostasis is the capacity of living organisms to keep internal conditions regulated at a constant level, despite environmental fluctuations. Integral feedback control is known to play a key role in this behaviour. Here, I show that a feedback system involving transcriptional and post-translational regulations of the same executor protein acts as a proportional integral (PI) controller, leading to enhanced transient performances in comparison with a classical integral loop. Such a biomolecular controller-which I call a level and activity-PI controller (LA-PI)-is involved in the regulation of ammonium uptake by Escherichia coli through the transporter AmtB. The P II molecules, which reflect the nitrogen status of the cell, inhibit both the production of AmtB and its activity (via the NtrB-NtrC system and the formation of a complex with GlnK, respectively). Other examples of LA-PI controller include copper and zinc transporters, and the redox regulation in photosynthesis. This scheme has thus emerged through evolution in many biological systems, surely because of the benefits it offers in terms of performances (rapid and perfect adaptation) and economy (protein production according to needs).

  15. Growth-Rate Dependent Regulation of tRNA Level and Charging in Bacillus licheniformis.

    Science.gov (United States)

    Ferro, Iolanda; Liebeton, Klaus; Ignatova, Zoya

    2017-10-13

    Cellular growth crucially depends on protein synthesis and the abundance of translational components. Among them, aminoacyl-tRNAs play a central role in biosynthesis and shape the kinetics of mRNA translation, thus influencing protein production. Here, we used microarray-based approaches to determine the charging levels and tRNA abundance of Bacillus licheniformis. We observed an interesting cross-talk among tRNA expression, charging pattern, and growth rate. For a large subset of tRNAs, we found a co-regulated and augmented expression at high growth rate. Their tRNA aminoacylation level is kept relatively constant through riboswitch-regulated expression of the cognate aminoacyl-tRNA-synthetase (AARS). We show that AARSs with putative riboswitch-controlled expression are those charging tRNAs with amino acids which disfavor cell growth when individually added to the nutrient medium. Our results suggest that the riboswitch-regulated AARS expression in B. licheniformis is a powerful mechanism not only to maintain a constant ratio of aminoacyl-tRNA independent of the growth rate but concomitantly to control the intracellular level of free amino acids. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. The disturbances of lipid metabolism regulation after the prenatal low-level irradiation

    International Nuclear Information System (INIS)

    Rogov, Yu.I.; Danil'chik, V.S.; Spivak, L.V.; Rubchenya, I.N.

    2000-01-01

    The objective of this study was to assess the influence of low-level irradiation on lipid metabolism in rats after prenatal exposure. Pregnant rats were irradiated during the period of gestation with the whole final dose 0,5 Gy/rat. The blood lipid fractions were investigated in newborn rats and in 6-month age rats. In irradiated offspring the lipo synthesis processes exceeded lipolysis in comparison with that of the control. The negative consequences of embryo low-level irradiation in the lipid metabolism regulation are discussed in this report. (authors)

  17. Effects of the lipid regulating drug clofibric acid on PPARα-regulated gene transcript levels in common carp (Cyprinus carpio) at pharmacological and environmental exposure levels.

    Science.gov (United States)

    Corcoran, Jenna; Winter, Matthew J; Lange, Anke; Cumming, Rob; Owen, Stewart F; Tyler, Charles R

    2015-04-01

    In mammals, the peroxisome proliferator-activated receptor α (PPARα) plays a key role in regulating various genes involved in lipid metabolism, bile acid synthesis and cholesterol homeostasis, and is activated by a diverse group of compounds collectively termed peroxisome proliferators (PPs). Specific PPs have been detected in the aquatic environment; however little is known on their pharmacological activity in fish. We investigated the bioavailability and persistence of the human PPARα ligand clofibric acid (CFA) in carp, together with various relevant endpoints, at a concentration similar to therapeutic levels in humans (20mg/L) and for an environmentally relevant concentration (4μg/L). Exposure to pharmacologically-relevant concentrations of CFA resulted in increased transcript levels of a number of known PPARα target genes together with increased acyl-coA oxidase (Acox1) activity, supporting stimulation of lipid metabolism pathways in carp which are known to be similarly activated in mammals. Although Cu,Zn-superoxide dismutase (Sod1) activity was not affected, mRNA levels of several biotransformation genes were also increased, paralleling previous reports in mammals and indicating a potential role in hepatic detoxification for PPARα in carp. Importantly, transcription of some of these genes (and Acox1 activity) were affected at exposure concentrations comparable with those reported in effluent discharges. Collectively, these data suggest that CFA is pharmacologically active in carp and has the potential to invoke PPARα-related responses in fish exposed in the environment, particularly considering that CFA may represent just one of a number of PPAR-active compounds present to which wild fish may be exposed. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  18. β-oxidation and rapid metabolism, but not uptake regulate brain eicosapentaenoic acid levels.

    Science.gov (United States)

    Chen, Chuck T; Bazinet, Richard P

    2015-01-01

    The brain has a unique polyunsaturated fatty acid composition, with high levels of arachidonic and docosahexaenoic acids (DHA) while levels of eicosapentaenoic acid (EPA) are several orders of magnitude lower. As evidence accumulated that fatty acid entry into the brain was not selective and, in fact, that DHA and EPA enter the brain at similar rates, new mechanisms were required to explain their large concentration differences in the brain. Here we summarize recent research demonstrating that EPA is rapidly and extensively β-oxidized upon entry into the brain. Although the ATP generated from the β-oxidation of EPA is low compared to the use of glucose, fatty acid β-oxidation may serve to regulate brain fatty acid levels in the absence of selective transportation. Furthermore, when β-oxidation of EPA is blocked, desaturation of EPA increases and Land׳s recycling decreases to maintain low EPA levels. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Regulation of hTERT by BCR-ABL at multiple levels in K562 cells

    International Nuclear Information System (INIS)

    Chai, Juin Hsien; Zhang, Yong; Tan, Wei Han; Chng, Wee Joo; Li, Baojie; Wang, Xueying

    2011-01-01

    The cytogenetic characteristic of Chronic Myeloid Leukemia (CML) is the formation of the Philadelphia chromosome gene product, BCR-ABL. Given that BCR-ABL is the specific target of Gleevec in CML treatment, we investigated the regulation of the catalytic component of telomerase, hTERT, by BCR-ABL at multiple levels in K562 cells. Molecular techniques such as over expression, knockdown, real-time PCR, immunoprecipitation, western blotting, reporter assay, confocal microscopy, telomerase assays and microarray were used to suggest that hTERT expression and activity is modulated by BCR-ABL at multiple levels. Our results suggest that BCR-ABL plays an important role in regulating hTERT in K562 (BCR-ABL positive human leukemia) cells. When Gleevec inhibited the tyrosine kinase activity of BCR-ABL, phosphorylation of hTERT was downregulated, therefore suggesting a positive correlation between BCR-ABL and hTERT. Gleevec treatment inhibited hTERT at mRNA level and significantly reduced telomerase activity (TA) in K562 cells, but not in HL60 or Jurkat cells (BCR-ABL negative cells). We also demonstrated that the transcription factor STAT5a plays a critical role in hTERT gene regulation in K562 cells. Knockdown of STAT5a, but not STAT5b, resulted in a marked downregulation of hTERT mRNA level, TA and hTERT protein level in K562 cells. Furthermore, translocation of hTERT from nucleoli to nucleoplasm was observed in K562 cells induced by Gleevec. Our data reveal that BCR-ABL can regulate TA at multiple levels, including transcription, post-translational level, and proper localization. Thus, suppression of cell growth and induction of apoptosis by Gleevec treatment may be partially due to TA inhibition. Additionally, we have identified STAT5a as critical mediator of the hTERT gene expression in BCR-ABL positive CML cells, suggesting that targeting STAT5a may be a promising therapeutic strategy for BCR-ABL positive CML patients

  20. Epalrestat increases intracellular glutathione levels in Schwann cells through transcription regulation

    Directory of Open Access Journals (Sweden)

    Keisuke Sato

    2014-01-01

    Full Text Available Epalrestat (EPS, approved in Japan, is the only aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy. Here we report that EPS at near-plasma concentration increases the intracellular levels of glutathione (GSH, which is important for protection against oxidative injury, through transcription regulation. Treatment of Schwann cells with EPS caused a dramatic increase in intracellular GSH levels. EPS increased the mRNA levels of γ-glutamylcysteine synthetase (γ-GCS, the enzyme catalyzing the first and rate-limiting step in de novo GSH synthesis. Nuclear factor erythroid 2-related factor 2 (Nrf2 is a key transcription factor that plays a central role in regulating the expression of γ-GCS. ELISA revealed that EPS increased nuclear Nrf2 levels. Knockdown of Nrf2 by siRNA suppressed the EPS-induced GSH biosynthesis. Furthermore, pretreatment with EPS reduced the cytotoxicity induced by H2O2, tert-butylhydroperoxide, 2,2'-azobis (2-amidinopropane dihydrochloride, and menadione, indicating that EPS plays a role in protecting against oxidative stress. This is the first study to show that EPS induces GSH biosynthesis via the activation of Nrf2. We suggest that EPS has new beneficial properties that may prevent the development and progression of disorders caused by oxidative stress.

  1. Is it possible to demonstrate compliance with the regulations for high-level-waste repositories?

    International Nuclear Information System (INIS)

    Bingham, F.W.

    1992-01-01

    The regulations that currently govern repositories for spent fuel and high-level waste require demonstrations that are sometimes described as impossible to make. To make them will require an understanding of the current and the future phenomena at repository sites; it will also require credible estimates of the probabilities that the phenomena will occur in the distant future. Experts in many fields emdash earth sciences, statistics, numerical modeling, and the law emdash have questioned whether any amount of data collection can allow modelers to meet these requirements with enough confidence to satisfy the regulators. In recent years some performance assessments have begun to shed light on this question because they use results of actual site investigations. Although these studies do not settle the question definitively, a review of a recent total-system assessment suggests that compliance may be possible to demonstrate. The review also suggests, however, that the demonstration can be only at the ''reasonable'' levels of assurance mentioned, but not defined, in the regulations

  2. Climate Change and Regulation in International and Regional Level, Especially the Built Environment

    Directory of Open Access Journals (Sweden)

    Putnoki Zsuzsanna

    2015-12-01

    Full Text Available The article starts with a brief insight into the history of climate change, with a scope on the international and legal aspects of ever-changing regulations. The regional level is in the article is The European Union, as the only regional economic integration organization under the Kyoto Protocol. It deals with the United Nation’s international agreements like UNFCCC its Kyoto’s Protocol and the Post-Kyoto era. It also analyses the EU’s system in the climate change law with correspondence the international rules. Comparison between international and regional legislation in the climate change is used as a tool of analysis. Finally an insight is given into a special field in the climate change, the build environment, reflecting on the related United Nation’s recommendation and the EU’s regulation.

  3. The Impact of Uniform Prudential Regulations Implemented at the Level of European Insurance Industry

    Directory of Open Access Journals (Sweden)

    Laura Elly Naghi

    2013-08-01

    Full Text Available While the financial markets have to face systemic and systematic risks, especially the insurance industries, the national supervisory authorities intend to implement regulation systems as uniform as possible at regional level and in the same time as conservatory as possible from the point of view of the risks accepted. The present paper intends to accurately analyze the regulation systems of important insurance markets (as tradition or volume of premiums – such as RBC, SST, Solvency II in order to stress the similarities of these models but more important the differences that generated a different rigidity degree of the insurance companies, in other words, a different minimum capital requirement. The paper intends to illustrate the financial and organizational impact of the European model Solvency has on the insurance companies, through its supplemental requirements, introduced by the supervisory authorities as a reaction to the recent financial crises.

  4. Critical thinking level in geometry based on self-regulated learning

    Science.gov (United States)

    Bayuningsih, A. S.; Usodo, B.; Subanti, S.

    2018-03-01

    Critical thinking ability of mathematics students affected by the student’s ability in solving a specific problem. This research aims to determine the level of critical thinking (LCT) students in solving problems of geometry regarding self-regulated learning (SRL) students. This is a qualitative descriptive study with the purpose to analyze the level of Junior High School student’s critical thinking in the Regency of Banyumas. The subject is taken one student from each category SRL (high, medium and low). Data collection is given problem-solving tests to find out the level of critical thinking student, questionnaire, interview and documentation. The result of the research shows that student with SRL high is at the level of critical thinking 2, then a student with SRL medium is at the level of critical thinking 1 and student with SRL low is at the level of critical thinking 0. So students with SRL high, medium or low can solve math problems based on the critical thinking level of each student.

  5. Influence of dexamethasone and weight loss on the regulation of serum leptin levels in obese individuals

    Directory of Open Access Journals (Sweden)

    D.D.G. Lerario

    2001-04-01

    Full Text Available The adipocyte hormone leptin is thought to serve as a signal to the central nervous system reflecting the status of fat stores. Serum leptin levels and adipocyte leptin messenger RNA levels are clearly increased in obesity. Nevertheless, the factors regulating leptin production are not fully understood. The aim of this study was to determine the effects of in vivo administration of the synthetic glucocorticoid dexamethasone and weight loss on serum leptin levels in two independent protocols. Twenty-five obese subjects were studied (18 women and 7 men, mean age 26.6 ± 6 years, BMI 31.1 ± 2.5 kg/m², %fat 40.3 ± 8.3 and compared at baseline to 22 healthy individuals. Serum levels of leptin, insulin, proinsulin and glucose were assessed at baseline and after ingestion of dexamethasone, 4 mg per day (2 mg, twice daily for two consecutive days. To study the effects of weight loss on serum leptin, 17 of the obese subjects were submitted to a low-calorie dietary intervention trial for 8 weeks and again blood samples were collected. Serum leptin levels were significantly higher in the obese group compared to the control group and a high positive correlation between leptinemia and the magnitude of fat mass was found (r = 0.88, P<0.0001. After dexamethasone, there was a significant increase in serum leptin levels (22.9 ± 12.3 vs 51.4 ± 23.3 ng/ml, P<0.05. Weight loss (86.1 ± 15.1 vs 80.6 ± 14.2 kg, P<0.05 led to a reduction in leptin levels (25.13 ± 12.8 vs 15.9 ± 9.1 ng/ml, P<0.05. We conclude that serum leptin levels are primordially dependent on fat mass magnitude. Glucocorticoids at supraphysiologic levels are potent secretagogues of leptin in obese subjects and a mild fat mass reduction leads to a disproportionate decrease in serum leptin levels. This suggests that, in addition to the changes in fat mass, complex nutritional and hormonal interactions may also play an important role in the regulation of leptin levels.

  6. Water level management of lakes connected to regulated rivers: An integrated modeling and analytical methodology

    Science.gov (United States)

    Hu, Tengfei; Mao, Jingqiao; Pan, Shunqi; Dai, Lingquan; Zhang, Peipei; Xu, Diandian; Dai, Huichao

    2018-07-01

    Reservoir operations significantly alter the hydrological regime of the downstream river and river-connected lake, which has far-reaching impacts on the lake ecosystem. To facilitate the management of lakes connected to regulated rivers, the following information must be provided: (1) the response of lake water levels to reservoir operation schedules in the near future and (2) the importance of different rivers in terms of affecting the water levels in different lake regions of interest. We develop an integrated modeling and analytical methodology for the water level management of such lakes. The data-driven method is used to model the lake level as it has the potential of producing quick and accurate predictions. A new genetic algorithm-based synchronized search is proposed to optimize input variable time lags and data-driven model parameters simultaneously. The methodology also involves the orthogonal design and range analysis for extracting the influence of an individual river from that of all the rivers. The integrated methodology is applied to the second largest freshwater lake in China, the Dongting Lake. The results show that: (1) the antecedent lake levels are of crucial importance for the current lake level prediction; (2) the selected river discharge time lags reflect the spatial heterogeneity of the rivers' impacts on lake level changes; (3) the predicted lake levels are in very good agreement with the observed data (RMSE ≤ 0.091 m; R2 ≥ 0.9986). This study demonstrates the practical potential of the integrated methodology, which can provide both the lake level responses to future dam releases and the relative contributions of different rivers to lake level changes.

  7. Thyroid hormone regulation of epidermal growth factor receptor levels in mouse mammary glands

    International Nuclear Information System (INIS)

    Vonderhaar, B.K.; Tang, E.; Lyster, R.R.; Nascimento, M.C.

    1986-01-01

    The specific binding of iodinated epidermal growth factor ([ 125 I]iodo-EGF) to membranes prepared from the mammary glands and spontaneous breast tumors of euthyroid and hypothyroid mice was measured in order to determine whether thyroid hormones regulate the EGF receptor levels in vivo. Membranes from hypothyroid mammary glands of mice at various developmental ages bound 50-65% less EGF than those of age-matched euthyroid controls. Treatment of hypothyroid mice with L-T4 before killing restored binding to the euthyroid control level. Spontaneous breast tumors arising in hypothyroid mice also bound 30-40% less EGF than tumors from euthyroid animals even after in vitro desaturation of the membranes of endogenous growth factors with 3 M MgCl2 treatment. The decrease in binding in hypothyroid membranes was due to a decrease in the number of binding sites, not to a change in affinity of the growth factor for its receptor, as determined by Scatchard analysis of the binding data. Both euthyroid and hypothyroid membranes bound EGF primarily to a single class of high affinity sites [dissociation constant (Kd) = 0.7-1.8 nM]. Euthyroid membranes bound 28.4 +/- (SE) 0.6 fmol/mg protein, whereas hypothyroid membranes bound 15.5 +/- 1.0 fmol/mg protein. These data indicate that EGF receptor levels in normal mammary glands and spontaneous breast tumors in mice are subject to regulation by thyroid status

  8. Amino acid limitation induces down-regulation of WNT5a at transcriptional level

    International Nuclear Information System (INIS)

    Wang Zuguang; Chen Hong

    2009-01-01

    An aberrant WNT signaling contributes to the development and progression of multiple cancers. WNT5a is one of the WNT signaling molecules. This study was designed to test the hypothesis that amino acid deprivation induces changes in the WNT signaling pathway in colon cancer cells. Results showed that targets of the amino acid response pathway, ATF3 and p21, were induced in the human colon cancer cell line SW480 during amino acid limitation. There was a significant decrease in the WNT5a mRNA level following amino acid deprivation. The down-regulation of WNT5a mRNA by amino acid deprivation is not due to mRNA destabilization. There is a reduction of nuclear β-catenin protein level by amino acid limitation. Under amino acid limitation, phosphorylation of ERK1/2 was increased and the blockage of ERK1/2 by the inhibitor U0126 partially restored WNT5a mRNA level. In conclusion, amino acid limitation in colon cancer cells induces phosphorylation of ERK1/2, which then down-regulates WNT5a expression.

  9. Fe and Mn levels regulated by agricultural activities in alluvial groundwaters underneath a flooded paddy field

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kangjoo [School of Civil and Environmental Engineering, Kunsan National University, Jeonbuk 573-701 (Korea, Republic of)], E-mail: kangjoo@kunsan.ac.kr; Kim, Hyun-Jung; Choi, Byoung-Young; Kim, Seok-Hwi; Park, Ki-hoon [School of Civil and Environmental Engineering, Kunsan National University, Jeonbuk 573-701 (Korea, Republic of); Park, Eungyu [Department of Geology, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Koh, Dong-Chan [Korea Institute of Geoscience and Mineral Resources, Daejeon 305-350 (Korea, Republic of); Yun, Seong-Taek [Department of Earth and Environmental Sciences, Korea University, Seoul 136-701 (Korea, Republic of)

    2008-01-15

    Iron and Mn concentrations in fresh groundwaters of alluvial aquifers are generally high in reducing conditions reflecting low SO{sub 4} concentrations. The mass balance and isotopic approaches of this study demonstrate that reduction of SO{sub 4}, supplied from agricultural activities such as fertilization and irrigation, is important in lowering Fe and Mn levels in alluvial groundwaters underneath a paddy field. This study was performed to investigate the processes regulating Fe and Mn levels in groundwaters of a point bar area, which has been intensively used for flood cultivation. Four multilevel-groundwater samplers were installed to examine the relationship between geology and the vertical changes in water chemistry. The results show that Fe and Mn levels are regulated by the presence of NO{sub 3} at shallow depths and by SO{sub 4} reduction at the greater depths. Isotopic and mass balance analyses revealed that NO{sub 3} and SO{sub 4} in groundwater are mostly supplied from the paddy field, suggesting that the Fe-and Mn-rich zone of the study area is confined by the agricultural activities. For this reason, the geologic conditions controlling the infiltration of agrochemicals are also important for the occurrence of Fe/Mn-rich groundwaters in the paddy field area.

  10. Fe and Mn levels regulated by agricultural activities in alluvial groundwaters underneath a flooded paddy field

    International Nuclear Information System (INIS)

    Kim, Kangjoo; Kim, Hyun-Jung; Choi, Byoung-Young; Kim, Seok-Hwi; Park, Ki-hoon; Park, Eungyu; Koh, Dong-Chan; Yun, Seong-Taek

    2008-01-01

    Iron and Mn concentrations in fresh groundwaters of alluvial aquifers are generally high in reducing conditions reflecting low SO 4 concentrations. The mass balance and isotopic approaches of this study demonstrate that reduction of SO 4 , supplied from agricultural activities such as fertilization and irrigation, is important in lowering Fe and Mn levels in alluvial groundwaters underneath a paddy field. This study was performed to investigate the processes regulating Fe and Mn levels in groundwaters of a point bar area, which has been intensively used for flood cultivation. Four multilevel-groundwater samplers were installed to examine the relationship between geology and the vertical changes in water chemistry. The results show that Fe and Mn levels are regulated by the presence of NO 3 at shallow depths and by SO 4 reduction at the greater depths. Isotopic and mass balance analyses revealed that NO 3 and SO 4 in groundwater are mostly supplied from the paddy field, suggesting that the Fe-and Mn-rich zone of the study area is confined by the agricultural activities. For this reason, the geologic conditions controlling the infiltration of agrochemicals are also important for the occurrence of Fe/Mn-rich groundwaters in the paddy field area

  11. Ectodermal-neural cortex 1 down-regulates Nrf2 at the translational level.

    Directory of Open Access Journals (Sweden)

    Xiao-Jun Wang

    Full Text Available The transcription factor Nrf2 is the master regulator of a cellular defense mechanism against environmental insults. The Nrf2-mediated antioxidant response is accomplished by the transcription of a battery of genes that encode phase II detoxifying enzymes, xenobiotic transporters, and antioxidants. Coordinated expression of these genes is critical in protecting cells from toxic and carcinogenic insults and in maintaining cellular redox homeostasis. Activation of the Nrf2 pathway is primarily controlled by Kelch-like ECH-associated protein 1 (Keap1, which is a molecular switch that turns on or off the Nrf2 signaling pathway according to intracellular redox conditions. Here we report our finding of a novel Nrf2 suppressor ectodermal-neural cortex 1 (ENC1, which is a BTB-Kelch protein and belongs to the same family as Keap1. Transient expression of ENC1 reduced steady-state levels of Nrf2 and its downstream gene expression. Although ENC1 interacted with Keap1 indirectly, the ENC1-mediated down-regulation of Nrf2 was independent of Keap1. The negative effect of ENC1 on Nrf2 was not due to a change in the stability of Nrf2 because neither proteasomal nor lysosomal inhibitors had any effects. Overexpression of ENC1 did not result in a change in the level of Nrf2 mRNA, rather, it caused a decrease in the rate of Nrf2 protein synthesis. These results demonstrate that ENC1 functions as a negative regulator of Nrf2 through suppressing Nrf2 protein translation, which adds another level of complexity in controlling the Nrf2 signaling pathway.

  12. Estrogen levels regulate the subcellular distribution of phosphorylated Akt in hippocampal CA1 dendrites.

    Science.gov (United States)

    Znamensky, Vladimir; Akama, Keith T; McEwen, Bruce S; Milner, Teresa A

    2003-03-15

    In addition to genomic pathways, estrogens may regulate gene expression by activating specific signal transduction pathways, such as that involving phosphatidylinositol 3-kinase (PI3-K) and the subsequent phosphorylation of Akt (protein kinase B). The Akt pathway regulates various cellular events, including the initiation of protein synthesis. Our previous studies showed that synaptogenesis in hippocampal CA1 pyramidal cell dendritic spines is highest when brain estrogen levels are highest. To address the role of Akt in this process, the subcellular distribution of phosphorylated Akt immunoreactivity (pAkt-I) in the hippocampus of female rats across the estrous cycle and male rats was analyzed by light microscopy (LM) and electron microscopy (EM). By LM, the density of pAkt-I in stratum radiatum of CA1 was significantly higher in proestrus rats (or in estrogen-supplemented ovariectomized females) compared with diestrus, estrus, or male rats. By EM, pAkt-I was found throughout the shafts and in select spines of stratum radiatum dendrites. Quantitative ultrastructural analysis identifying pAkt-I with immunogold particles revealed that proestrus rats compared with diestrus, estrus, and male rats contained significantly higher pAkt-I associated with (1) dendritic spines (both cytoplasm and plasmalemma), (2) spine apparati located within 0.1 microm of dendritic spine bases, (3) endoplasmic reticula and polyribosomes in the cytoplasm of dendritic shafts, and (4) the plasmalemma of dendritic shafts. These findings suggest that estrogens may regulate spine formation in CA1 pyramidal neurons via Akt-mediated signaling events.

  13. Bilirubin Increases Insulin Sensitivity by Regulating Cholesterol Metabolism, Adipokines and PPARγ Levels

    Science.gov (United States)

    Liu, Jinfeng; Dong, Huansheng; Zhang, Yong; Cao, Mingjun; Song, Lili; Pan, Qingjie; Bulmer, Andrew; Adams, David B.; Dong, Xiao; Wang, Hongjun

    2015-01-01

    Obesity can cause insulin resistance and type 2 diabetes. Moderate elevations in bilirubin levels have anti-diabetic effects. This study is aimed at determining the mechanisms by which bilirubin treatment reduces obesity and insulin resistance in a diet-induced obesity (DIO) mouse model. DIO mice were treated with bilirubin or vehicle for 14 days. Body weights, plasma glucose, and insulin tolerance tests were performed prior to, immediately, and 7 weeks post-treatment. Serum lipid, leptin, adiponectin, insulin, total and direct bilirubin levels were measured. Expression of factors involved in adipose metabolism including sterol regulatory element-binding protein (SREBP-1), insulin receptor (IR), and PPARγ in liver were measured by RT-PCR and Western blot. Compared to controls, bilirubin-treated mice exhibited reductions in body weight, blood glucose levels, total cholesterol (TC), leptin, total and direct bilirubin, and increases in adiponectin and expression of SREBP-1, IR, and PPARγ mRNA. The improved metabolic control achieved by bilirubin-treated mice was persistent: at two months after treatment termination, bilirubin-treated DIO mice remained insulin sensitive with lower leptin and higher adiponectin levels, together with increased PPARγ expression. These results indicate that bilirubin regulates cholesterol metabolism, adipokines and PPARγ levels, which likely contribute to increased insulin sensitivity and glucose tolerance in DIO mice. PMID:26017184

  14. Role of the state in the regulation of low-level radioactive waste

    International Nuclear Information System (INIS)

    Brenneman, F.N.; Salomon, S.N.

    1983-03-01

    This document describes the role of the State in the regulation of low-level radioactive waste in the context of the Low-Level Radioactive Waste Policy Act of 1980 (Public Law 96-573), which recognizes that the States are responsible for disposal of the waste and as such may develop interstate compacts. The perspective is the present national regulatory framework for the waste system, including generation, transport, treatment, storage and disposal. Although not a definitive legal statement of the area in which States may properly act, the regulatory authority of all Compact States as Agreement States, States with a limited Agreement, and as non-Agreement States is described. The analysis is based on the assumption that the disposal site is State land

  15. F-box only protein 2 (Fbxo2) regulates amyloid precursor protein levels and processing.

    Science.gov (United States)

    Atkin, Graham; Hunt, Jack; Minakawa, Eiko; Sharkey, Lisa; Tipper, Nathan; Tennant, William; Paulson, Henry L

    2014-03-07

    The amyloid precursor protein (APP) is an integral membrane glycoprotein whose cleavage products, particularly amyloid-β, accumulate in Alzheimer disease (AD). APP is present at synapses and is thought to play a role in both the formation and plasticity of these critical neuronal structures. Despite the central role suggested for APP in AD pathogenesis, the mechanisms regulating APP in neurons and its processing into cleavage products remain incompletely understood. F-box only protein 2 (Fbxo2), a neuron-enriched ubiquitin ligase substrate adaptor that preferentially binds high-mannose glycans on glycoproteins, was previously implicated in APP processing by facilitating the degradation of the APP-cleaving β-secretase, β-site APP-cleaving enzyme. Here, we sought to determine whether Fbxo2 plays a similar role for other glycoproteins in the amyloid processing pathway. We present in vitro and in vivo evidence that APP is itself a substrate for Fbxo2. APP levels were decreased in the presence of Fbxo2 in non-neuronal cells, and increased in both cultured hippocampal neurons and brain tissue from Fbxo2 knock-out mice. The processing of APP into its cleavage products was also increased in hippocampi and cultured hippocampal neurons lacking Fbxo2. In hippocampal slices, this increase in cleavage products was accompanied by a significant reduction in APP at the cell surface. Taken together, these results suggest that Fbxo2 regulates APP levels and processing in the brain and may play a role in modulating AD pathogenesis.

  16. Energy Conservation Analysis and Control of Hybrid Active Semiactive Suspension with Three Regulating Damping Levels

    Directory of Open Access Journals (Sweden)

    Long Chen

    2016-01-01

    Full Text Available Active suspension has not been popularized for high energy consumption. To address this issue, this paper introduces the concept of a new kind of suspension. The linear motor is considered to be integrated into an adjustable shock absorber to form the hybrid active semiactive suspension (HASAS. To realize the superiority of HASAS, its energy consumption and regeneration mechanisms are revealed. And the system controller which is composed of linear quadratic regulator (LQR controller, mode decision and switch controller, and the sliding mode control based thrust controller is developed. LQR controller is designed to maintain the suspension control objectives, while mode decision and switch controller decides the optimal damping level to tune motor thrust. The thrust controller ensures motor thrust tracking. An adjustable shock absorber with three regulating levels to be used in HASAS is trial produced and tested to obtain its working characteristics. Finally, simulation analysis is made with the experimental three damping characteristics. The impacts of adjustable damping on the motor force and energy consumption are investigated. Simulation results demonstrate the advantages of HASAS in energy conservation with various suspension control objectives. Even self-powered active control and energy regenerated to the power source can be realized.

  17. Ethylene Regulates Levels of Ethylene Receptor/CTR1 Signaling Complexes in Arabidopsis thaliana*

    Science.gov (United States)

    Shakeel, Samina N.; Gao, Zhiyong; Amir, Madiha; Chen, Yi-Feng; Rai, Muneeza Iqbal; Haq, Noor Ul; Schaller, G. Eric

    2015-01-01

    The plant hormone ethylene is perceived by a five-member family of receptors in Arabidopsis thaliana. The receptors function in conjunction with the Raf-like kinase CTR1 to negatively regulate ethylene signal transduction. CTR1 interacts with multiple members of the receptor family based on co-purification analysis, interacting more strongly with receptors containing a receiver domain. Levels of membrane-associated CTR1 vary in response to ethylene, doing so in a post-transcriptional manner that correlates with ethylene-mediated changes in levels of the ethylene receptors ERS1, ERS2, EIN4, and ETR2. Interactions between CTR1 and the receptor ETR1 protect ETR1 from ethylene-induced turnover. Kinetic and dose-response analyses support a model in which two opposing factors control levels of the ethylene receptor/CTR1 complexes. Ethylene stimulates the production of new complexes largely through transcriptional induction of the receptors. However, ethylene also induces turnover of receptors, such that levels of ethylene receptor/CTR1 complexes decrease at higher ethylene concentrations. Implications of this model for ethylene signaling are discussed. PMID:25814663

  18. Galanin regulates blood glucose level in the zebrafish: a morphological and functional study.

    Science.gov (United States)

    Podlasz, P; Jakimiuk, A; Chmielewska-Krzesinska, M; Kasica, N; Nowik, N; Kaleczyc, J

    2016-01-01

    The present study has demonstrated the galaninergic innervation of the endocrine pancreas including sources of the galaninergic nerve fibers, and the influence of galanin receptor agonists on blood glucose level in the zebrafish. For the first time, a very abundant galaninergic innervation of the endocrine pancreas during development is shown, from the second day post-fertilization to adulthood. The fibers originated from ganglia consisting of galanin-IR, non-adrenergic (non-sensory) neurons located rostrally to the pancreatic tissue. The ganglia were found on the dorsal side of the initial part of the anterior intestinal segment, close to the intestinal branch of the vagus nerve. The galanin-IR neurons did not show immunoreactivity for applied antibodies against tyrosine hydroxylase, choline acetyltransferase, and vesicular acetylcholine transporter. Intraperitoneal injections of galanin analog NAX 5055 resulted in a statistically significant increase in the blood glucose level. Injections of another galanin receptor agonist, galnon, also caused a rise in blood glucose level; however, it was not statistically significant. The present findings suggest that, like in mammals, in the zebrafish galanin is involved in the regulation of blood glucose level. However, further studies are needed to elucidate the exact mechanism of the galanin action.

  19. The influence of high and low levels of estrogen on diurnal urine regulation in young women

    Directory of Open Access Journals (Sweden)

    Bie Peter

    2008-11-01

    Full Text Available Abstract Background Sex hormones have a pronounced effect on arginine vasopressin (AVP, and therefore on the diurnal water homeostasis. Low and high levels of plasma-estradiol as seen in the follicular phase of the menstrual cycle may therefore alter the diurnal regulation of urine production. Furthermore the structural resemblance of oxytocin to vasopressin has led to speculations about the possible antidiuretic properties of oxytocin under normal physiological conditions. To elucidate the influence of high and low p-estradiol on the regulation of the diurnal urine production, 15 normal menstruating women (21–33 y underwent two circadian in-patient investigations, both situated in follicular phase. Methods Admitting the participants solely in the follicular phase resulted in high and low plasma-estradiol whereas plasma-progesterone was similar. Urine and blood samples were taken at predetermined time points to determine plasma AVP, plasma oxytocin, plasma aldosterone, plasma natriuretic peptide (ANP, urinary solute excretions, and urinary excretions of prostaglandin E2 (PGE-2 and aquaporin-2 (AQP-2. Blood pressure was measured every hour. Results Plasma AVP, plasma aldosterone and plasma ANP were unaffected by the different levels of estradiol. All had marked circadian variations whereas oxytocin did not display any circadian rhythm. High estradiol resulted in lower p-osmolality and p-sodium reflecting the downward resetting of the osmoreceptors. Oxytocin did not correlate with either diuresis or urine osmolality. The diurnal urine production was similar in the two groups as were urine osmolality, excretion of PGE-2 and AQP-2. AQP-2 does not have a circadian rhythm and is not significantly correlated to either AVP or oxytocin under normal physiological conditions. Conclusion High and low level of estradiol has no influence on the circadian rhythm of AVP or the subsequent urine production. High p-estradiol resets the osmoreceptors for AVP

  20. [THE INCONSISTENCIES OF REGULATION OF METABOLISM IN PHYLOGENESIS AT THREE LEVELS OF "RELATIVE BIOLOGICAL PERFECTION": ETIOLOGY OF METABOLIC PANDEMICS].

    Science.gov (United States)

    Titov, V N

    2015-11-01

    The regulation of metabolism in vivo can be comprehended by considering stages of becoming inphylogenesis of humoral, hormonal, vegetative regulators separately: at the level of cells; in paracrin-regulated cenosises of cells; organs and systems under open blood circulation and closed system of blood flow. The levels of regulations formed at different stages of phylogenesis. Their completion occurred at achievement of "relative biological perfection". Only this way need of cells in functional, structural interaction and forming of multicellular developed. The development of organs and systems of organs also completed at the level of "relative biological perfection". From the same level the third stage of becoming of regulation of metabolism at the level of organism started. When three conditions of "relative biological perfection" achieved consequently at level in vivo are considered in species Homo sapiens using system approach it is detected that "relative biological perfection" in vivo is accompanied by different inconsistencies of regulation of metabolism. They are etiologic factors of "metabolic pandemics ". The inconsistencies (etiological factors) are consider as exemplified by local (at the level of paracrin-regulated cenosises of cells) and system (at the level of organism) regulation of biological reaction metabolism-microcirculation that results in dysfunction of target organs and development of pathogenesis of essential metabolic arterial hypertension. The article describes phylogenetic difference between visceral fatty cells and adpocytes, regulation of metabolism by phylogenetically late insulin, reaction of albumin at increasing of content of unesterified fatty acids in blood plasma, difference of function of resident macrophage and monocytes-macrophages in pathogenesis of atherosclerosis, metabolic syndrome, insulin resistance, obesity, under diabetes mellitus and essential metabolic arterial hypertension.

  1. Novel E3 ubiquitin ligases that regulate histone protein levels in the budding yeast Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Rakesh Kumar Singh

    Full Text Available Core histone proteins are essential for packaging the genomic DNA into chromatin in all eukaryotes. Since multiple genes encode these histone proteins, there is potential for generating more histones than what is required for chromatin assembly. The positively charged histones have a very high affinity for negatively charged molecules such as DNA, and any excess of histone proteins results in deleterious effects on genomic stability and cell viability. Hence, histone levels are known to be tightly regulated via transcriptional, posttranscriptional and posttranslational mechanisms. We have previously elucidated the posttranslational regulation of histone protein levels by the ubiquitin-proteasome pathway involving the E2 ubiquitin conjugating enzymes Ubc4/5 and the HECT (Homologous to E6-AP C-Terminus domain containing E3 ligase Tom1 in the budding yeast. Here we report the identification of four additional E3 ligases containing the RING (Really Interesting New Gene finger domains that are involved in the ubiquitylation and subsequent degradation of excess histones in yeast. These E3 ligases are Pep5, Snt2 as well as two previously uncharacterized Open Reading Frames (ORFs YKR017C and YDR266C that we have named Hel1 and Hel2 (for Histone E3 Ligases respectively. Mutants lacking these E3 ligases are sensitive to histone overexpression as they fail to degrade excess histones and accumulate high levels of endogenous histones on histone chaperones. Co-immunoprecipitation assays showed that these E3 ligases interact with the major E2 enzyme Ubc4 that is involved in the degradation related ubiquitylation of histones. Using mutagenesis we further demonstrate that the RING domains of Hel1, Hel2 and Snt2 are required for histone regulation. Lastly, mutants corresponding to Hel1, Hel2 and Pep5 are sensitive to replication inhibitors. Overall, our results highlight the importance of posttranslational histone regulatory mechanisms that employ multiple E3

  2. The Csr System Regulates Escherichia coli Fitness by Controlling Glycogen Accumulation and Energy Levels.

    Science.gov (United States)

    Morin, Manon; Ropers, Delphine; Cinquemani, Eugenio; Portais, Jean-Charles; Enjalbert, Brice; Cocaign-Bousquet, Muriel

    2017-10-31

    In the bacterium Escherichia coli , the posttranscriptional regulatory system Csr was postulated to influence the transition from glycolysis to gluconeogenesis. Here, we explored the role of the Csr system in the glucose-acetate transition as a model of the glycolysis-to-gluconeogenesis switch. Mutations in the Csr system influence the reorganization of gene expression after glucose exhaustion and disturb the timing of acetate reconsumption after glucose exhaustion. Analysis of metabolite concentrations during the transition revealed that the Csr system has a major effect on the energy levels of the cells after glucose exhaustion. This influence was demonstrated to result directly from the effect of the Csr system on glycogen accumulation. Mutation in glycogen metabolism was also demonstrated to hinder metabolic adaptation after glucose exhaustion because of insufficient energy. This work explains how the Csr system influences E. coli fitness during the glycolysis-gluconeogenesis switch and demonstrates the role of glycogen in maintenance of the energy charge during metabolic adaptation. IMPORTANCE Glycogen is a polysaccharide and the main storage form of glucose from bacteria such as Escherichia coli to yeasts and mammals. Although its function as a sugar reserve in mammals is well documented, the role of glycogen in bacteria is not as clear. By studying the role of posttranscriptional regulation during metabolic adaptation, for the first time, we demonstrate the role of sugar reserve played by glycogen in E. coli Indeed, glycogen not only makes it possible to maintain sufficient energy during metabolic transitions but is also the key component in the capacity of cells to resume growth. Since the essential posttranscriptional regulatory system Csr is a major regulator of glycogen accumulation, this work also sheds light on the central role of posttranscriptional regulation in metabolic adaptation. Copyright © 2017 Morin et al.

  3. A Systems-Level Analysis Reveals Circadian Regulation of Splicing in Colorectal Cancer.

    Science.gov (United States)

    El-Athman, Rukeia; Fuhr, Luise; Relógio, Angela

    2018-06-20

    Accumulating evidence points to a significant role of the circadian clock in the regulation of splicing in various organisms, including mammals. Both dysregulated circadian rhythms and aberrant pre-mRNA splicing are frequently implicated in human disease, in particular in cancer. To investigate the role of the circadian clock in the regulation of splicing in a cancer progression context at the systems-level, we conducted a genome-wide analysis and compared the rhythmic transcriptional profiles of colon carcinoma cell lines SW480 and SW620, derived from primary and metastatic sites of the same patient, respectively. We identified spliceosome components and splicing factors with cell-specific circadian expression patterns including SRSF1, HNRNPLL, ESRP1, and RBM 8A, as well as altered alternative splicing events and circadian alternative splicing patterns of output genes (e.g., VEGFA, NCAM1, FGFR2, CD44) in our cellular model. Our data reveals a remarkable interplay between the circadian clock and pre-mRNA splicing with putative consequences in tumor progression and metastasis. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Voyageurs National Park: Water-level regulation and effects on water quality and aquatic biology

    Science.gov (United States)

    Christensen, Victoria G.; Maki, Ryan P.; LeDuc, Jaime F.

    2018-01-01

    Following dam installations in the remote Rainy Lake Basin during the early 1900s, water-level fluctuations were considered extreme (1914–1949) compared to more natural conditions. In 1949, the International Joint Commission (IJC), which sets rules governing dam operation on waters shared by the United States and Canada, established the first rule curves to regulate water levels on these waterbodies. However, rule curves established prior to 2000 were determined to be detrimental to the ecosystem. Therefore, the IJC implemented an order in 2000 to change rule curves and to restore a more natural water regime. After 2000, measured chlorophyll-a concentrations in the two most eutrophic water bodies decreased whereas concentrations in oligotrophic lakes did not show significant water-quality differences. Fish mercury data were inconclusive, due to the variation in water levels and fish mercury concentrations, but can be used by the IJC as part of a long term data set.

  5. BolA inhibits cell elongation and regulates MreB expression levels.

    Science.gov (United States)

    Freire, Patrick; Moreira, Ricardo Neves; Arraiano, Cecília Maria

    2009-02-06

    The morphogene bolA is a general stress response gene in Escherichia coli that induces a round morphology when overexpressed. Results presented in this report show that increased BolA levels can inhibit cell elongation mechanisms. MreB polymerization is crucial for the bacterial cell cytoskeleton, and this protein is essential for the maintenance of a cellular rod shape. In this report, we demonstrate that bolA overexpression affects the architecture of MreB filaments. An increase in BolA leads to a significant reduction in MreB protein levels and mreB transcripts. BolA affects the mreBCD operon in vivo at the level of transcription. Furthermore, our results show that BolA is a new transcriptional repressor of MreB. The alterations in cell morphology induced by bolA seem to be mediated by a complex pathway that integrates PBP5, PBP6, MreB, and probably other regulators of cell morphology/elongation.

  6. Low-level radioactive waste disposal in the United States: An overview of current commercial regulations and concepts

    International Nuclear Information System (INIS)

    Kennedy, W.E. Jr.

    1993-08-01

    Commercial low-level radioactive waste disposal in the United States is regulated by the US Nuclear Regulatory Commission (NRC) under 10 CFR 61 (1991). This regulation was issued in 1981 after a lengthy and thorough development process that considered the radionuclide concentrations and characteristics associated with commercial low-level radioactive waste streams; alternatives for waste classification; alternative technologies for low-level radioactive waste disposal; and data, modeling, and scenario analyses. The development process also included the publication of both draft and final environmental impact statements. The final regulation describes the general provisions; licenses; performance objectives; technical requirements for land disposal; financial assurances; participation by state governments and Indian tribes; and records, reports, tests, and inspections. This paper provides an overview of, and tutorial on, current commercial low-level radioactive waste disposal regulations in the United States

  7. NRC regulations for disposal of high-level radioactive wastes in geologic repositories: technical criteria

    International Nuclear Information System (INIS)

    Martin, J.B.; Bell, M.J.; Regnier, E.P.

    1983-01-01

    The Nuclear Regulatory Commission is promulgating regulations specifying the technical criteria fo disposal of high-level radioactive wastes in geologic repositories. The proposed rule was published for public comment in July 1981. Public comments have been received and considered by the Commission staff. The Commission will soon approve and publish a revised final rule. While the final rule being considered by the Commission is fundamentally the same as the proposed rule, provisions have been added to permit flexibility in the application of numerical criteria, some detailed design requirements have been deleted, and other changes have been made in response to comments. The rule is consistent with the recently enacted Nuclear Waste Policy Act of 1982

  8. Regulating Emotional Responses to Climate Change – A Construal Level Perspective

    Directory of Open Access Journals (Sweden)

    Emma Ejelöv

    2018-05-01

    Full Text Available This experimental study (N = 139 examines the role of emotions in climate change risk communication. Drawing on Construal Level Theory, we tested how abstract vs. concrete descriptions of climate threat affect basic and self-conscious emotions and three emotion regulation strategies: changing oneself, repairing the situation and distancing oneself. In a 2 × 2 between subjects factorial design, climate change consequences were described as concrete/abstract and depicted as spatially proximate/distant. Results showed that, as hypothesized, increased self-conscious emotions mediate overall positive effects of abstract description on self-change and repair attempts. Unexpectedly and independent of any emotional process, a concrete description of a spatially distant consequence is shown to directly increase self-change and repair attempts, while it has no such effects when the consequence is spatially proximate. “Concretizing the remote” might refer to a potentially effective strategy for overcoming spatial distance barriers and motivating mitigating behavior.

  9. Low-level feedback control for the phase regulation of CLIC Drive Beam Klystrons

    CERN Document Server

    AUTHOR|(SzGeCERN)752526

    2015-01-01

    The requirement of luminosity loss below 1% raises tight tolerances for the phase and power stability of the CLIC drive beam (DB) klystrons and consequently for the high voltage pulse ripple of the modulators. A low-level RF (LLRF) feedback system needs to be developed and combined with the modulator in order to guarantee the phase and amplitude tolerances. To this aim, three feedback control strategies were investigated, i) Proportional Integral (PI) controller, ii) Linear Quadratic Integral Regulator (LQI) and iii) Model Predictive Controller (MPC). The klystron, as well as the incident phase noise were modelled and used for the design and evaluation of the controllers. First simulation results are presented along with future steps and directions.

  10. Human Lung Mast Cell Products Regulate Airway Smooth Muscle CXCL10 Levels.

    Science.gov (United States)

    Alkhouri, H; Cha, V; Tong, K; Moir, L M; Armour, C L; Hughes, J M

    2014-01-01

    In asthma, the airway smooth muscle (ASM) produces CXCL10 which may attract CXCR3(+) mast/T cells to it. Our aim was to investigate the effects of mast cell products on ASM cell CXCL10 production. ASM cells from people with and without asthma were stimulated with IL-1 β , TNF- α , and/or IFN γ and treated with histamine (1-100  μ M) ± chlorpheniramine (H1R antagonist; 1  μ M) or ranitidine (H2R antagonist; 50  μ M) or tryptase (1 nM) ± leupeptin (serine protease inhibitor; 50  μ M), heat-inactivated tryptase, or vehicle for 4 h or 24 h. Human lung mast cells (MC) were isolated and activated with IgE/anti-IgE and supernatants were collected after 2 h or 24 h. The supernatants were added to ASM cells for 48 h and ASM cell CXCL10 production detected using ELISA (protein) and real-time PCR (mRNA). Histamine reduced IL-1 β /TNF- α -induced CXCL10 protein, but not mRNA, levels independent of H1 and H2 receptor activation, whereas tryptase and MC 2 h supernatants reduced all cytokine-induced CXCL10. Tryptase also reduced CXCL10 levels in a cell-free system. Leupeptin inhibited the effects of tryptase and MC 2 h supernatants. MC 24 h supernatants contained TNF- α and amplified IFN γ -induced ASM cell CXCL10 production. This is the first evidence that MC can regulate ASM cell CXCL10 production and its degradation. Thus MC may regulate airway myositis in asthma.

  11. Nitric oxide mitigates salt stress by regulating levels of osmolytes and antioxidant enzymes in chickpea

    Directory of Open Access Journals (Sweden)

    Parvaiz eAhmad

    2016-03-01

    Full Text Available This work was designed to evaluate whether external application of nitric oxide (NO in the form of its donor S-nitroso-N-acetylpenicillamine (SNAP could mitigate the deleterious effects of NaCl stress on chickpea (Cicer arietinum L. plants. SNAP (50 μM was applied to chickpea plants grown under non-saline and saline conditions (50 and 100 mM NaCl. Salt stress negatively affected growth and biomass yield, leaf relative water content (LRWC and chlorophyll content of chickpea plants. High salinity increased electrolyte leakage, carotenoid content and the levels of osmolytes (proline, glycine betaine, soluble proteins and soluble sugars, hydrogen peroxide (H2O2 and malondialdehyde (MDA, as well as the activities of antioxidant enzymes, such as superoxide dismutase (SOD, catalase (CAT, ascorbate peroxidase (APX, and glutathione reductase (GR in chickpea plants. Expression of the representative SOD, CAT and APX genes examined was also up-regulated in chickpea plants by salt stress. On the other hand, exogenous application of NO to salinized plants enhanced the growth parameters, LRWC, photosynthetic pigment production and levels of osmolytes, as well as the activities of examined antioxidant enzymes which is correlated with up-regulation of the examined SOD, CAT and APX genes, in comparison with plants treated with NaCl only. Furthermore, electrolyte leakage, H2O2 and MDA contents showed decline in salt-stressed plants supplemented with NO as compared with those in NaCl-treated plants alone. Thus, the exogenous application of NO protected chickpea plants against salt-induced oxidative damage by enhancing the biosynthesis of antioxidant enzymes, thereby improving plant growth under saline stress. Taken together, our results demonstrate that NO has capability to mitigate the adverse effects of high salinity on chickpea plants by improving LRWC, photosynthetic pigment biosyntheses, osmolyte accumulation and antioxidative defense system.

  12. Circulating levels of human salusin-β, a potent hemodynamic and atherogenesis regulator.

    Directory of Open Access Journals (Sweden)

    Kazumi Fujimoto

    Full Text Available Using bioinformatics analysis, we previously identified salusin-β, an endogenous bioactive peptide with diverse physiological activities. Salusin-β is abundantly expressed in the neuroendocrine system and in systemic endocrine cells/macrophages. Salusin-β acutely regulates hemodynamics and chronically induces atherosclerosis, but its unique physicochemical characteristics to tightly adhere to all types of plastic and glassware have prevented elucidation of its precise pathophysiological role. To quantitate plasma total salusin-β concentrations, we produced rabbit and chicken polyclonal antibodies against the C- and N-terminal end sequences, circumvented its sticky nature, and successfully established a sandwich enzyme-linked immunosorbent assay (ELISA. Salusin-β was abundantly present in the plasma of healthy volunteers, ranging from 1.9 to 6.6 nmol/L. Reverse phase-high performance liquid chromatography analysis showed that a single immunoreactive salusin-β peak coincided with synthetic authentic salusin-β. Plasma salusin-β concentrations were unaffected by postural changes and by potent vasopressin release stimuli, such as hypertonic saline infusion or smoking. However, salusin-β concentrations showed significant circadian variation; concentrations were high during the daytime and reached the lowest concentrations in the early morning. Plasma salusin-β levels in subjects with diabetes mellitus, coronary artery disease, and cerebrovascular disease showed distinctly higher levels than healthy controls. Patients with panhypopituitarism combined with complete central diabetes insipidus also showed significantly higher plasma salusin-β levels. Therefore, the ELISA system developed in this study will be useful for evaluating circulating total salusin-β levels and for confirming the presence of authentic salusin-β in human plasma. The obtained results suggest a limited contribution of the neuroendocrine system to peripheral total salusin

  13. Does dietary iodine regulate oxidative stress and adiponectin levels in human breast milk?

    Science.gov (United States)

    Gutiérrez-Repiso, Carolina; Velasco, Inés; Garcia-Escobar, Eva; Garcia-Serrano, Sara; Rodríguez-Pacheco, Francisca; Linares, Francisca; Ruiz de Adana, Maria Soledad; Rubio-Martin, Elehazara; Garrido-Sanchez, Lourdes; Cobos-Bravo, Juan Francisco; Priego-Puga, Tatiana; Rojo-Martinez, Gemma; Soriguer, Federico; García-Fuentes, Eduardo

    2014-02-10

    Little is known about the association between iodine and human milk composition. In this study, we investigated the association between iodine and different markers of oxidative stress and obesity-related hormones in human breast milk. This work is composed of two cross-sectional studies (in lactating women and in the general population), one prospective and one in vitro. In the cross-sectional study in lactating women, the breast milk iodine correlated negatively with superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) activities, and with adiponectin levels. An in vitro culture of human adipocytes with 1 μM potassium iodide (KI, dose similar to the human breast milk iodine concentration) produced a significant decrease in adiponectin, GSH-Px, SOD1, and SOD2 mRNA expression. However, after 2 months of treatment with KI in the prospective study, a positive correlation was found between 24-h urinary iodine and serum adiponectin. Our observations lead to the hypothesis that iodine may be a factor directly involved in the regulation of oxidative stress and adiponectin levels in human breast milk.

  14. How exogenous nitric oxide regulates nitrogen assimilation in wheat seedlings under different nitrogen sources and levels.

    Science.gov (United States)

    Balotf, Sadegh; Islam, Shahidul; Kavoosi, Gholamreza; Kholdebarin, Bahman; Juhasz, Angela; Ma, Wujun

    2018-01-01

    Nitrogen (N) is one of the most important nutrients for plants and nitric oxide (NO) as a signaling plant growth regulator involved in nitrogen assimilation. Understanding the influence of exogenous NO on nitrogen metabolism at the gene expression and enzyme activity levels under different sources of nitrogen is vitally important for increasing nitrogen use efficiency (NUE). This study investigated the expression of key genes and enzymes in relation to nitrogen assimilation in two Australian wheat cultivars, a popular high NUE cv. Spitfire and a normal NUE cv. Westonia, under different combinations of nitrogen and sodium nitroprusside (SNP) as the NO donor. Application of NO increased the gene expressions and activities of nitrogen assimilation pathway enzymes in both cultivars at low levels of nitrogen. At high nitrogen supplies, the expressions and activities of N assimilation genes increased in response to exogenous NO only in cv. Spitfire but not in cv. Westonia. Exogenous NO caused an increase in leaf NO content at low N supplies in both cultivars, while under high nitrogen treatments, cv. Spitfire showed an increase under ammonium nitrate (NH4NO3) treatment but cv. Westonia was not affected. N assimilation gene expression and enzyme activity showed a clear relationship between exogenous NO, N concentration and N forms in primary plant nitrogen assimilation. Results reveal the possible role of NO and different nitrogen sources on nitrogen assimilation in Triticum aestivum plants.

  15. Down-regulated resistin level in consequence of decreased neutrophil counts in untreated Grave's disease.

    Science.gov (United States)

    Peng, Ying; Qi, Yicheng; Huang, Fengjiao; Chen, Xinxin; Zhou, Yulin; Ye, Lei; Wang, Weiqing; Ning, Guang; Wang, Shu

    2016-11-29

    Resistin, belongs to cysteine-rich secretory protein, is mainly produced by circulating leukocytes, such as neutrophils monocytes and macrophages in humans. To date, few but controversial studies have reported about resistin concentrations in hyperthyroid patients, especially in Graves' disease (GD). We undertaked a controlled, prospective study to explore the serum resistin concentration in GD patients before and after -MMI treatment. In addition, we also investigated the main influencing factor on serum resistin level and discuessed the potential role of serum resistin plays in GD patients. 39 untreated GD (uGD) patients, including 8 males and 31 females, were enrolled in our investigation. All of these patients were prescribed with MMI treatment, in addition to 25 healthy controls. Anthropometric parameters and hormone assessment were measured. Enzyme-linked immunosorbent assay was used to detect serum resistin concentration in different stages of GD patients. Furthermore, neutrophil cell line NB4 with or without T3 treatment to detect the effect of thyroid hormones on resistin expression. The serum resistin level and neutrophil counts in untreated GD patients were significantly declined. And all of these parameters were recovered to normal after MMI treatment in ethyroid GD (eGD) and TRAb-negative conversion (nGD) patients. Resistin concentration exhibited a negative correlation with FT3 and FT4, but a positive correlation with absolute number of neutrophiles in uGD patients, whereas did not correlate with thyroid autoimmune antibodies and BMI. Neutrophile cell line, NB4, produced decreased expression of resistin when stimulated with T3. Our study showed a decrease of serum resistin level in GD patients and we suggested that the serum resistin might primarily secreted from circulating neutrophils and down-regulated by excessive thyroid hormones in GD patients.

  16. Genetic regulation of serum phytosterol levels and risk of coronary artery disease.

    Science.gov (United States)

    Teupser, Daniel; Baber, Ronny; Ceglarek, Uta; Scholz, Markus; Illig, Thomas; Gieger, Christian; Holdt, Lesca M; Leichtle, Alexander; Greiser, Karin H; Huster, Dominik; Linsel-Nitschke, Patrick; Schäfer, Arne; Braund, Peter S; Tiret, Laurence; Stark, Klaus; Raaz-Schrauder, Dorette; Fiedler, Georg M; Wilfert, Wolfgang; Beutner, Frank; Gielen, Stephan; Grosshennig, Anika; König, Inke R; Lichtner, Peter; Heid, Iris M; Kluttig, Alexander; El Mokhtari, Nour E; Rubin, Diana; Ekici, Arif B; Reis, André; Garlichs, Christoph D; Hall, Alistair S; Matthes, Gert; Wittekind, Christian; Hengstenberg, Christian; Cambien, Francois; Schreiber, Stefan; Werdan, Karl; Meitinger, Thomas; Loeffler, Markus; Samani, Nilesh J; Erdmann, Jeanette; Wichmann, H-Erich; Schunkert, Heribert; Thiery, Joachim

    2010-08-01

    Phytosterols are plant-derived sterols that are taken up from food and can serve as biomarkers of cholesterol uptake. Serum levels are under tight genetic control. We used a genomic approach to study the molecular regulation of serum phytosterol levels and potential links to coronary artery disease (CAD). A genome-wide association study for serum phytosterols (campesterol, sitosterol, brassicasterol) was conducted in a population-based sample from KORA (Cooperative Research in the Region of Augsburg) (n=1495) with subsequent replication in 2 additional samples (n=1157 and n=1760). Replicated single-nucleotide polymorphisms (SNPs) were tested for association with premature CAD in a metaanalysis of 11 different samples comprising 13 764 CAD cases and 13 630 healthy controls. Genetic variants in the ATP-binding hemitransporter ABCG8 and at the blood group ABO locus were significantly associated with serum phytosterols. Effects in ABCG8 were independently related to SNPs rs4245791 and rs41360247 (combined P=1.6 x 10(-50) and 6.2 x 10(-25), respectively; n=4412). Serum campesterol was elevated 12% for each rs4245791 T-allele. The same allele was associated with 40% decreased hepatic ABCG8 mRNA expression (P=0.009). Effects at the ABO locus were related to SNP rs657152 (combined P=9.4x10(-13)). Alleles of ABCG8 and ABO associated with elevated phytosterol levels displayed significant associations with increased CAD risk (rs4245791 odds ratio, 1.10; 95% CI, 1.06 to 1.14; P=2.2 x 10(-6); rs657152 odds ratio, 1.13; 95% CI, 1.07 to 1.19; P=9.4 x 10(-6)), whereas alleles at ABCG8 associated with reduced phytosterol levels were associated with reduced CAD risk (rs41360247 odds ratio, 0.84; 95% CI, 0.78 to 0.91; P=1.3 x 10(-5)). Common variants in ABCG8 and ABO are strongly associated with serum phytosterol levels and show concordant and previously unknown associations with CAD.

  17. A Study of Translation Students' Self-Regulation and Metacognitive Awareness in Association with their Gender and Educational Level

    Directory of Open Access Journals (Sweden)

    Mona Hashempour

    2015-07-01

    Full Text Available The present study sought to investigate the probable link between Iranian English translation studies students’ metacognitive awareness, self-regulation, and gender. Furthermore, the role of educational level of translation students in metacognitive awareness and self-regulation was explored. For the purpose of the study, a sample of 230 M.A and B.A senior English translation students comprised the participants of the research. They were asked to complete two questionnaires of Metacognitive Awareness Inventory (MAI and Self-regulation Trait (SRT.The Metacognitive Awareness Inventory (MAI was developed by Schraw and Dennison (1994 and consists of 52 statements. It measures two components of metacognition: metacognitive knowledge and metacognitive regulation. Metacognitive knowledge comprises three subscales: Declarative knowledge, Procedural knowledge, and Conditional knowledge. Metacognitive regulation consists of five subscales: Planning, Information management, Monitoring, Debugging, and Evaluation. The self-regulation trait (SRT questionnaire was designed by O'Neil and Herl (1998. It was developed based on Zimmerman's self –regulation model. It consists of 32 Likert-scale questions. The scale seeks to measure metacognition and motivation dimensions.  Each dimension comprises two sub-scales. Meta-cognition covers the constructs of planning and self-monitoring, and motivation contains effort and self-efficacy. Independent samples t-tests were run to investigate the role of gender and educational level in the level of translation students’ metacognitive awareness and self-regulation. The results of t-test demonstrated that there are not any differences between male and female translation students regarding metacognitive awareness and self-regulation. It was also found that there is a negative significant impact of educational level on total metacognitive awareness, and some components of metacognitive awareness: declarative knowledge

  18. No-observed effect levels are associated with up-regulation of MGMT following MMS exposure.

    Science.gov (United States)

    Doak, Shareen H; Brüsehafer, Katja; Dudley, Ed; Quick, Emma; Johnson, George; Newton, Russell P; Jenkins, Gareth J S

    2008-12-15

    The alkylating agents methyl methanesulphonate (MMS) and ethyl methanesulphonate (EMS) have non-linear dose-response curves, with a no-observed effect level (NOEL) and a lowest observed effect level (LOEL) for both gross chromosomal damage and mutagenicity. However, the biological mechanism responsible for the NOEL has yet to be identified. A strong candidate is DNA repair as it may be able to efficiently remove alkyl adducts at low doses resulting in a NOEL, but at higher doses fails to fully remove all lesions due to saturation of enzymatic activity resulting in a LOEL and subsequent linear increases in mutagenicity. We therefore assessed the transcriptional status of N-methylpurine-DNA glycoslase (MPG) and O(6)-methylguanine DNA methyltransferase (MGMT), which represent the first line of defence following exposure to alkylating agents through the respective enzymatic removal of N7-alkylG and O(6)-alkylG. The relative MPG and MGMT gene expression profiles were assessed by real-time RT-PCR following exposure to 0-2 microg/ml MMS for 1-24h. MPG expression remained fairly steady, but in contrast significant up-regulation of MGMT was observed when cells were treated with 0.5 and 1.0 microg/ml MMS for 4h (2.5- and 6.5-fold increases respectively). These doses lie within the NOEL for MMS mutagenicity (LOEL is 1.25 microg/ml), thus this boost in MGMT expression at low doses may be responsible for efficiently repairing O(6)methylG lesions and creating the non-linear response for mutations. However, as the LOEL for MMS clastogenicity is 0.85 microg/ml, O(6)-alkylG is unlikely to be responsible for the clastogenicity observed at these concentrations. Consequently, at low doses N7-methylG is possibly the predominant cause of MMS clastogenicity, while O(6)-methylG is more likely to be responsible for MMS mutagenicity, with MGMT up-regulation playing a key role in removal of O(6)-alkylG lesions before they are fixed as permanent point mutations, resulting in non-linear dose

  19. Pairwise comparisons of ten porcine tissues identify differential transcriptional regulation at the gene, isoform, promoter and transcription start site level

    DEFF Research Database (Denmark)

    Farajzadeh, Leila; Hornshøj, Henrik; Momeni, Jamal

    2013-01-01

    , isoform, and transcription start site (TSS), and promoter level showed that several of the genes differed at all four levels. Interestingly, these genes were mainly annotated to the "electron transport chain" and neuronal differentiation, emphasizing that "tissue important" genes are regulated at several...

  20. Auxins differentially regulate root system architecture and cell cycle protein levels in maize seedlings.

    Science.gov (United States)

    Martínez-de la Cruz, Enrique; García-Ramírez, Elpidio; Vázquez-Ramos, Jorge M; Reyes de la Cruz, Homero; López-Bucio, José

    2015-03-15

    Maize (Zea mays) root system architecture has a complex organization, with adventitious and lateral roots determining its overall absorptive capacity. To generate basic information about the earlier stages of root development, we compared the post-embryonic growth of maize seedlings germinated in water-embedded cotton beds with that of plants obtained from embryonic axes cultivated in liquid medium. In addition, the effect of four different auxins, namely indole-3-acetic acid (IAA), 1-naphthaleneacetic acid (NAA), indole-3-butyric acid (IBA) and 2,4-dichlorophenoxyacetic acid (2,4-D) on root architecture and levels of the heat shock protein HSP101 and the cell cycle proteins CKS1, CYCA1 and CDKA1 were analyzed. Our data show that during the first days after germination, maize seedlings develop several root types with a simultaneous and/or continuous growth. The post-embryonic root development started with the formation of the primary root (PR) and seminal scutellar roots (SSR) and then continued with the formation of adventitious crown roots (CR), brace roots (BR) and lateral roots (LR). Auxins affected root architecture in a dose-response fashion; whereas NAA and IBA mostly stimulated crown root formation, 2,4-D showed a strong repressing effect on growth. The levels of HSP101, CKS1, CYCA1 and CDKA in root and leaf tissues were differentially affected by auxins and interestingly, HSP101 registered an auxin-inducible and root specific expression pattern. Taken together, our results show the timing of early branching patterns of maize and indicate that auxins regulate root development likely through modulation of the HSP101 and cell cycle proteins. Copyright © 2014 Elsevier GmbH. All rights reserved.

  1. Let-7 and MicroRNA-148 Regulate Parathyroid Hormone Levels in Secondary Hyperparathyroidism.

    Science.gov (United States)

    Shilo, Vitali; Mor-Yosef Levi, Irit; Abel, Roy; Mihailović, Aleksandra; Wasserman, Gilad; Naveh-Many, Tally; Ben-Dov, Iddo Z

    2017-08-01

    Secondary hyperparathyroidism commonly complicates CKD and associates with morbidity and mortality. We profiled microRNA (miRNA) in parathyroid glands from experimental hyperparathyroidism models and patients receiving dialysis and studied the function of specific miRNAs. miRNA deep-sequencing showed that human and rodent parathyroids share similar profiles. Parathyroids from uremic and normal rats segregated on the basis of their miRNA expression profiles, and a similar finding was observed in humans. We identified parathyroid miRNAs that were dysregulated in experimental hyperparathyroidism, including miR-29, miR-21, miR-148, miR-30, and miR-141 (upregulated); and miR-10, miR-125, and miR-25 (downregulated). Inhibition of the abundant let-7 family increased parathyroid hormone (PTH) secretion in normal and uremic rats, as well as in mouse parathyroid organ cultures. Conversely, inhibition of the upregulated miR-148 family prevented the increase in serum PTH level in uremic rats and decreased levels of secreted PTH in parathyroid cultures. The evolutionary conservation of abundant miRNAs in normal parathyroid glands and the regulation of these miRNAs in secondary hyperparathyroidism indicates their importance for parathyroid function and the development of hyperparathyroidism. Specifically, let-7 and miR-148 antagonism modified PTH secretion in vivo and in vitro , implying roles for these specific miRNAs. These findings may be utilized for therapeutic interventions aimed at altering PTH expression in diseases such as osteoporosis and secondary hyperparathyroidism. Copyright © 2017 by the American Society of Nephrology.

  2. Lung surfactant levels are regulated by Ig-Hepta/GPR116 by monitoring surfactant protein D.

    Directory of Open Access Journals (Sweden)

    Taku Fukuzawa

    Full Text Available Lung surfactant is a complex mixture of lipids and proteins, which is secreted from the alveolar type II epithelial cell and coats the surface of alveoli as a thin layer. It plays a crucial role in the prevention of alveolar collapse through its ability to reduce surface tension. Under normal conditions, surfactant homeostasis is maintained by balancing its release and the uptake by the type II cell for recycling and the internalization by alveolar macrophages for degradation. Little is known about how the surfactant pool is monitored and regulated. Here we show, by an analysis of gene-targeted mice exhibiting massive accumulation of surfactant, that Ig-Hepta/GPR116, an orphan receptor, is expressed on the type II cell and sensing the amount of surfactant by monitoring one of its protein components, surfactant protein D, and its deletion results in a pulmonary alveolar proteinosis and emphysema-like pathology. By a coexpression experiment with Sp-D and the extracellular region of Ig-Hepta/GPR116 followed by immunoprecipitation, we identified Sp-D as the ligand of Ig-Hepta/GPR116. Analyses of surfactant metabolism in Ig-Hepta(+/+ and Ig-Hepta(-/- mice by using radioactive tracers indicated that the Ig-Hepta/GPR116 signaling system exerts attenuating effects on (i balanced synthesis of surfactant lipids and proteins and (ii surfactant secretion, and (iii a stimulating effect on recycling (uptake in response to elevated levels of Sp-D in alveolar space.

  3. Longevity-relevant regulation of autophagy at the level of the acetylproteome.

    Science.gov (United States)

    Mariño, Guillermo; Morselli, Eugenia; Bennetzen, Martin V; Eisenberg, Tobias; Megalou, Evgenia; Schroeder, Sabrina; Cabrera, Sandra; Bénit, Paule; Rustin, Pierre; Criollo, Alfredo; Kepp, Oliver; Galluzzi, Lorenzo; Shen, Shensi; Malik, Shoaib A; Maiuri, Maria Chiara; Horio, Yoshiyuki; López-Otín, Carlos; Andersen, Jens S; Tavernarakis, Nektarios; Madeo, Frank; Kroemer, Guido

    2011-06-01

    The acetylase inhibitor, spermidine and the deacetylase activator, resveratrol, both induce autophagy and prolong life span of the model organism Caenorhabditis elegans in an autophagydependent fashion. Based on these premises, we investigated the differences and similarities in spermidine and resveratrol-induced autophagy. The deacetylase sirtuin 1 (SIRT1) and its orthologs are required for the autophagy induction by resveratrol but dispensable for autophagy stimulation by spermidine in human cells, Saccharomyces cerevisiae and C. elegans. SIRT1 is also dispensable for life-span extension by spermidine. Mass spectrometry analysis of the human acetylproteome revealed that resveratrol and/or spermidine induce changes in the acetylation of 560 peptides corresponding to 375 different proteins. Among these, 170 proteins are part of the recently elucidated human autophagy protein network. Importantly, spermidine and resveratrol frequently affect the acetylation pattern in a similar fashion. In the cytoplasm, spermidine and resveratrol induce convergent protein de-acetylation more frequently than convergent acetylation, while in the nucleus, acetylation is dominantly triggered by both agents. We surmise that subtle and concerted alterations in the acetylproteome regulate autophagy at multiple levels.

  4. BDNF Up-Regulates α7 Nicotinic Acetylcholine Receptor Levels on Subpopulations of Hippocampal Interneurons

    Science.gov (United States)

    Massey, Kerri A.; Zago, Wagner M.; Berg, Darwin K.

    2006-01-01

    In the hippocampus, brain-derived neurotrophic factor (BDNF) regulates a number of synaptic components. Among these are nicotinic acetylcholine receptors containing α7 subunits (α7-nAChRs), which are interesting because of their relative abundance in the hippocampus and their high relative calcium permeability. We show here that BDNF elevates surface and intracellular pools of α7-nAChRs on cultured hippocampal neurons and that glutamatergic activity is both necessary and sufficient for the effect. Blocking transmission through NMDA receptors with APV blocked the BDNF effect; increasing spontaneous excitatory activity with the GABAA receptor antagonist bicuculline replicated the BDNF effect. BDNF antibodies blocked the BDNF-mediated increase but not the bicuculline one, consistent with enhanced glutamatergic activity acting downstream from BDNF. Increased α7-nAChR clusters were most prominent on interneuron subtypes known to innervate directly excitatory neurons. The results suggest that BDNF, acting through glutamatergic transmission, can modulate hippocampal output in part by controlling α7-nAChR levels. PMID:17029981

  5. A local maximum in gibberellin levels regulates maize leaf growth by spatial control of cell division.

    Science.gov (United States)

    Nelissen, Hilde; Rymen, Bart; Jikumaru, Yusuke; Demuynck, Kirin; Van Lijsebettens, Mieke; Kamiya, Yuji; Inzé, Dirk; Beemster, Gerrit T S

    2012-07-10

    Plant growth rate is largely determined by the transition between the successive phases of cell division and expansion. A key role for hormone signaling in determining this transition was inferred from genetic approaches and transcriptome analysis in the Arabidopsis root tip. We used the developmental gradient at the maize leaf base as a model to study this transition, because it allows a direct comparison between endogenous hormone concentrations and the transitions between dividing, expanding, and mature tissue. Concentrations of auxin and cytokinins are highest in dividing tissues, whereas bioactive gibberellins (GAs) show a peak at the transition zone between the division and expansion zone. Combined metabolic and transcriptomic profiling revealed that this GA maximum is established by GA biosynthesis in the division zone (DZ) and active GA catabolism at the onset of the expansion zone. Mutants defective in GA synthesis and signaling, and transgenic plants overproducing GAs, demonstrate that altering GA levels specifically affects the size of the DZ, resulting in proportional changes in organ growth rates. This work thereby provides a novel molecular mechanism for the regulation of the transition from cell division to expansion that controls organ growth and size. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Level of compliance with the radiation protection regulation-A survey among Norwegian hospitals and X-ray institutes

    International Nuclear Information System (INIS)

    Friberg, E. G.; Widmark, A.; Solberg, M.; Woehni, T.

    2011-01-01

    To identify the level of compliance with the new radiation protection regulation among Norwegian health care enterprises (HCEs). Totally, 41 HCEs were authorised to use advanced X-ray equipment for medical purposes during 2005-07. Follow-up inspections with 14 HCEs were carried out during 2007-09. Main topics for the inspections were those requirements identified as most challenging to implement in the authorisation process. Totally, 192 non-conformities with the regulation were revealed during the authorisation process. The inspections revealed that 93 % of the inspected HCEs had non-conformities with the regulation. Most common non-conformities dealt with skills in radiation protection, establishment of local diagnostic reference levels, access to medical physicists and performance of quality control of X-ray equipment. Inspections are an effective tool for implementation of regulation the requirements at the HCEs, thus improving radiation protection awareness. (authors)

  7. State - Level Regulation's Effectiveness in Addressing Global Climate Change and Promoting Solar Energy Deployment

    Science.gov (United States)

    Peterman, Carla Joy

    Paper 1, Local Solutions to Global Problems: Climate Change Policies and Regulatory Jurisdiction, considers the efficacy of various types of environmental regulations when they are applied locally to pollutants whose damages extend beyond the jurisdiction of the local regulators. Local regulations of a global pollutant may be ineffective if producers and consumers can avoid them by transacting outside the reach of the local regulator. In many cases, this may involve the physical relocation of the economic activity, a problem often referred to as "leakage." This paper highlights another way in which local policies can be circumvented: through the shuffling of who buys from whom. The paper maintains that the problems of reshuffling are exacerbated when the options for compliance with the regulations are more flexible. Numerical analyses is presented demonstrating that several proposed policies to limit greenhouse gas emissions from the California electricity sector may have very little effect on carbon emissions if they are applied only within that state. Paper 1 concludes that although local subsidies for energy efficiency, renewable electricity, and transportation biofuels constitute attempts to pick technology winners, they may be the only mechanisms that local jurisdictions, acting alone, have at their disposal to address climate change. Paper 2, Pass-Through of Solar PV Incentives to Consumers: The Early Years of California's Solar PV Incentives, examines the pass through of incentives to California solar PV system owners. The full post-subsidy price consumers pay for solar power is a key metric of the success of solar PV incentive programs and of overall PV market performance. This study examines the early years of California's most recent wave of distributed solar PV incentives (2000-2008) to determine the pass-through of incentives. Examination of this period is both intellectually and pragmatically important due to the high level of incentives provided and

  8. Relationship between degree of risk, cost and level of compliance to occupational health and safety regulations in construction

    Directory of Open Access Journals (Sweden)

    Abimbola Olukemi Windapo

    2013-06-01

    Full Text Available This paper investigates the role of statutory health and safety (H&S regulations in managing construction project risks. The study examines whether the decision made by contractors to comply with the regulations, the cost of compliance and savings of H&S regulatory requirements is influenced by the degree or level of risk, which the regulations are trying to prevent. The rationale for the examination stems from previous studies which establish that building designers and contractors perceive the cost of complying with regulations as additional burdens, which they have to conform to, and which are in some cases unnecessary, and also the fact that construction related injuries and fatalities are on the increase. Qualitative and quantitative data obtained from a descriptive survey and H&S site audit by the Master Builder Association of the Western Cape (MBAWC were used as the measurements of risk, level of compliance to regulations, cost of compliance and savings. By correlating the quantitative and qualitative data, there is empirical evidence to support a negative relationship between the degree of risk, level and cost of compliance and cost savings. Based on the study’s findings, this paper concludes that the decision made by contractors to comply with H&S regulatory requirements is influenced by the perceived cost saving on account of compliance and that cost savings are influenced by the probability of accident occurrence which is an element of the degree of risk which the regulation is trying to prevent or control. 

  9. Relationship between degree of risk, cost and level of compliance to occupational health and safety regulations in construction

    Directory of Open Access Journals (Sweden)

    Abimbola Olukemi Windapo

    2013-06-01

    Full Text Available This paper investigates the role of statutory health and safety (H&S regulations in managing construction project risks. The study examines whether the decision made by contractors to comply with the regulations, the cost of compliance and savings of H&S regulatory requirements is influenced by the degree or level of risk, which the regulations are trying to prevent. The rationale for the examination stems from previous studies which establish that building designers and contractors perceive the cost of complying with regulations as additional burdens, which they have to conform to, and which are in some cases unnecessary, and also the fact that construction related injuries and fatalities are on the increase. Qualitative and quantitative data obtained from a descriptive survey and H&S site audit by the Master Builder Association of the Western Cape (MBAWC were used as the measurements of risk, level of compliance to regulations, cost of compliance and savings. By correlating the quantitative and qualitative data, there is empirical evidence to support a negative relationship between the degree of risk, level and cost of compliance and cost savings. Based on the study’s findings, this paper concludes that the decision made by contractors to comply with H&S regulatory requirements is influenced by the perceived cost saving on account of compliance and that cost savings are influenced by the probability of accident occurrence which is an element of the degree of risk which the regulation is trying to prevent or control.

  10. AhR and SHP regulate phosphatidylcholine and S-adenosylmethionine levels in the one-carbon cycle.

    Science.gov (United States)

    Kim, Young-Chae; Seok, Sunmi; Byun, Sangwon; Kong, Bo; Zhang, Yang; Guo, Grace; Xie, Wen; Ma, Jian; Kemper, Byron; Kemper, Jongsook Kim

    2018-02-07

    Phosphatidylcholines (PC) and S-adenosylmethionine (SAM) are critical determinants of hepatic lipid levels, but how their levels are regulated is unclear. Here, we show that Pemt and Gnmt, key one-carbon cycle genes regulating PC/SAM levels, are downregulated after feeding, leading to decreased PC and increased SAM levels, but these effects are blunted in small heterodimer partner (SHP)-null or FGF15-null mice. Further, aryl hydrocarbon receptor (AhR) is translocated into the nucleus by insulin/PKB signaling in the early fed state and induces Pemt and Gnmt expression. This induction is blocked by FGF15 signaling-activated SHP in the late fed state. Adenoviral-mediated expression of AhR in obese mice increases PC levels and exacerbates steatosis, effects that are blunted by SHP co-expression or Pemt downregulation. PEMT, AHR, and PC levels are elevated in simple steatosis patients, but PC levels are robustly reduced in steatohepatitis-fibrosis patients. This study identifies AhR and SHP as new physiological regulators of PC/SAM levels.

  11. Regulation of hepatic level of fatty-acid-binding protein by hormones and clofibric acid in the rat.

    Science.gov (United States)

    Nakagawa, S; Kawashima, Y; Hirose, A; Kozuka, H

    1994-01-01

    Regulation of the hepatic level of fatty-acid-binding protein (FABP) by hormones and p-chlorophenoxyisobutyric acid (clofibric acid) was studied. The hepatic level of FABP, measured as the oleic acid-binding capacity of the cytosolic FABP fraction, was decreased in streptozotocin-diabetic rats. The level of FABP was markedly increased in adrenalectomized rats, and the elevation was prevented by the administration of dexamethasone. Hypothyroidism decreased the level of FABP and hyperthyroidism increased it. A high correlation between the incorporation of [14C]oleic acid in vivo into hepatic triacylglycerol and the level of FABP was found for normal, diabetic and adrenalectomized rats. The level of FABP was increased by administration of clofibric acid to rats in any altered hormonal states, as was microsomal 1-acylglycerophosphocholine (1-acyl-GPC) acyltransferase, a peroxisome-proliferator-responsive parameter. These results suggest that the hepatic level of FABP is under regulation by multiple hormones and that clofibric acid induces FABP and 1-acyl-GPC acyltransferase by a mechanism which may be distinct from that by which hormones regulate the level of FABP. PMID:8110197

  12. Intrinsic MYH7 expression regulation contributes to tissue level allelic imbalance in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Montag, Judith; Syring, Mandy; Rose, Julia; Weber, Anna-Lena; Ernstberger, Pia; Mayer, Anne-Kathrin; Becker, Edgar; Keyser, Britta; Dos Remedios, Cristobal; Perrot, Andreas; van der Velden, Jolanda; Francino, Antonio; Navarro-Lopez, Francesco; Ho, Carolyn Yung; Brenner, Bernhard; Kraft, Theresia

    2017-08-01

    HCM, the most common inherited cardiac disease, is mainly caused by mutations in sarcomeric genes. More than a third of the patients are heterozygous for mutations in the MYH7 gene encoding for the β-myosin heavy chain. In HCM-patients, expression of the mutant and the wildtype allele can be unequal, thus leading to fractions of mutant and wildtype mRNA and protein which deviate from 1:1. This so-called allelic imbalance was detected in whole tissue samples but also in individual cells. There is evidence that the severity of HCM not only depends on the functional effect of the mutation itself, but also on the fraction of mutant protein in the myocardial tissue. Allelic imbalance has been shown to occur in a broad range of genes. Therefore, we aimed to examine whether the MYH7-alleles are intrinsically expressed imbalanced or whether the allelic imbalance is solely associated with the disease. We compared the expression of MYH7-alleles in non-HCM donors and in HCM-patients with different MYH7-missense mutations. In the HCM-patients, we identified imbalanced as well as equal expression of both alleles. Also at the protein level, allelic imbalance was determined. Most interestingly, we also discovered allelic imbalance and balance in non-HCM donors. Our findings therefore strongly indicate that apart from mutation-specific mechanisms, also non-HCM associated allelic-mRNA expression regulation may account for the allelic imbalance of the MYH7 gene in HCM-patients. Since the relative amount of mutant mRNA and protein or the extent of allelic imbalance has been associated with the severity of HCM, individual analysis of the MYH7-allelic expression may provide valuable information for the prognosis of each patient.

  13. Plasma levels of hypoxia-regulated factors in patients with age-related macular degeneration.

    Science.gov (United States)

    Ioanna, Zygoula; Christian, Schori; Christian, Grimm; Daniel, Barthelmes

    2018-02-01

    Various hypoxia-related proteins are differentially expressed in the retina and secreted to the vitreous and/or aqueous humor of patients affected by dry or neovascular age-related macular degeneration (nAMD). To determine whether these conditions alter concentrations of cytokines also in the systemic circulation, we measured plasma levels of six hypoxia-related proteins. Plasma was prepared from EDTA blood that was collected from patients affected by dry AMD (n = 5), nAMD (n = 11), proliferative diabetic retinopathy (PDR; n = 9), and patients with an epiretinal membrane (ERM; n = 11). ERM samples served as negative controls, PDR samples as positive controls. Protein concentrations of vascular endothelial growth factor (VEGF), erythropoietin (EPO), angiopoietin-like 4 (ANGPTL4), placental growth factor (PlGF), tumor necrosis factor alpha (TNF-α), and pigment epithelium-derived factor (PEDF) were determined by enzyme-linked immunosorbent assay (ELISA). The concentration of PlGF was significantly increased in plasma of patients affected by nAMD. Although no statistically significant differences were found for EPO, ANGPTL4, PlGF, TNF-α, and PEDF, the mean concentration of VEGF was lowest in the nAMD group. Plasma concentrations of the six factors did not correlate with gender or age of patients. nAMD may increase plasma concentrations of PlGF, making it a candidate as a biomarker for the neovascular form of AMD. Other factors, however, were not differentially regulated, suggesting that their systemic concentrations are not generally increased in hypoxia-related retinal diseases.

  14. Reference values on safety regulation of land disposal of low level radioactive solid waste (the second interim report) and its incorporation into legal regulations

    International Nuclear Information System (INIS)

    Aoki, Terumi

    1994-01-01

    Safety regulation of land disposal of low level radioactive solid waste in Japan is based on 'the basic philosophy on the safety regulation of land disposal of low level radioactive solid waste' determined by the Nuclear safety Committee (October 1985). The basic philosophy on the upper limit of radioactivity of disposed wastes was published as the reference values in the interim report (February 1987) and in the second interim report (June 1992). In the second interim report, the upper limits of radioactivity are established for three types of solid radioactive wastes: 1) metals, incombustible or flame resistant wastes generated nuclear reactor facilities and solidified in vessels, 2) large metallic structures generated from decommissioning of reactor facilities and difficult to solidify in vessels, and 3) radioactive concrete waste generated from decommissioning of reactor facilities. The upper limits of radioactivity are presented for C-14, Co-60, Ni-63, Sr-90, Cs-137, alfa-emmitters, Ca-41 (for concrete) and Eu-152 (for concrete). Related laws and regulations in Japan on safe disposal of low level wastes are explained. (T.H.)

  15. Uroguanylin levels in intestine and plasma are regulated by nutritional status in a leptin-dependent manner.

    Science.gov (United States)

    Folgueira, C; Sanchez-Rebordelo, E; Barja-Fernandez, S; Leis, R; Tovar, S; Casanueva, F F; Dieguez, C; Nogueiras, R; Seoane, L M

    2016-03-01

    Uroguanylin (UGN) is a 16 amino acid peptide produced mainly by intestinal epithelial cells. Nutrients intake increases circulating levels of prouroguanylin that is processed and converted to UGN to activate the guanylyl cyclase 2C receptor (GUCY2C). Given that the UGN-GUCY2C system has been proposed as a novel gut-brain endocrine axis regulating energy balance, the aim of the present study was to investigate the regulation of UGN protein levels in duodenum and circulating levels in lean and obese mice under different nutritional conditions and its potential interaction with leptin. Swiss, C57BL/6 wild-type and ob/ob male adult mice under different nutritional conditions were used: fed ad libitum standard diet (control); 48 h fasting (fasted); 48 h fasting followed by 24 h of feeding (refed); and fed high-fat diet (45 %) during 10 weeks. In addition, peripheral leptin administration was performed. Intestinal uroguanylin expression was studied by Western blot analysis; plasma levels were measured by ELISA. Food deprivation significantly reduced plasma UGN levels, which were correlated with the lower protein levels of UGN in duodenum. These effects were reverted after refeeding and leptin challenge. Consistently, in ob/ob mice UGN expression was decreased, whereas leptin treatment up-regulated UGN levels in duodenum in these genetically modified mice compared to WT. Diet-induced obese mice displayed increased UGN levels in intestine and plasma in comparison with lean mice. Our findings suggest that UGN levels are correlated with energy balance status and that the regulation of UGN by nutritional status is leptin-dependent.

  16. A Community Level Theory of Organizational Resistance to Anti Smoking Regulation

    NARCIS (Netherlands)

    Vermeulen, P.A.M.; Simons, T.; Knoben, J.

    2012-01-01

    This study aims to investigate organizations’ resistance to the introduction of new legislation in an established institutional field, which exhibits an intriguing combination of both high consensus as well as intense contestation. Specifically it focuses on smoking regulations affecting the

  17. Regulation

    International Nuclear Information System (INIS)

    Ballereau, P.

    1999-01-01

    The different regulations relative to nuclear energy since the first of January 1999 are given here. Two points deserve to be noticed: the decree of the third august 1999 authorizing the national Agency for the radioactive waste management to install and exploit on the commune of Bures (Meuse) an underground laboratory destined to study the deep geological formations where could be stored the radioactive waste. The second point is about the uranium residues and the waste notion. The judgment of the administrative tribunal of Limoges ( 9. july 1998) forbidding the exploitation of a storage installation of depleted uranium considered as final waste and qualifying it as an industrial waste storage facility has been annulled bu the Court of Appeal. It stipulated that, according to the law number 75663 of the 15. july 1965, no criteria below can be applied to depleted uranium: production residue (possibility of an ulterior enrichment), abandonment of a personal property or simple intention to do it ( future use aimed in the authorization request made in the Prefecture). This judgment has devoted the primacy of the waste notion on this one of final waste. (N.C.)

  18. An Analysis of the Convergence Level of Tangible Assets (PPE) According to Romanian National Accounting Regulation and IFRS for Smes

    OpenAIRE

    Maria Madalina Buculescu (Costica); Bogdan Nicolae Velicescu

    2014-01-01

    This paper aims a comparative analysis between IFRS for SMEs and Romanian national accounting regulations concerning measurement of formal convergence level of definitions, treatment and policies of Property, Plant and Equipment (PPE) and highlighting main national fiscal rules related. With the purpose to not contribute only to the measurement of PPE formal level of harmonization, we intend to analyze some PPE related accounting practices used by Romanian certified accountants. To this effec...

  19. The effect of intracellular calcium level regulators on the synthesis of pollen tube callose in Oenothera biennis L.

    Directory of Open Access Journals (Sweden)

    Elżbieta Bednarska

    2014-01-01

    Full Text Available It is shown that callose synthesis in the Oenothera biennis pollen tube is regulated by the endogenous Ca2+ level. Calcium antagonists reduced the amount of callose in the wall above the tip of the pollen tube (Verapamil - calcium channels blocker and at the tube tip after stopping tube growth (La3+ - a Ca2+ substitute. Ruthenium red and ionophore A 23187, which raise the Ca 21 level in the cytoplasm, induced callose synthesis at the tip of pollen tube.

  20. Examining the Level of Convergence among Self-Regulated Learning Microanalytic Processes, Achievement, and a Self-Report Questionnaire

    Science.gov (United States)

    Cleary, Timothy J.; Callan, Gregory L.; Malatesta, Jaime; Adams, Tanya

    2015-01-01

    This study examined the convergent and predictive validity of self-regulated learning (SRL) microanalytic measures. Specifically, theoretically based relations among a set of self-reflection processes, self-efficacy, and achievement were examined as was the level of convergence between a microanalytic strategy measure and a SRL self-report…

  1. G protein-coupled receptor kinase 2 negatively regulates chemokine signaling at a level downstream from G protein subunits

    NARCIS (Netherlands)

    Jimenez-Sainz, MC; Murga, C; Kavelaars, A; Jurado-Pueyo, M; Krakstad, BF; Heijnen, CJ; Mayor, F; Aragay, AM

    The G protein-coupled receptor kinase 2 (GRK2) phosphorylates and desensitizes ligand-activated G protein-coupled-receptors. Here, evidence is shown for a novel role of GRK2 in regulating chemokine-mediated signals. The presence of increased levels of GRK2 in human embryonic kidney (HEK) 293 cells

  2. Learning English as a Second Language at the University Level in Jordan: Motivation, Self-Regulation and Learning Environment Perceptions

    Science.gov (United States)

    Alzubaidi, Eman; Aldridge, Jill M.; Khine, Myint Swe

    2016-01-01

    The overarching aim of this study was to investigate students' perceptions of the learning environment and whether these influenced their motivation and self-regulation in learning English as a second language at the university level in Jordan. Our sample involved 994 students, drawn from 13 schools, within three faculties (humanities, health…

  3. Mesoporous silica nanoparticles as smart and safe devices for regulating blood biomolecule levels

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Yan [Iowa State Univ., Ames, IA (United States)

    2011-01-01

    Stimuli-responsive end-capped MSN materials are promising drug carriers that securely deliver a large payload of drug molecules without degradation or premature release. A general review of the recent progress in this field is presented, including a summary of a series of hard and soft caps for drug encapsulation and a variety of internal and external stimuli for controlled release of different therapeutics, a discussion of the biocompatibility of MSN both in vitro and in vivo, and a description of the sophisticated stimuli-responsive systems with novel capping agents and controlled release mechanism. The unique internal and external surfaces of MSN were utilized for the development of a glucose-responsive double delivery system end-capped with insulin. This unique system consists of functionalized MSNs capable of releasing insulin when the concentration of sugar in blood exceeds healthy levels. The insulin-free nanoparticles are then up taken by pancreatic cells, and release inside of them another biomolecule that stimulates the production of more insulin. The in vivo application of this system for the treatment of diabetes requires further understanding on the biological behaviors of these nanoparticles in blood vessels. The research presented in this dissertation demonstrated the size and surface effects on the interaction of MSNs with red blood cell membranes, and discovered how the surface of the nanoparticles can be modified to improve their compatibility with red blood cells and avoid their dangerous side effects. In order to optimize the properties of MSN for applying them as efficient intracellular drug carriers it is necessary to understand the factors that can regulate their internalization into and exocytosis out of the cells. The correlation between the particle morphology and aggregation of MSNs to the effectiveness of cellular uptake is discussed and compared with different cell lines. The differences in the degree of exocytosis of MSNs between

  4. Measurement and regulation of the level of a homogeneous plutonium reactor; Mesure et regulation du niveau d'un reacteur homogene au plutonium

    Energy Technology Data Exchange (ETDEWEB)

    Berger, F; Bertrand, J

    1958-12-01

    Reactivity depends strongly on disturbances of the level of the plutonium solution In the homogeneous reactor. Proserpine has a small cylindrical core, 250 mm diameter, and 10 liters volume. With a view to reducing the dangers due to corrosion and contamination, the solution level in the core is raised by pneumatic pressure. The level is stabilized by means of a regulating system. During critical experiments the variations of the level are less than one hundredth part of a millimeter. (author) [French] Les variations du niveau de la solution de plutonium dans le reacteur homogene Proserpine ont une grosse influence sur la reactivite, car le coeur est petit (10 litres de solution dans un cylindre de diametre 250 mm). En vue de reduire les dangers dus a la corrosion et a la contamination, la commande du volume liquide est pneumatique. Nous avons realise la stabilite du niveau par une regulation qui, dans les essais en regime critique, limite les variations du plan liquide a une fraction de centieme de millimetre. (auteur)

  5. Impacts of transportation regulations on spent fuel and high level waste cask design

    International Nuclear Information System (INIS)

    Lake, W.H.

    1992-01-01

    The regulation of radioactive material transport has a long and successful history. Prior to 1966, these activities were regulated by the Interstate Commerce Commission (ICC) Bureau of Explosives (the ICC was predecessor to the Department of Transportation (DOT)). In 1966, the Atomic Energy Commission (AEC) developed what is now 10 CFR 71, concurrently with the development of similar international standards. In 1975, the AEC was reorganized and the Nuclear Regulatory Commission (NRC) was established as an independent regulatory commission. The NRC was given responsibility for the regulation of commercial use of radioactive materials, including transportation. This paper discusses various aspects of the NRC's role in the transport of radioactive material as well as its role in the design and certification of casks necessary to the transport of this material

  6. ["Entero-insular axis" and regulation of blood sugar and insulin levels following oral glucose loading].

    Science.gov (United States)

    Kuznetsov, B G

    1978-11-01

    The mineral water Essentuki 17 administered per so with glucose exerted a modifying effect on the regulation of glycaemia and insulinaemia in intact rats. This effect undergoes a few phases of changing and disappears by the 30th day. Under conditions of this adaptation, the glycaemia regulation is somewhat worsening. After i.v. administration of glucose during this period the regulation of glycaemia and insulinaemia remains unaltered. This suggests that the mineral water exerts its biological effect, mainly, on the entero-insular axis system (Unger and Eisentraut, 1969) and that the modifying effect is due not to a concrete complex of the mineral water electrolytes but rather to the unspecific factor of "perturbation" in the enteral medium.

  7. The Pseudomonas aeruginosa Chp Chemosensory System Regulates Intracellular cAMP Levels by Modulating Adenylate Cyclase Activity

    Science.gov (United States)

    Fulcher, Nanette B.; Holliday, Phillip M.; Klem, Erich; Cann, Martin J.; Wolfgang, Matthew C.

    2010-01-01

    Summary Multiple virulence systems in the opportunistic pathogen Pseudomonas aeruginosa are regulated by the second messenger signaling molecule adenosine 3’, 5’-cyclic monophosphate (cAMP). Production of cAMP by the putative adenylate cyclase enzyme CyaB represents a critical control point for virulence gene regulation. To identify regulators of CyaB, we screened a transposon insertion library for mutants with reduced intracellular cAMP. The majority of insertions resulting in reduced cAMP mapped to the Chp gene cluster encoding a putative chemotaxis-like chemosensory system. Further genetic analysis of the Chp system revealed that it has both positive and negative effects on intracellular cAMP and that it regulates cAMP levels by modulating CyaB activity. The Chp system was previously implicated in the production and function of type IV pili (TFP). Given that cAMP and the cAMP-dependent transcriptional regulator Vfr control TFP biogenesis gene expression, we explored the relationship between cAMP, the Chp system and TFP regulation. We discovered that the Chp system controls TFP production through modulation of cAMP while control of TFP-dependent twitching motility is cAMP-independent. Overall, our data define a novel function for a chemotaxis-like system in controlling cAMP production and establish a regulatory link between the Chp system, TFP and other cAMP-dependent virulence systems. PMID:20345659

  8. Impacts of hazardous waste regulation on low-level waste management

    International Nuclear Information System (INIS)

    Sharples, F.E.; Eyman, L.D.

    1986-01-01

    The Hazardous and Solid Waste Amendments of 1984 have greatly expanded the universe of what, and who, is regulated under Resource Conservation and Recovery Act (RCRA). Handling requirements for hazardous waste are becoming increasingly more stringent, particularly where land disposal is concerned. DOE needs to begin actively pursuing strategies directed at keeping the management of LLW clearly separated from wastes that are legitimately regulated under RCRA. Such strategies would include instituting systemwide changes in internal management practices, establishing improved location standards for LLW disposal, and negotiating interagency compromise agreements to obtain variances from RCRA requirements where necessary and appropriate

  9. Physiological Regulation of Gut Peptide Hormone (PYY) Levels by Age, Sex, Hormonal and Nutritional Status in Rats

    International Nuclear Information System (INIS)

    Hebashy, M.I.A.; Mazen, G.M.A.

    2007-01-01

    Peptide YY hormone (PYY) was recently appreciated as an important gut hormonal regulator of appetite. PYY is produced by the gut and released into the circulation after food intake and is found to decrease appetite. The main form of PYY, both stored and circulated, is PYY(3-36), the N-terminal truncated form of the full length peptide so, peripheral injections of PYY(3-36) in rats inhibit food intake in experimental animals as well as in lean and obese human subjects. Also, this hormone has been suggested to be an attractive therapeutic option for obesity. PYY levels are influenced by age and the highest hormone level is achieved in early postnatal life (day 30) and is decreased thereafter. PYY levels were also dependent on thyroid hormone status and being decreased in hyperthyroid rats. The PYY levels observed in acute and chronic food restricted rats indicated that, in situations of decreased energy intake, the lower PYY levels could serve to regulate central pathways and facilitate food intake. Contrary, in pregnant rats, PYY levels were enhanced at late gestation. The aim of this study was to assess the influence of age, sex, thyroid status, pregnancy and food restriction on PYY levels in rats. The underling mechanisms through which PYY levels alternated as a result of sex, age, pregnancy, thyroidal and nutritional status were discussed in the light of recent research outcomes

  10. Effects of Group Awareness and Self-Regulation Level on Online Learning Behaviors

    Science.gov (United States)

    Lin, Jian-Wei; Szu, Yu-Chin; Lai, Ching-Neng

    2016-01-01

    Group awareness can affect student online learning while self-regulation also can substantially influence student online learning. Although some studies identify that these two variables may partially determine learning behavior, few empirical studies or thorough analyses elucidate the simultaneous impact of these two variables (group awareness…

  11. Regulating private human suborbital flight at the international and European level: Tendencies and suggestions

    Science.gov (United States)

    Masson-Zwaan, Tanja; Moro-Aguilar, Rafael

    2013-12-01

    In the context of the FAST20XX project (Future High-Altitude High-Speed Transport) that started in 2009 under the 7th Framework Programme of the European Union (EU), the authors reexamined the legal status of private human suborbital flight, and researched whether it might be regulated as aviation or as spaceflight. International space law is ambiguous as to accommodating suborbital activities. While some provisions of the UN outer space treaties would seem to exclude them, generally there is not any explicit condition in terms of reaching orbit as a requirement for application. International air law presents equal difficulties in dealing with this activity. The classic definition of "aircraft" as contained in the Annexes to the Chicago Convention does not really encompass the kind of rocket-powered vehicles that are envisaged here. As a result, it is unclear whether the United Nations Committee on the Peaceful Uses of Outer Space (COPUOS), the International Civil Aviation Organization (ICAO), or both could be involved in an eventual international regulation of suborbital flight. In the absence of a uniform international regime, each state has the sovereign right to regulate human suborbital flights operating within its airspace. So far, two practical solutions have been realised or proposed, and will be analyzed. On the one hand, the USA granted power for regulation and licensing over private human suborbital flight to the Office of Commercial Space Transportation of the Federal Aviation Administration (FAA/AST). Subsequent regulations by the FAA have set out a series of requirements for companies that want to operate these flights, enabling a market to develop. On the other side of the Atlantic, both the European Space Agency (ESA) and a group of representatives of the European Aviation Safety Agency (EASA) of the European Union (EU) seem to rather regard this activity as aviation, potentially subject to the regulation and certification competences of EASA

  12. Regulation of Budding Yeast CENP-A levels Prevents Misincorporation at Promoter Nucleosomes and Transcriptional Defects.

    Directory of Open Access Journals (Sweden)

    Erica M Hildebrand

    2016-03-01

    Full Text Available The exclusive localization of the histone H3 variant CENP-A to centromeres is essential for accurate chromosome segregation. Ubiquitin-mediated proteolysis helps to ensure that CENP-A does not mislocalize to euchromatin, which can lead to genomic instability. Consistent with this, overexpression of the budding yeast CENP-A(Cse4 is lethal in cells lacking Psh1, the E3 ubiquitin ligase that targets CENP-A(Cse4 for degradation. To identify additional mechanisms that prevent CENP-A(Cse4 misincorporation and lethality, we analyzed the genome-wide mislocalization pattern of overexpressed CENP-A(Cse4 in the presence and absence of Psh1 by chromatin immunoprecipitation followed by high throughput sequencing. We found that ectopic CENP-A(Cse4 is enriched at promoters that contain histone H2A.Z(Htz1 nucleosomes, but that H2A.Z(Htz1 is not required for CENP-A(Cse4 mislocalization. Instead, the INO80 complex, which removes H2A.Z(Htz1 from nucleosomes, promotes the ectopic deposition of CENP-A(Cse4. Transcriptional profiling revealed gene expression changes in the psh1Δ cells overexpressing CENP-A(Cse4. The down-regulated genes are enriched for CENP-A(Cse4 mislocalization to promoters, while the up-regulated genes correlate with those that are also transcriptionally up-regulated in an htz1Δ strain. Together, these data show that regulating centromeric nucleosome localization is not only critical for maintaining centromere function, but also for ensuring accurate promoter function and transcriptional regulation.

  13. Profiling of Human Molecular Pathways Affected by Retrotransposons at the Level of Regulation by Transcription Factor Proteins

    Science.gov (United States)

    Nikitin, Daniil; Penzar, Dmitry; Garazha, Andrew; Sorokin, Maxim; Tkachev, Victor; Borisov, Nicolas; Poltorak, Alexander; Prassolov, Vladimir; Buzdin, Anton A.

    2018-01-01

    Endogenous retroviruses and retrotransposons also termed retroelements (REs) are mobile genetic elements that were active until recently in human genome evolution. REs regulate gene expression by actively reshaping chromatin structure or by directly providing transcription factor binding sites (TFBSs). We aimed to identify molecular processes most deeply impacted by the REs in human cells at the level of TFBS regulation. By using ENCODE data, we identified ~2 million TFBS overlapping with putatively regulation-competent human REs located in 5-kb gene promoter neighborhood (~17% of all TFBS in promoter neighborhoods; ~9% of all RE-linked TFBS). Most of REs hosting TFBS were highly diverged repeats, and for the evolutionary young (0–8% diverged) elements we identified only ~7% of all RE-linked TFBS. The gene-specific distributions of RE-linked TFBS generally correlated with the distributions for all TFBS. However, several groups of molecular processes were highly enriched in the RE-linked TFBS regulation. They were strongly connected with the immunity and response to pathogens, with the negative regulation of gene transcription, ubiquitination, and protein degradation, extracellular matrix organization, regulation of STAT signaling, fatty acids metabolism, regulation of GTPase activity, protein targeting to Golgi, regulation of cell division and differentiation, development and functioning of perception organs and reproductive system. By contrast, the processes most weakly affected by the REs were linked with the conservative aspects of embryo development. We also identified differences in the regulation features by the younger and older fractions of the REs. The regulation by the older fraction of the REs was linked mainly with the immunity, cell adhesion, cAMP, IGF1R, Notch, Wnt, and integrin signaling, neuronal development, chondroitin sulfate and heparin metabolism, and endocytosis. The younger REs regulate other aspects of immunity, cell cycle progression and

  14. Profiling of Human Molecular Pathways Affected by Retrotransposons at the Level of Regulation by Transcription Factor Proteins

    Directory of Open Access Journals (Sweden)

    Daniil Nikitin

    2018-01-01

    Full Text Available Endogenous retroviruses and retrotransposons also termed retroelements (REs are mobile genetic elements that were active until recently in human genome evolution. REs regulate gene expression by actively reshaping chromatin structure or by directly providing transcription factor binding sites (TFBSs. We aimed to identify molecular processes most deeply impacted by the REs in human cells at the level of TFBS regulation. By using ENCODE data, we identified ~2 million TFBS overlapping with putatively regulation-competent human REs located in 5-kb gene promoter neighborhood (~17% of all TFBS in promoter neighborhoods; ~9% of all RE-linked TFBS. Most of REs hosting TFBS were highly diverged repeats, and for the evolutionary young (0–8% diverged elements we identified only ~7% of all RE-linked TFBS. The gene-specific distributions of RE-linked TFBS generally correlated with the distributions for all TFBS. However, several groups of molecular processes were highly enriched in the RE-linked TFBS regulation. They were strongly connected with the immunity and response to pathogens, with the negative regulation of gene transcription, ubiquitination, and protein degradation, extracellular matrix organization, regulation of STAT signaling, fatty acids metabolism, regulation of GTPase activity, protein targeting to Golgi, regulation of cell division and differentiation, development and functioning of perception organs and reproductive system. By contrast, the processes most weakly affected by the REs were linked with the conservative aspects of embryo development. We also identified differences in the regulation features by the younger and older fractions of the REs. The regulation by the older fraction of the REs was linked mainly with the immunity, cell adhesion, cAMP, IGF1R, Notch, Wnt, and integrin signaling, neuronal development, chondroitin sulfate and heparin metabolism, and endocytosis. The younger REs regulate other aspects of immunity, cell cycle

  15. Theorizing and Researching Levels of Processing in Self-Regulated Learning

    Science.gov (United States)

    Winne, Philip H.

    2018-01-01

    Background: Deep versus surface knowledge is widely discussed by educational practitioners. A corresponding construct, levels of processing, has received extensive theoretical and empirical attention in learning science and psychology. In both arenas, lower levels of information and shallower levels of processing are predicted and generally…

  16. Status report on the Nuclear Regulatory Commission regulations for land disposal of low-level radioactive wastes and geologic repository disposal of high-level wastes

    International Nuclear Information System (INIS)

    Browning, R.E.; Bell, M.J.; Dragonette, K.S.; Johnson, T.C.; Roles, G.W.; Lohaus, P.H.; Regnier, E.P.

    1984-01-01

    On 27 December 1982, the United States Nuclear Regulatory Commission (NRC) amended its regulations to provide specific requirements for licensing the land disposal of low-level radioactive wastes. The regulations establish performance objectives for land disposal of waste; technical requirements for the siting, design, operations, and closure activities for a near-surface disposal facility; technical requirements concerning waste form and classification that waste generators must meet for the land disposal of waste; institutional requirements; financial assurance requirements; and administrative and procedural requirements for licensing a disposal facility. Waste generators must comply with the waste form and classification provisions of the new rule, on 27 December 1983, one year later. During this implementation period, licensees must develop programmes to ensure compliance with the new waste form and classification provisions. The NRC is also promulgating regulations specifying the technical criteria for disposal of high-level radioactive wastes in geological repositories. The proposed rule was published for public comment in July 1981. Public comments have been received and considered by the Commission staff. The Commission will soon approve and publish a revised final rule. While the final rule being considered by the Commission is fundamentally the same as the proposed rule, provisions have been added to permit flexibility in the application of numerical criteria, some detailed design requirements have been deleted, and other changes have been made in response to comments. The rule is consistent with the recently enacted Nuclear Waste Policy Act of 1982. (author)

  17. Systems Level Regulation of Rhythmic Growth Rate and Biomass Accumulation in Grasses

    Energy Technology Data Exchange (ETDEWEB)

    Kay, Steve A. [Univ. of Southern California, Los Angeles, CA (United States)

    2017-10-20

    Objectives: Several breakthroughs have been recently made in our understanding of plant growth and biomass accumulation. It was found that plant growth is rhythmically controlled throughout the day by the circadian clock through a complex interplay of light and phytohormone signaling pathways. While plants such as the C4 energy crop sorghum (Sorghum bicolor (L.) Moench) and possibly the C3 grass Brachypodium distachyon also exhibit daily rhythms in growth rate, the molecular details of its regulation remain to be explored. A better understanding of diurnally regulated growth behavior in grasses may lead to species-specific mechanisms highly relevant to future strategies to optimize energy crop biomass yield. Here we propose to devise a systems approach to identify, in parallel, regulatory hubs associated with rhythmic growth in C3 and C4 plants. We propose to use rhythmicity in daily growth patterns to drive the discovery of regulatory network modules controlling biomass accumulation. Description: The project is divided in three main parts: 1) Performing time-lapse imaging and growth measurement in B. distachyon and S. bicolor to determine growth rate dynamic during the day/night cycle. Identifying growth-associated genes whose expression patterns follow the observed growth dynamics using deep sequencing technology, 2) identifying regulators of these genes by screening for DNA-binding proteins interacting with the growth-associated gene promoters identified in Aim 1. Screens will be performed using a validated yeast-one hybrid strategy paired with a specifically designed B. distachyon and S. bicolor transcription factor libraries (1000 clones each), and 3) Selecting 50 potential growth regulators from the screen for downstream characterization. The selection will be made by using a sytems biology approach by calculating the connectivity between growth rate, rhythmic gene expression profiles and TF expression profile and determine which TF is likely part of a hub

  18. Contribution of Hfe expression in macrophages to the regulation of hepatic hepcidin levels and iron loading

    OpenAIRE

    Makui, Hortence; Soares, Ricardo J.; Jiang, Wenlei; Constante, Marco; Santos, Manuela M.

    2005-01-01

    Hereditary hemochromatosis (HH), an iron overload disease associated with mutations in the HFE gene, is characterized by increased intestinal iron absorption and consequent deposition of excess iron, primarily in the liver. Patients with HH and Hfe-deficient (Hfe−/−) mice manifest inappropriate expression of the iron absorption regulator hepcidin, a peptide hormone produced by the liver in response to iron loading. In this study, we investigated the contribution of Hfe expression in macrophag...

  19. Regulation of connexins expression levels by microRNAs, an update

    Directory of Open Access Journals (Sweden)

    Juan Francisco Calderon

    2016-11-01

    Full Text Available Control of cell-cell coordination and communication is regulated by several factors, including paracrine and autocrine release of biomolecules, and direct exchange of soluble factors between cells through gap junction channels. Additionally, hemichannels also participate in cell-cell coordination through the release of signaling molecules, such as ATP and glutamate. A family of transmembrane proteins named connexins forms both gap junction channels and hemichannels. Because of their importance in cell and tissue coordination, connexins are controlled both by post-translational and post-transcriptional modifications. In recent years, non-coding RNAs have garnered research interest due to their ability to exert post-transcriptional regulation of gene expression. One of the most recent, well-documented control mechanisms of protein synthesis is found through the action of small, single-stranded RNA, called micro RNAs (miRNAs or miRs. Put simply, miRNAs are negative regulators of the expression of a myriad proteins involved in many physiological and pathological processes. This mini review will briefly summarize what is currently known about the action of miRNAs over Cxs expression/function in different organs under some relevant physiological and pathological conditions

  20. Regulation of mRNA Levels by Decay-Promoting Introns that Recruit the Exosome Specificity Factor Mmi1

    Directory of Open Access Journals (Sweden)

    Cornelia Kilchert

    2015-12-01

    Full Text Available In eukaryotic cells, inefficient splicing is surprisingly common and leads to the degradation of transcripts with retained introns. How pre-mRNAs are committed to nuclear decay is unknown. Here, we uncover a mechanism by which specific intron-containing transcripts are targeted for nuclear degradation in fission yeast. Sequence elements within these “decay-promoting” introns co-transcriptionally recruit the exosome specificity factor Mmi1, which induces degradation of the unspliced precursor and leads to a reduction in the levels of the spliced mRNA. This mechanism negatively regulates levels of the RNA helicase DDX5/Dbp2 to promote cell survival in response to stress. In contrast, fast removal of decay-promoting introns by co-transcriptional splicing precludes Mmi1 recruitment and relieves negative expression regulation. We propose that decay-promoting introns facilitate the regulation of gene expression. Based on the identification of multiple additional Mmi1 targets, including mRNAs, long non-coding RNAs, and sn/snoRNAs, we suggest a general role in RNA regulation for Mmi1 through transcript degradation.

  1. IL-15 up-regulates the MMP-9 expression levels and induces inflammatory infiltration of macrophages in polymyositis through regulating the NF-kB pathway.

    Science.gov (United States)

    Yan, Wang; Fan, Weinv; Chen, Caijing; Wu, Yunqin; Fan, Zhenyi; Chen, Jiaqi; Chen, Zhaoying; Chen, Huimin

    2016-10-10

    This study was aimed to research the effects of IL-15 on inducing inflammatory infiltration of macrophages in polymyositis (PM) through the NF-kB pathway, and whether IL-15 was able to further regulate MMP-9 expression levels. Prepared PM cells, collected from the patients suffering from PM, were administered to SD rats. Also, a group of healthy SD rats was undergoing the same treatment as the control group. The test animals were treated with either anti-IL-15, IL-15, MMP-9 siRNA or ERK1/2 inhibitor. The blood toxicological parameters creatine kinase (CK) and CD163 were tested by using ELISA and immunohistochemistry assay. In addition, NF-kB expression in macrophages was measured by immunocytochemical assay. To measure the degree of cell infiltration the Transwell assay was performed. Lastly, western blot and zymography were carried out to compare MMP-9 and ERK expression levels between the two groups, both in vivo and in vitro. The results showed that S-CK, IL-15 and IL-15Rα levels increased rapidly after the conventional treatment was introduced to the PM infected SD rats. The PM model establishment and IL-15 treatment significantly increased the expressions of IL-15Rα, MMP-9, p-ERK and p-IKBα. However, the same effect can be suppressed by using anti-IL-15, MMP-9 siRNA or ERK1/2 inhibitor (P kB in the macrophages. IL-15 is able to significantly regulate the inflammatory infiltration of macrophages in PM patients through affecting the NF-kB pathway and MMP-9 expression levels. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. LIN28 expression in malignant germ cell tumors down-regulates let-7 and increases oncogene levels

    Science.gov (United States)

    Murray, Matthew J.; Saini, Harpreet K.; Siegler, Charlotte A.; Hanning, Jennifer E.; Barker, Emily M.; van Dongen, Stijn; Ward, Dawn M.; Raby, Katie L.; Groves, Ian J.; Scarpini, Cinzia G.; Pett, Mark R.; Thornton, Claire M.; Enright, Anton J.; Nicholson, James C.; Coleman, Nicholas

    2013-01-01

    Despite their clinico-pathologic heterogeneity, malignant germ-cell-tumors (GCTs) share molecular abnormalities that are likely to be functionally important. In this study, we investigated the potential significance of down-regulation of the let-7 family of tumor-suppressor microRNAs in malignant-GCTs. Microarray results from pediatric and adult samples (n=45) showed that LIN28, the negative-regulator of let-7 biogenesis, was abundant in malignant-GCTs, regardless of patient age, tumor site or histologic subtype. Indeed, a strong negative-correlation existed between LIN28 and let-7 levels in specimens with matched datasets. Low let-7 levels were biologically significant, since the sequence complementary to the 2-7nt common let-7 seed ‘GAGGUA’ was enriched in the 3′untranslated regions of mRNAs up-regulated in pediatric and adult malignant-GCTs, compared with normal gonads (a mixture of germ cells and somatic cells). We identified 27 mRNA targets of let-7 that were up-regulated in malignant-GCT cells, confirming significant negative-correlations with let-7 levels. Among 16 mRNAs examined in a largely independent set of specimens by qRT-PCR, we defined negative-associations with let-7e levels for six oncogenes, including MYCN, AURKB, CCNF, RRM2, MKI67 and C12orf5 (when including normal control tissues). Importantly, LIN28 depletion in malignant-GCT cells restored let-7 levels and repressed all of these oncogenic let-7 mRNA targets, with LIN28 levels correlating with cell proliferation and MYCN levels. Conversely, ectopic expression of let-7e was sufficient to reduce proliferation and down-regulate MYCN, AURKB and LIN28, the latter via a double-negative feedback loop. We concluded that the LIN28/let-7 pathway has a critical pathobiological role in malignant-GCTs and therefore offers a promising target for therapeutic intervention. PMID:23774216

  3. Effects of SO2 emission regulations and fuel prices on levellized energy costs for industrial steam generation options

    International Nuclear Information System (INIS)

    Ozdogan, Sibel; Arikol, Mahir

    1992-01-01

    We discuss the impacts of SO 2 emission regulations and fuel prices on levellized energy costs of industrial steam generation options. A computer model called INDUSTEAM has been utilized. The steam-supply options comprise conventional grate-firing, bubbling and circulating fluidized beds, fuel-oil, and natural-gas-fired systems. Fuels of different SO 2 pollution potential have been evaluated assuming six environmental scenarios and varying fuel prices. A capacity range of 10-90 MW th is covered. (author)

  4. Intestinal levels of anandamide and oleoylethanolamide in food-deprived rats are regulated through their precursors

    DEFF Research Database (Denmark)

    Petersen, Gitte; Sørensen, Camilla; Schmid, Patricia C

    2006-01-01

    The anorectic lipid oleoylethanolamide and the orexigenic lipid anandamide both belong to the group of N-acylethanolamines that are generated by the enzyme N-acylphosphatidylethanolamine-hydrolyzing phospholipase D. The levels of the two bioactive lipids were investigated in rat intestines after 24...... h of starvation as well as after 1 and 4 h of re-feeding. Total levels of precursor phospholipids and N-acylethanolamines were decreased upon food-deprivation whereas the level of the anandamide precursor molecule was significantly increased. The level of 2-arachidonoyl-glycerol was unchanged...... as was the activity of N-acyltransferase, N-acylphosphatidylethanolamine-hydrolyzing phospholipase D, and fatty acid amide hydrolase upon starvation and re-feeding. It is concluded that remodeling of the amide-linked fatty acids of N-acylphosphatidylethanolamine is responsible for the opposite effects on levels...

  5. Vice and virtue in regulating the disposal of high level nuclear waste

    Energy Technology Data Exchange (ETDEWEB)

    Fleming, P.A. [Creighton University, Omaha, NE (United States)

    1999-04-01

    The disagreement over whether standards governing radioactive release should be general, internationally acceptable principles or site specific, contextualized standards reminds the ethicist of the deep disagreement between egalitarian and utilitarian ideals. One should set criteria for health and environment standards that would be acceptable to all rational agents, despite the contexts of needs and desires within which the agents are enmeshed. Remove the veil which masks the moral agent and were she to discover herself to be a subset critical-group member (e.g. a pregnant woman living in Armagosa Valley, Nevada), she would nevertheless find the standards acceptable. This egalitarianism is further justified by the belief that it is morally impermissible not to respect every human being, oneself or any other, as a rational creature. Site-specific standards are viewed with askance in the belief that regulations tailored to specific situations will more likely than not result in political opportunism, i.e. treating some human beings with inequity. But, one need only cite the difficulties of the egalitarian position to provide the human community with practical solutions to easily see why one might think that the utilitarian view supports site-specific standards. Appealing to the John Stuart Mill`s principle of utility, whereby one`s moral obligation is to achieve the greater overall good, regulators who seek to create these standards are freed from the moral constraints imposed by the pure rational agent. Impure reasoning, which attends to context, is not only permissible, it is desirable and even obligatory. Regulators are motivated by pragmatic considerations, which morally legitimate the imposition of risks on a small number for the benefit of the overall good. Site specific standards infused with utility get a needed job done and that is good enough 10 refs.

  6. Vice and virtue in regulating the disposal of high level nuclear waste

    International Nuclear Information System (INIS)

    Fleming, P.A.

    1999-01-01

    The disagreement over whether standards governing radioactive release should be general, internationally acceptable principles or site specific, contextualized standards reminds the ethicist of the deep disagreement between egalitarian and utilitarian ideals. One should set criteria for health and environment standards that would be acceptable to all rational agents, despite the contexts of needs and desires within which the agents are enmeshed. Remove the veil which masks the moral agent and were she to discover herself to be a subset critical-group member (e.g. a pregnant woman living in Armagosa Valley, Nevada), she would nevertheless find the standards acceptable. This egalitarianism is further justified by the belief that it is morally impermissible not to respect every human being, oneself or any other, as a rational creature. Site-specific standards are viewed with askance in the belief that regulations tailored to specific situations will more likely than not result in political opportunism, i.e. treating some human beings with inequity. But, one need only cite the difficulties of the egalitarian position to provide the human community with practical solutions to easily see why one might think that the utilitarian view supports site-specific standards. Appealing to the John Stuart Mill's principle of utility, whereby one's moral obligation is to achieve the greater overall good, regulators who seek to create these standards are freed from the moral constraints imposed by the pure rational agent. Impure reasoning, which attends to context, is not only permissible, it is desirable and even obligatory. Regulators are motivated by pragmatic considerations, which morally legitimate the imposition of risks on a small number for the benefit of the overall good. Site specific standards infused with utility get a needed job done and that is good enough

  7. The effect of proposed changes to the IAEA transport regulations on decommissioning and other low level waste transportation

    International Nuclear Information System (INIS)

    Shetler, A.P.; Jayawardene, N.

    1986-01-01

    Ontario Hydro has studied the proposed changes to the IAEA Transport Regulations contained in the 1985 4th draft edition. The study shows that these proposed changes will have significant strategic and economic effects on the transportation of radioactive decommissioning and other low-level wastes. Under the 1985 4th draft edition, the definition of Low Specific Activity (LSA) material is revised and a new regulation is proposed which restricts the quantity of LSA material or Surface Contaminated Object (SCO) in a single package to that which would have an unshielded dose rate of 10 mSv/h (1 rem/h) at 3 m. The objective of this paper is to highlight the implications of the proposed regulatory changes. An example of the impact of these changes is presented by considering the transportation of typical CANDU decommissioning wastes which arise through piece-by-piece removal of a reactor assembly. The potential effect of the changes is that less decommissioning waste can be shipped in a single low-level waste package. This results in the requirement for so many small, low-level waste packages that Type B shipments are strategically and economically more attractive. However, use of Type B shipments would also result in higher dose uptake and waste management costs than under the 1973 Regulations

  8. BAG3 regulates total MAP1LC3B protein levels through a translational but not transcriptional mechanism.

    Science.gov (United States)

    Rodríguez, Andrea E; López-Crisosto, Camila; Peña-Oyarzún, Daniel; Salas, Daniela; Parra, Valentina; Quiroga, Clara; Morawe, Tobias; Chiong, Mario; Behl, Christian; Lavandero, Sergio

    2016-01-01

    Autophagy is mainly regulated by post-translational and lipid modifications of ATG proteins. In some scenarios, the induction of autophagy is accompanied by increased levels of certain ATG mRNAs such as MAP1LC3B/LC3B, ATG5 or ATG12. However, little is known about the regulation of ATG protein synthesis at the translational level. The cochaperone of the HSP70 system BAG3 (BCL2-associated athanogene 3) has been associated to LC3B lipidation through an unknown mechanism. In the present work, we studied how BAG3 controls autophagy in HeLa and HEK293 cells. Our results showed that BAG3 regulates the basal amount of total cellular LC3B protein by controlling its mRNA translation. This effect was apparently specific to LC3B because other ATG protein levels were not affected. BAG3 knockdown did not affect LC3B lipidation induced by nutrient deprivation or proteasome inhibition. We concluded that BAG3 maintains the basal amount of LC3B protein by controlling the translation of its mRNA in HeLa and HEK293 cells.

  9. Systems Level Regulation of Rhythmic Growth Rate and Biomass Accumulation in Grasses

    Energy Technology Data Exchange (ETDEWEB)

    Kay, Steve A. [Scripps Research Inst., La Jolla, CA (United States); Hazen, Samuel [Scripps Research Inst., San Diego, CA (United States); Mullet, John [Texas A & M Univ., College Station, TX (United States)

    2017-11-22

    Critical to the development of renewable energy sources from biofuels is the improvement of biomass from energy feedstocks, such as sorghum and maize. The specific goals of this project include 1) characterize the growth and gene expression patterns under diurnal and circadian conditions, 2) select transcription factors associated with growth and build a cis-regulatory network in yeast, and 3) perturb these transcription factors in planta using transgenic Brachypodium and sorghum, and characterize the phenotypic outcomes as they relate to biomass accumulation. A better understanding of diurnally regulated growth behavior in grasses may lead to species-specific mechanisms highly relevant to future strategies to optimize energy crop biomass yield.

  10. Regulation of 2-5A Dependent RNase at the Level of its Phosphorylation

    Science.gov (United States)

    1991-06-26

    extract as follows: 25 ul wheat germ extract 10 ul H2O 1 ul RNasin ribonuclease inhibitor (40 u/ml) 7 ul ImM amino acid mixture 1 ul IM...diacylglycerol (DAG) 2. TPA 3. Indolactam Figure 6. Chemical structure of: 1. H-7 (A kinase inhibitor) 2. okadaic acid (A phosphatase inhibitor) Figure 7...elevating agents: Forskolin and Cholera toxin Figure 17. Down-regulation of 2-5A-depRNase by Okadaic 77 acid : A phosphatase inhibitor Figure 18

  11. Circulating IGF1 regulates hippocampal IGF1 levels and brain gene expression during adolescence

    OpenAIRE

    Yan, Han; Mitschelen, Matthew; Bixler, Georgina V; Brucklacher, Robert M; Farley, Julie A; Han, Song; Freeman, Willard M; Sonntag, William E

    2011-01-01

    GH and its anabolic mediator, IGF1, are important not only in somatic growth but also in the regulation of brain function. Even though GH treatment has been used clinically to improve body composition and exercise capacity in adults, its influence on central nervous system function has only recently been recognized. This is also the case for children with childhood-onset GH deficiency (GHD) where GH has been used to stimulate bone growth and enhance final adult height. Circulating IGF1 is tra...

  12. Laminin and Matrix metalloproteinase 11 regulate Fibronectin levels in the zebrafish myotendinous junction.

    Science.gov (United States)

    Jenkins, Molly H; Alrowaished, Sarah S; Goody, Michelle F; Crawford, Bryan D; Henry, Clarissa A

    2016-01-01

    Remodeling of the extracellular matrix (ECM) regulates cell adhesion as well as signaling between cells and their microenvironment. Despite the importance of tightly regulated ECM remodeling for normal muscle development and function, mechanisms underlying ECM remodeling in vivo remain elusive. One excellent paradigm in which to study ECM remodeling in vivo is morphogenesis of the myotendinous junction (MTJ) during zebrafish skeletal muscle development. During MTJ development, there are dramatic shifts in the primary components comprising the MTJ matrix. One such shift involves the replacement of Fibronectin (Fn)-rich matrix, which is essential for both somite and early muscle development, with laminin-rich matrix essential for normal function of the myotome. Here, we investigate the mechanism underlying this transition. We show that laminin polymerization indirectly promotes Fn downregulation at the MTJ, via a matrix metalloproteinase 11 (Mmp11)-dependent mechanism. Laminin deposition and organization is required for localization of Mmp11 to the MTJ, where Mmp11 is both necessary and sufficient for Fn downregulation in vivo. Furthermore, reduction of residual Mmp11 in laminin mutants promotes a Fn-rich MTJ that partially rescues skeletal muscle architecture. These results identify a mechanism for Fn downregulation at the MTJ, highlight crosstalk between laminin and Fn, and identify a new in vivo function for Mmp11. Taken together, our data demonstrate a novel signaling pathway mediating Fn downregulation. Our data revealing new regulatory mechanisms that guide ECM remodeling during morphogenesis in vivo may inform pathological conditions in which Fn is dysregulated.

  13. The Relationship between Structure-Related Food Parenting Practices and Children's Heightened Levels of Self-Regulation in Eating.

    Science.gov (United States)

    Frankel, Leslie A; Powell, Elisabeth; Jansen, Elena

    Food parenting practices influence children's eating behaviors and weight status. Food parenting practices also influence children's self-regulatory abilities around eating, which has important implications for children's eating behaviors. The purpose of the following study is to examine use of structure-related food parenting practices and the potential impact on children's ability to self-regulate energy intake. Parents (n = 379) of preschool age children (M = 4.10 years, SD = 0.92) were mostly mothers (68.6%), Non-White (54.5%), and overweight/obese (50.1%). Hierarchical Multiple Regression was conducted to predict child self-regulation in eating from structure-related food parenting practices (structured meal setting, structured meal timing, family meal setting), while accounting for child weight status, parent age, gender, BMI, race, and yearly income. Hierarchical Multiple Regression results indicated that structure-related feeding practices (structured meal setting and family meal setting, but not structured meal timing) are associated with children's heightened levels of self-regulation in eating. Models examining the relationship within children who were normal weight and overweight/obese indicated the following: a relationship between structured meal setting and heightened self-regulation in eating for normal-weight children and a relationship between family meal setting and heightened self-regulation in eating for overweight/obese children. Researchers should further investigate these potentially modifiable parent feeding behaviors as a protective parenting technique, which possibly contributes to a healthy weight development by enhancing self-regulation in eating.

  14. USP2-45 Is a Circadian Clock Output Effector Regulating Calcium Absorption at the Post-Translational Level.

    Directory of Open Access Journals (Sweden)

    Daniel Pouly

    Full Text Available The mammalian circadian clock influences most aspects of physiology and behavior through the transcriptional control of a wide variety of genes, mostly in a tissue-specific manner. About 20 clock-controlled genes (CCGs oscillate in virtually all mammalian tissues and are generally considered as core clock components. One of them is Ubiquitin-Specific Protease 2 (Usp2, whose status remains controversial, as it may be a cogwheel regulating the stability or activity of core cogwheels or an output effector. We report here that Usp2 is a clock output effector related to bodily Ca2+ homeostasis, a feature that is conserved across evolution. Drosophila with a whole-body knockdown of the orthologue of Usp2, CG14619 (dUsp2-kd, predominantly die during pupation but are rescued by dietary Ca2+ supplementation. Usp2-KO mice show hyperabsorption of dietary Ca2+ in small intestine, likely due to strong overexpression of the membrane scaffold protein NHERF4, a regulator of the Ca2+ channel TRPV6 mediating dietary Ca2+ uptake. In this tissue, USP2-45 is found in membrane fractions and negatively regulates NHERF4 protein abundance in a rhythmic manner at the protein level. In clock mutant animals (Cry1/Cry2-dKO, rhythmic USP2-45 expression is lost, as well as the one of NHERF4, confirming the inverse relationship between USP2-45 and NHERF4 protein levels. Finally, USP2-45 interacts in vitro with NHERF4 and endogenous Clathrin Heavy Chain. Taken together these data prompt us to define USP2-45 as the first clock output effector acting at the post-translational level at cell membranes and possibly regulating membrane permeability of Ca2+.

  15. Elevated levels of circulating IL-18BP and perturbed regulation of IL-18 in schizophrenia

    Directory of Open Access Journals (Sweden)

    Palladino Ilaria

    2012-08-01

    Full Text Available Abstract Background The pleiotropic pro-inflammatory cytokine Interleukin (IL-18 has been proposed to play a role in schizophrenia, since elevated circulating levels of its protein and altered frequencies of genetic variants in its molecular system are reported in schizophrenic patients. Methods We analyzed 77 patients with schizophrenia diagnosis (SCZ and 77 healthy control subjects (HC for serum concentration of both IL-18 and its natural inhibitor, the IL-18 binding protein (IL-18BP. Results We confirmed that serum levels of total IL-18 are significantly increased in SCZ, as compared to HC. However, due to a highly significant increase in levels of circulating IL-18BP in SCZ, as compared to HC, the levels of free, bioactive IL-18 are not significantly different between the two groups. In addition, the relationships between the levels of IL-18 and its inhibitor, as well as between the two molecules and age appear dissimilar for SCZ and HC. In particular, the elevated levels of IL-18BP, likely a consequence of the body’s attempt to counteract the early prominent inflammation which characterizes schizophrenia, are maintained in earlier and later stages of the disease. However, the IL-18BP elevation appears ineffective to balance the IL-18 system in younger SCZ patients, while in older patients the levels of circulating bioactive IL-18 are comparable to those of HC, if not lower. Conclusions In conclusion, these findings indicate that the IL-18 system is perturbed in schizophrenia, supporting the idea that this pro-inflammatory cytokine might be part of a pathway of genetic and environmental components for vulnerability to the disease.

  16. Axial level-specific regulation of neuronal development: lessons from PITX2.

    Science.gov (United States)

    Waite, Mindy R; Martin, Donna M

    2015-02-01

    Transcriptional regulation of gene expression is vital for proper control of proliferation, migration, differentiation, and survival of developing neurons. Pitx2 encodes a homeodomain transcription factor that is highly expressed in the developing and adult mammalian brain. In humans, mutations in PITX2 result in Rieger syndrome, characterized by defects in the development of the eyes, umbilicus, and teeth and variable abnormalities in the brain, including hydrocephalus and cerebellar hypoplasia. Alternative splicing of Pitx2 in the mouse results in three isoforms, Pitx2a, Pitx2b, and Pitx2c, each of which is expressed symmetrically along the left-right axis of the brain throughout development. Here, we review recent evidence for axial and brain region-specific requirements for Pitx2 during neuronal migration and differentiation, highlighting known isoform contributions. © 2014 Wiley Periodicals, Inc.

  17. Energy regulation at EU level. The role of the European Commission and ACER in the context of REMIT

    International Nuclear Information System (INIS)

    Konar, Selma

    2015-01-01

    The regulatory act of promulgating REMIT, the Regulation on Wholesale Market Integrity and Transparency, has highlighted the commanding position of both the European Commission and ACER, the Agency for the Cooperation of Energy Regulators, in the regulation of energy affairs in the European Union. Furthermore it has led to major changes in how surveillance is organized at the national level. The first part of this publication is dedicated to the organization of market surveillance following the promulgation of REMIT. It depicts the tasks of the European Commission and ACER in this context. The Regulation has accorded the authorities a central role in managing the European Union's responsibilities with regard to energy wholesale trade. The act of delegating such far-reaching competence to the authorities deserves careful review however. The article shows how, given ACER's lack of practical experience in market surveillance, as well as its lack of human resources, the task of surveilling the European energy wholesale market confronts the agency with a significant challenge. How successfully the EU energy agency will master this challenge will depend on a number of different factors. Stringent requirements will be needed for the data registration offices in order to ensure optimal data processing. National authorities and supervisory bodies should be made to participate in the data monitoring process. ACER's efficiency in surveilling the market will furthermore depend decisively on its IT infrastructure.

  18. The implications of RCRA [Resource Conservation and Recovery Act] regulation for the disposal of transuranic and high-level waste

    International Nuclear Information System (INIS)

    Sigmon, C.F.; Sharples, F.E.; Smith, E.D.

    1988-01-01

    In May of 1987 the Department of Energy (DOE) published a rule interpreting the definition of ''byproduct'' under the Atomic Energy Act. This byproduct rule clarified the role of the Resource Conservation and Recovery Act (RCRA) in the regulation of DOE's radioactive waste management activities. According to the rule, only the radioactive portion of DOE's mixed radioactive and hazardous waste (mixed waste), including mixed transuranic (TRU) and high-level waste (HLW), is exempt from RCRA under the byproduct exemption. The portion of a waste that is hazardous as defined by RCRA is subject to full regulation under RCRA. Because the radioactive and hazardous portions of m any, if not most, DOE wastes are likely to be inseparable, the rule in effect makes most mixed wastes subject to dual regulation. The potential application of RCRA to facilities such as the Waste Isolation Pilot Plant (WIPP) and the HLW repository creates unique challenges for both the DOE and regulatory authorities. Strategies must be developed to assure compliance with RCRA without either causing excessive administrative burdens or abandoning the goal of minimizing radiation exposure. This paper will explore some of the potential regulatory options for and recent trends in the regulation of TRU and HLW under RCRA

  19. Involvement of α(2)-adrenergic receptor in the regulation of the blood glucose level induced by immobilization stress.

    Science.gov (United States)

    Kang, Yu-Jung; Sim, Yun-Beom; Park, Soo-Hyun; Sharma, Naveen; Suh, Hong-Won

    2015-01-01

    The blood glucose profiles were characterized after mice were forced into immobilization stress with various exposure durations. The blood glucose level was significantly enhanced by immobilization stress for 30 min or 1 h, respectively. On the other hand, the blood glucose level was not affected in the groups which were forced into immobilization stress for 2 or 4 h. We further examined the effect of yohimbine (an α2-adrenergic receptor antagonist) administered systemically or centrally in the immobilization stress model. Mice were pretreated intraperitoneally (i.p.; from 0.5 to 5 mg/kg), intracerebroventricularly (i.c.v.; from 1 to 10 µg/5 µl), or intrathecally (i.t.; from 1 to 10 µg/5 µl) with yohimbine for 10 min and then, forced into immobilization stress for 30 min. The blood glucose level was measured right after immobilization stress. We found that up-regulation of the blood glucose level induced by immobilization stress was abolished by i.p. pretreatment with yohimbine. And the immobilization stress-induced blood glucose level was not inhibited by i.c.v. or i.t. pretreatment with yohimbine at a lower dose (1 µg/5 µl). However, immobilization stress-induced blood glucose level was significantly inhibited by i.c.v. or i.t. pretreatment with yohimbine at higher doses (5 and 10 µg/5 µl). In addition, the i.p. (5 mg/kg), i.c.v. (10 µg/5 µl), or i.t. (10 µg/5 µl) pretreatment with yohimbine reduced hypothalamic glucose transporter 4 expression. The involvement of α2-adrenergic receptor in regulation of immobilization stress- induced blood glucose level was further confirmed by the i.p, i.c.v, or i.t pretreatment with idazoxan, another specific α2-adrenergic receptor antagonist. Finally, i.p., i.c.v., or i.t. pretreatment with yohimbine attenuated the blood glucose level in D-glucose-fed model. We suggest that α2-adrenergic receptors located at the peripheral, the brain and the spinal cord play important roles in the up-regulation

  20. Glycogen synthase kinase 3 has a limited role in cell cycle regulation of cyclin D1 levels.

    Science.gov (United States)

    Yang, Ke; Guo, Yang; Stacey, William C; Harwalkar, Jyoti; Fretthold, Jonathan; Hitomi, Masahiro; Stacey, Dennis W

    2006-08-30

    The expression level of cyclin D1 plays a vital role in the control of proliferation. This protein is reported to be degraded following phosphorylation by glycogen synthase kinase 3 (GSK3) on Thr-286. We recently showed that phosphorylation of Thr-286 is responsible for a decline in cyclin D1 levels during S phase, an event required for efficient DNA synthesis. These studies were undertaken to test the possibility that phosphorylation by GSK3 is responsible for the S phase specific decline in cyclin D1 levels, and that this event is regulated by the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway which controls GSK3. We found, however, that neither PI3K, AKT, GSK3, nor proliferative signaling activity in general is responsible for the S phase decline in cyclin D1 levels. In fact, the activity of these signaling kinases does not vary through the cell cycle of proliferating cells. Moreover, we found that GSK3 activity has little influence over cyclin D1 expression levels during any cell cycle phase. Inhibition of GSK3 activity by siRNA, LiCl, or other chemical inhibitors failed to influence cyclin D1 phosphorylation on Thr-286, even though LiCl efficiently blocked phosphorylation of beta-catenin, a known substrate of GSK3. Likewise, the expression of a constitutively active GSK3 mutant protein failed to influence cyclin D1 phosphorylation or total protein expression level. Because we were unable to identify any proliferative signaling molecule or pathway which is regulated through the cell cycle, or which is able to influence cyclin D1 levels, we conclude that the suppression of cyclin D1 levels during S phase is regulated by cell cycle position rather than signaling activity. We propose that this mechanism guarantees the decline in cyclin D1 levels during each S phase; and that in so doing it reduces the likelihood that simple over expression of cyclin D1 can lead to uncontrolled cell growth.

  1. Dopamine D1 receptor-dependent regulation of extracellular citrulline level in the rat nucleus accumbens during conditioned fear response.

    Science.gov (United States)

    Saulskaya, Natalia B; Fofonova, Nellia V; Sudorghina, Polina V; Saveliev, Sergey A

    2008-08-01

    Nucleus accumbens (N.Acc) contains a subclass of nitric oxide (NO)-generating interneurons that are presumably regulated by the dopamine input. Receptor mechanisms underlying dopamine-NO interaction in the N.Acc are poorly understood. In the current study, we used in vivo microdialysis combined with high-performance liquid chromatography to examine participation of dopamine D1 receptors in regulation of extracellular levels of citrulline (an NO co-product) in the medial N.Acc of Sprague-Dawley rats during both pharmacological challenge and a conditioned fear response. The intraaccumbal infusion of the D1 receptor agonist SKF-38393 (100-500 microM) increased dose-dependently the local dialysate citrulline levels. The SKF-38393-induced increase in extracellular citrulline was prevented by intraaccumbal infusions of 500 microM 7-nitroindazole, a neuronal NO synthase inhibitor. In behavioral microdialysis experiment, the accumbal levels of extracellular citrulline markedly increased in rats given a mild footshock paired with tone. The presentation of the tone previously paired with footshock (the conditioned fear response) produced a "conditioned" rise of extracellular citrulline levels in the N.Acc which was attenuated by intraaccumbal infusion of 100 microM SCH-23390, a dopamine D1 receptor antagonist, and prevented by intraaccumbal infusion of 500 microM 7-nitroindazole. The results suggest that in the N.Acc, the dopamine D1 receptors might regulate the neuronal NO synthase activity; this dopamine-dependent mechanism seems to participate in activation of the neuronal NO synthase and probably NO formation in this brain area during the conditioned fear response.

  2. Biological/Genetic Regulation of Physical Activity Level : Consensus from GenBioPAC

    NARCIS (Netherlands)

    Lightfoot, J Timothy; De Geus, Eco J C; Booth, Frank W; Bray, Molly S; den Hoed, Marcel; Kaprio, Jaakko; Kelly, Scott A; Pomp, Daniel; Saul, Michael C; Thomis, Martine A; Garland, Theodore; Bouchard, Claude

    2017-01-01

    PURPOSE: Physical activity unquestionably maintains and improves health; however, physical activity levels globally are low and not rising despite all the resources devoted to this goal. Attention in both the research literature and the public policy domain has focused on social-behavioral factors;

  3. Nonlinear Dynamics in Gene Regulation Promote Robustness and Evolvability of Gene Expression Levels.

    Science.gov (United States)

    Steinacher, Arno; Bates, Declan G; Akman, Ozgur E; Soyer, Orkun S

    2016-01-01

    Cellular phenotypes underpinned by regulatory networks need to respond to evolutionary pressures to allow adaptation, but at the same time be robust to perturbations. This creates a conflict in which mutations affecting regulatory networks must both generate variance but also be tolerated at the phenotype level. Here, we perform mathematical analyses and simulations of regulatory networks to better understand the potential trade-off between robustness and evolvability. Examining the phenotypic effects of mutations, we find an inverse correlation between robustness and evolvability that breaks only with nonlinearity in the network dynamics, through the creation of regions presenting sudden changes in phenotype with small changes in genotype. For genotypes embedding low levels of nonlinearity, robustness and evolvability correlate negatively and almost perfectly. By contrast, genotypes embedding nonlinear dynamics allow expression levels to be robust to small perturbations, while generating high diversity (evolvability) under larger perturbations. Thus, nonlinearity breaks the robustness-evolvability trade-off in gene expression levels by allowing disparate responses to different mutations. Using analytical derivations of robustness and system sensitivity, we show that these findings extend to a large class of gene regulatory network architectures and also hold for experimentally observed parameter regimes. Further, the effect of nonlinearity on the robustness-evolvability trade-off is ensured as long as key parameters of the system display specific relations irrespective of their absolute values. We find that within this parameter regime genotypes display low and noisy expression levels. Examining the phenotypic effects of mutations, we find an inverse correlation between robustness and evolvability that breaks only with nonlinearity in the network dynamics. Our results provide a possible solution to the robustness-evolvability trade-off, suggest an explanation for

  4. Nonlinear Dynamics in Gene Regulation Promote Robustness and Evolvability of Gene Expression Levels.

    Directory of Open Access Journals (Sweden)

    Arno Steinacher

    Full Text Available Cellular phenotypes underpinned by regulatory networks need to respond to evolutionary pressures to allow adaptation, but at the same time be robust to perturbations. This creates a conflict in which mutations affecting regulatory networks must both generate variance but also be tolerated at the phenotype level. Here, we perform mathematical analyses and simulations of regulatory networks to better understand the potential trade-off between robustness and evolvability. Examining the phenotypic effects of mutations, we find an inverse correlation between robustness and evolvability that breaks only with nonlinearity in the network dynamics, through the creation of regions presenting sudden changes in phenotype with small changes in genotype. For genotypes embedding low levels of nonlinearity, robustness and evolvability correlate negatively and almost perfectly. By contrast, genotypes embedding nonlinear dynamics allow expression levels to be robust to small perturbations, while generating high diversity (evolvability under larger perturbations. Thus, nonlinearity breaks the robustness-evolvability trade-off in gene expression levels by allowing disparate responses to different mutations. Using analytical derivations of robustness and system sensitivity, we show that these findings extend to a large class of gene regulatory network architectures and also hold for experimentally observed parameter regimes. Further, the effect of nonlinearity on the robustness-evolvability trade-off is ensured as long as key parameters of the system display specific relations irrespective of their absolute values. We find that within this parameter regime genotypes display low and noisy expression levels. Examining the phenotypic effects of mutations, we find an inverse correlation between robustness and evolvability that breaks only with nonlinearity in the network dynamics. Our results provide a possible solution to the robustness-evolvability trade-off, suggest

  5. Is Collaborative Learners' Adoption of Metacognitive Regulation Related to Students' Content Processing Strategies and the Level of Transactivity in Their Peer Discussions?

    Science.gov (United States)

    De Backer, Liesje; Van Keer, Hilde; Valcke, Martin

    2017-01-01

    The present study investigates collaborative learners' adoption of key regulation activities (i.e., orienting, planning, monitoring, and evaluating) and a deep-level regulation approach in relation to characteristics of their collaboration on the cognitive and communicative level. More specifically, the correlation of collaborative learners'…

  6. KERDO INFORMATIVE INDEX TO DETERMINE THE LEVEL OF VIOLATIONS OF AUTONOMIC REGULATION AT OSTEOCHONDROSIS OF THE CERVICAL S PINE

    Directory of Open Access Journals (Sweden)

    V. P. Martsenyuk

    2013-05-01

    Full Text Available This paper evaluated t he informative value of the index Kerdo in patients with і mpaired autonomic regulation at osteochondrosis of the cervical spine. The calculated value of the information in these reports: the content of adrenaline and noradrenaline in daily urine acetylcholinesterase activity in capillary blood, systolic, diastolic pressure and heart rate in patients with neurological syndromes of degenerative disc disease of the cervical spine. They were more than the value of information in the index Kerdo with relevant pathology. We could not find sufficient information of Kerdo index to determine the level and direction of disorders of autonomic regulation in patients with neurological syndromes of osteochondrosis of the cervical spine.

  7. Trafficking of plant plasma membrane aquaporins: multiple regulation levels and complex sorting signals.

    Science.gov (United States)

    Chevalier, Adrien S; Chaumont, François

    2015-05-01

    Aquaporins are small channel proteins which facilitate the diffusion of water and small neutral molecules across biological membranes. Compared with animals, plant genomes encode numerous aquaporins, which display a large variety of subcellular localization patterns. More specifically, plant aquaporins of the plasma membrane intrinsic protein (PIP) subfamily were first described as plasma membrane (PM)-resident proteins, but recent research has demonstrated that the trafficking and subcellular localization of these proteins are complex and highly regulated. In the past few years, PIPs emerged as new model proteins to study subcellular sorting and membrane dynamics in plant cells. At least two distinct sorting motifs (one cytosolic, the other buried in the membrane) are required to direct PIPs to the PM. Hetero-oligomerization and interaction with SNAREs (soluble N-ethylmaleimide-sensitive factor protein attachment protein receptors) also influence the subcellular trafficking of PIPs. In addition to these constitutive processes, both the progression of PIPs through the secretory pathway and their dynamics at the PM are responsive to changing environmental conditions. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  8. Vulnerability of US thermoelectric power generation to climate change when incorporating state-level environmental regulations

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Lu; Hejazi, Mohamad; Li, Hongyi; Forman, Barton; Zhang, Xiao

    2017-07-10

    This study explores the interactions between climate and thermoelectric generation in the U.S. by coupling an Earth System Model with a thermoelectric power generation model. We validated model simulations of power production for selected power plants (~44% of existing thermoelectric capacity) against reported values. In addition, we projected future usable capacity for existing power plants under two different climate change scenarios. Results indicate that climate change alone may reduce average thermoelectric generating capacity by 2%-3% by the 2060s. Reductions up to 12% are expected if environmental requirements are enforced without waivers for thermal variation. This study concludes that the impact of climate change on the U.S. thermoelectric power system is less than previous estimates due to an inclusion of a spatially-disaggregated representation of environmental regulations and provisional variances that temporarily relieve power plants from permit requirements. This work highlights the significance of accounting for legal constructs in which the operation of power plants are managed, and underscores the effects of provisional variances in addition to environmental requirements.

  9. Pairwise comparisons of ten porcine tissues identify differential transcriptional regulation at the gene, isoform, promoter and transcription start site level

    International Nuclear Information System (INIS)

    Farajzadeh, Leila; Hornshøj, Henrik; Momeni, Jamal; Thomsen, Bo; Larsen, Knud; Hedegaard, Jakob; Bendixen, Christian; Madsen, Lone Bruhn

    2013-01-01

    Highlights: •Transcriptome sequencing yielded 223 mill porcine RNA-seq reads, and 59,000 transcribed locations. •Establishment of unique transcription profiles for ten porcine tissues including four brain tissues. •Comparison of transcription profiles at gene, isoform, promoter and transcription start site level. •Highlights a high level of regulation of neuro-related genes at both gene, isoform, and TSS level. •Our results emphasize the pig as a valuable animal model with respect to human biological issues. -- Abstract: The transcriptome is the absolute set of transcripts in a tissue or cell at the time of sampling. In this study RNA-Seq is employed to enable the differential analysis of the transcriptome profile for ten porcine tissues in order to evaluate differences between the tissues at the gene and isoform expression level, together with an analysis of variation in transcription start sites, promoter usage, and splicing. Totally, 223 million RNA fragments were sequenced leading to the identification of 59,930 transcribed gene locations and 290,936 transcript variants using Cufflinks with similarity to approximately 13,899 annotated human genes. Pairwise analysis of tissues for differential expression at the gene level showed that the smallest differences were between tissues originating from the porcine brain. Interestingly, the relative level of differential expression at the isoform level did generally not vary between tissue contrasts. Furthermore, analysis of differential promoter usage between tissues, revealed a proportionally higher variation between cerebellum (CBE) versus frontal cortex and cerebellum versus hypothalamus (HYP) than in the remaining comparisons. In addition, the comparison of differential transcription start sites showed that the number of these sites is generally increased in comparisons including hypothalamus in contrast to other pairwise assessments. A comprehensive analysis of one of the tissue contrasts, i

  10. Excess boron responsive regulations of antioxidative mechanism at physio-biochemical and molecular levels in Arabidopsis thaliana.

    Science.gov (United States)

    Kayıhan, Doğa Selin; Kayıhan, Ceyhun; Çiftçi, Yelda Özden

    2016-12-01

    This work was aimed to evaluate the effect of boron (B) toxicity on oxidative damage level, non-enzymatic antioxidant accumulation such as anthocyanin, flavonoid and proline and expression levels of antioxidant enzymes including superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT) and glutathione reductase (GR) and their respective activities as well as expression levels of miR398 and miR408 in Arabidopsis thaliana. Plants were germinated and grown on MS medium containing 1 mM B (1B) and 3 mM B (3B) for 14 d. Toxic B led to a decrease of photosynthetic pigments and an increase in accumulation of total soluble and insoluble sugars in accordance with phenotypically viewed chlorosis of seedlings through increasing level of B concentration. Along with these inhibitions, a corresponding increase in contents of flavonoid, anthocyanin and proline occurred that provoked oxidative stress tolerance. 3B caused a remarkable increase in total SOD activity whereas the activities of APX, GR and CAT remained unchanged as verified by expected increase in H 2 O 2 content. In contrast to GR, the coincidence was found between the expressions of SOD and APX genes and their respective activities. 1B induced mir398 expression, whereas 3B did not cause any significant change in expression of mir408 and mir398. Expression levels of GR genes were coordinately regulated with DHAR2 expression. Moreover, the changes in expression level of MDAR2 was in accordance with changes in APX6 expression and total APX activity, indicating fine-tuned regulation of ascorbate-glutathione cycle which might trigger antioxidative responses against B toxicity in Arabidopsis thaliana. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  11. Regulation of tissue levels of metallothionein with emphasis on metallothionein degradation

    International Nuclear Information System (INIS)

    Chen, M.L.

    1988-01-01

    The synthesis and degradation of metallothionein (MT) was studied in streptozotocin-induced diabetic rats and monolayer cultures of adult rat hepatocytes. Critical analysis of in vivo studies with diabetic rats and other literature revealed that cytoplasmic turnover of MT may not reflect actual degradation of this protein. Therefore, the characteristics of MT degradation in primary cultures of hepatocytes were investigated in subsequent studies. Hepatocytes were incubated in medium containing 35 S-cysteine and 100 μM Zn overnight to induce MT synthesis. The level of 35 S-MT was quantified in heat stable extracts of cell homogenates by Fast Protein Liquid Chromatography (FPLC). When Zn was removed from medium, the rate of 35 S-MT turnover was found times faster than general 3 H-protein. This decrease in cellular MT level reflected degradation since less than 1% of cellular MT was secreted. The rate of MT degradation was inversely proportional to cellular Zn status

  12. Atmospheric oxygen regulation at low Proterozoic levels by incomplete oxidative weathering of sedimentary organic carbon

    Science.gov (United States)

    Daines, Stuart J.; Mills, Benjamin J. W.; Lenton, Timothy M.

    2017-02-01

    It is unclear why atmospheric oxygen remained trapped at low levels for more than 1.5 billion years following the Paleoproterozoic Great Oxidation Event. Here, we use models for erosion, weathering and biogeochemical cycling to show that this can be explained by the tectonic recycling of previously accumulated sedimentary organic carbon, combined with the oxygen sensitivity of oxidative weathering. Our results indicate a strong negative feedback regime when atmospheric oxygen concentration is of order pO2~0.1 PAL (present atmospheric level), but that stability is lost at pO2counterbalancing changes in the weathering of isotopically light organic carbon. This can explain the lack of secular trend in the Precambrian δ13C record, and reopens the possibility that increased biological productivity and resultant organic carbon burial drove the Great Oxidation Event.

  13. Effects of industrial processing on essential elements and regulated and emerging contaminant levels in seafood

    DEFF Research Database (Denmark)

    Rasmussen, Rie Romme; Bøge Søndergaard, Annette; Bøknæs, Niels

    2017-01-01

    Mitigation of contaminants in industrial processing was studied for prawns (cooked and peeled), Greenland halibut (cold smoked) and Atlantic salmon (cold smoked and trimmed). Raw prawns had significantly higher cadmium, chromium, iron, selenium and zinc content in autumn than in spring, while...... summer levels typically were intermediate. Peeling raw prawns increased mercury concentration but reduced the concentration of all other elements including inorganic arsenic, total arsenic, chromium, zinc, selenium but especially cadmium, copper and iron (p

  14. Experience with disposal of low-level radioactive waste: building confidence for and against the regulations

    Energy Technology Data Exchange (ETDEWEB)

    Kastenberg, W.E.; Lowenthal, M.D. [University of California, Dept. of Nuclear Engineering, CA (United States)

    2001-07-01

    Following the controversy regarding the potential use of the Ward Valley site in California as a low level radioactive waste facility, an Advisory Group and a Scientific Panel were formed to recommend alternatives to the Governor. During the course of the Group and Panel deliberations, the arguments for and against near surface burial and waste classification were crystallized. In this paper we discuss the bases upon which the arguments were formed and what we can learn from them. (author)

  15. A constant level liquefied gas regulator sensitive to ± 0,2 mm (1960)

    International Nuclear Information System (INIS)

    Moreau, C.

    1960-01-01

    This device has been designed to maintain a constant level of liquid nitrogen around an adsorption bulb used for the determination of specific surface areas by the BET method. We have in fact already shown elsewhere the necessity of defining carefully the temperature in the bulb and of reducing fluctuations to a minimum. Various apparatus has already been described but it did not offer the sensitivity and the safety in use which we have particularly sought to achieve. (author) [fr

  16. Experience with disposal of low-level radioactive waste: building confidence for and against the regulations

    International Nuclear Information System (INIS)

    Kastenberg, W.E.; Lowenthal, M.D.

    2001-01-01

    Following the controversy regarding the potential use of the Ward Valley site in California as a low level radioactive waste facility, an Advisory Group and a Scientific Panel were formed to recommend alternatives to the Governor. During the course of the Group and Panel deliberations, the arguments for and against near surface burial and waste classification were crystallized. In this paper we discuss the bases upon which the arguments were formed and what we can learn from them. (author)

  17. GRP94 Regulates Circulating Cholesterol Levels through Blockade of PCSK9-Induced LDLR Degradation

    Directory of Open Access Journals (Sweden)

    Steve Poirier

    2015-12-01

    Full Text Available Clearance of circulating low-density lipoprotein cholesterol (LDLc by hepatic LDL receptors (LDLR is central for vascular health. Secreted by hepatocytes, PCSK9 induces the degradation of LDLR, resulting in higher plasma LDLc levels. Still, it remains unknown why LDLR and PCSK9 co-exist within the secretory pathway of hepatocytes without leading to complete degradation of LDLR. Herein, we identified the ER-resident GRP94, and more precisely its client-binding C-terminal domain, as a PCSK9-LDLR inhibitory binding protein. Depletion of GRP94 did not affect calcium homeostasis, induce ER stress, nor did it alter PCSK9 processing or its secretion but greatly increased its capacity to induce LDLR degradation. Accordingly, we found that hepatocyte-specific Grp94-deficient mice have higher plasma LDLc levels correlated with ∼80% reduction in hepatic LDLR protein levels. Thus, we provide evidence that, in physiological conditions, binding of PCSK9 to GRP94 protects LDLR from degradation likely by preventing early binding of PCSK9 to LDLR within the ER.

  18. Regulation of elastin synthesis in developing sheep nuchal ligament by elastin mRNA levels

    International Nuclear Information System (INIS)

    Davidson, J.M.; Smith, K.; Shibahara, S.; Tolstoshev, P.; Crystal, R.G.

    1982-01-01

    Levels of elastin production in explant culture of fetal sheep nuchal ligament and corresponding levels of translatable elastin mRNA were determined in parallel studies during a period of rapid growth of the embryo. The identity of the explant culture and cell-free proucts was confirmed by peptide mapping, immunoprecipitation, and the characteristic lack of histidine and methionine. Elastin production was quantitated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and radioimmune precipitation. The translation products could be labeled with methionine only when NH 2 -terminally donated as f-Met-tRNA/sup Met//sub f/. Explant cultures showed a large rise in elastin production from 70 days after conception to 150 days after conception. Cell free translation of RNA demonstrated a parallel in elastin mRNA levels and in elastin mRNA per cell. It appears, therefore, that the marked emphasis the differentiating muchal ligament places on elastin production is modulated, at least in part, by the quantities of available elastin in mRNA

  19. Brain and Behavioral Assessment of Executive Functions for Self-Regulating Levels of Language in Reading Brain.

    Science.gov (United States)

    Berninger, Virginia W; Richards, Todd L; Abbott, Robert D

    2017-11-01

    This brief research report examines brain-behavioral relationships specific to levels of language in the complex reading brain. The first specific aim was to examine prior findings for significant fMRI connectivity from four seeds (left precuneus, left occipital temporal, left supramarginal, left inferior frontal) for each of four levels of language-subword, word (word-specific spelling or affixed words), syntax (with and without homonym foils or affix foils), and multi-sentence text to identify significant fMRI connectivity (a) unique to the lower level of language when compared to the immediately higher adjacent level of language across subword-word, word-syntax, and syntax-text comparisons; and (b) involving a brain region associated with executive functions. The second specific aim was to correlate the magnitude of that connectivity with standard scores on tests of Focused Attention (D-K EFS Color Word Form Inhibition) and Switching Attention (Wolf & Denckla Rapid Automatic Switching). Seven correlations were significant. Focused Attention was significantly correlated with the word level (word-specific spellings of real words) fMRI task in left cingulum from left inferior frontal seed. Switching Attention was significantly correlated with the (a) subword level (grapheme-phoneme correspondence) fMRI task in left and right Cerebellum V from left supramarginal seed; (b) the word level (word-specific spelling) fMRI task in right Cerebellum V from left precuneus seed; (c) the syntax level (with and without homonym foils) fMRI task in right Cerebellum V from left precuneus seed and from left supramarginal seed; and (d) syntax level (with and without affix foils) fMRI task in right Cerebellum V from left precuneus seed. Results are discussed in reference to neuropsychological assessment of supervisory attention (focused and switching) for specific levels of language related to reading acquisition in students with and without language-related specific learning

  20. Cost-optimal levels of minimum energy performance requirements in the Danish Building Regulations

    Energy Technology Data Exchange (ETDEWEB)

    Aggerholm, S.

    2013-09-15

    The purpose of the report is to analyse the cost optimality of the energy requirements in the Danish Building Regulations 2010, BR10 to new building and to existing buildings undergoing major renovation. The energy requirements in the Danish Building Regulations have by tradition always been based on the cost and benefits related to the private economical or financial perspective. Macro economical calculations have in the past only been made in addition. The cost optimum used in this report is thus based on the financial perspective. Due to the high energy taxes in Denmark there is a significant difference between the consumer price and the macro economical for energy. Energy taxes are also paid by commercial consumers when the energy is used for building operation e.g. heating, lighting, ventilation etc. In relation to the new housing examples the present minimum energy requirements in BR 10 all shows gaps that are negative with a deviation of up till 16 % from the point of cost optimality. With the planned tightening of the requirements to new houses in 2015 and in 2020, the energy requirements can be expected to be tighter than the cost optimal point, if the costs for the needed improvements don't decrease correspondingly. In relation to the new office building there is a gap of 31 % to the point of cost optimality in relation to the 2010 requirement. In relation to the 2015 and 2020 requirements there are negative gaps to the point of cost optimality based on today's prices. If the gaps for all the new buildings are weighted to an average based on mix of building types and heat supply for new buildings in Denmark there is a gap of 3 % in average for the new building. The excessive tightness with today's prices is 34 % in relation to the 2015 requirement and 49 % in relation to the 2020 requirement. The component requirement to elements in the building envelope and to installations in existing buildings adds up to significant energy efficiency

  1. Participation of glyceraldehyde-3-phosphate dehydrogenase in the regulation of 2,3-diphosphoglycerate level in erythrocytes.

    Science.gov (United States)

    Fokina, K V; Yazykova, M Y; Danshina, P V; Schmalhausen, E V; Muronetz, V I

    2000-04-01

    Data are presented concerning the possible participation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in regulation of the glycolytic pathway and the level of 2,3-diphosphoglycerate in erythrocytes. Experimental support has been obtained for the hypothesis according to which a mild oxidation of GAPDH must result in acceleration of glycolysis and in decrease in the level of 2, 3-diphosphoglycerate due to the acyl phosphatase activity of the mildly oxidized enzyme. Incubation of erythrocytes in the presence of 1 mM hydrogen peroxide decreases 2,3-diphosphoglycerate concentration and causes accumulation of 3-phosphoglycerate. It is assumed that the acceleration of glycolysis in the presence of oxidative agents described previously by a number of authors could be attributed to the acyl phosphatase activity of GAPDH. A pH-dependent complexing of GAPDH and 3-phosphoglycerate kinase or 2, 3-diphosphoglycerate mutase is found to determine the fate of 1,3-diphosphoglycerate that serves as a substrate for the synthesis of 2,3-diphosphoglycerate as well as for the 3-phosphoglycerate kinase reaction in glycolysis. A withdrawal of the two-enzyme complexes from the erythrocyte lysates using Sepharose-bound anti-GAPDH antibodies prevents the pH-dependent accumulation of the metabolites. The role of GAPDH in the regulation of glycolysis and the level of 2,3-diphosphoglycerate in erythrocytes is discussed.

  2. Genetic regulation of IL1RL1 methylation and IL1RL1-a protein levels in asthma.

    Science.gov (United States)

    Dijk, F Nicole; Xu, Chengjian; Melén, Erik; Carsin, Anne-Elie; Kumar, Asish; Nolte, Ilja M; Gruzieva, Olena; Pershagen, Goran; Grotenboer, Neomi S; Savenije, Olga E M; Antó, Josep Maria; Lavi, Iris; Dobaño, Carlota; Bousquet, Jean; van der Vlies, Pieter; van der Valk, Ralf J P; de Jongste, Johan C; Nawijn, Martijn C; Guerra, Stefano; Postma, Dirkje S; Koppelman, Gerard H

    2018-03-01

    Interleukin-1 receptor-like 1 ( IL1RL1 ) is an important asthma gene. (Epi)genetic regulation of IL1RL1 protein expression has not been established. We assessed the association between IL1RL1 single nucleotide polymorphisms (SNPs), IL1RL1 methylation and serum IL1RL1-a protein levels, and aimed to identify causal pathways in asthma.Associations of IL1RL1 SNPs with asthma were determined in the Dutch Asthma Genome-wide Association Study cohort and three European birth cohorts, BAMSE (Children/Barn, Allergy, Milieu, Stockholm, an Epidemiological survey), INMA (Infancia y Medio Ambiente) and PIAMA (Prevention and Incidence of Asthma and Mite Allergy), participating in the Mechanisms of the Development of Allergy study. We performed blood DNA IL1RL1 methylation quantitative trait locus (QTL) analysis (n=496) and (epi)genome-wide protein QTL analysis on serum IL1RL1-a levels (n=1462). We investigated the association of IL1RL1 CpG methylation with asthma (n=632) and IL1RL1-a levels (n=548), with subsequent causal inference testing. Finally, we determined the association of IL1RL1-a levels with asthma and its clinical characteristics (n=1101). IL1RL1 asthma-risk SNPs strongly associated with IL1RL1 methylation (rs1420101; p=3.7×10 -16 ) and serum IL1RL1-a levels (p=2.8×10 -56 ). IL1RL1 methylation was not associated with asthma or IL1RL1-a levels. IL1RL1-a levels negatively correlated with blood eosinophil counts, whereas there was no association between IL1RL1-a levels and asthma.In conclusion, asthma-associated IL1RL1 SNPs strongly regulate IL1RL1 methylation and serum IL1RL1-a levels, yet neither these IL1RL1- methylation CpG sites nor IL1RL1-a levels are associated with asthma. Copyright ©ERS 2018.

  3. Resveratrol attenuates bone cancer pain through regulating the expression levels of ASIC3 and activating cell autophagy.

    Science.gov (United States)

    Zhu, Haili; Ding, Jieqiong; Wu, Ji; Liu, Tingting; Liang, Jing; Tang, Qiong; Jiao, Ming

    2017-11-01

    Bone cancer pain (BCP) is one of the most common pains in patients with malignant cancers. The mechanism underlying BCP is largely unknown. Our previous studies and the increasing evidence both have shown that acid-sensing ion channels 3 (ASIC3) is an important protein in the pathological pain state in some pain models. We hypothesized that the expression change of ASIC3 might be one of the factors related to BCP. In this study, we established the BCP model through intrathecally injecting rat mammary gland carcinoma cells (MRMT-1) into the left tibia of Sprague-Dawley female rats, and found that the BCP rats showed bone destruction, increased mechanical pain sensitivities and up-regulated ASIC3 protein expression levels in L4-L6 dorsal root ganglion. Then, resveratrol, which was intraperitoneally injected into the BCP rats on post-operative Day 21, dose-dependently increased the paw withdrawal threshold of BCP rats, reversed the pain behavior, and had an antinociceptive effect on BCP rats. In ASIC3-transfected SH-SY5Y cells, the ASIC3 protein expression levels were regulated by resveratrol in a dose- and time-dependent manner. Meanwhile, resveratrol also had an antinociceptive effect in ASIC3-mediated pain rat model. Furthermore, resveratrol also enhanced the phosphorylation of AMPK, SIRT1, and LC3-II levels in ASIC3-transfected SH-SY5Y cells, indicating that resveratrol could activate the AMPK-SIRT1-autophagy signal pathway in ASIC3-transfected SH-SY5Y cells. In BCP rats, SIRT1 and LC3-II were also down-regulated. These findings provide new evidence for the use of resveratrol as a therapeutic treatment during BCP states. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Effects of industrial processing on essential elements and regulated and emerging contaminant levels in seafood.

    Science.gov (United States)

    Rasmussen, Rie Romme; Søndergaard, Annette Bøge; Bøknæs, Niels; Cederberg, Tommy Licht; Sloth, Jens Jørgen; Granby, Kit

    2017-06-01

    Mitigation of contaminants in industrial processing was studied for prawns (cooked and peeled), Greenland halibut (cold smoked) and Atlantic salmon (cold smoked and trimmed). Raw prawns had significantly higher cadmium, chromium, iron, selenium and zinc content in autumn than in spring, while summer levels typically were intermediate. Peeling raw prawns increased mercury concentration but reduced the concentration of all other elements including inorganic arsenic, total arsenic, chromium, zinc, selenium but especially cadmium, copper and iron (p processing was observed. Non-toxic organic arsenic in raw Greenland halibut (N = 10) and salmon (N = 4) did not transform to carcinogenic inorganic arsenic during industrial cold smoking. Hence inorganic arsenic was low (Processing salmon did not significantly change any levels (calculated both per wet weight, dry weight or lipid content). Cold smoking decreased total arsenic (17%) and increased PCB congeners (10-22%) in Greenland halibut (wet weight). However PFOS, PCB and PBDE congeners were not different in processed Greenland halibut when corrected for water loss or lipid content. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Circulating levels of IGF-1 directly regulate bone growth and density

    Science.gov (United States)

    Yakar, Shoshana; Rosen, Clifford J.; Beamer, Wesley G.; Ackert-Bicknell, Cheryl L.; Wu, Yiping; Liu, Jun-Li; Ooi, Guck T.; Setser, Jennifer; Frystyk, Jan; Boisclair, Yves R.; LeRoith, Derek

    2002-01-01

    IGF-1 is a growth-promoting polypeptide that is essential for normal growth and development. In serum, the majority of the IGFs exist in a 150-kDa complex including the IGF molecule, IGF binding protein 3 (IGFBP-3), and the acid labile subunit (ALS). This complex prolongs the half-life of serum IGFs and facilitates their endocrine actions. Liver IGF-1–deficient (LID) mice and ALS knockout (ALSKO) mice exhibited relatively normal growth and development, despite having 75% and 65% reductions in serum IGF-1 levels, respectively. Double gene disrupted mice were generated by crossing LID+ALSKO mice. These mice exhibited further reductions in serum IGF-1 levels and a significant reduction in linear growth. The proximal growth plates of the tibiae of LID+ALSKO mice were smaller in total height as well as in the height of the proliferative and hypertrophic zones of chondrocytes. There was also a 10% decrease in bone mineral density and a greater than 35% decrease in periosteal circumference and cortical thickness in these mice. IGF-1 treatment for 4 weeks restored the total height of the proximal growth plate of the tibia. Thus, the double gene disruption LID+ALSKO mouse model demonstrates that a threshold concentration of circulating IGF-1 is necessary for normal bone growth and suggests that IGF-1, IGFBP-3, and ALS play a prominent role in the pathophysiology of osteoporosis. PMID:12235108

  6. Specialist-generalist model of body temperature regulation can be applied at the intraspecific level.

    Science.gov (United States)

    Przybylska, Anna S; Boratyński, Jan S; Wojciechowski, Michał S; Jefimow, Małgorzata

    2017-07-01

    According to theoretical predictions, endothermic homeotherms can be classified as either thermal specialists or thermal generalists. In high cost environments, thermal specialists are supposed to be more prone to using facultative heterothermy than generalists. We tested this hypothesis at the intraspecific level using male laboratory mice (C57BL/cmdb) fasted under different thermal conditions (20 and 10°C) and for different time periods (12-48 h). We predicted that variability of body temperature ( T b ) and time spent with T b below normothermy would increase with the increase of environmental demands (duration of fasting and cold). To verify the above prediction, we measured T b and energy expenditure of fasted mice. We did not record torpor bouts but we found that variations in T b and time spent in hypothermia increased with environmental demands. In response to fasting, mice also decreased their energy expenditure. Moreover, animals that showed more precise thermoregulation when fed had more variable T b when fasted. We postulate that the prediction of the thermoregulatory generalist-specialist trade-off can be applied at the intraspecific level, offering a valid tool for identifying mechanistic explanations of the differences in animal responses to variations in energy supply. © 2017. Published by The Company of Biologists Ltd.

  7. The effect of the photoperiod on the level of endogenous growth regulators in pine (Pinus silvestris L. seedlings

    Directory of Open Access Journals (Sweden)

    Krystyna Kriesel

    2014-01-01

    Full Text Available The investigations were performed on pine seedlings growing under 12, 16 and 20 hour photoperiods. In 4 succesive stages of seedling development i.e. after 2, 12, 18 and 30 weeks of culture morphological characters of the seedlings were measured and the levels of auxins-, gibberellins-, cytokininsand abscisic acid-like inhibitor were determined. The intensity of growth and development of juvenile leaves, needles and of the shoot was the lowest in plants growing under 12 hour photoperiod conditions. As the length of the photoperiod increased so did the intensity of these processes. Under the 12 hour photoperiod the development of scale leaves, axillary buds and the formation of the terminal bud started earliest. This process reached completion under the 12 hour photoperiod and the bud remained in a state of dormancy. Seedlings growing under the 12 hour photoperiod were characterized by a low level of stimulators, and at the same time by a high level of inhibitors. On the other hand in seedlings grown at 16 and 20 hour photoperiods the content of stimulators was higher and that of inhibitors lower. A high intensity of growth and development processes was correlated with a high level of stimulators while a high level of inhibitors was correlated with a low intensity of these processes.The obtained results suggest the participation of gibberellins and cytokinins in the processes of regulation of the initiation of scale leaves and axillary buds, and the participation of these hormones and of abscisic acid in the regulation of needle elongation.

  8. Impact of MicroRNA Levels, Target-Site Complementarity, and Cooperativity on Competing Endogenous RNA-Regulated Gene Expression.

    Science.gov (United States)

    Denzler, Rémy; McGeary, Sean E; Title, Alexandra C; Agarwal, Vikram; Bartel, David P; Stoffel, Markus

    2016-11-03

    Expression changes of competing endogenous RNAs (ceRNAs) have been proposed to influence microRNA (miRNA) activity and thereby regulate other transcripts containing miRNA-binding sites. Here, we find that although miRNA levels define the extent of repression, they have little effect on the magnitude of the ceRNA expression change required to observe derepression. Canonical 6-nt sites, which typically mediate modest repression, can nonetheless compete for miRNA binding, with potency ∼20% of that observed for canonical 8-nt sites. In aggregate, low-affinity/background sites also contribute to competition. Sites with extensive additional complementarity can appear as more potent, but only because they induce miRNA degradation. Cooperative binding of proximal sites for the same or different miRNAs does increase potency. These results provide quantitative insights into the stoichiometric relationship between miRNAs and target abundance, target-site spacing, and affinity requirements for ceRNA-mediated gene regulation, and the unusual circumstances in which ceRNA-mediated gene regulation might be observed. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Thyroid hormone coordinately regulates Na sup + -K sup + -ATPase. alpha. - and. beta. -subunit mRNA levels in kidney

    Energy Technology Data Exchange (ETDEWEB)

    McDonough, A.A.; Brown, T.A.; Horowitz, B.; Chiu, R.; Schlotterbeck, J.; Bowen, J.; Schmitt, C.A. (Univ. of Southern California School of Medicine, Los Angeles (USA))

    1988-02-01

    Synthesis of the sodium pump, Na{sup +}-K{sup +}-ATPase, is regulated by thyroid hormone in responsive tissues. The purpose of this study was to determine if triiodothyronine (T{sub 3}) regulates the concentration of the mRNAs coding for the two enzyme subunits, {alpha} and {beta}, and the time course of the response. A single dose of T{sub 3} was administered to hypothyroid rats that were killed at various times after injection. In the kidney cortexes of the T{sub 3}-injected animals, as well as hypothyroid and euthyroid rats, {alpha}- and {beta}-mRNA concentrations were measured by dot blot using cDNAs corresponding to the two mRNAs; {alpha}-subunit abundance was measured by Western blot using antibodies to the enzyme, and Na{sup +}-K{sup +}-ATPase activity was measured enzymatically. {alpha}- and {beta}-mRNAs increased coordinately to 1.6-fold over hypothyroid levels by 12 h after T{sub 3}. The authors conclude that T{sub 3} regulates Na{sup +}-K{sup +}-ATPase synthesis and activity by coordinately increasing the mRNAs of both the {alpha}- and {beta}-subunits of the enzyme.

  10. Dietary fatty acids regulate hepatic low density lipoprotein (LDL) transport by altering LDL receptor protein and mRNA levels.

    Science.gov (United States)

    Horton, J D; Cuthbert, J A; Spady, D K

    1993-01-01

    The concentration of LDL in plasma is strongly influenced by the amount and the type of lipid in the diet. Recent studies in the hamster have shown that dietary fatty acids differentially affect circulating LDL levels primarily by altering receptor-dependent LDL uptake in the liver. To investigate the mechanistic basis of this effect, rates of receptor-dependent LDL transport in the liver were correlated with LDL receptor protein and mRNA levels in hamsters fed safflower oil or coconut oil and varying amounts of cholesterol. Hepatic LDL receptor activity was significantly lower in animals fed coconut oil than in animals fed safflower oil at all levels of cholesterol intake (26, 53, and 61% lower at cholesterol intakes of 0, 0.06, and 0.12%, respectively). These fatty acid-induced changes in hepatic LDL receptor activity were accompanied by parallel changes in hepatic LDL receptor protein and mRNA levels, suggesting that dietary fatty acids regulate the LDL receptor pathway largely at the mRNA level. Images PMID:8349814

  11. Morphological response of the saltmarsh habitats of the Guadiana estuary due to flow regulation and sea-level rise

    Science.gov (United States)

    Sampath, D. M. R.; Boski, T.

    2016-12-01

    In the context of rapid sea-level rise in the 21st century, the reduction of fluvial sediment supply due to the regulation of river discharge represents a major challenge for the management of estuarine ecosystems. Therefore, the present study aims to assess the cumulative impacts of the reduction of river discharge and projected sea-level rise on the morphological evolution of the Guadiana estuary during the 21st century. The assessment was based on a set of analytical solutions to simplified equations of tidal wave propagation in shallow waters and empirical knowledge of the system. As methods applied to estimate environmental flows do not take into consideration the fluvial discharge required to maintain saltmarsh habitats and the impact of sea-level rise, simulations were carried out for ten cases in terms of base river flow and sea-level rise so as to understand their sensitivity on the deepening of saltmarsh platforms. Results suggest saltmarsh habitats may not be affected severely in response to lower limit scenarios of sea-level rise and sedimentation. A similar behaviour can be expected even due to the upper limit scenarios until 2050, but with a significant submergence afterwards. In the case of the upper limit scenarios under scrutiny, there was a net erosion of sediment from the estuary. Multiplications of amplitudes of the base flow function by factors 1.5, 2, and 5 result in reduction of the estimated net eroded sediment volume by 25, 40, and 80%, respectively, with respect to the net eroded volume for observed river discharge. The results also indicate that defining the minimum environmental flow as a percentage of dry season flow (as done presently) should be updated to include the full spectrum of natural flows, incorporating temporal variability to better anticipate scenarios of sea-level rise during this century. As permanent submergence of intertidal habitats can be significant after 2050, due to the projected 79 cm rise of sea-level by the year

  12. Brain Aromatase Modulates Serotonergic Neuron by Regulating Serotonin Levels in Zebrafish Embryos and Larvae

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    Zulvikar Syambani Ulhaq

    2018-05-01

    Full Text Available Teleost fish are known to express two isoforms of P450 aromatase, a key enzyme for estrogen synthesis. One of the isoforms, brain aromatase (AroB, cyp19a1b, is highly expressed during early development of zebrafish, thereby suggesting its role in brain development. On the other hand, early development of serotonergic neuron, one of the major monoamine neurons, is considered to play an important role in neurogenesis. Therefore, in this study, we investigated the role of AroB in development of serotonergic neuron by testing the effects of (1 estradiol (E2 exposure and (2 morpholino (MO-mediated AroB knockdown. When embryos were exposed to E2, the effects were biphasic. The low dose of E2 (0.005 µM significantly increased serotonin (5-HT positive area at 48 hour post-fertilization (hpf detected by immunohistochemistry and relative mRNA levels of tryptophan hydroxylase isoforms (tph1a, tph1b, and tph2 at 96 hpf measured by semi-quantitative PCR. To test the effects on serotonin transmission, heart rate and thigmotaxis, an indicator of anxiety, were analyzed. The low dose also significantly increased heart rate at 48 hpf and decreased thigmotaxis. The high dose of E2 (1 µM exhibited opposite effects in all parameters. The effects of both low and high doses were reversed by addition of estrogen receptor (ER blocker, ICI 182,780, thereby suggesting that the effects were mediated through ER. When AroB MO was injected to fertilized eggs, 5-HT-positive area was significantly decreased, while the significant decrease in relative tph mRNA levels was found only with tph2 but not with two other isoforms. AroB MO also decreased heart rate and increased thigmotaxis. All the effects were rescued by co-injection with AroB mRNA and by exposure to E2. Taken together, this study demonstrates the role of brain aromatase in development of serotonergic neuron in zebrafish embryos and larvae, implying that brain-formed estrogen is an important factor to

  13. Alternative Polyadenylation and Nonsense-Mediated Decay Coordinately Regulate the Human HFE mRNA Levels

    Science.gov (United States)

    Martins, Rute; Proença, Daniela; Silva, Bruno; Barbosa, Cristina; Silva, Ana Luísa; Faustino, Paula; Romão, Luísa

    2012-01-01

    Nonsense-mediated decay (NMD) is an mRNA surveillance pathway that selectively recognizes and degrades defective mRNAs carrying premature translation-termination codons. However, several studies have shown that NMD also targets physiological transcripts that encode full-length proteins, modulating their expression. Indeed, some features of physiological mRNAs can render them NMD-sensitive. Human HFE is a MHC class I protein mainly expressed in the liver that, when mutated, can cause hereditary hemochromatosis, a common genetic disorder of iron metabolism. The HFE gene structure comprises seven exons; although the sixth exon is 1056 base pairs (bp) long, only the first 41 bp encode for amino acids. Thus, the remaining downstream 1015 bp sequence corresponds to the HFE 3′ untranslated region (UTR), along with exon seven. Therefore, this 3′ UTR encompasses an exon/exon junction, a feature that can make the corresponding physiological transcript NMD-sensitive. Here, we demonstrate that in UPF1-depleted or in cycloheximide-treated HeLa and HepG2 cells the HFE transcripts are clearly upregulated, meaning that the physiological HFE mRNA is in fact an NMD-target. This role of NMD in controlling the HFE expression levels was further confirmed in HeLa cells transiently expressing the HFE human gene. Besides, we show, by 3′-RACE analysis in several human tissues that HFE mRNA expression results from alternative cleavage and polyadenylation at four different sites – two were previously described and two are novel polyadenylation sites: one located at exon six, which confers NMD-resistance to the corresponding transcripts, and another located at exon seven. In addition, we show that the amount of HFE mRNA isoforms resulting from cleavage and polyadenylation at exon seven, although present in both cell lines, is higher in HepG2 cells. These results reveal that NMD and alternative polyadenylation may act coordinately to control HFE mRNA levels, possibly varying its

  14. Water Level and Fire Regulate Carbon Sequestration in a Subtropical Peat Marsh

    Science.gov (United States)

    Graham, S.; Sumner, D.; Shoemaker, B.; Benscoter, B.; Hinkle, C. R.

    2014-12-01

    Managed wetlands provide valuable ecosystem services, including carbon storage. Management practices, such as water-level manipulation and prescribed fire, can have a profound effect on the carbon dynamics of these ecosystems. Fluxes of carbon dioxide have been measured by eddy covariance methods over a subtropical peat marsh in Florida, USA since 2009. During this 5-year period, the site has experienced hydroperiods ranging from nine to twelve months. Hydroperiod was found to affect net ecosystem productivity, which was relatively low (70-130 grams carbon per square meter) in years with periodic drying events and much higher (300-600 grams carbon per square meter) during years with constant marsh inundation. The site experienced a prescribed fire in Spring of 2014, which consumed approximately 80% of the aboveground biomass (800 grams carbon per square meter). In addition to the carbon released by the fire, photosynthetic uptake during what would normally be the most productive part of the year was reduced relative to previous years due to low leaf area. These results illustrate how management practices can affect carbon sequestration, which is important for both atmospheric greenhouse gas concentrations and maintenance of peat topography.

  15. The Csr System Regulates Escherichia coli Fitness by Controlling Glycogen Accumulation and Energy Levels

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    Manon Morin

    2017-10-01

    Full Text Available In the bacterium Escherichia coli, the posttranscriptional regulatory system Csr was postulated to influence the transition from glycolysis to gluconeogenesis. Here, we explored the role of the Csr system in the glucose-acetate transition as a model of the glycolysis-to-gluconeogenesis switch. Mutations in the Csr system influence the reorganization of gene expression after glucose exhaustion and disturb the timing of acetate reconsumption after glucose exhaustion. Analysis of metabolite concentrations during the transition revealed that the Csr system has a major effect on the energy levels of the cells after glucose exhaustion. This influence was demonstrated to result directly from the effect of the Csr system on glycogen accumulation. Mutation in glycogen metabolism was also demonstrated to hinder metabolic adaptation after glucose exhaustion because of insufficient energy. This work explains how the Csr system influences E. coli fitness during the glycolysis-gluconeogenesis switch and demonstrates the role of glycogen in maintenance of the energy charge during metabolic adaptation.

  16. Conceptual Principles for Developing and Regulating the Energy Policy of Ukraine at a Competitive Level

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    Klymchuk Oleksandr V.

    2016-02-01

    Full Text Available The article is aimed at studying the current trends of regulatory policy in the global energy market and identifying potent ways for energy efficiency growth in terms of the Ukrainian economy. An analysis of the main trends of energy policy development in the world has been carried out and a priority direction for the development of Ukrainian energy on the basis of the biofuel industry has been determined. The article substantiates actuality of the matter that one of the main directions of overcoming the energy crisis in Ukraine, along with ensuring recovery and sustainable growth of the gross domestic product, is transition to the industrial use of biofuels. The process of production and consumption of biofuels must be seen as a means to raise the level of decentralization, while ensuring energy sources. It is determined that the State must provide information support for producers of biofuels, defining their market range and encouraging beneficial business partners. Increased production of biofuels in Ukraine will serve as a fundamental factor in achieving international competitiveness of the national economy, as well as its growth on innovation basis.

  17. Down-Regulation of Neuropathy Target Esterase in Preeclampsia Placenta Inhibits Human Trophoblast Cell Invasion via Modulating MMP-9 Levels

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    Ting Zhong

    2018-02-01

    Full Text Available Background/Aims: Neuropathy target esterase (NTE, also known as neurotoxic esterase is proven to deacylate phosphatidylcholine (PC to glycerophosphocholine as a phospholipase B. Recently; studies showed that artificial phosphatidylserine/PC microvesicles can induce preeclampsia (PE-like changes in pregnant mice. However, it is unclear whether NTE plays a key role in the pathology of PE, a pregnancy-related disease, which was characterized by deficient trophoblast invasion and reduced trophoblast-mediated remodeling of spiral arteries. The aim of this study was to investigate the expression pattern of NTE in the placenta from women with PE and normal pregnancy, and the molecular mechanism of NTE involved in the development of PE. Methods: NTE expression levels in placentas from 20 pregnant women with PE and 20 healthy pregnant women were detected using quantitative PCR and immunohistochemistry staining. The effect of NTE on trophoblast migration and invasion and the underlying mechanisms were examined in HTR-8/SVneo cell lines by transfection method. Results: NTE mRNA and protein expression levels were significantly decreased in preeclamptic placentas than normal control. Over-expression of NTE in HTR-8/SVneo cells significantly promoted trophoblast cells migration and invasion and was associated with increased MMP-9 levels. Conversely, shRNA-mediated down-regulation of NTE markedly inhibited the cell migration and invasion. In addition, silencing NTE reduced the MMP-9 activity and phosphorylated Erk1/2 and AKT levels. Conclusions: Our results suggest that the decreased NTE may contribute to the development of PE through impairing trophoblast invasion by down-regulating MMP-9 via the Erk1/2 and AKT signaling pathway.

  18. Role of Feedback Regulation of Pantothenate Kinase (CoaA) in Control of Coenzyme A Levels in Escherichia coli

    Science.gov (United States)

    Rock, Charles O.; Park, Hee-Won; Jackowski, Suzanne

    2003-01-01

    Pantothenate kinase (CoaA) is a key regulator of coenzyme A (CoA) biosynthesis in Escherichia coli, and its activity is controlled by feedback inhibition by CoA and its thioesters. The importance of feedback inhibition in the control of the intracellular CoA levels was tested by constructing three site-directed mutants of CoaA that were predicted to be feedback resistant based on the crystal structure of the CoaA-CoA binary complex. CoaA[R106A], CoaA[H177Q], and CoaA[F247V] were purified and shown to retain significant catalytic activity and be refractory to inhibition by CoA. CoaA[R106A] retained 50% of the catalytic activity of CoaA, whereas the CoaA[H177Q] and CoaA[F247V] mutants were less active. The importance of feedback control of CoaA to the intracellular CoA levels was assessed by expressing either CoaA or CoaA[R106A] in strain ANS3 [coaA15(Ts) panD2]. Cells expressing CoaA[R106A] had significantly higher levels of phosphorylated pantothenate-derived metabolites and CoA in vivo and excreted significantly more 4′-phosphopantetheine into the medium compared to cells expressing the wild-type protein. These data illustrate the key role of feedback regulation of pantothenate kinase in the control of intracellular CoA levels. PMID:12754240

  19. General and Simple Decision Method for DG Penetration Level in View of Voltage Regulation at Distribution Substation Transformers

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    Joon-Ho Choi

    2013-09-01

    Full Text Available A distribution system was designed and operated by considering unidirectional power flow from a utility source to end-use loads. The large penetrations of distributed generation (DG into the existing distribution system causes a variety of technical problems, such as frequent tap changing problems of the on-load tap changer (OLTC transformer, local voltage rise, protection coordination, exceeding short-circuit capacity, and harmonic distortion. In view of voltage regulation, the intermittent fluctuation of the DG output power results in frequent tap changing operations of the OLTC transformer. Thus, many utilities limit the penetration level of DG and are eager to find the reasonable penetration limits of DG in the distribution system. To overcome this technical problem, utilities have developed a new voltage regulation method in the distribution system with a large DG penetration level. In this paper, the impact of DG on the OLTC operations controlled by the line drop compensation (LDC method is analyzed. In addition, a generalized determination methodology for the DG penetration limits in a distribution substation transformer is proposed. The proposed DG penetration limits could be adopted for a simplified interconnection process in DG interconnection guidelines.

  20. Transcription initiation patterns indicate divergent strategies for gene regulation at the chromatin level.

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    Elizabeth A Rach

    2011-01-01

    Full Text Available The application of deep sequencing to map 5' capped transcripts has confirmed the existence of at least two distinct promoter classes in metazoans: "focused" promoters with transcription start sites (TSSs that occur in a narrowly defined genomic span and "dispersed" promoters with TSSs that are spread over a larger window. Previous studies have explored the presence of genomic features, such as CpG islands and sequence motifs, in these promoter classes, but virtually no studies have directly investigated the relationship with chromatin features. Here, we show that promoter classes are significantly differentiated by nucleosome organization and chromatin structure. Dispersed promoters display higher associations with well-positioned nucleosomes downstream of the TSS and a more clearly defined nucleosome free region upstream, while focused promoters have a less organized nucleosome structure, yet higher presence of RNA polymerase II. These differences extend to histone variants (H2A.Z and marks (H3K4 methylation, as well as insulator binding (such as CTCF, independent of the expression levels of affected genes. Notably, differences are conserved across mammals and flies, and they provide for a clearer separation of promoter architectures than the presence and absence of CpG islands or the occurrence of stalled RNA polymerase. Computational models support the stronger contribution of chromatin features to the definition of dispersed promoters compared to focused start sites. Our results show that promoter classes defined from 5' capped transcripts not only reflect differences in the initiation process at the core promoter but also are indicative of divergent transcriptional programs established within gene-proximal nucleosome organization.

  1. Complex mutual regulation of facilitates chromatin transcription (FACT) subunits on both mRNA and protein levels in human cells.

    Science.gov (United States)

    Safina, Alfiya; Garcia, Henry; Commane, Mairead; Guryanova, Olga; Degan, Seamus; Kolesnikova, Kateryna; Gurova, Katerina V

    2013-08-01

    Facilitates chromatin transcription (FACT) is a chromatin remodeling complex with two subunits: SSRP1 and SPT16. Mechanisms controlling FACT levels are of interest, since the complex is not expressed in most differentiated cells, but is frequently upregulated in cancer, particularly in poorly differentiated, aggressive tumors. Moreover, inhibition of FACT expression or function in tumor cells interferes with their survival. Here we demonstrate that SSRP1 and SPT16 protein levels decline upon induction of cellular differentiation or senescence in vitro and that similar declines in protein levels for both SSRP1 and SPT16 occur upon RNAi-mediated knockdown of either SSRP1 or SPT16. The interdependence of SSRP1 and SPT16 protein levels was found to be due to their association with SSRP1 and SPT16 mRNAs, which stabilizes the proteins. In particular, presence of SSRP1 mRNA is critical for SPT16 protein stability. In addition, binding of SSRP1 and SPT16 mRNAs to the FACT complex increases the stability and efficiency of translation of the mRNAs. These data support a model in which the FACT complex is stable when SSRP1 mRNA is present, but quickly degrades when SSRP1 mRNA levels drop. In the absence of FACT complex, SSRP1 and SPT16 mRNAs are unstable and inefficiently translated, making reactivation of FACT function unlikely in normal cells. Thus, we have described a complex and unusual mode of regulation controlling cellular FACT levels that results in amplified and stringent control of FACT activity. The FACT dependence of tumor cells suggests that mechanisms controlling FACT levels could be targeted for anticancer therapy.

  2. Evaluation of safety issues on newly regulated nuclear power plant by tsunami-level 1 PRA

    International Nuclear Information System (INIS)

    Tsuji, Yutaro; Miwa, Shuichiro; Mori, Michitsugu

    2014-01-01

    The tsunami caused by the Great East Japan Earthquake triggered severe accidents involving the units 1 to 4 at the Fukushima Dai-ichi nuclear power station (NPS). In order to re-operate existing nuclear power plants it should be necessary to reduce the core damage frequency on risk by tsunami. In this work, effects of the off-site power supply installation on resuming operation of nuclear power plants were investigated by utilizing the Tsunami-Level 1 Probability Risk Assessment (PRA). Unit 2 of the Onagawa nuclear power station, which resembled units 2 and 3 of Fukushima Dai-ichi, was selected for PRA. First, event-tree was created for the units of the Onagawa nuclear power station with the safety systems such as Emergency Core Cooling System (ECCS), investigating the plant situation at the time of the earthquake and tsunami occurrences. It was assumed that the magnitude of the tsunami was equivalent to the Great East Japan Earthquake. The accident-analytical progression-time was 36 hours, determined from the core-damage occurrence of the unit 3 of Fukushima Dai-ichi nuclear power station. Failure probabilities were calculated by the fault tree, which was created from the elements listed in the event tree. For the calculation, failure rates reported by the NUCIA (NUClear Information Archives) were primarily utilized. Then, obtained failure probabilities were embedded to the event tree. Core damage probabilities were evaluated by calculating success and failure rates for each accidental progression and scenarios. Restoration of the failed equipment and machineries was not considered in the analysis. Installation of the power supply vehicles at the nuclear power plant site reduced the core damage probability from 2.58×10 -6 to 8.56×10 -7 . However, continued addition of the power supply vehicles could not lower the core damage probability further more. In the case of Unit 2 of Onagawa nuclear power station, there could be a limit to lower the core damage

  3. Sulfate-driven elemental sparing is regulated at the transcriptional and posttranscriptional levels in a filamentous cyanobacterium.

    Science.gov (United States)

    Gutu, Andrian; Alvey, Richard M; Bashour, Sami; Zingg, Daniel; Kehoe, David M

    2011-03-01

    Sulfur is an essential nutrient that can exist at growth-limiting concentrations in freshwater environments. The freshwater cyanobacterium Fremyella diplosiphon (also known as Tolypothrix sp. PCC 7601) is capable of remodeling the composition of its light-harvesting antennae, or phycobilisomes, in response to changes in the sulfur levels in its environment. Depletion of sulfur causes these cells to cease the accumulation of two forms of a major phycobilisome protein called phycocyanin and initiate the production of a third form of phycocyanin, which possesses a minimal number of sulfur-containing amino acids. Since phycobilisomes make up approximately 50% of the total protein in these cells, this elemental sparing response has the potential to significantly influence the fitness of this species under low-sulfur conditions. This response is specific for sulfate and occurs over the physiological range of sulfate concentrations likely to be encountered by this organism in its natural environment. F. diplosiphon has two separate sulfur deprivation responses, with low sulfate levels activating the phycobilisome remodeling response and low sulfur levels activating the chlorosis or bleaching response. The phycobilisome remodeling response results from changes in RNA abundance that are regulated at both the transcriptional and posttranscriptional levels. The potential of this response, and the more general bleaching response of cyanobacteria, to provide sulfur-containing amino acids during periods of sulfur deprivation is examined.

  4. Sulfate-Driven Elemental Sparing Is Regulated at the Transcriptional and Posttranscriptional Levels in a Filamentous Cyanobacterium▿ †

    Science.gov (United States)

    Gutu, Andrian; Alvey, Richard M.; Bashour, Sami; Zingg, Daniel; Kehoe, David M.

    2011-01-01

    Sulfur is an essential nutrient that can exist at growth-limiting concentrations in freshwater environments. The freshwater cyanobacterium Fremyella diplosiphon (also known as Tolypothrix sp. PCC 7601) is capable of remodeling the composition of its light-harvesting antennae, or phycobilisomes, in response to changes in the sulfur levels in its environment. Depletion of sulfur causes these cells to cease the accumulation of two forms of a major phycobilisome protein called phycocyanin and initiate the production of a third form of phycocyanin, which possesses a minimal number of sulfur-containing amino acids. Since phycobilisomes make up approximately 50% of the total protein in these cells, this elemental sparing response has the potential to significantly influence the fitness of this species under low-sulfur conditions. This response is specific for sulfate and occurs over the physiological range of sulfate concentrations likely to be encountered by this organism in its natural environment. F. diplosiphon has two separate sulfur deprivation responses, with low sulfate levels activating the phycobilisome remodeling response and low sulfur levels activating the chlorosis or bleaching response. The phycobilisome remodeling response results from changes in RNA abundance that are regulated at both the transcriptional and posttranscriptional levels. The potential of this response, and the more general bleaching response of cyanobacteria, to provide sulfur-containing amino acids during periods of sulfur deprivation is examined. PMID:21239582

  5. Ecdysteroids regulate the levels of Molt-Inhibiting Hormone (MIH expression in the blue crab, Callinectes sapidus.

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    Sirinart Techa

    Full Text Available Arthropod molt is coordinated through the interplay between ecdysteroids and neuropeptide hormones. In crustaceans, changes in the activity of Y-organs during the molt cycle have been regulated by molt-inhibiting hormone (MIH and crustacean hyperglycemic hormone (CHH. Little has been known of the mode of direct effects of ecdysteroids on the levels of MIH and CHH in the eyestalk ganglia during the molt cycle. This study focused on a putative feedback of ecdysteroids on the expression levels of MIH transcripts using in vitro incubation study with ecdysteroids and in vivo RNAi in the blue crab, Callinectes sapidus. Our results show a specific expression of ecdysone receptor (EcR in which EcR1 is the major isoform in eyestalk ganglia. The initial elevation of MIH expression at the early premolt stages is replicated by in vitro incubations of eyestalk ganglia with ecdysteroids that mimic the intrinsic conditions of D0 stage: the concentration (75 ng/ml and composition (ponasterone A and 20-hydroxyecdysone at a 3:1 (w:w ratio. Additionally, multiple injections of EcR1-dsRNA reduce MIH expression by 67%, compared to the controls. Our data provide evidence on a putative feedback mechanism of hormonal regulation during molting cycle, specifically how the molt cycle is repeated during the life cycle of crustaceans. The elevated concentrations of ecdysteroids at early premolt stage may act positively on the levels of MIH expression in the eyestalk ganglia. Subsequently, the increased MIH titers in the hemolymph at postmolt would inhibit the synthesis and release of ecdysteroids by Y-organs, resulting in re-setting the subsequent molt cycle.

  6. Ecdysteroids regulate the levels of Molt-Inhibiting Hormone (MIH) expression in the blue crab, Callinectes sapidus.

    Science.gov (United States)

    Techa, Sirinart; Chung, J Sook

    2015-01-01

    Arthropod molt is coordinated through the interplay between ecdysteroids and neuropeptide hormones. In crustaceans, changes in the activity of Y-organs during the molt cycle have been regulated by molt-inhibiting hormone (MIH) and crustacean hyperglycemic hormone (CHH). Little has been known of the mode of direct effects of ecdysteroids on the levels of MIH and CHH in the eyestalk ganglia during the molt cycle. This study focused on a putative feedback of ecdysteroids on the expression levels of MIH transcripts using in vitro incubation study with ecdysteroids and in vivo RNAi in the blue crab, Callinectes sapidus. Our results show a specific expression of ecdysone receptor (EcR) in which EcR1 is the major isoform in eyestalk ganglia. The initial elevation of MIH expression at the early premolt stages is replicated by in vitro incubations of eyestalk ganglia with ecdysteroids that mimic the intrinsic conditions of D0 stage: the concentration (75 ng/ml) and composition (ponasterone A and 20-hydroxyecdysone at a 3:1 (w:w) ratio). Additionally, multiple injections of EcR1-dsRNA reduce MIH expression by 67%, compared to the controls. Our data provide evidence on a putative feedback mechanism of hormonal regulation during molting cycle, specifically how the molt cycle is repeated during the life cycle of crustaceans. The elevated concentrations of ecdysteroids at early premolt stage may act positively on the levels of MIH expression in the eyestalk ganglia. Subsequently, the increased MIH titers in the hemolymph at postmolt would inhibit the synthesis and release of ecdysteroids by Y-organs, resulting in re-setting the subsequent molt cycle.

  7. THE ANALYSE OF THE REGULATIONS AT THE EUROPEAN LEVEL REGARDING CARTELS. CASE SUDY: CARTEL BETWEEN THE COMPANIES CHIQUITA AND PACIFIC

    Directory of Open Access Journals (Sweden)

    Berinde Mihai

    2012-07-01

    Full Text Available The present paper tries to make an analyse of the policy in the field of competition, at the level of the European Union, more exactly the policy applied on cartels. It is important to know the regulations regarding cartels, especially the way in which procedures are done in the case of a cartel. Cartels have a negative impact on competition and consumers, and that’s why it is extremely important that they are discovered on time and after that, by using correction measures to try to recuperate the created damage. The used research method is the analyze of the legislation in force regarding cartels and the study of the existing literature in this field, and in order to give an example of the procedures in the case of a cartel, we analyzed the cartel between two companies Chiquita and Pacific. It is extremely important for these regulations to be known, and in order to discourage such practices, the European Committee has thought of a series of advantages for the companies that give information and evidence regarding the existence of a cartel. Among these advantages we could mention immunity to fine, that permits the company to be absolved of all its fines. The paper presents schematically the legislation that forbids anti-competitive practices, at the level of the European Union, and after that the applied procedure when a law violation is discovered. The modality in which the procedures are applied, in the case of suspecting a cartel, have been presented step by step, and after that, the case study does not exist only to give an example of procedures, but also to present the applied methods, in the case of success in proving the existence of a cartel. The importance of competition policy at a European level cannot be denied because of the fact that only by implementing of a proper policy in this field, an economy can develop further.

  8. Differences in academic performance and self-regulated learning based on level of student participation in supplemental instruction

    Science.gov (United States)

    Mack, Ana C.

    This study examined differences in academic performance and self-regulated learning based on levels of student participation in Supplemental Instruction (SI) sessions in two introductory undergraduate biology and chemistry courses offered at University of Central Florida in the Spring 2006 semester. The sample consisted of 282 students enrolled in the biology class and 451 students enrolled in chemistry. Academic performance was measured using students' final course grades and rates of withdrawal from the courses. The self-regulated learning constructs of motivation, cognition, metacognition, and resource management were measured using the Motivated Strategies for Learning Questionnaire (MSLQ). Relationships between students' gender and ethnic background and levels of SI participation were also analyzed in this research. Findings in both biology and chemistry courses revealed a statistically significant decrease in student motivation from beginning to end of semester. In chemistry, frequent SI participants also showed statistically significantly higher levels of motivation at the end of the semester than occasional and non-SI participants. There were no statistically significant gains in cognitive, metacognitive, and resource management strategies from beginning to end of semester. However, statistically significant differences in resource management were observed at the end of the semester among SI attendance groups in both courses. Students in the high SI attendance group were more likely to use learning resources than those who did not participate regularly or did not participate at all. Statistically significant differences in academic performance based on students' SI participation were found in both biology and chemistry courses. Frequent SI participants had significantly higher final percentage grades and were more likely to receive grades of A, B, or C, than those who either did not attend SI regularly of did not participate at all. They were also less

  9. Reduced Levels of the Synaptic Functional Regulator FMRP in Dentate Gyrus of the Aging Sprague-Dawley Rat

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    Roman Smidak

    2017-11-01

    Full Text Available Fragile X mental retardation protein (FMRP encoded by Fragile X mental retardation 1 (FMR1 gene is a RNA-binding regulator of mRNA translation, transport and stability with multiple targets responsible for proper synaptic function. Epigenetic silencing of FMR1 gene expression leads to the development of Fragile X syndrome (FXS that is characterized by intellectual disability and other behavioral problems including autism. In the rat FXS model, the lack of FMRP caused a deficit in hippocampal-dependent memory. However, the hippocampal changes of FMRP in aging rats are not fully elucidated. The current study addresses the changes in FMRP levels in dentate gyrus (DG from young (17 weeks and aging (22 months Sprague – Dawley rats. The aging animal group showed significant decline in spatial reference memory. Protein samples from five rats per each group were analyzed by quantitative proteomic analysis resulting in 153 significantly changed proteins. FMRP showed significant reduction in aging animals which was confirmed by immunoblotting and immunofluorescence microscopy. Furthermore, bioinformatic analysis of the differential protein dataset revealed several functionally related protein groups with individual interactions with FMRP. These include high representation of the RNA translation and processing machinery connected to FMRP and other RNA-binding regulators including CAPRIN1, the members of Pumilio (PUM and CUG-BP, Elav-like (CELF family, and YTH N(6-methyladenosine RNA-binding proteins (YTHDF. The results of the current study point to the important role of FMRP and regulation of RNA processing in the rat DG and memory decline during the aging process.

  10. Expression of Arabidopsis FCS-Like Zinc finger genes is differentially regulated by sugars, cellular energy level, and abiotic stress

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    Muhammed eJamsheer K

    2015-09-01

    Full Text Available Cellular energy status is an important regulator of plant growth, development, and stress mitigation. Environmental stresses ultimately lead to energy deficit in the cell which activates the SNF1-RELATED KINASE 1 (SnRK1 signaling cascade which eventually triggering a massive reprogramming of transcription to enable the plant to survive under low-energy conditions. The role of Arabidopsis thaliana FCS-Like Zinc finger (FLZ gene family in energy and stress signaling is recently come to highlight after their interaction with kinase subunits of SnRK1 were identified. In a detailed expression analysis in different sugars, energy starvation, and replenishment series, we identified that the expression of most of the FLZ genes is differentially modulated by cellular energy level. It was found that FLZ gene family contains genes which are both positively and negatively regulated by energy deficit as well as energy-rich conditions. Genetic and pharmacological studies identified the role of HEXOKINASE 1- dependent and energy signaling pathways in the sugar-induced expression of FLZ genes. Further, these genes were also found to be highly responsive to different stresses as well as abscisic acid. In over-expression of kinase subunit of SnRK1, FLZ genes were found to be differentially regulated in accordance with their response towards energy fluctuation suggesting that these genes may work downstream to the established SnRK1 signaling under low-energy stress. Taken together, the present study provides a conceptual framework for further studies related to SnRK1-FLZ interaction in relation to sugar and energy signaling and stress response.

  11. Polybrominated diphenyl ethers fate in China: a review with an emphasis on environmental contamination levels, human exposure and regulation.

    Science.gov (United States)

    Chen, Yuan; Li, Jinhui; Liu, Lili; Zhao, Nana

    2012-12-30

    Because of their highly effective flame-retardant capability, polybrominated diphenyl ethers (PBDEs) have been extensively used as flame retardants in consumer goods. However, compelling evidence shows that many congeners of PBDEs have been accumulating in the environment, in biota and in human populations worldwide. In China, although octabrominated diphenyl ether (octaBDE) has never been produced or used, pentabrominated diphenyl ether (pentaBDE) and decabrominated diphenyl ether (decaBDE) have been produced and used in large quantities. In the face of increasing evidence about PBDE pollution and the adoption of international conventions, there is a growing push for China to develop more stringent methods of managing PBDE waste. This paper summarizes the information about PBDE production and application, describes the flame-retarding mechanism, and then reviews the toxicity and levels of PBDEs in China's environmental media and human tissues. Based on international regulations on PBDEs, the paper finally puts forward some suggestions for Chinese policy making and for self-regulation within the flame retardant industry. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Chorionic gonadotropin regulates the transcript level of VHL, p53, and HIF-2alpha in human granulosa lutein cells.

    Science.gov (United States)

    Herr, D; Keck, C; Tempfer, C; Pietrowski, Detlef

    2004-12-01

    The ovarian corpus luteum plays a critical role in reproduction being the primary source of circulating progesterone. After ovulation the corpus luteum is build by avascular granulosa lutein cells through rapid vascularization regulated by gonadotropic hormones. The present study was performed to investigate whether this process might be influenced by the human chorionic gonadotropin (hCG)-dependent expression of different tumor suppressor genes and hypoxia dependent transcription factors. RNA was isolated from cultured granulosa lutein cells, transcribed into cDNA, and the transcript level of following genes were determined: RB-1, VHL, NF-1, NF-2, Wt-1, p53, APC, and hypoxia inducible factor-1 (HIF-1), -2, and -3alpha. Additionally, the influence of hCG on the expression of VHL, p53, and HIf2alpha were investigated. We demonstrate that in human granulosa lutein cells the tumor suppressor genes RB-1, VHL, NF-1, NF-2, Wt-1, p53, and APC and the hypoxia dependent transcription factors HIF-1alpha, -2alpha, and -3alpha are expressed. In addition, we showed that hCG regulates the expression of p53, VHL, and HIF-2alpha. Our results indicate that hCG may determine the growth and development of the corpus luteum by mediating hypoxic and apoptotic pathways in human granulosa lutein cells. Copyright 2004 Wiley-Liss, Inc.

  13. Regulation of the glucocorticoid receptor mRNA levels in the gills of Atlantic salmon (Salmo salar during smoltification

    Directory of Open Access Journals (Sweden)

    MAZURAIS D.

    1998-07-01

    Full Text Available The regulation of the Glucocorticoid Receptor (GR transcript was investigated in the gills of Atlantic salmon (Salmo salar during the parr-smolt transformation. Sampling of parr and smolt fish was performed between December and July and in particular during the smoltification period occurring in spring. Quantification of GR transcripts revealed differences between the two groups in March and at the beginning of April. During these dates, the amounts of GR mRNA in parr gills were respectively three and two fold lower than those measured in smolts. In order to determine which factors are responsible for these differences, we studied the long-term effects of prolactin and Cortisol treatments on GR transcript in the gills of presmolt fish. The plasma levels of these two hormones respectively drop and rise during smoltification. Contrary to Cortisol long-term treatment which did not modify the amount of gill GR transcript, short-term treatment induced a significant decrease within 12 hours. Prolactin long-term treatment caused a significant increase of GR transcript abundance after 13 days of implant treatment. This result is unexpected with regard to those obtained in the smoltification analysis but is in agreement with previous studies performed in mammary gland revealing a positive control of PRL on GR in epithelial cells. Our data suggest that the regulation of the GR transcript during the parr-smolt transformation probably involves several hormonal factors.

  14. Higher plasma motilin levels in obese patients decrease after Roux-en-Y gastric bypass surgery and regulate hunger.

    Science.gov (United States)

    Deloose, E; Janssen, P; Lannoo, M; Van der Schueren, B; Depoortere, I; Tack, J

    2016-07-01

    Motilin-induced phase III contractions of the migrating motor complex (MMC) signal hunger in healthy volunteers. The current aim was to study the role of motilin as a hunger-inducing factor in obese patients and to evaluate the effect of Roux-en-Y gastric bypass (RYGB) surgery on plasma motilin levels and hunger scores. Motilin and ghrelin plasma levels were determined during a complete MMC cycle in controls and obese patients selected for RYGB before, 6 months and 1 year after surgery. 20 min after the end of the second phase III, obese patients received an intravenous infusion of 40 mg erythromycin. Hunger was scored every 5 min. Hedonic hunger was assessed in obese patients with the Power of Food Scale questionnaire. Obesity caused a switch in the origin of phase III from antrum to duodenum. Obese patients had significantly higher motilin levels compared with controls during the MMC but tended to lack the motilin peak prior to phase III necessary to trigger hunger. Hunger scores during phase III were significantly lower in obese patients, but could be restored to control levels through the administration of a low dose of the motilin agonist, erythromycin. After RYGB surgery motilin, but not ghrelin, levels decreased in parallel with hedonic hunger scores. Motilin may be an important regulator involved in the pathogenesis of obesity. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  15. High-fructose corn syrup and sucrose have equivalent effects on energy-regulating hormones at normal human consumption levels.

    Science.gov (United States)

    Yu, Zhiping; Lowndes, Joshua; Rippe, James

    2013-12-01

    Intake of high-fructose corn syrup (HFCS) has been suggested to contribute to the increased prevalence of obesity, whereas a number of studies and organizations have reported metabolic equivalence between HFCS and sucrose. We hypothesized that HFCS and sucrose would have similar effects on energy-regulating hormones and metabolic substrates at normal levels of human consumption and that these values would not change over a 10-week, free-living period at these consumption levels. This was a randomized, prospective, double-blind, parallel group study in which 138 adult men and women consumed 10 weeks of low-fat milk sweetened with either HFCS or sucrose at levels of the 25th, 50th, and 90th percentile population consumption of fructose (the equivalent of 40, 90, or 150 g of sugar per day in a 2000-kcal diet). Before and after the 10-week intervention, 24-hour blood samples were collected. The area under the curve (AUC) for glucose, insulin, leptin, active ghrelin, triglyceride, and uric acid was measured. There were no group differences at baseline or posttesting for all outcomes (interaction, P > .05). The AUC response of glucose, active ghrelin, and uric acid did not change between baseline and posttesting (P > .05), whereas the AUC response of insulin (P < .05), leptin (P < .001), and triglyceride (P < .01) increased over the course of the intervention when the 6 groups were averaged. We conclude that there are no differences in the metabolic effects of HFCS and sucrose when compared at low, medium, and high levels of consumption. © 2013 Elsevier Inc. All rights reserved.

  16. SET overexpression in HEK293 cells regulates mitochondrial uncoupling proteins levels within a mitochondrial fission/reduced autophagic flux scenario

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Luciana O.; Goto, Renata N. [Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Neto, Marinaldo P.C. [Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Sousa, Lucas O. [Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Curti, Carlos [Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Leopoldino, Andréia M., E-mail: andreiaml@usp.br [Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil)

    2015-03-06

    We hypothesized that SET, a protein accumulated in some cancer types and Alzheimer disease, is involved in cell death through mitochondrial mechanisms. We addressed the mRNA and protein levels of the mitochondrial uncoupling proteins UCP1, UCP2 and UCP3 (S and L isoforms) by quantitative real-time PCR and immunofluorescence as well as other mitochondrial involvements, in HEK293 cells overexpressing the SET protein (HEK293/SET), either in the presence or absence of oxidative stress induced by the pro-oxidant t-butyl hydroperoxide (t-BHP). SET overexpression in HEK293 cells decreased UCP1 and increased UCP2 and UCP3 (S/L) mRNA and protein levels, whilst also preventing lipid peroxidation and decreasing the content of cellular ATP. SET overexpression also (i) decreased the area of mitochondria and increased the number of organelles and lysosomes, (ii) increased mitochondrial fission, as demonstrated by increased FIS1 mRNA and FIS-1 protein levels, an apparent accumulation of DRP-1 protein, and an increase in the VDAC protein level, and (iii) reduced autophagic flux, as demonstrated by a decrease in LC3B lipidation (LC3B-II) in the presence of chloroquine. Therefore, SET overexpression in HEK293 cells promotes mitochondrial fission and reduces autophagic flux in apparent association with up-regulation of UCP2 and UCP3; this implies a potential involvement in cellular processes that are deregulated such as in Alzheimer's disease and cancer. - Highlights: • SET, UCPs and autophagy prevention are correlated. • SET action has mitochondrial involvement. • UCP2/3 may reduce ROS and prevent autophagy. • SET protects cell from ROS via UCP2/3.

  17. Regulator's Workshop on The Role of Future Society and Biosphere in Demonstrating Compliance with High-Level Radioactive Waste Disposal Standards and Regulations

    Energy Technology Data Exchange (ETDEWEB)

    Avila, R. [Swedish Radiation Protection Authority, Stockholm (Sweden); Blommaert, W. [Agence Federale de Controle Nucleaire, Bruxelles (Belgium); Clark, R. [US Environmental Protection Agency (United States)] [and others

    2002-09-01

    This report summarizes the proceedings of a workshop, co-sponsored by the U.S. Environmental Protection Agency (US EPA) and the Swedish Radiation Protection Authority (SSI). The invitations to participate in the Workshop were primarily extended to authorities in countries with major nuclear waste programs involving geological disposal and using performance assessment methodology. The main objective of the Workshop was to develop a common understanding among regulators of the role of society and the biosphere in demonstrating compliance with regulations.

  18. Regulator's Workshop on The Role of Future Society and Biosphere in Demonstrating Compliance with High-Level Radioactive Waste Disposal Standards and Regulations

    International Nuclear Information System (INIS)

    Avila, R.; Blommaert, W.; Clark, R.

    2002-09-01

    This report summarizes the proceedings of a workshop, co-sponsored by the U.S. Environmental Protection Agency (US EPA) and the Swedish Radiation Protection Authority (SSI). The invitations to participate in the Workshop were primarily extended to authorities in countries with major nuclear waste programs involving geological disposal and using performance assessment methodology. The main objective of the Workshop was to develop a common understanding among regulators of the role of society and the biosphere in demonstrating compliance with regulations

  19. Investment choice and perceived mating intentions regulated by external resource cues and internal fluctuation in blood glucose levels.

    Science.gov (United States)

    Rao, Li-Lin; Wang, Xiao-Tian; Li, Shu

    2014-01-01

    We examined resource allocation priorities in the framework of an updated Maslow hierarchy of fundamental human needs. In Experiment 1, the participants in the food abundance priming condition viewing photos of high-calorie food allocated more money to savings than to spending. However, the participants preferred spending to savings under the condition of mating availability priming with romantic photographs. In Experiment 2, before and after drinking either water or a sugary beverage, fasting participants rated photos of a conversation between a man and a woman. Water drinking lowered the rating scores of mating intentions as well as blood glucose (BG) levels. The sugary drink buffered this decline in sexual perceptivity. Overall, the change in BG levels was positively associated with changes in the ratings of mating intentions but was not associated with other likelihood ratings. These results suggest that both external cues of food and mating resources and internal BG fluctuation regulate the cognitive priority of physiological needs vs. mate acquisition and retention.

  20. Investment Choice and Perceived Mating Intentions Regulated by External Resource Cues and Internal Fluctuation in Blood Glucose Levels

    Directory of Open Access Journals (Sweden)

    Li-Lin eRao

    2015-01-01

    Full Text Available We examined resource allocation priorities in the framework of an updated Maslow hierarchy of fundamental human needs. In Experiment 1, the participants in the food abundance priming condition viewing photos of high-calorie food allocated more money to savings than to spending. However, the participants preferred spending to savings under the condition of mating availability priming with romantic photographs. In Experiment 2, before and after drinking either water or a sugary beverage, fasting participants rated photos of a conversation between a man and a woman. Water drinking lowered the rating scores of mating intentions as well as blood glucose (BG levels. The sugary drink buffered this decline in sexual perceptivity. Overall, the change in BG levels was positively associated with changes in the ratings of mating intentions but was not associated with other likelihood ratings. These results suggest that both external cues of food and mating resources and internal BG fluctuation regulate the cognitive priority of physiological needs versus mate acquisition and retention.

  1. A hairpin within YAP mRNA 3′UTR functions in regulation at post-transcription level

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Yuen; Wang, Yuan; Feng, Jinyan; Feng, Guoxing; Zheng, Minying; Yang, Zhe; Xiao, Zelin; Lu, Zhanping [State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071 (China); Ye, Lihong [State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071 (China); Zhang, Xiaodong, E-mail: zhangxd@nankai.edu.cn [State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071 (China)

    2015-04-03

    The central dogma of gene expression is that DNA is transcribed into messenger RNAs, which in turn serve as the template for protein synthesis. Recently, it has been reported that mRNAs display regulatory roles that rely on their ability to compete for microRNA binding, independent of their protein-coding function. However, the regulatory mechanism of mRNAs remains poorly understood. Here, we report that a hairpin within YAP mRNA 3′untranslated region (3′UTR) functions in regulation at post-transcription level through generating endogenous siRNAs (esiRNAs). Bioinformatics analysis for secondary structure showed that YAP mRNA displayed a hairpin structure (termed standard hairpin, S-hairpin) within its 3′UTR. Surprisingly, we observed that the overexpression of S-hairpin derived from YAP 3′UTR (YAP-sh) increased the luciferase reporter activities of transcriptional factor NF-κB and AP-1 in 293T cells. Moreover, we identified that a fragment from YAP-sh, an esiRNA, was able to target mRNA 3′UTR of NF2 (a member of Hippo-signaling pathway) and YAP mRNA 3′UTR itself in hepatoma cells. Thus, we conclude that the YAP-sh within YAP mRNA 3′UTR may serve as a novel regulatory element, which functions in regulation at post-transcription level. Our finding provides new insights into the mechanism of mRNAs in regulatory function. - Highlights: • An S-hairpin within YAP mRNA 3′UTR possesses regulatory function. • YAP-sh acts as a regulatory element for YAP at post-transcription level. • YAP-sh-3p20, an esiRNA derived from YAP-sh, targets mRNAs of YAP and NF2. • YAP-sh-3p20 depresses the proliferation of HepG2 cells in vitro.

  2. A hairpin within YAP mRNA 3′UTR functions in regulation at post-transcription level

    International Nuclear Information System (INIS)

    Gao, Yuen; Wang, Yuan; Feng, Jinyan; Feng, Guoxing; Zheng, Minying; Yang, Zhe; Xiao, Zelin; Lu, Zhanping; Ye, Lihong; Zhang, Xiaodong

    2015-01-01

    The central dogma of gene expression is that DNA is transcribed into messenger RNAs, which in turn serve as the template for protein synthesis. Recently, it has been reported that mRNAs display regulatory roles that rely on their ability to compete for microRNA binding, independent of their protein-coding function. However, the regulatory mechanism of mRNAs remains poorly understood. Here, we report that a hairpin within YAP mRNA 3′untranslated region (3′UTR) functions in regulation at post-transcription level through generating endogenous siRNAs (esiRNAs). Bioinformatics analysis for secondary structure showed that YAP mRNA displayed a hairpin structure (termed standard hairpin, S-hairpin) within its 3′UTR. Surprisingly, we observed that the overexpression of S-hairpin derived from YAP 3′UTR (YAP-sh) increased the luciferase reporter activities of transcriptional factor NF-κB and AP-1 in 293T cells. Moreover, we identified that a fragment from YAP-sh, an esiRNA, was able to target mRNA 3′UTR of NF2 (a member of Hippo-signaling pathway) and YAP mRNA 3′UTR itself in hepatoma cells. Thus, we conclude that the YAP-sh within YAP mRNA 3′UTR may serve as a novel regulatory element, which functions in regulation at post-transcription level. Our finding provides new insights into the mechanism of mRNAs in regulatory function. - Highlights: • An S-hairpin within YAP mRNA 3′UTR possesses regulatory function. • YAP-sh acts as a regulatory element for YAP at post-transcription level. • YAP-sh-3p20, an esiRNA derived from YAP-sh, targets mRNAs of YAP and NF2. • YAP-sh-3p20 depresses the proliferation of HepG2 cells in vitro

  3. Hydrostatic Pressure Regulates MicroRNA Expression Levels in Osteoarthritic Chondrocyte Cultures via the Wnt/β-Catenin Pathway

    Directory of Open Access Journals (Sweden)

    Sara Cheleschi

    2017-01-01

    Full Text Available Mechanical loading and hydrostatic pressure (HP regulate chondrocytes’ metabolism; however, how mechanical stimulation acts remain unclear. MicroRNAs (miRNAs play an important role in cartilage homeostasis, mechanotransduction, and in the pathogenesis of osteoarthritis (OA. This study investigated the effects of a cyclic HP (1–5 MPa, in both normal and OA human chondrocytes, on the expression of miR-27a/b, miR-140, miR-146a/b, and miR-365, and of their target genes (MMP-13, ADAMTS-5, IGFBP-5, and HDAC-4. Furthermore, we assessed the possible involvement of Wnt/β-catenin pathway in response to HP. Chondrocytes were exposed to HP for 3h and the evaluations were performed immediately after pressurization, and following 12, 24, and 48 h. Total RNA was extracted and used for real-time PCR. β-catenin was detected by Western blotting analysis and immunofluorescence. In OA chondrocytes, HP induced a significant increase (p < 0.01 of the expression levels of miR-27a/b, miR-140, and miR-146a, and a significant reduction (p < 0.01 of miR-365 at all analyzed time points. MMP-13, ADAMTS-5, and HDAC-4 were significantly downregulated following HP, while no significant modification was found for IGFBP-5. β-catenin levels were significantly increased (p < 0.001 in OA chondrocytes at basal conditions and significantly reduced (p < 0.01 by HP. Pressurization did not cause any significant modification in normal cells. In conclusion, in OA chondrocytes, HP restores the expression levels of some miRNAs, downregulates MMP-13, ADAMTS-5, and HDAC-4, and modulates the Wnt/β-catenin pathway activation.

  4. An analysis of potential barriers and enablers to regulating the television marketing of unhealthy foods to children at the state government level in Australia.

    Science.gov (United States)

    Chung, Alexandra; Shill, Jane; Swinburn, Boyd; Mavoa, Helen; Lawrence, Mark; Loff, Bebe; Crammond, Bradley; Sacks, Gary; Allender, Steven; Peeters, Anna

    2012-12-28

    In Australia there have been many calls for government action to halt the effects of unhealthy food marketing on children's health, yet implementation has not occurred. The attitudes of those involved in the policy-making process towards regulatory intervention governing unhealthy food marketing are not well understood. The objective of this research was to understand the perceptions of senior representatives from Australian state and territory governments, statutory authorities and non-government organisations regarding the feasibility of state-level government regulation of television marketing of unhealthy food to children in Australia. Data from in-depth semi-structured interviews with senior representatives from state and territory government departments, statutory authorities and non-government organisations (n=22) were analysed to determine participants' views about regulation of television marketing of unhealthy food to children at the state government level. Data were analysed using content and thematic analyses. Regulation of television marketing of unhealthy food to children was supported as a strategy for obesity prevention. Barriers to implementing regulation at the state level were: the perception that regulation of television advertising is a Commonwealth, not state/territory, responsibility; the power of the food industry and; the need for clear evidence that demonstrates the effectiveness of regulation. Evidence of community support for regulation was also cited as an important factor in determining feasibility. The regulation of unhealthy food marketing to children is perceived to be a feasible strategy for obesity prevention however barriers to implementation at the state level exist. Those involved in state-level policy making generally indicated a preference for Commonwealth-led regulation. This research suggests that implementation of regulation of the television marketing of unhealthy food to children should ideally occur under the direction

  5. An analysis of potential barriers and enablers to regulating the television marketing of unhealthy foods to children at the state government level in Australia

    Directory of Open Access Journals (Sweden)

    Chung Alexandra

    2012-12-01

    Full Text Available Abstract Background In Australia there have been many calls for government action to halt the effects of unhealthy food marketing on children's health, yet implementation has not occurred. The attitudes of those involved in the policy-making process towards regulatory intervention governing unhealthy food marketing are not well understood. The objective of this research was to understand the perceptions of senior representatives from Australian state and territory governments, statutory authorities and non-government organisations regarding the feasibility of state-level government regulation of television marketing of unhealthy food to children in Australia. Method Data from in-depth semi-structured interviews with senior representatives from state and territory government departments, statutory authorities and non-government organisations (n=22 were analysed to determine participants' views about regulation of television marketing of unhealthy food to children at the state government level. Data were analysed using content and thematic analyses. Results Regulation of television marketing of unhealthy food to children was supported as a strategy for obesity prevention. Barriers to implementing regulation at the state level were: the perception that regulation of television advertising is a Commonwealth, not state/territory, responsibility; the power of the food industry and; the need for clear evidence that demonstrates the effectiveness of regulation. Evidence of community support for regulation was also cited as an important factor in determining feasibility. Conclusions The regulation of unhealthy food marketing to children is perceived to be a feasible strategy for obesity prevention however barriers to implementation at the state level exist. Those involved in state-level policy making generally indicated a preference for Commonwealth-led regulation. This research suggests that implementation of regulation of the television marketing of

  6. Myb-binding protein 1a (Mybbp1a) regulates levels and processing of pre-ribosomal RNA.

    Science.gov (United States)

    Hochstatter, Julia; Hölzel, Michael; Rohrmoser, Michaela; Schermelleh, Lothar; Leonhardt, Heinrich; Keough, Rebecca; Gonda, Thomas J; Imhof, Axel; Eick, Dirk; Längst, Gernot; Németh, Attila

    2012-07-13

    Ribosomal RNA gene transcription, co-transcriptional processing, and ribosome biogenesis are highly coordinated processes that are tightly regulated during cell growth. In this study we discovered that Mybbp1a is associated with both the RNA polymerase I complex and the ribosome biogenesis machinery. Using a reporter assay that uncouples transcription and RNA processing, we show that Mybbp1a represses rRNA gene transcription. In addition, overexpression of the protein reduces RNA polymerase I loading on endogenous rRNA genes as revealed by chromatin immunoprecipitation experiments. Accordingly, depletion of Mybbp1a results in an accumulation of the rRNA precursor in vivo but surprisingly also causes growth arrest of the cells. This effect can be explained by the observation that the modulation of Mybbp1a protein levels results in defects in pre-rRNA processing within the cell. Therefore, the protein may play a dual role in the rRNA metabolism, potentially linking and coordinating ribosomal DNA transcription and pre-rRNA processing to allow for the efficient synthesis of ribosomes.

  7. Low-Level Waste Regulation: Putting Principles Into Practice - 13297 - The Richard S. Hodes, M.D., Honor Lecture Award

    International Nuclear Information System (INIS)

    Kennedy, James E.

    2013-01-01

    In carrying out its mission to ensure the safe use of radioactive materials for beneficial civilian purposes while protecting people and the environment, the U.S. Nuclear Regulatory Commission (NRC) adheres to its Principles of Good Regulation. The Principles-Independence, Openness, Efficiency, Clarity, and Reliability-apply to the agency as a whole in its decision-making and to the individual conduct of NRC employees. This paper describes the application of the Principles in a real-life staff activity, a guidance document used in the NRC's low-level radioactive waste (LLW) program, the Concentration Averaging and Encapsulation Branch Technical Position (CA BTP). The staff's process to revise the document, as well as the final content of the document, were influenced by following the Principles. For example, consistent with the Openness Principle, the staff conducted a number of outreach activities and received many comments on three drafts of the document. Stakeholder comments affected the final staff positions in some cases. The revised CA BTP, once implemented, is expected to improve management and disposal of LLW in the United States. Its positions have an improved nexus to health and safety; are more performance-based than previously, thus providing licensees with options for how they achieve the required outcome of protecting an inadvertent human intruder into a disposal facility; and provide for disposal of more sealed radioactive sources, which are a potential threat to national security. (author)

  8. Analysis of low-level wastes. Review of hazardous waste regulations and identification of radioactive mixed wastes. Final report

    International Nuclear Information System (INIS)

    Bowerman, B.S.; Kempf, C.R.; MacKenzie, D.R.; Siskind, B.; Piciulo, P.L.

    1985-12-01

    Regulations governing the management and disposal of hazardous wastes have been promulgated by the US Environmental Protection Agency under authority of the Resource Conservation and Recovery Act. These were reviewed and compared with the available information on the properties and characteristics of low-level radioactive wastes (LLW). In addition, a survey was carried out to establish a data base on the nature and composition of LLW in order to determine whether some LLW streams could also be considered hazardous as defined in 40 CFR Part 261. For the survey, an attempt was made to obtain data on the greatest volume of LLW; hence, as many large LLW generators as possible were contacted. The list of 238 generators contacted was based on information obtained from NRC and other sources. The data base was compiled from completed questionnaires which were returned by 97 reactor and non-reactor facilities. The waste volumes reported by these respondents corresponded to approximately 29% of all LLW disposed of in 1984. The analysis of the survey results indicated that three broad categories of LLW may be radioactive mixed wastes. They include: waste containing organic liquids, disposed of by all types of generators; wastes containing lead metal, i.e., discarded shielding or lead containers; wastes containing chromates, i.e., nuclear power plant process wastes where chromates are used as corrosion inhibitors. Certain wastes, specific to particular generators, were identified as potential mixed wastes as well. 8 figs., 48 tabs

  9. Low-Level Waste Regulation: Putting Principles Into Practice - 13297 - The Richard S. Hodes, M.D., Honor Lecture Award

    Energy Technology Data Exchange (ETDEWEB)

    Kennedy, James E. [Low-Level Waste Branch Division of Waste Management and Environmental Protection, U.S. Nuclear Regulatory Commission, Washington, DC, 20555-0001 (United States)

    2013-07-01

    In carrying out its mission to ensure the safe use of radioactive materials for beneficial civilian purposes while protecting people and the environment, the U.S. Nuclear Regulatory Commission (NRC) adheres to its Principles of Good Regulation. The Principles-Independence, Openness, Efficiency, Clarity, and Reliability-apply to the agency as a whole in its decision-making and to the individual conduct of NRC employees. This paper describes the application of the Principles in a real-life staff activity, a guidance document used in the NRC's low-level radioactive waste (LLW) program, the Concentration Averaging and Encapsulation Branch Technical Position (CA BTP). The staff's process to revise the document, as well as the final content of the document, were influenced by following the Principles. For example, consistent with the Openness Principle, the staff conducted a number of outreach activities and received many comments on three drafts of the document. Stakeholder comments affected the final staff positions in some cases. The revised CA BTP, once implemented, is expected to improve management and disposal of LLW in the United States. Its positions have an improved nexus to health and safety; are more performance-based than previously, thus providing licensees with options for how they achieve the required outcome of protecting an inadvertent human intruder into a disposal facility; and provide for disposal of more sealed radioactive sources, which are a potential threat to national security. (author)

  10. An optimized method for measuring hypocretin-1 peptide in the mouse brain reveals differential circadian regulation of hypocretin-1 levels rostral and caudal to the hypothalamus

    DEFF Research Database (Denmark)

    Justinussen, J L; Holm, A; Kornum, B R

    2015-01-01

    an optimized peptide quantification method for hypocretin-1 extracted from different mouse brain areas and use this method for investigating circadian fluctuations of hypocretin-1 levels in these areas. The results show that hypocretin-1 peptide can be extracted from small pieces of intact tissue...... as does prepro-hypocretin mRNA in the hypothalamus. However, in midbrain and brainstem tissue caudal to the hypothalamus, there was less circadian fluctuation and a tendency for higher levels during the light phase. These data suggest that regulation of the hypocretin system differs between brain areas.......The hypocretin/orexin system regulates, among other things, sleep and energy homeostasis. The system is likely regulated by both homeostatic and circadian mechanisms. Little is known about local differences in the regulation of hypocretin activity. The aim of this study was to establish...

  11. [The role of cognitive emotional self-regulation in adolescence in levels of depression, psychosomatic symptoms and subjective well-being].

    Science.gov (United States)

    Kriston, Pálma; Pikó, Bettina

    More and more studies suggest that mental health may be determined by processes of emotional self-regulation. Emotion regulation is a complex concept which can be explicit and implicit and includes different cognitive and behavioral processes: evaluation, modifying of emotional reaction to accomplish goals. Our research aim was to explore the use of cognitive emotional self-regulation strategies related to mental health indicators among adolescents. The youth study was performed with a sample size of 1245 participants in Makó, in 2016. Data collection was based on self-administrated questionnaries that contained items on mental health, subjective well-being and background of sociodemographics. The data were compared on the basis of gender differences and tested by multiple linear regression analysis to map associations between the regulation strategies and mental health indicators: depression, psychosomatic symptoms, satisfaction with life. Girls reported higher levels of depression and psychosomatic symptoms and lower satisfaction with life than boys. Significant differences were observed between boys and girls in using rumination, positive refocusing, selfblame, others-blame and putting into perspective regulation strategy. In addition the nonadaptive strategies were proved to be related to higher depression and psychosomatic symptom scores, whereas adaptive strategies to higher level of satisfaction with life in both boys and girls. The study draws attention to the importance of cognitive emotion regulation strategies from the point of view of mental health and to explore the background factors of cognitive processes of emotional self-regulation.

  12. Assessing tobacco marketing regulation implementation level in Georgia: evidence from Non Communicable Disease Risk Factors STEPS Survey Georgia 2016

    Directory of Open Access Journals (Sweden)

    Lela Sturua

    2018-03-01

    Full Text Available Background Tobacco use continues to be the leading cause of preventable deaths worldwide; the biggest burden of it falls on low- and middle-income countries and this trend is expected to widen further in case of inaction. The overall objective of the study is to describe and analyze the findings of the Noncommunicable Disease Risk Factors STEPS Survey Georgia 2016 related to tobacco marketing regulation. Methods The current study in Georgia was a population-based STEPS survey of randomly selected adults aged 18-69 within each sex and 10-year age-group. A multi-stage cluster sample design was used to produce representative data for that age range in Georgia. A total of 5554 adults participated in the current survey. We assessed level o tobacco marketing regulation implementation in Georgia. Results Study results reported high prevalence of tobacco use in Georgian population (31.1% (95 % CI: 29.0-33.1. Study findings showed that about half of the current smokers are exposed to anti-tobacco information on TV or radio 52.3% (95% CI: 48.9 - 55.7, whereas 35.5% (95% CI: 32.2 - 38.8 reported being exposed to cigarette marketing at points of sales of tobacco products and 4.7% (95% CI: 3.2-6.1 to any cigarette promotions. Health warnings on cigarette packs was reported to be noticed by 88.7% (95% CI: 85.8-91.6 of current smokers; only 33% (95% CI: 25.4 - 40.7 of them reported having thought about quitting because of these warnings. Conclusions The prevalence of smoking in Georgia is high compared to other countries of the European Region and it is very likely that smoking related NCDs burden will increase. Stricter tobacco control policies coupled with anti-tobacco media campaigns can address this problem. Improved health warnings on tobacco packages and total ban of tobacco advertisement, promotion and sponsorship should be implemented in order to overcome prevailed tobacco industry marketing strategies.

  13. The regulation on commercial reactors and the management of high-level radioactive wastes in U.S

    International Nuclear Information System (INIS)

    Shimomura, Hidetsugu

    2013-01-01

    This article shows U.S. NRC's substantial and procedural regulations regarding commercial reactors and radioactive wastes. The commercial reactor's regulations are analyzed from an ensuring safety, and the radioactive waste' management is done from a locating a disposal site. (author)

  14. The Relation between English Learning Students' Levels of Self-Regulation and Metacognitive Skills and Their English Academic Achievements

    Science.gov (United States)

    Adigüzel, Abdullah; Orhan, Ali

    2017-01-01

    It is remarkable that there are only a few studies that measures to what extent metacognitive and self-regulation skills affect students' academic achievements in the English lesson. This study is important for identifying the personal variables that have an impact on metacognitive and self-regulation skill and determining the relationship between…

  15. Academic Procrastination of Undergraduates: Low Self-Efficacy to Self-Regulate Predicts Higher Levels of Procrastination

    Science.gov (United States)

    Klassen, Robert M.; Krawchuk, Lindsey L.; Rajani, Sukaina

    2008-01-01

    This article reports two studies exploring the academic procrastination of 456 undergraduates. Study 1 explores the relationships among academic procrastination, self-regulation, academic self-efficacy, self-esteem, and self-efficacy for self-regulation. Results reveal that although other self-variables are related to procrastination,…

  16. The modulatory role of spinally located histamine receptors in the regulation of the blood glucose level in d-glucose-fed mice.

    Science.gov (United States)

    Sim, Yun-Beom; Park, Soo-Hyun; Kim, Sung-Su; Kim, Chea-Ha; Kim, Su-Jin; Lim, Su-Min; Jung, Jun-Sub; Ryu, Ohk-Hyun; Choi, Moon-Gi; Suh, Hong-Won

    2014-02-01

    The possible roles of spinal histamine receptors in the regulation of the blood glucose level were studied in ICR mice. Mice were intrathecally (i.t.) treated with histamine 1 (H1) receptor agonist (2-pyridylethylamine) or antagonist (cetirizine), histamine 2 (H2) receptor agonist (dimaprit) or antagonist (ranitidine), histamine 3 (H3) receptor agonist (α-methylhistamine) or antagonist (carcinine) and histamine 4 (H4) receptor agonist (VUF 8430) or antagonist (JNJ 7777120), and the blood glucose level was measured at 30, 60 and 120 min after i.t. administration. The i.t. injection with α-methylhistamine, but not carcinine slightly caused an elevation of the blood glucose level. In addition, histamine H1, H2, and H4 receptor agonists and antagonists did not affect the blood glucose level. In D-glucose-fed model, i.t. pretreatment with cetirizine enhanced the blood glucose level, whereas 2-pyridylethylamine did not affect. The i.t. pretreatment with dimaprit, but not ranitidine, enhanced the blood glucose level in D-glucose-fed model. In addition, α-methylhistamine, but not carcinine, slightly but significantly enhanced the blood glucose level D-glucose-fed model. Finally, i.t. pretreatment with JNJ 7777120, but not VUF 8430, slightly but significantly increased the blood glucose level. Although histamine receptors themselves located at the spinal cord do not exert any effect on the regulation of the blood glucose level, our results suggest that the activation of spinal histamine H2 receptors and the blockade of spinal histamine H1 or H3 receptors may play modulatory roles for up-regulation and down-regulation, respectively, of the blood glucose level in D-glucose fed model.

  17. NRC Task Force report on review of the federal/state program for regulation of commercial low-level radioactive waste burial grounds

    International Nuclear Information System (INIS)

    1977-01-01

    The underlying issue explored in this report is that of Federal vs State regulation of commercial radioactive waste burial grounds. The need for research and development, a comprehensive set of standards and criteria, a national plan for low-level waste management, and perpetual care funding are closely related to the central issue and are also discussed. Five of the six commercial burial grounds are regulated by Agreement States; the sixth is regulated solely by the NRC (NRC also regulates Special Nuclear Material at the sites). The sites are operated commercially. The operators contribute to the perpetual care funds for the sites at varying rates. The States have commitments for the perpetual care of the decommissioned sites except for one site, located on Federally owned land. Three conclusions are reached. Federal control over the disposal of low-level waste should be increased by requiring joint Federal/State site approval, NRC licensing, Federal ownership of the land, and a Federally administered perpetual care program. The NRC should accelerate the development of its regulatory program for the disposal of low-level waste. The undisciplined proliferation of low-level burial sites must be avoided. NRC should evaluate alternative disposal methods, conduct necessary studies, and develop a comprehensive low-level waste regulatory program (i.e., accomplish the above recommendations) prior to the licensing of new disposal sites

  18. The modulatory role of alpha-melanocyte stimulating hormone administered spinally in the regulation of blood glucose level in d-glucose-fed and restraint stress mouse models.

    Science.gov (United States)

    Sim, Yun-Beom; Park, Soo-Hyun; Kim, Sung-Su; Lim, Su-Min; Jung, Jun-Sub; Suh, Hong-Won

    2014-08-01

    Alpha-melanocyte stimulating hormone (α-MSH) is known as a regulator of the blood glucose homeostasis and food intake. In the present study, the possible roles of α-MSH located in the spinal cord in the regulation of the blood glucose level were investigated in d-glucose-fed and immobilization stress (IMO) mouse models. We found in the present study that intrathecal (i.t.) injection with α-MSH alone did not affect the blood glucose level. However, i.t. administration with α-MSH reduced the blood glucose level in d-glucose-fed model. The plasma insulin level was increased in d-glucose-fed model and was further increased by α-MSH, whereas α-MSH did not affect plasma corticosterone level in d-glucose-fed model. In addition, i.t. administration with glucagon alone enhanced blood glucose level and, i.t. injection with glucagon also increased the blood glucose level in d-glucose-fed model. In contrasted to results observed in d-glucose-fed model, i.t. treatment with α-MSH caused enhancement of the blood glucose level in IMO model. The plasma insulin level was increased in IMO model. The increased plasma insulin level by IMO was reduced by i.t. treatment with α-MSH, whereas i.t. pretreatment with α-MSH did not affect plasma corticosterone level in IMO model. Taken together, although spinally located α-MSH itself does not alter the blood glucose level, our results suggest that the activation of α-MSH system located in the spinal cord play important modulatory roles for the reduction of the blood glucose level in d-glucose fed model whereas α-MSH is responsible for the up-regulation of the blood glucose level in IMO model. The enhancement of insulin release may be responsible for modulatory action of α-MSH in down-regulation of the blood glucose in d-glucose fed model whereas reduction of insulin release may be responsible for modulatory action of α-MSH in up-regulation of the blood glucose in IMO model. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Top Level Results of a Study of Czech Households´ Awareness of the Food Advertising Industry’s Self-Regulation Related to Children

    Directory of Open Access Journals (Sweden)

    Markéta Lhotáková

    2015-06-01

    Full Text Available This paper is primarily focused on analyses of the research undertaken to understand the awareness of food advertising’s self-regulation authority (Council for Advertising and of the Czech Code of Conduct in the context of the growing issue of child obesity. The objective is to find out the perception of food advertising to children and awareness of regulation and industry self-regulation amongst Czech mothers. Our theoretical framework presumes dependence between the awareness levels and selected demographic variables. We conclude several actions to overcome low awareness of the Council of Advertising and its Code of Conduct and to transfer the industry’s self-regulation into an efficient and recognized tool of shaping the culture of responsible advertising in the Czech Republic. The conclusions lead towards stronger protection of children.

  20. Glial cell line-derived neurotrophic factor up-regulates GTP-cyclohydrolase I activity and tetrahydrobiopterin levels in primary dopaminergic neurones

    DEFF Research Database (Denmark)

    Bauer, M; Suppmann, S; Meyer, M

    2002-01-01

    in tetrahydrobiopterin levels whereas tyrosine 3-monooxygenase activity was not altered. Actinomycin D, asan inhibitor of de novo biosynthesis, abolished any GDNF-mediated up-regulation of GTPCH I activity. However, GTPCH I mRNA levels in primary dopaminergic neurones were not altered by GDNF treatment, suggesting...... by triggering activation of GTP-cyclohydrolase I (GTPCH I), a key enzyme in catecholamine biosynthesis. GDNF stimulation of primary dopaminergic neurones expressing both tyrosine 3-monooxygenase and GTPCH I resulted in a dose-dependent doubling of GTPCH I activity, and a concomitant increase...... that the mode of action for that up-regulation is not directly connected to the regulation of GTPCH I transcription. We conclude that GDNF, in addition to its action in structural differentiation, also promotes differentiation regarding expression and enzymatic activity of a crucial component...

  1. Endothelial cells the site of the regulation of IgG LEVEL by salvaging and transcytosis of immunoglobulin

    International Nuclear Information System (INIS)

    Antohe, Felicia; Radulescu, Luminita; Simionescu, Maya; Ghetie, Victor

    2002-01-01

    ), transferrin (Tavassoli et al 1986), ceruloplasmin (Tarsio et al 1987), transcobalamin II (Soda et al 1985) the complex biochemical events taking place at the blood-vessel wall interface are not fully understood. This is the case of IgG transfer from mother to fetus. The process is thought to involve specific receptors that bind to the Fc region of the IgG molecule namely the MHC class I related receptor FcRn (Brambel 1970, Rodewald 1980). Until now, the reported data showed that FcRn was occasional (Kristofersen et al 1996) low level (Leach et al 1996) or not at all expressed (Simister et al 1996) in fetal endothelial cells. Taking advantage of the successful isolation and cultivation of microvascular endothelial cells from human term placenta (Jinga V et al 1999) we can now appropriately investigate the presence, distribution and function of FcRn in placental endothelial cells.Transfer of maternal gammaglobulin (IgG) to the fetus provides the neonate with humoral immunity during early lifetime. The mechanism of selective transport of IgG from the placental stroma to the lumen of the fetal blood vessels has not been elucidated, yet. It was postulated that the specific transport as well as the regulation of IgG concentration in the blood, involves the MHC class I related receptor - FcRn - for the Fc domain of IgG. We questioned whether, human placental endothelial cells (HPEC) express FcRn, and if present, whether it is in a functionally active form. The experiments were performed on cultured HPEC; as positive control, cultured human trophoblastic cells (JEG3) and mouse SV-40 transformed EC line (SVEC) shown to express mRNA for the human FcRn, were used. The double chamber system. The permeability coefficient expression of FcRn was tested by indirect immunofluorescence. The role of FcRn was assessed on HPEC grown on filters in a double chamber system by quantifying the transcytosis of [ 125 I]-human IgG or [ 125 I]-rF(ab') 2 fragments (as control) from the apical to

  2. REGULATION OF THE RAT OXYTOCIN GENE BY ESTRADIOL - EXAMINATION OF PROMOTER ACTIVITY IN TRANSFECTED CELLS AND OF MESSENGER-RIBONUCLEIC-ACID AND PEPTIDE LEVELS IN THE HYPOTHALAMONEUROHYPOPHYSEAL SYSTEM

    NARCIS (Netherlands)

    BURBACH, JPH; ADAN, RAH; VANTOL, HHM; VERBEECK, MAE; AXELSON, JF; VANLEEUWEN, FW; BEEKMAN, JM; AB, G

    1990-01-01

    Oxytocin (OT) plays a role in reproduction at the level of the pituitary and mammary glands and uterus. This OT is synthesized in the hypothalamo-neurohypophyseal system (HNS). A number of observations have suggested that estrogens regulate the production of OT in the HNS. In this study the effect

  3. Adaptor protein containing PH domain, PTB domain and leucine zipper (APPL1) regulates the protein level of EGFR by modulating its trafficking

    International Nuclear Information System (INIS)

    Lee, Jae-Rin; Hahn, Hwa-Sun; Kim, Young-Hoon; Nguyen, Hong-Hoa; Yang, Jun-Mo; Kang, Jong-Sun; Hahn, Myong-Joon

    2011-01-01

    Highlights: ► APPL1 regulates the protein level of EGFR in response to EGF stimulation. ► Depletion of APPL1 accelerates the movement of EGF/EGFR from the cell surface to the perinuclear region in response to EGF. ► Knockdown of APPL1 enhances the activity of Rab5. -- Abstract: The EGFR-mediated signaling pathway regulates multiple biological processes such as cell proliferation, survival and differentiation. Previously APPL1 (adaptor protein containing PH domain, PTB domain and leucine zipper 1) has been reported to function as a downstream effector of EGF-initiated signaling. Here we demonstrate that APPL1 regulates EGFR protein levels in response to EGF stimulation. Overexpression of APPL1 enhances EGFR stabilization while APPL1 depletion by siRNA reduces EGFR protein levels. APPL1 depletion accelerates EGFR internalization and movement of EGF/EGFR from cell surface to the perinuclear region in response to EGF treatment. Conversely, overexpression of APPL1 decelerates EGFR internalization and translocation of EGF/EGFR to the perinuclear region. Furthermore, APPL1 depletion enhances the activity of Rab5 which is involved in internalization and trafficking of EGFR and inhibition of Rab5 in APPL1-depleted cells restored EGFR levels. Consistently, APPL1 depletion reduced activation of Akt, the downstream signaling effector of EGFR and this is restored by inhibition of Rab5. These findings suggest that APPL1 is required for EGFR signaling by regulation of EGFR stabilities through inhibition of Rab5.

  4. Environmental Regulation of Plant Gene Expression: An Rt-qPCR Laboratory Project for an Upper-Level Undergraduate Biochemistry or Molecular Biology Course

    Science.gov (United States)

    Eickelberg, Garrett J.; Fisher, Alison J.

    2013-01-01

    We present a novel laboratory project employing "real-time" RT-qPCR to measure the effect of environment on the expression of the "FLOWERING LOCUS C" gene, a key regulator of floral timing in "Arabidopsis thaliana" plants. The project requires four 3-hr laboratory sessions and is aimed at upper-level undergraduate…

  5. Evolution of alternative splicing regulation: changes in predicted exonic splicing regulators are not associated with changes in alternative splicing levels in primates

    DEFF Research Database (Denmark)

    Irimia, Manuel; Rukov, Jakob Lewin; Roy, Scott William

    2009-01-01

    and changes in alternative splicing levels. This observation holds across different ESR exon positions, exon lengths, and 5' splice site strengths. We suggest that this lack of association is mainly due to the great importance of context for ESR functionality: many ESR-like motifs in primates may have little...

  6. A chemical biology approach to interrogate quorum-sensing regulated behaviors at the molecular and cellular level.

    Science.gov (United States)

    Lowery, Colin A; Matamouros, Susana; Niessen, Sherry; Zhu, Jie; Scolnick, Jonathan; Lively, Jenny M; Cravatt, Benjamin F; Miller, Samuel I; Kaufmann, Gunnar F; Janda, Kim D

    2013-07-25

    Small molecule probes have been used extensively to explore biologic systems and elucidate cellular signaling pathways. In this study, we use an inhibitor of bacterial communication to monitor changes in the proteome of Salmonella enterica serovar Typhimurium with the aim of discovering unrecognized processes regulated by AI-2-based quorum-sensing (QS), a mechanism of bacterial intercellular communication that allows for the coordination of gene expression in a cell density-dependent manner. In S. typhimurium, this system regulates the uptake and catabolism of intercellular signals and has been implicated in pathogenesis, including the invasion of host epithelial cells. We demonstrate that our QS antagonist is capable of selectively inhibiting the expression of known QS-regulated proteins in S. typhimurium, thus attesting that QS inhibitors may be used to confirm proposed and elucidate previously unidentified QS pathways without relying on genetic manipulation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. The Rho GTPase Effector ROCK Regulates Cyclin A, Cyclin D1, and p27Kip1 Levels by Distinct Mechanisms

    OpenAIRE

    Croft, Daniel R.; Olson, Michael F.

    2006-01-01

    The members of the Rho GTPase family are well known for their regulation of actin cytoskeletal structures. In addition, they influence progression through the cell cycle. The RhoA and RhoC proteins regulate numerous effector proteins, with a central and vital signaling role mediated by the ROCK I and ROCK II serine/threonine kinases. The requirement for ROCK function in the proliferation of numerous cell types has been revealed by studies utilizing ROCK-selective inhibitors such as Y-27632. H...

  8. Adaptor protein SH2-B linking receptor-tyrosine kinase and Akt promotes adipocyte differentiation by regulating peroxisome proliferator-activated receptor gamma messenger ribonucleic acid levels.

    Science.gov (United States)

    Yoshiga, Daigo; Sato, Naoichi; Torisu, Takehiro; Mori, Hiroyuki; Yoshida, Ryoko; Nakamura, Seiji; Takaesu, Giichi; Kobayashi, Takashi; Yoshimura, Akihiko

    2007-05-01

    Adipocyte differentiation is regulated by insulin and IGF-I, which transmit signals by activating their receptor tyrosine kinase. SH2-B is an adaptor protein containing pleckstrin homology and Src homology 2 (SH2) domains that have been implicated in insulin and IGF-I receptor signaling. In this study, we found a strong link between SH2-B levels and adipogenesis. The fat mass and expression of adipogenic genes including peroxisome proliferator-activated receptor gamma (PPARgamma) were reduced in white adipose tissue of SH2-B-/- mice. Reduced adipocyte differentiation of SH2-B-deficient mouse embryonic fibroblasts (MEFs) was observed in response to insulin and dexamethasone, whereas retroviral SH2-B overexpression enhanced differentiation of 3T3-L1 preadipocytes to adipocytes. SH2-B overexpression enhanced mRNA level of PPARgamma in 3T3-L1 cells, whereas PPARgamma levels were reduced in SH2-B-deficient MEFs in response to insulin. SH2-B-mediated up-regulation of PPARgamma mRNA was blocked by a phosphatidylinositol 3-kinase inhibitor, but not by a MAPK kinase inhibitor. Insulin-induced Akt activation and the phosphorylation of forkhead transcription factor (FKHR/Foxo1), a negative regulator of PPARgamma transcription, were up-regulated by SH2-B overexpression, but reduced in SH2-B-deficient MEFs. These data indicate that SH2-B is a key regulator of adipogenesis both in vivo and in vitro by regulating the insulin/IGF-I receptor-Akt-Foxo1-PPARgamma pathway.

  9. Regulation of gene expression by low levels of ultraviolet-B radiation in Pisum sativum: Isolation of novel genes by suppression subtractive hybridisation

    International Nuclear Information System (INIS)

    Sävenstrand, H.; Brosché, M.; Strid, A.

    2002-01-01

    Suppression subtractive hybridisation was used to isolate genes differentially regulated by low levels (UV-B BE,300 0.13 W m -2 ) of ultraviolet-B radiation (UV-B; 290–320 nm) in Pisum sativum. Six genes were regulated, two of which were novel. The mRNA levels for these two (PsTSDC and PsUOS1) were increased and depressed by UV-B treatment, respectively. Domains in the PsTSDC translation product was similar to TIR (Toll-Interleukin-1 receptor-similar) domains and a NB-ARC domain (nucleotide-binding domain in APAF-1, R gene products and CED-4). The PsUOS1 translation product was similar to an open reading frame in Arabidopsis. Genes encoding embryo-abundant protein (PsEMB) and S-adenosyl-l-methionine synthase (PsSAMS) were induced by UV-B, whereas the transcript levels for genes encoding sucrose transport protein (PsSUT) or ribulose-5-phosphate 3-epimerase (PsR5P3E) were decreased. These regulation patterns are novel, and the PsEMB and PsR5P3E sequences are reported for the first time. The stress-specificity of regulation of these genes were tested by ozone fumigation (100 ppb O 3 ). Qualitatively, the similarity of expression after both UV-B and ozone exposure suggests that, for these genes, similar stress-response pathways are in action. (author)

  10. An optimized method for measuring hypocretin-1 peptide in the mouse brain reveals differential circadian regulation of hypocretin-1 levels rostral and caudal to the hypothalamus.

    Science.gov (United States)

    Justinussen, J L; Holm, A; Kornum, B R

    2015-12-03

    The hypocretin/orexin system regulates, among other things, sleep and energy homeostasis. The system is likely regulated by both homeostatic and circadian mechanisms. Little is known about local differences in the regulation of hypocretin activity. The aim of this study was to establish an optimized peptide quantification method for hypocretin-1 extracted from different mouse brain areas and use this method for investigating circadian fluctuations of hypocretin-1 levels in these areas. The results show that hypocretin-1 peptide can be extracted from small pieces of intact tissue, with sufficient yield for measurements in a standard radioimmunoassay. Utilizing the optimized method, it was found that prepro-hypocretin mRNA and peptide show circadian fluctuations in the mouse brain. This study further demonstrates that the hypocretin-1 peptide level in the frontal brain peaks during dark as does prepro-hypocretin mRNA in the hypothalamus. However, in midbrain and brainstem tissue caudal to the hypothalamus, there was less circadian fluctuation and a tendency for higher levels during the light phase. These data suggest that regulation of the hypocretin system differs between brain areas. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Agp2, a Member of the Yeast Amino Acid Permease Family, Positively Regulates Polyamine Transport at the Transcriptional Level

    KAUST Repository

    Aouida, Mustapha

    2013-06-03

    Agp2 is a plasma membrane protein of the Saccharomyces cerevisiae amino acid transporter family, involved in high-affinity uptake of various substrates including L-carnitine and polyamines. The discovery of two high affinity polyamine permeases, Dur3 and Sam3, prompted us to investigate whether Agp2 directly transports polyamines or acts instead as a regulator. Herein, we show that neither dur3? nor sam3? single mutant is defective in polyamine transport, while the dur3? sam3? double mutant exhibits a sharp decrease in polyamine uptake and an increased resistance to polyamine toxicity similar to the agp2? mutant. Studies of Agp2 localization indicate that in the double mutant dur3? sam3?, Agp2-GFP remains plasma membrane-localized, even though transport of polyamines is strongly reduced. We further demonstrate that Agp2 controls the expression of several transporter genes including DUR3 and SAM3, the carnitine transporter HNM1 and several hexose, nucleoside and vitamin permease genes, in addition to SKY1 encoding a SR kinase that positively regulates low-affinity polyamine uptake. Furthermore, gene expression analysis clearly suggests that Agp2 is a strong positive regulator of additional biological processes. Collectively, our data suggest that Agp2 might respond to environmental cues and thus regulate the expression of several genes including those involved in polyamine transport. © 2013 Aouida et al.

  12. Association of Cocaine- and Amphetamine-Regulated Transcript (CART) Messenger RNA Level, Food Intake, and Growth in Channel Catfish

    Science.gov (United States)

    Cocaine-and Amphetamine-Regulated Transcript (CART) is a potent hypothalamic anorectic peptide in mammals and fish. We hypothesized that increased food intake is associated with changes in expression of CART mRNA within the brain of channel catfish. Objectives were to clone the CART gene, examine ...

  13. Regulation of glutamate dehydrogenase expression in the developing rat liver: control at different levels in the prenatal period

    NARCIS (Netherlands)

    Das, A. T.; Salvadó, J.; Boon, L.; Biharie, G.; Moorman, A. F.; Lamers, W. H.

    1996-01-01

    To study the regulation of the expression of glutamate dehydrogenase (Glu-DH) in rat liver during development, the Glu-DH mRNA concentration in the liver of rats ranging in age from 14 days prenatal development to 3 months after birth was determined. This concentration increased up to two days

  14. Agp2, a Member of the Yeast Amino Acid Permease Family, Positively Regulates Polyamine Transport at the Transcriptional Level

    KAUST Repository

    Aouida, Mustapha; Texeira, Marta Rubio; Thevelein, Johan M.; Poulin, Richard; Ramotar, Dindial

    2013-01-01

    Agp2 is a plasma membrane protein of the Saccharomyces cerevisiae amino acid transporter family, involved in high-affinity uptake of various substrates including L-carnitine and polyamines. The discovery of two high affinity polyamine permeases, Dur3 and Sam3, prompted us to investigate whether Agp2 directly transports polyamines or acts instead as a regulator. Herein, we show that neither dur3? nor sam3? single mutant is defective in polyamine transport, while the dur3? sam3? double mutant exhibits a sharp decrease in polyamine uptake and an increased resistance to polyamine toxicity similar to the agp2? mutant. Studies of Agp2 localization indicate that in the double mutant dur3? sam3?, Agp2-GFP remains plasma membrane-localized, even though transport of polyamines is strongly reduced. We further demonstrate that Agp2 controls the expression of several transporter genes including DUR3 and SAM3, the carnitine transporter HNM1 and several hexose, nucleoside and vitamin permease genes, in addition to SKY1 encoding a SR kinase that positively regulates low-affinity polyamine uptake. Furthermore, gene expression analysis clearly suggests that Agp2 is a strong positive regulator of additional biological processes. Collectively, our data suggest that Agp2 might respond to environmental cues and thus regulate the expression of several genes including those involved in polyamine transport. © 2013 Aouida et al.

  15. Radon levels in domestic dwellings built since the introduction of the 1997 building regulations. Report of a pilot survey in Ennis, County Clare

    International Nuclear Information System (INIS)

    Synnott, H.; Pollard, D.; Colgan, P.A.

    2003-04-01

    Amending Building Regulations were introduced in December 1997, which require that measures be taken during construction to prevent the entry of radon into buildings from the underlying soil. These Regulations apply to buildings built on or after the 1 July 1998. During 2001, the Radiological Protection Institute of Ireland (RPII) undertook a pilot study of radon levels in houses built since that date with the aim of assessing the impact of these new Regulations. The area selected for this study was the 10 km Irish National Grid square including the town of Ennis, Co Clare. The RPII's National Radon Survey predicts that 27% of all dwellings in this grid square have radon concentrations in excess of the national Reference Level of 200 Bq/m3. Two hundred and seventy nine householders, whose houses were built since the amending Regulations came into effect, were invited to participate in a free survey and 97 of these agreed to do so. Participating householders were asked to complete a questionnaire aimed at assessing their knowledge of the radon preventive measures included in their house. Twelve percent of the houses measured in this survey were found to have radon levels in excess of the national Reference Level. This figure indicates a significant reduction as compared with the National Radon Survey prediction for the same grid square. It is difficult, however, to draw definitive conclusions from these data regarding the effectiveness of the new Regulations due to the very different age distribution for the two sets of houses and differences between current and historic building practices. Further work is underway comparing radon levels in houses built both immediately before and after the introduction of the 1997 Regulations, which aims to address outstanding questions. Householders' level of awareness of the radon preventive measures included in their house was low; 45% and 36% respectively of respondents were unaware of whether their house had a radon sump or

  16. Response rate of fibrosarcoma cells to cytotoxic drugs on the expression level correlates to the therapeutic response rate of fibrosarcomas and is mediated by regulation of apoptotic pathways

    International Nuclear Information System (INIS)

    Lehnhardt, Marcus; Mueller, Oliver; Klein-Hitpass, Ludger; Kuhnen, Cornelius; Homann, Heinz Herbert; Daigeler, Adrien; Steinau, Hans Ulrich; Roehrs, Sonja; Schnoor, Laura; Steinstraesser, Lars

    2005-01-01

    Because of the high resistance rate of fibrosarcomas against cytotoxic agents clinical chemotherapy of these tumors is not established. A better understanding of the diverse modes of tumor cell death following cytotoxic therapies will provide a molecular basis for new chemotherapeutic strategies. In this study we elucidated the response of a fibrosarcoma cell line to clinically used cytostatic agents on the level of gene expression. HT1080 fibrosarcoma cells were exposed to the chemotherapeutic agents doxorubicin, actinomycin D or vincristine. Total RNA was isolated and the gene expression patterns were analyzed by microarray analysis. Expression levels for 46 selected candidate genes were validated by quantitative real-time PCR. The analysis of the microarray data resulted in 3.309 (actinomycin D), 1.019 (doxorubicin) and 134 (vincristine) probesets that showed significant expression changes. For the RNA synthesis blocker actinomycin D, 99.4% of all differentially expressed probesets were under-represented. In comparison, probesets down-regulated by doxorubicin comprised only 37.4% of all genes effected by this agent. Closer analysis of the differentially regulated genes revealed that doxorubicin induced cell death of HT1080 fibrosarcoma cells mainly by regulating the abundance of factors mediating the mitochondrial (intrinsic) apoptosis pathway. Furthermore doxorubicin influences other pathways and crosstalk to other pathways (including to the death receptor pathway) at multiple levels. We found increased levels of cytochrome c, APAF-1 and members of the STAT-family (STAT1, STAT3), while Bcl-2 expression was decreased. Caspase-1, -3, -6, -8, and -9 were increased indicating that these proteases are key factors in the execution of doxorubicin mediated apoptosis. This study demonstrates that chemotherapy regulates the expression of apoptosis-related factors in fibrosarcoma cells. The number and the specific pattern of the genes depend on the used cytotoxic drug

  17. A mathematical model of metabolism an regulation provides a systems-level view of how Escherichia coli responds to oxigen

    NARCIS (Netherlands)

    Ederer, M.; Steinsiek, S.; Stagge, S.; Rolfe, M.D.; ter Beek, A.; Knies, D.; Teixeira De Mattos, M.J.; Sauter, T.; Green, J.; Poole, R.K.; Bettenbrock, K.; Sawodny, O.

    2014-01-01

    The efficient redesign of bacteria for biotechnological purposes, such as biofuel production, waste disposal or specific biocatalytic functions, requires a quantitative systems-level understanding of energy supply, carbon, and redox metabolism. The measurement of transcript levels, metabolite

  18. Azilsartan increases levels of IL-10, down-regulates MMP-2, MMP-9, RANKL/RANK, Cathepsin K and up-regulates OPG in an experimental periodontitis model.

    Directory of Open Access Journals (Sweden)

    Aurigena Antunes de Araújo

    Full Text Available AIMS: The aim of this study was to evaluate the effects of azilsartan (AZT on bone loss, inflammation, and the expression of matrix metallo proteinases (MMPs, receptor activator of nuclear factor κB ligand (RANKL, receptor activator of nuclear factor κB (RANK, osteoprotegerin (OPG, cyclooxygenase-2 (COX-2, and cathepsin K in periodontal tissue in a rat model of ligature-induced periodontitis. MATERIALS AND METHODS: Male Wistar albino rats were randomly divided into 5 groups of 10 rats each: (1 nonligated, water; (2 ligated, water; (3 ligated, 1 mg/kg AZT; (4 ligated, 5 mg/kg AZT; and (5 ligated, 10 mg/kg AZT. All groups were treated with saline or AZT for 10 days. Periodontal tissues were analyzed by histopathology and immunohistochemical detection of MMP-2, MMP-9, COX-2, RANKL, RANK, OPG, and cathepsin K. Levels of IL-1β, IL-10, TNF-α, myeloperoxidase (MPO, and glutathione (GSH were determined by ELISA. RESULTS: Treatment with 5 mg/kg AZT resulted in reduced MPO (p<0.05 and IL-1β (p<0.05, increased levels of IL-10 (p<0.05, and reduced expression of MMP-2, MMP-9, COX-2, RANK, RANKL, cathepsin K, and increased expression of OPG. CONCLUSIONS: These findings reveal that AZT increases anti-inflammatory cytokines and GSH and decreases bone loss in ligature-induced periodontitis in rats.

  19. Combined Effect of Levels in Personal Self-Regulation and Regulatory Teaching on Meta-Cognitive, on Meta-Motivational, and on Academic Achievement Variables in Undergraduate Students.

    Science.gov (United States)

    de la Fuente, Jesús; Sander, Paul; Martínez-Vicente, José M; Vera, Mariano; Garzón, Angélica; Fadda, Salvattore

    2017-01-01

    The Theory of Self- vs . Externally-Regulated Learning™ (SRL vs. ERL) proposed different types of relationships among levels of variables in Personal Self-Regulation (PSR) and Regulatory Teaching (RT) to predict the meta-cognitive, meta-motivational and -emotional variables of learning, and of Academic Achievement in Higher Education. The aim of this investigation was empirical in order to validate the model of the combined effect of low-medium-high levels in PSR and RT on the dependent variables. For the analysis of combinations, a selected sample of 544 undergraduate students from two Spanish universities was used. Data collection was obtained from validated instruments, in Spanish versions. Using an ex-post-facto design, different Univariate and Multivariate Analyses (3 × 1, 3 × 3, and 4 × 1) were conducted. Results provide evidence for a consistent effect of low-medium-high levels of PSR and of RT, thus giving significant partial confirmation of the proposed rational model. As predicted, (1) the levels of PSR and positively and significantly effected the levels of learning approaches, resilience, engagement, academic confidence, test anxiety, and procedural and attitudinal academic achievement; (2) the most favorable type of interaction was a high level of PSR with a high level RT process. The limitations and implications of these results in the design of effective teaching are analyzed, to improve university teaching-learning processes.

  20. Extracellular Na+ levels regulate formation and activity of the NaX/alpha1-Na+/K+-ATPase complex in neuronal cells.

    Directory of Open Access Journals (Sweden)

    Emmanuelle eBerret

    2014-12-01

    Full Text Available MnPO neurons play a critical role in hydromineral homeostasis regulation by acting as sensors of extracellular sodium concentration ([Na+]out. The mechanism underlying Na+-sensing involves Na+-flow through the NaX channel, directly regulated by the Na+/K+-ATPase α1-isoform which controls Na+-influx by modulating channel permeability. Together, these two partners form a complex involved in the regulation of intracellular sodium ([Na+]in. Here we aim to determine whether environmental changes in Na+ could actively modulate the NaX/Na+/K+-ATPase complex activity.We investigated the complex activity using patch-clamp recordings from rat MnPO neurons and Neuro2a cells. When the rats were fed with a high-salt-diet, or the [Na+] in the culture medium was increased, the activity of the complex was up-regulated. In contrast, drop in environmental [Na+] decreased the activity of the complex. Interestingly under hypernatremic condition, the colocalization rate and protein level of both partners were up-regulated. Under hyponatremic condition, only NaX protein expression was increased and the level of NaX/Na+/K+-ATPase remained unaltered. This unbalance between NaX and Na+/K+-ATPase pump proportion would induce a bigger portion of Na+/K+-ATPase-control-free NaX channel. Thus we suggest that hypernatremic environment increases NaX/Na+/K+-ATPase α1-isoform activity by increasing the number of both partners and their colocalization rate, whereas hyponatremic environment down-regulates complex activity via a decrease in the relative number of NaX channels controlled by the pump.

  1. Public involvement in multi-objective water level regulation development projects-evaluating the applicability of public involvement methods

    International Nuclear Information System (INIS)

    Vaentaenen, Ari; Marttunen, Mika

    2005-01-01

    Public involvement is a process that involves the public in the decision making of an organization, for example a municipality or a corporation. It has developed into a widely accepted and recommended policy in environment altering projects. The EU Water Framework Directive (WFD) took force in 2000 and stresses the importance of public involvement in composing river basin management plans. Therefore, the need to develop public involvement methods for different situations and circumstances is evident. This paper describes how various public involvement methods have been applied in a development project involving the most heavily regulated lake in Finland. The objective of the project was to assess the positive and negative impacts of regulation and to find possibilities for alleviating the adverse impacts on recreational use and the aquatic ecosystem. An exceptional effort was made towards public involvement, which was closely connected to planning and decision making. The applied methods were (1) steering group work, (2) survey, (3) dialogue, (4) theme interviews, (5) public meeting and (6) workshops. The information gathered using these methods was utilized in different stages of the project, e.g., in identifying the regulation impacts, comparing alternatives and compiling the recommendations for regulation development. After describing our case and the results from the applied public involvement methods, we will discuss our experiences and the feedback from the public. We will also critically evaluate our own success in coping with public involvement challenges. In addition to that, we present general recommendations for dealing with these problematic issues based on our experiences, which provide new insights for applying various public involvement methods in multi-objective decision making projects

  2. The Competence Promoting by NNSA for Keeping High Level Nuclear Safety: The Corner Stone of the Nuclear Safety Regulation Edifice

    International Nuclear Information System (INIS)

    Hu, L.

    2016-01-01

    Facing the fast development of the nuclear power industry and the application of radioactive sources, The MEP(NNSA) is endeavoured to promoting its competency, including: complementing the law system, training and recruiting staff to keep a capable team, constructing the R&D base to keep the basic capability, promoting safety culture both for the industry and the regulator. After the Fukushima nuclear accident, the MEP(NNSA) planned to construct R&D base, in which the Platform Nuclear Safety Monitoring and Emergency Responding, the Platform of Safety Technology of PWR Testing, the Laboratory of Safety Management Technology of Nuclear Waste Verification, the Laboratory of Environmental Radiation Monitoring and the Center of International Cooperation are included. On the other hand, the MEP(NNSA) issued Chinese nuclear safety culture policy declaration in 2014, and carried out a large scale Specialized Action for Nuclear Safety Promotion to promote the nuclear safety culture both for the industry and herself. For the nuclear regulator, It is essential to conduct the competence promoting by both “hardware” and “software”, the former is the material foundation of regulation authority, which will be effectively functioning under the facilitating of the latter. (author)

  3. Reexamination of the Physiological Role of PykA in Escherichia coli Revealed that It Negatively Regulates the Intracellular ATP Levels under Anaerobic Conditions.

    Science.gov (United States)

    Zhao, Chunhua; Lin, Zhao; Dong, Hongjun; Zhang, Yanping; Li, Yin

    2017-06-01

    Pyruvate kinase is one of the three rate-limiting glycolytic enzymes that catalyze the last step of glycolysis, conversion of phosphoenolpyruvate (PEP) into pyruvate, which is associated with ATP generation. Two isozymes of pyruvate kinase, PykF and PykA, are identified in Escherichia coli PykF is considered important, whereas PykA has a less-defined role. Prior studies inactivated the pykA gene to increase the level of its substrate, PEP, and thereby increased the yield of end products derived from PEP. We were surprised when we found a pykA ::Tn 5 mutant in a screen for increased yield of an end product derived from pyruvate ( n -butanol), suggesting that the role of PykA needs to be reexamined. We show that the pykA mutant exhibited elevated intracellular ATP levels, biomass concentrations, glucose consumption, and n -butanol production. We also discovered that the pykA mutant expresses higher levels of a presumed pyruvate transporter, YhjX, permitting the mutant to recapture and metabolize excreted pyruvate. Furthermore, we demonstrated that the nucleotide diphosphate kinase activity of PykA leads to negative regulation of the intracellular ATP levels. Taking the data together, we propose that inactivation of pykA can be considered a general strategy to enhance the production of pyruvate-derived metabolites under anaerobic conditions. IMPORTANCE This study showed that knocking out pykA significantly increased the intracellular ATP level and thus significantly increased the levels of glucose consumption, biomass formation, and pyruvate-derived product formation under anaerobic conditions. pykA was considered to be encoding a dispensable pyruvate kinase; here we show that pykA negatively regulates the anaerobic glycolysis rate through regulating the energy distribution. Thus, knocking out pykA can be used as a general strategy to increase the level of pyruvate-derived fermentative products. Copyright © 2017 American Society for Microbiology.

  4. Epigenetic and conventional regulation is distributed among activators of FLO11 allowing tuning of population-level heterogeneity in its expression.

    Directory of Open Access Journals (Sweden)

    Leah M Octavio

    2009-10-01

    Full Text Available Epigenetic switches encode their state information either locally, often via covalent modification of DNA or histones, or globally, usually in the level of a trans-regulatory factor. Here we examine how the regulation of cis-encoded epigenetic switches controls the extent of heterogeneity in gene expression, which is ultimately tied to phenotypic diversity in a population. We show that two copies of the FLO11 locus in Saccharomyces cerevisiae switch between a silenced and competent promoter state in a random and independent fashion, implying that the molecular event leading to the transition occurs locally at the promoter, in cis. We further quantify the effect of trans regulators both on the slow epigenetic transitions between a silenced and competent promoter state and on the fast promoter transitions associated with conventional regulation of FLO11. We find different classes of regulators affect epigenetic, conventional, or both forms of regulation. Distributing kinetic control of epigenetic silencing and conventional gene activation offers cells flexibility in shaping the distribution of gene expression and phenotype within a population.

  5. MicroRNA miR-9 modifies motor neuron columns by a tuning regulation of FoxP1 levels in developing spinal cords

    OpenAIRE

    Otaegi, Gaizka; Pollock, Andrew; Hong, Janet; Sun, Tao

    2011-01-01

    The precise organization of motor neuron subtypes in a columnar pattern in developing spinal cords is controlled by cross-interactions of multiple transcription factors and segmental expressions of Hox genes and their accessory proteins. Accurate expression levels and domains of these regulators are essential for organizing spinal motor neuron columns and axonal projections to target muscles. Here, we show that microRNA miR-9 is transiently expressed in a motor neuron subtype and displays ove...

  6. A jasmonate ZIM-domain protein NaJAZd regulates floral jasmonic acid levels and counteracts flower abscission in Nicotiana attenuata plants.

    Directory of Open Access Journals (Sweden)

    Youngjoo Oh

    Full Text Available Jasmonic acid is an important regulator of plant growth, development and defense. The jasmonate-ZIM domain (JAZ proteins are key regulators in jasmonate signaling ubiquitously present in flowering plants but their functional annotation remains largely incomplete. Recently, we identified 12 putative JAZ proteins in native tobacco, Nicotiana attenuata, and initiated systematic functional characterization of these proteins by reverse genetic approaches. In this report, Nicotiana attenuata plants silenced in the expression of NaJAZd (irJAZd by RNA interference were used to characterize NaJAZd function. Although NaJAZd transcripts were strongly and transiently up-regulated in the rosette leaves by simulated herbivory treatment, we did not observe strong defense-related phenotypes, such as altered herbivore performance or the constitutive accumulation of defense-related secondary metabolites in irJAZd plants compared to wild type plants, both in the glasshouse and the native habitat of Nicotiana attenuata in the Great Basin Desert, Utah, USA. Interestingly, irJAZd plants produced fewer seed capsules than did wild type plants as a result of increased flower abscission in later stages of flower development. The early- and mid-developmental stages of irJAZd flowers had reduced levels of jasmonic acid and jasmonoyl-L-isoleucine, while fully open flowers had normal levels, but these were impaired in NaMYB305 transcript accumulations. Previously, NaMYB305-silenced plants were shown to have strong flower abscission phenotypes and contained lower NECTARIN 1 transcript levels, phenotypes which are copied in irJAZd plants. We propose that the NaJAZd protein is required to counteract flower abscission, possibly by regulating jasmonic acid and jasmonoyl-L-isoleucine levels and/or expression of NaMYB305 gene in Nicotiana attenuata flowers. This novel insight into the function of JAZ proteins in flower and seed development highlights the diversity of functions

  7. Thyroid hormone deiodinase type 2 mRNA levels in sea lamprey (Petromyzon marinus) are regulated during metamorphosis and in response to a thyroid challenge.

    Science.gov (United States)

    Stilborn, S Salina M; Manzon, Lori A; Schauenberg, Jennifer D; Manzon, Richard G

    2013-03-01

    Thyroid hormones (THs) are crucial for normal vertebrate development and are the one obligate morphogen that drives amphibian metamorphosis. However, contrary to other metamorphosing vertebrates, lampreys exhibit a sharp drop in serum TH early in metamorphosis, and anti-thyroid agents such as potassium perchlorate (KClO(4)) induce metamorphosis. The type 2 deiodinase (D2) enzyme is a key regulator of TH availability during amphibian metamorphosis. We set out to determine how D2 may be involved in the regulation of lamprey metamorphosis and thyroid homeostasis. We cloned a 1.8Kb Petromyzon marinus D2 cDNA that includes the entire protein coding region and a selenocysteine (Sec) codon. Northern blotting indicated that the lamprey D2 mRNA is the longest reported to date (>9Kb). Using real-time PCR, we showed that intestinal and hepatic D2 mRNA levels were elevated prior to and during the early stages of metamorphosis and then declined dramatically to low levels that were sustained for the remainder of metamorphosis. These data are consistent with previously reported changes in serum TH levels and deiodinase activity. Treatment of larvae with either TH or KClO(4) significantly affected D2 mRNA levels in the intestine and liver. These D2 mRNA levels during metamorphosis and in response to thyroid challenges suggest that D2 may function in the regulation of TH levels during lamprey metamorphosis and the maintenance of TH homeostasis. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Sex-lethal enables germline stem cell differentiation by down-regulating Nanos protein levels during Drosophila oogenesis.

    Science.gov (United States)

    Chau, Johnnie; Kulnane, Laura Shapiro; Salz, Helen K

    2012-06-12

    Drosophila ovarian germ cells require Sex-lethal (Sxl) to exit from the stem cell state and to enter the differentiation pathway. Sxl encodes a female-specific RNA binding protein and in somatic cells serves as the developmental switch gene for somatic sex determination and X-chromosome dosage compensation. None of the known Sxl target genes are required for germline differentiation, leaving open the question of how Sxl promotes the transition from stem cell to committed daughter cell. We address the mechanism by which Sxl regulates this transition through the identification of nanos as one of its target genes. Previous studies have shown that Nanos protein is necessary for GSC self-renewal and is rapidly down-regulated in the daughter cells fated to differentiate in the adult ovary. We find that this dynamic expression pattern is limited to female germ cells and is under Sxl control. In the absence of Sxl, or in male germ cells, Nanos protein is continuously expressed. Furthermore, this female-specific expression pattern is dependent on the presence of canonical Sxl binding sites located in the nanos 3' untranslated region. These results, combined with the observation that nanos RNA associates with the Sxl protein in ovarian extracts and loss and gain of function studies, suggest that Sxl enables the switch from germline stem cell to committed daughter cell by posttranscriptional down-regulation of nanos expression. These findings connect sexual identity to the stem cell self-renewal/differentiation decision and highlight the importance of posttranscriptional gene regulatory networks in controlling stem cell behavior.

  9. Maximizing the retention level for proportional reinsurance under  -regulation of the finite time surplus process with unit-equalized interarrival time

    Directory of Open Access Journals (Sweden)

    Sukanya Somprom

    2016-07-01

    Full Text Available The research focuses on an insurance model controlled by proportional reinsurance in the finite-time surplus process with a unit-equalized time interval. We prove the existence of the maximal retention level for independent and identically distributed claim processes under α-regulation, i.e., a model where the insurance company has to manage the probability of insolvency to be at most α. In addition, we illustrate the maximal retention level for exponential claims by applying the bisection technique.

  10. Regulation of blood glucose level by kainic acid in mice: involvement of glucocorticoid system and non-NMDA receptors.

    Science.gov (United States)

    Kim, Chea-Ha; Park, Soo-Hyun; Sim, Yun-Beom; Kim, Sung-Su; Jung, Jun-Sub; Sharma, Naveen; Suh, Hong-Won

    2017-02-28

    Kainic acid (KA) is a well-known excitatory neurotoxic substance. In the present study, effects of KA-injected intraperitoneally (i.p.), intracerebroventricularly (i.c.v.) or intrathecally (i.t.) on the blood glucose level were investigated in ICR mice. We found that KA administered intraperitoneally (i.p.), intracerebroventricularly (i.c.v.) or intrathecally (i.t.) increased the blood glucose and corticosterone levels, suggesting that KA-induced hyperglycemia appeared to be due to increased blood corticosterone level. In support of this finding, adrenalectomy causes a reduction of KA-induced hyperglycemia and neuronal cell death in CA3 regions of the hippocampus. In addition, pretreatment with i.c.v. or i.t. injection of CNQX (6-cyano-7-nitroquinoxaline-2, 3-dione; a non-NMDA receptor blocker) attenuated the i.p. and i.c.v. administered KA-induced hyperglycemia. KA administered i.c.v. caused an elevation of the blood corticosterone level whereas the plasma insulin level was reduced. Moreover, i.c.v. pretreatment with CNQX inhibited the decrease of plasma insulin level induced by KA i.c.v. injection, whereas the KA-induced plasma corticosterone level was further enhanced by CNQX pretreatment. Our results suggest that KA administered systemically or centrally produces hyperglycemia. A glucocorticoid system appears to be involved in KA-induced hyperglycemia. Furthermore, central non-N-methyl-D-aspartate receptors may be responsible for KA-induced hyperglycemia.

  11. Neurotrophins and their receptors in the rat pituitary gland: regulation of BDNF and trkB mRNA levels by adrenal hormones.

    Science.gov (United States)

    Kononen, J; Soinila, S; Persson, H; Honkaniemi, J; Hökfelt, T; Pelto-Huikko, M

    1994-12-01

    We studied the expression of messenger ribonucleic acids (mRNAs) for neurotrophins and neurotrophin receptors in the rat pituitary gland and examined the influence of adrenal hormones on their mRNA levels, using in situ hybridization and Northern blot analysis. The only neurotrophin present at detectable levels in the pituitary was brain-derived neurotrophic factor (BDNF), which was observed in the anterior and intermediate lobes. Several transcripts of the putative receptor for BDNF, trkB, were present in the anterior and posterior lobes of the pituitary. A low amount of trkC mRNA was found in both the anterior and the intermediate lobe. Dexamethasone treatment decreased both BDNF and trkB mRNA levels in the anterior lobe of the pituitary. Adrenalectomy had no effect on trkB expression, but it decreased BDNF mRNA levels in comparison to the control animals. This effect could not be reversed by dexamethasone substitution, suggesting that BDNF, mRNA levels may be regulated not only by glucocorticoids but also by other adrenal hormones. These results demonstrate that BDNF, trkB and trkC are expressed in the pituitary gland and that glucocorticoids and possibly other adrenal hormones may modulate pituitary functions by regulating the expression of neurotrophic factors and their receptors. Whether BDNF acts as a secreted hormone, a trophic factor, or has autocrine/paracrine functions within the pituitary through its receptor, trkB, remains to be studied.

  12. Transcriptomic and proteomic approach to identify differentially expressed genes and proteins in Arabidopsis thaliana mutants lacking chloroplastic 1 and cytosolic FBPases reveals several levels of metabolic regulation.

    Science.gov (United States)

    Soto-Suárez, Mauricio; Serrato, Antonio J; Rojas-González, José A; Bautista, Rocío; Sahrawy, Mariam

    2016-12-01

    During the photosynthesis, two isoforms of the fructose-1,6-bisphosphatase (FBPase), the chloroplastidial (cFBP1) and the cytosolic (cyFBP), catalyse the first irreversible step during the conversion of triose phosphates (TP) to starch or sucrose, respectively. Deficiency in cyFBP and cFBP1 isoforms provokes an imbalance of the starch/sucrose ratio, causing a dramatic effect on plant development when the plastidial enzyme is lacking. We study the correlation between the transcriptome and proteome profile in rosettes and roots when cFBP1 or cyFBP genes are disrupted in Arabidopsis thaliana knock-out mutants. By using a 70-mer oligonucleotide microarray representing the genome of Arabidopsis we were able to identify 1067 and 1243 genes whose expressions are altered in the rosettes and roots of the cfbp1 mutant respectively; whilst in rosettes and roots of cyfbp mutant 1068 and 1079 genes are being up- or down-regulated respectively. Quantitative real-time PCR validated 100% of a set of 14 selected genes differentially expressed according to our microarray analysis. Two-dimensional (2-D) gel electrophoresis-based proteomic analysis revealed quantitative differences in 36 and 26 proteins regulated in rosettes and roots of cfbp1, respectively, whereas the 18 and 48 others were regulated in rosettes and roots of cyfbp mutant, respectively. The genes differentially expressed and the proteins more or less abundant revealed changes in protein metabolism, RNA regulation, cell signalling and organization, carbon metabolism, redox regulation, and transport together with biotic and abiotic stress. Notably, a significant set (25%) of the proteins identified were also found to be regulated at a transcriptional level. This transcriptomic and proteomic analysis is the first comprehensive and comparative study of the gene/protein re-adjustment that occurs in photosynthetic and non-photosynthetic organs of Arabidopsis mutants lacking FBPase isoforms.

  13. (Review Draft) Radiation Site Cleanup Regulations: Technical Support Document For The Development Of Radionuclide Cleanup Levels For Soil

    Science.gov (United States)

    This document describes parts of the technical analysis being undertaken in support of standards that ensure certain sites are cleaned up to a level that is protective of human health and the environment before they are released for public use.

  14. An evaluation of the exemption level for the radiation protection regulation based on the social risk acceptance in Korea

    International Nuclear Information System (INIS)

    Yoon, Ki Don

    1998-02-01

    Radiation protection is based not only on the science but also on the political, social, economical and emotional factors, so a policy decision for a factor like the exemption level in this field must be considered social expectation and valuation as well as scientific evaluation. In this paper, an attempt was made to get a rationale on the exemption level, which has a significant meaning in radiation protection, by means of surveying the social risk acceptance in Korea. Risk perception data were collected by mail surveys to the respondents randomly selected in the city of Seoul. A poor response rate, 156 out of 400, was observed. The result showed that the majority of the respondents agreed upon setting a de mini mis level of risk and the favoured de mini mis level appeared to be in the range of 10 -6 yr -1 to 10 -7 yr -1 , which is consistent with the level suggested by other organizations: ICRP, EPA and NRPB. Approximately the same risk level, unfortunately, was obtained for the risk limits against a harmful agent, which makes no sense. It can be attributed to mis-communication due to the questionnaires inadequately designed. The acceptable risk level for a single practice was selected to be 1/100 or less of the risk limits, which seemed overly conservative, but could be understood in the light of the public attitude of outrage. There seems to be tendency that the public recognize the risk significant if it is not de mini mis. This study should not be regarded as one giving a satisfactory conclusion but a preliminary attempt to evaluate the acceptable risk level. More endeavors in design of questionnaires are needed to communicate successfully with the members of the public

  15. Nitrate Reductases Are Relocalized to the Nucleus by AtSIZ1 and Their Levels Are Negatively Regulated by COP1 and Ammonium

    Directory of Open Access Journals (Sweden)

    Joo Yong Kim

    2018-04-01

    Full Text Available Nitrate reductases (NRs catalyze the first step in the reduction of nitrate to ammonium. NR activity is regulated by sumoylation through the E3 ligase activity of AtSIZ1. However, it is not clear how NRs interact with AtSIZ1 in the cell, or how nitrogen sources affect NR levels and their cellular localization. Here, we show that the subcellular localization of NRs is modulated by the E3 SUMO (Small ubiquitin-related modifier ligase AtSIZ1 and that NR protein levels are regulated by nitrogen sources. Transient expression analysis of GFP fusion proteins in onion epidermal cells showed that the NRs NIA1 and NIA2 localize to the cytoplasmic membrane, and that AtSIZ1 localizes to the nucleoplasm, including nuclear bodies, when expressed separately, whereas NRs and AtSIZ1 localize to the nucleus when co-expressed. Nitrate did not affect the subcellular localization of the NRs, but it caused AtSIZ1 to move from the nucleus to the cytoplasm. NRs were not detected in ammonium-treated cells, whereas the localization of AtSIZ1 was not altered by ammonium treatment. NR protein levels increased in response to nitrate but decreased in response to ammonium. In addition, NR protein levels increased in response to a 26S proteasome inhibitor and in cop1-4 and DN-COP1-overexpressing transgenic plants. NR protein degradation occurred later in cop1-4 than in the wild-type, although the NR proteins did not interact with COP1. Therefore, AtSIZ1 controls nuclear localization of NR proteins, and ammonium negatively regulates their levels. The function and stability of NR proteins might be post-translationally modulated by ubiquitination.

  16. Genome-wide identification of physically clustered genes suggests chromatin-level co-regulation in male reproductive development in Arabidopsis thaliana.

    Science.gov (United States)

    Reimegård, Johan; Kundu, Snehangshu; Pendle, Ali; Irish, Vivian F; Shaw, Peter; Nakayama, Naomi; Sundström, Jens F; Emanuelsson, Olof

    2017-04-07

    Co-expression of physically linked genes occurs surprisingly frequently in eukaryotes. Such chromosomal clustering may confer a selective advantage as it enables coordinated gene regulation at the chromatin level. We studied the chromosomal organization of genes involved in male reproductive development in Arabidopsis thaliana. We developed an in-silico tool to identify physical clusters of co-regulated genes from gene expression data. We identified 17 clusters (96 genes) involved in stamen development and acting downstream of the transcriptional activator MS1 (MALE STERILITY 1), which contains a PHD domain associated with chromatin re-organization. The clusters exhibited little gene homology or promoter element similarity, and largely overlapped with reported repressive histone marks. Experiments on a subset of the clusters suggested a link between expression activation and chromatin conformation: qRT-PCR and mRNA in situ hybridization showed that the clustered genes were up-regulated within 48 h after MS1 induction; out of 14 chromatin-remodeling mutants studied, expression of clustered genes was consistently down-regulated only in hta9/hta11, previously associated with metabolic cluster activation; DNA fluorescence in situ hybridization confirmed that transcriptional activation of the clustered genes was correlated with open chromatin conformation. Stamen development thus appears to involve transcriptional activation of physically clustered genes through chromatin de-condensation. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  17. A Mathematical Model of Metabolism and Regulation Provides a Systems-Level View of How Escherichia coli Responds to Oxygen

    Directory of Open Access Journals (Sweden)

    Michael eEderer

    2014-03-01

    Full Text Available The efficient redesign of bacteria for biotechnological purposes, such as biofuel production, waste disposal or specific biocatalytic functions, requires a quantitative systems-level understanding of energy supply, carbon and redox metabolism. The measurement of transcript levels, metabolite concentrations and metabolic fluxes per se gives an incomplete picture. An appreciation of the interdependencies between the different measurement values is essential for systems-level understanding. Mathematical modeling has the potential to provide a coherent and quantitative description of the interplay between gene expression, metabolite concentrations and metabolic fluxes. Escherichia coli undergoes major adaptations in central metabolism when the availability of oxygen changes. Thus, an integrated description of the oxygen response provides a benchmark of our understanding of carbon, energy and redox metabolism. We present the first comprehensive model of the central metabolism of E. coli that describes steady-state metabolism at different levels of oxygen availability. Variables of the model are metabolite concentrations, gene expression levels, transcription factor activities, metabolic fluxes and biomass concentration. We analyze the model with respect to the production capabilities of central metabolism of E. coli. In particular, we predict how precursor and biomass concentration are affected by product formation.

  18. CYP2E1 epigenetic regulation in chronic, low-level toluene exposure: Relationship with oxidative stress and smoking habit

    Energy Technology Data Exchange (ETDEWEB)

    Jiménez-Garza, Octavio, E-mail: ojimenezgarza@ugto.mx [Health Sciences Division, University of Guanajuato Campus León, Blvd. Puente del Milenio 1001, Fracción del Predio San Carlos, C.P. 37670 León, Guanajuato (Mexico); Baccarelli, Andrea A.; Byun, Hyang-Min [Laboratory of Environmental Epigenetics, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115 (United States); Márquez-Gamiño, Sergio [Health Sciences Division, University of Guanajuato Campus León, Blvd. Puente del Milenio 1001, Fracción del Predio San Carlos, C.P. 37670 León, Guanajuato (Mexico); Barrón-Vivanco, Briscia Socorro [Environmental Toxicology and Pollution Laboratory, Nayarit Autonomous University, Av. Ciudad de la Cultura s/n, “Amado Nervo”, Tepic, Nayarit C.P. 63155 (Mexico); Albores, Arnulfo [Department of Toxicology, CINVESTAV, Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, 07360 Mexico DF (Mexico)

    2015-08-01

    Background: CYP2E1 is a versatile phase I drug-metabolizing enzyme responsible for the biotransformation of most volatile organic compounds, including toluene. Human toluene exposure increases CYP2E1 mRNA and modifies its activity in leucocytes; however, epigenetic implications of this interaction have not been investigated. Goal: To determine promoter methylation of CYP2E1 and other genes known to be affected by toluene exposure. Methods: We obtained venous blood from 24 tannery workers exposed to toluene (mean levels: 10.86 +/− 7 mg/m{sup 3}) and 24 administrative workers (reference group, mean levels 0.21 +/− 0.02 mg/m{sup 3}) all of them from the city of León, Guanajuato, México. After DNA extraction and bisulfite treatment, we performed PCR-pyrosequencing in order to measure methylation levels at promoter region of 13 genes. Results: In exposed group we found significant correlations between toluene airborne levels and CYP2E1 promoter methylation (r = − .36, p < 0.05), as well as for IL6 promoter methylation levels (r = .44, p < 0.05). Moreover, CYP2E1 promoter methylation levels where higher in toluene-exposed smokers compared to nonsmokers (p = 0.009). We also observed significant correlations for CYP2E1 promoter methylation with GSTP1 and SOD1 promoter methylation levels (r = − .37, p < 0.05 and r = − .34, p < 0.05 respectively). Conclusion: These results highlight the importance of considering CYP2E1 epigenetic modifications, as well as its interactions with other genes, as key factors for unraveling the sub cellular mechanisms of toxicity exerted by oxidative stress, which can initiate disease process in chronic, low-level toluene exposure. People co-exposed to toluene and tobacco smoke are in higher risk due to a possible CYP2E1 repression. - Highlights: • We investigated gene-specific methylation in persons chronically exposed to toluene. • In a previous study, a reduced CYP2E1 activity was observed in these participants. • CYP2E1

  19. CYP2E1 epigenetic regulation in chronic, low-level toluene exposure: Relationship with oxidative stress and smoking habit

    International Nuclear Information System (INIS)

    Jiménez-Garza, Octavio; Baccarelli, Andrea A.; Byun, Hyang-Min; Márquez-Gamiño, Sergio; Barrón-Vivanco, Briscia Socorro; Albores, Arnulfo

    2015-01-01

    Background: CYP2E1 is a versatile phase I drug-metabolizing enzyme responsible for the biotransformation of most volatile organic compounds, including toluene. Human toluene exposure increases CYP2E1 mRNA and modifies its activity in leucocytes; however, epigenetic implications of this interaction have not been investigated. Goal: To determine promoter methylation of CYP2E1 and other genes known to be affected by toluene exposure. Methods: We obtained venous blood from 24 tannery workers exposed to toluene (mean levels: 10.86 +/− 7 mg/m 3 ) and 24 administrative workers (reference group, mean levels 0.21 +/− 0.02 mg/m 3 ) all of them from the city of León, Guanajuato, México. After DNA extraction and bisulfite treatment, we performed PCR-pyrosequencing in order to measure methylation levels at promoter region of 13 genes. Results: In exposed group we found significant correlations between toluene airborne levels and CYP2E1 promoter methylation (r = − .36, p < 0.05), as well as for IL6 promoter methylation levels (r = .44, p < 0.05). Moreover, CYP2E1 promoter methylation levels where higher in toluene-exposed smokers compared to nonsmokers (p = 0.009). We also observed significant correlations for CYP2E1 promoter methylation with GSTP1 and SOD1 promoter methylation levels (r = − .37, p < 0.05 and r = − .34, p < 0.05 respectively). Conclusion: These results highlight the importance of considering CYP2E1 epigenetic modifications, as well as its interactions with other genes, as key factors for unraveling the sub cellular mechanisms of toxicity exerted by oxidative stress, which can initiate disease process in chronic, low-level toluene exposure. People co-exposed to toluene and tobacco smoke are in higher risk due to a possible CYP2E1 repression. - Highlights: • We investigated gene-specific methylation in persons chronically exposed to toluene. • In a previous study, a reduced CYP2E1 activity was observed in these participants. • CYP2E1 promoter

  20. Is the regulation of the electronic properties of organic molecules by polynuclear superhalogens more effective than that by mononuclear superhalogens? A high-level ab initio case study.

    Science.gov (United States)

    Li, Miao-Miao; Li, Jin-Feng; Bai, Hongcun; Sun, Yin-Yin; Li, Jian-Li; Yin, Bing

    2015-08-21

    The regulation of the electronic properties of organic molecules induced by polynuclear superhalogens is theoretically explored here for sixteen composite structures. It is clearly indicated by the higher vertical electron detachment energy (VDE) that polynuclear superhalogens are more effective in regulating the electronic properties than mononuclear structures. However, this enhanced regulation is not only determined by superhalogens themselves but also related to the distribution of the extra electron of the final composites. The composites, in which the extra electron is mainly aggregated into the superhalogen moiety, will possess higher VDE values, as reported in the case of C1', 7.12 eV at the CCSD(T) level. This is probably due to the fact that, compared with organic molecules, superhalogens possess stronger attraction towards the extra electron and thus should lead to lower energies of the extra electrons and to higher VDE values eventually. Compared with CCSD(T), the Outer Valence Green's Function (OVGF) method fails completely for composite structures containing Cl atoms, while MP2 results are generally consistent in terms of the relative order of VDEs. Actually if the extra electron distribution of the systems could be approximated by the HOMO, the results at the OVGF level will be consistent with the CCSD(T) results. Conversely, the difference in VDEs between OVGF and CCSD(T) is significantly large. Besides superhalogen properties, the structures, relative stabilities and thermodynamic stabilities with respect to various fragmentation channels were also investigated for all the composite structures.

  1. Nitrite reductase expression is regulated at the post-transcriptional level by the nitrogen source in Nicotiana plumbaginifolia and Arabidopsis thaliana.

    Science.gov (United States)

    Crété, P; Caboche, M; Meyer, C

    1997-04-01

    Higher plant nitrite reductase (NiR) is a monomeric chloroplastic protein catalysing the reduction of nitrite, the product of nitrate reduction, to ammonium. The expression of this enzyme is controlled at the transcriptional level by light and by the nitrogen source. In order to study the post-transcriptional regulation of NiR, Nicotiana plumbaginifolia and Arabidopsis thaliana were transformed with a chimaeric NiR construct containing the tobacco leaf NiR1 coding sequence driven by the CaMV 35S RNA promoter. Transformed plants did not show any phenotypic difference when compared with the wild-type, although they overexpressed NiR activity in the leaves. When these plants were grown in vitro on media containing either nitrate or ammonium as sole nitrogen source, NiR mRNA derived from transgene expression was constitutively expressed, whereas NiR activity and protein level were strongly reduced on ammonium-containing medium. These results suggest that, together with transcriptional control, post-transcriptional regulation by the nitrogen source is operating on NiR expression. This post-transcriptional regulation of tobacco leaf NiR1 expression was observed not only in the closely related species N. plumbaginifolia but also in the more distant species A. thaliana.

  2. HbA1c levels as a function of emotional regulation and emotional intelligence in patients with type 2 diabetes.

    Science.gov (United States)

    Coccaro, Emil F; Drossos, Tina; Phillipson, Louis

    2016-10-01

    Understanding the role of emotion in glycemic control may be critical for the long-term treatment of patients with type 2 diabetes (T2D). In this study we investigated the relationship between measures of emotional regulation and emotional intelligence and HbA1c levels in adult patients with T2 diabetes. 100 adult patients with T2 diabetes completed assessments of emotional regulation (i.e., affect intensity/lability) and emotional intelligence and were then correlated with HbA1c levels with several relevant covariates. HbA1c levels were significantly associated with affect intensity (AI: r=.24, p=.018) and with emotional intelligence (EI: r=-.29, p=.004), but not affect lability. These results were the same even after adding income, state depression scores, insulin-dependent status, serum cholesterol, diabetes literacy and self-care as covariates (AI: β=.33, p=.001; EI: β=-.31, p=.002). Diabetes self-care, but not diabetes literacy, was also associated with HbA1c levels (β=-.29, p=.003). These data suggest that aspects of emotional regulation and emotional intelligence play a role in glycemic control in adult patients with T2 diabetes and do so even in the context of several variables relevant to diabetes. If so, interventions that can reduce affect intensity and/or increase emotional intelligence may represent a new strategy in the glycemic control of adult patients with T2 diabetes. Copyright © 2016 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  3. CYP2E1 epigenetic regulation in chronic, low-level toluene exposure: Relationship with oxidative stress and smoking habit.

    Science.gov (United States)

    Jiménez-Garza, Octavio; Baccarelli, Andrea A; Byun, Hyang-Min; Márquez-Gamiño, Sergio; Barrón-Vivanco, Briscia Socorro; Albores, Arnulfo

    2015-08-01

    CYP2E1 is a versatile phase I drug-metabolizing enzyme responsible for the biotransformation of most volatile organic compounds, including toluene. Human toluene exposure increases CYP2E1 mRNA and modifies its activity in leucocytes; however, epigenetic implications of this interaction have not been investigated. To determine promoter methylation of CYP2E1 and other genes known to be affected by toluene exposure. We obtained venous blood from 24 tannery workers exposed to toluene (mean levels: 10.86+/-7mg/m(3)) and 24 administrative workers (reference group, mean levels 0.21+/-0.02mg/m(3)) all of them from the city of León, Guanajuato, México. After DNA extraction and bisulfite treatment, we performed PCR-pyrosequencing in order to measure methylation levels at promoter region of 13 genes. In exposed group we found significant correlations between toluene airborne levels and CYP2E1 promoter methylation (r=-.36, psmoke are in higher risk due to a possible CYP2E1 repression. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Depletion of norepinephrine of the central nervous system Down-regulates the blood glucose level in d-glucose-fed and restraint stress models.

    Science.gov (United States)

    Park, Soo-Hyun; Kim, Sung-Su; Lee, Jae-Ryeong; Sharma, Naveen; Suh, Hong-Won

    2016-05-04

    DSP-4[N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride] is a neurotoxin that depletes norepinephrine. The catecholaminergic system has been implicated in the regulation of blood glucose level. In the present study, the effect of DSP-4 administered intracerebroventricularly (i.c.v.) or intrathecally (i.t.) on blood glucose level was examined in d-glucose-fed and restraint stress mice models. Mice were pretreated once i.c.v. or i.t. with DSP-4 (10-40μg) for 3days, and d-glucose (2g/kg) was fed orally. Blood glucose level was measured 0 (prior to glucose feeding or restraint stress), 30, 60, and 120min after d-glucose feeding or restraint stress. The i.c.v. or i.t. pretreatment with DSP-4 attenuated blood glucose level in the d-glucose-fed model. Plasma corticosterone level was downregulated in the d-glucose-fed model, whereas plasma insulin level increased in the d-glucose-fed group. The i.c.v. or i.t. pretreatment with DSP-4 reversed the downregulation of plasma corticosterone induced by feeding d-glucose. In addition, the d-glucose-induced increase in plasma insulin was attenuated by the DSP-4 pretreatment. Furthermore, i.c.v. or i.t. pretreatment with DSP-4 reduced restraint stress-induced increases in blood glucose levels. Restraint stress increased plasma corticosterone and insulin levels. The i.c.v. pretreatment with DSP-4 attenuated restraint stress-induced plasma corticosterone and insulin levels. Our results suggest that depleting norepinephrine at the supraspinal and spinal levels appears to be responsible for downregulating blood glucose levels in both d-glucose-fed and restraint stress models. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Translational up-regulation and high-level protein expression from plasmid vectors by mTOR activation via different pathways in PC3 and 293T cells.

    Directory of Open Access Journals (Sweden)

    Prashanthi Karyala

    Full Text Available BACKGROUND: Though 293T cells are widely used for expression of proteins from transfected plasmid vectors, the molecular basis for the high-level expression is yet to be understood. We recently identified the prostate carcinoma cell line PC3 to be as efficient as 293T in protein expression. This study was undertaken to decipher the molecular basis of high-level expression in these two cell lines. METHODOLOGY/PRINCIPAL FINDINGS: In a survey of different cell lines for efficient expression of platelet-derived growth factor-B (PDGF-B, β-galactosidase (β-gal and green fluorescent protein (GFP from plasmid vectors, PC3 was found to express at 5-50-fold higher levels compared to the bone metastatic prostate carcinoma cell line PC3BM and many other cell lines. Further, the efficiency of transfection and level of expression of the reporters in PC3 were comparable to that in 293T. Comparative analyses revealed that the high level expression of the reporters in the two cell lines was due to increased translational efficiency. While phosphatidic acid (PA-mediated activation of mTOR, as revealed by drastic reduction in reporter expression by n-butanol, primarily contributed to the high level expression in PC3, multiple pathways involving PA, PI3K/Akt and ERK1/2 appear to contribute to the abundant reporter expression in 293T. Thus the extent of translational up-regulation attained through the concerted activation of mTOR by multiple pathways in 293T could be achieved through its activation primarily by the PA pathway in PC3. CONCLUSIONS/SIGNIFICANCE: Our studies reveal that the high-level expression of proteins from plasmid vectors is effected by translational up-regulation through mTOR activation via different signaling pathways in the two cell lines and that PC3 is as efficient as 293T for recombinant protein expression. Further, PC3 offers an advantage in that the level of expression of the protein can be regulated by simple addition of n-butanol to

  6. Environmental regulation of plant gene expression: an RT-qPCR laboratory project for an upper-level undergraduate biochemistry or molecular biology course.

    Science.gov (United States)

    Eickelberg, Garrett J; Fisher, Alison J

    2013-01-01

    We present a novel laboratory project employing "real-time" RT-qPCR to measure the effect of environment on the expression of the FLOWERING LOCUS C gene, a key regulator of floral timing in Arabidopsis thaliana plants. The project requires four 3-hr laboratory sessions and is aimed at upper-level undergraduate students in biochemistry or molecular biology courses. The project provides students with hands-on experience with RT-qPCR, the current "gold standard" for gene expression analysis, including detailed data analysis using the common 2-ΔΔCT method. Moreover, it provides a convenient starting point for many inquiry-driven projects addressing diverse questions concerning ecological biochemistry, naturally occurring genetic variation, developmental biology, and the regulation of gene expression in nature. Copyright © 2013 Wiley Periodicals, Inc.

  7. Blocking signaling at the level of GLI regulates downstream gene expression and inhibits proliferation of canine osteosarcoma cells.

    Science.gov (United States)

    Shahi, Mehdi Hayat; Holt, Roseline; Rebhun, Robert B

    2014-01-01

    The Hedgehog-GLI signaling pathway is active in a variety of human malignancies and is known to contribute to the growth and survival of human osteosarcoma cells. In this study, we examined the expression and regulation of GLI transcription factors in multiple canine osteosarcoma cell lines and analyzed the effects of inhibiting GLI with GANT61, a GLI-specific inhibitor. Compared with normal canine osteoblasts, real-time PCR showed that GLI1 and GLI2 were highly expressed in two out of three cell lines and correlated with downstream target gene expression of PTCH1and PAX6. Treatment of canine osteosarcoma cells with GANT61 resulted in decreased expression of GLI1, GLI2, PTCH1, and PAX6. Furthermore, GANT61 inhibited proliferation and colony formation in all three canine osteosarcoma cell lines. The finding that GLI signaling activity is present and active in canine osteosarcoma cells suggests that spontaneously arising osteosarcoma in dogs might serve as a good model for future preclinical testing of GLI inhibitors.

  8. Blocking signaling at the level of GLI regulates downstream gene expression and inhibits proliferation of canine osteosarcoma cells.

    Directory of Open Access Journals (Sweden)

    Mehdi Hayat Shahi

    Full Text Available The Hedgehog-GLI signaling pathway is active in a variety of human malignancies and is known to contribute to the growth and survival of human osteosarcoma cells. In this study, we examined the expression and regulation of GLI transcription factors in multiple canine osteosarcoma cell lines and analyzed the effects of inhibiting GLI with GANT61, a GLI-specific inhibitor. Compared with normal canine osteoblasts, real-time PCR showed that GLI1 and GLI2 were highly expressed in two out of three cell lines and correlated with downstream target gene expression of PTCH1and PAX6. Treatment of canine osteosarcoma cells with GANT61 resulted in decreased expression of GLI1, GLI2, PTCH1, and PAX6. Furthermore, GANT61 inhibited proliferation and colony formation in all three canine osteosarcoma cell lines. The finding that GLI signaling activity is present and active in canine osteosarcoma cells suggests that spontaneously arising osteosarcoma in dogs might serve as a good model for future preclinical testing of GLI inhibitors.

  9. miR-375-3p negatively regulates osteogenesis by targeting and decreasing the expression levels of LRP5 and β-catenin.

    Directory of Open Access Journals (Sweden)

    Tianhao Sun

    Full Text Available Wnt signaling pathways are essential for bone formation. Previous studies showed that Wnt signaling pathways were regulated by miR-375. Thus, we aim to explore whether miR-375 could affect osteogenesis. In the present study, we investigated the roles of miR-375 and its downstream targets. Firstly, we revealed that miR-375-3p negatively modulated osteogenesis by suppressing positive regulators of osteogenesis and promoting negative regulators of osteogenesis. In addition, the results of TUNEL cell apoptosis assay showed that miR-375-3p induced MC3T3-E1 cell apoptosis. Secondly, miR-375-3p targeted low-density lipoprotein receptor-related protein 5 (LRP5, a co-receptor of the Wnt signaling pathways, and β-catenin as determined by luciferase activity assay, and it decreased the expression levels of LRP5 and β-catenin. Thirdly, the decline of protein levels of β-catenin was determined by immunocytochemistry and immunofluorescence. Finally, silence of LRP5 in osteoblast precursor cells resulted in diminished cell viability and cell proliferation as detected by WST-1-based colorimetric assay. Additionally, all the parameters including the relative bone volume from μCT measurement suggested that LRP5 knockout in mice resulted in a looser and worse-connected trabeculae. The mRNA levels of important negative modulators relating to osteogenesis increased after the functions of LRP5 were blocked in mice. Last but not least, the expression levels of LRP5 increased during the osteogenesis of MC3T3-E1, while the levels of β-catenin decreased in bone tissues from osteoporotic patients with vertebral compression fractures. In conclusion, we revealed miR-375-3p negatively regulated osteogenesis by targeting LRP5 and β-catenin. In addition, loss of functions of LRP5 damaged bone formation in vivo. Clinically, miR-375-3p and its targets might be used as diagnostic biomarkers for osteoporosis and might be also as novel therapeutic agents in osteoporosis

  10. Sulfate-Driven Elemental Sparing Is Regulated at the Transcriptional and Posttranscriptional Levels in a Filamentous Cyanobacterium▿ †

    OpenAIRE

    Gutu, Andrian; Alvey, Richard M.; Bashour, Sami; Zingg, Daniel; Kehoe, David M.

    2011-01-01

    Sulfur is an essential nutrient that can exist at growth-limiting concentrations in freshwater environments. The freshwater cyanobacterium Fremyella diplosiphon (also known as Tolypothrix sp. PCC 7601) is capable of remodeling the composition of its light-harvesting antennae, or phycobilisomes, in response to changes in the sulfur levels in its environment. Depletion of sulfur causes these cells to cease the accumulation of two forms of a major phycobilisome protein called phycocyanin and ini...

  11. Regulation to create environments conducive to physical activity: understanding the barriers and facilitators at the Australian state government level.

    Science.gov (United States)

    Shill, Jane; Mavoa, Helen; Crammond, Brad; Loff, Bebe; Peeters, Anna; Lawrence, Mark; Allender, Steven; Sacks, Gary; Swinburn, Boyd A

    2012-01-01

    Policy and regulatory interventions aimed at creating environments more conducive to physical activity (PA) are an important component of strategies to improve population levels of PA. However, many potentially effective policies are not being broadly implemented. This study sought to identify potential policy/regulatory interventions targeting PA environments, and barriers/facilitators to their implementation at the Australian state/territory government level. In-depth interviews were conducted with senior representatives from state/territory governments, statutory authorities and non-government organisations (n = 40) to examine participants': 1) suggestions for regulatory interventions to create environments more conducive to PA; 2) support for preselected regulatory interventions derived from a literature review. Thematic and constant comparative analyses were conducted. POLICY INTERVENTIONS MOST COMMONLY SUGGESTED BY PARTICIPANTS FELL INTO TWO AREAS: 1) urban planning and provision of infrastructure to promote active travel; 2) discouraging the use of private motorised vehicles. Of the eleven preselected interventions presented to participants, interventions relating to walkability/cycling and PA facilities received greatest support. Interventions involving subsidisation (of public transport, PA-equipment) and the provision of more public transport infrastructure received least support. These were perceived as not economically viable or unlikely to increase PA levels. Dominant barriers were: the powerful 'road lobby', weaknesses in the planning system and the cost of potential interventions. Facilitators were: the provision of evidence, collaboration across sectors, and synergies with climate change/environment agendas. This study points to how difficult it will be to achieve policy change when there is a powerful 'road lobby' and government investment prioritises road infrastructure over PA-promoting infrastructure. It highlights the pivotal role of the

  12. The human ubiquitin-conjugating enzyme Cdc34 controls cellular proliferation through regulation of p27Kip1 protein levels

    International Nuclear Information System (INIS)

    Butz, Nicole; Ruetz, Stephan; Natt, Francois; Hall, Jonathan; Weiler, Jan; Mestan, Juergen; Ducarre, Monique; Grossenbacher, Rita; Hauser, Patrick; Kempf, Dominique; Hofmann, Francesco

    2005-01-01

    Ubiquitin-mediated degradation of the cyclin-dependent kinase inhibitor p27 Kip1 was shown to be required for the activation of key cyclin-dependent kinases, thereby triggering the onset of DNA replication and cell cycle progression. Although the SCF Skp2 ubiquitin ligase has been reported to mediate p27 Kip1 degradation, the nature of the human ubiquitin-conjugating enzyme involved in this process has not yet been determined at the cellular level. Here, we show that antisense oligonucleotides targeting the human ubiquitin-conjugating enzyme Cdc34 downregulate its expression, inhibit the degradation of p27 Kip1 , and prevent cellular proliferation. Elevation of p27 Kip1 protein level is found to be the sole requirement for the inhibition of cellular proliferation induced upon downregulation of Cdc34. Indeed, reducing the expression of p27 Kip1 with a specific antisense oligonucleotide is sufficient to reverse the anti-proliferative phenotype elicited by the Cdc34 antisense. Furthermore, downregulation of Cdc34 is found to specifically increase the abundance of the SCF Skp2 ubiquitin ligase substrate p27 Kip1 , but has no concomitant effect on the level of IkBα and β-catenin, which are known substrates of a closely related SCF ligase

  13. Cranial electrotherapy stimulation affects mood state but not levels of peripheral neurotrophic factors or hypothalamic- pituitary-adrenal axis regulation.

    Science.gov (United States)

    Roh, Hee-Tae; So, Wi-Young

    2017-01-01

    Cranial electrotherapy stimulation (CES) is reported to aid in relieving symptoms of depression and anxiety, though the mechanism underlying this effect remains unclear. Therefore, the present study aimed to evaluate changes in the hypothalamic-pituitary-adrenal (HPA) axis response and levels of neurotrophic factors, as well as changes in mood state, in patients undergoing CES therapy. Fifty healthy postmenopausal women were randomly assigned to either a Sham CES group (n = 25) or an Active CES group (n = 25). CES treatment was conducted in 20-minute sessions, three times per week for 8 weeks, using a micro current cranial electrotherapy stimulator. Blood samples were collected prior to and following the 8-week treatment period for measurement of cortisol, adrenocorticotropic hormone (ACTH), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) levels. Changes in mood state were also examined at the time of blood collection using the Profile of Mood States (POMS). No significant differences in cortisol, ACTH, BDNF, or NGF were observed between the two participant groups (p > 0.05) following the treatment period. However, those in the Active CES group exhibited significantly decreased Tension-Anxiety and Depression-Dejection scores on the POMS relative to pre-treatment scores (p 0.05). These results suggest that 8 weeks of CES treatment does not induce changes in blood levels of neurotrophic factors or HPA-axis-related hormones, though such treatment may be effective in treating symptoms of anxiety and depression.

  14. Modeling wetland plant community response to assess water-level regulation scenarios in the Lake Ontario-St. Lawrence River basin

    Science.gov (United States)

    Hudon, Christiane; Wilcox, Douglas; Ingram, Joel

    2006-01-01

    The International Joint Commission has recently completed a five-year study (2000-2005) to review the operation of structures controlling the flows and levels of the Lake Ontario - St. Lawrence River system. In addition to addressing the multitude of stakeholder interests, the regulation plan review also considers environmental sustainability and integrity of wetlands and various ecosystem components. The present paper outlines the general approach, scientific methodology and applied management considerations of studies quantifying the relationships between hydrology and wetland plant assemblages (% occurrence, surface area) in Lake Ontario and the Upper and Lower St. Lawrence River. Although similar study designs were used across the study region, different methodologies were required that were specifically adapted to suit the important regional differences between the lake and river systems, range in water-level variations, and confounding factors (geomorphic types, exposure, sediment characteristics, downstream gradient of water quality, origin of water masses in the Lower River). Performance indicators (metrics), such as total area of wetland in meadow marsh vegetation type, that link wetland response to water levels will be used to assess the effects of different regulation plans under current and future (climate change) water-supply scenarios.

  15. The protein phosphatase-1/inhibitor-2 complex differentially regulates GSK3 dephosphorylation and increases sarcoplasmic/endoplasmic reticulum calcium ATPase 2 levels

    International Nuclear Information System (INIS)

    King, Taj D.; Gandy, Johanna C.; Bijur, Gautam N.

    2006-01-01

    The ubiquitously expressed protein glycogen synthase kinase-3 (GSK3) is constitutively active, however its activity is markedly diminished following phosphorylation of Ser21 of GSK3α and Ser9 of GSK3β. Although several kinases are known to phosphorylate Ser21/9 of GSK3, for example Akt, relatively much less is known about the mechanisms that cause the dephosphorylation of GSK3 at Ser21/9. In the present study KCl-induced plasma membrane depolarization of SH-SY5Y cells, which increases intracellular calcium concentrations caused a transient decrease in the phosphorylation of Akt at Thr308 and Ser473, and GSK3 at Ser21/9. Overexpression of the selective protein phosphatase-1 inhibitor protein, inhibitor-2, increased basal GSK3 phosphorylation at Ser21/9 and significantly blocked the KCl-induced dephosphorylation of GSK3β, but not GSK3α. The phosphorylation of Akt was not affected by the overexpression of inhibitor-2. GSK3 activity is known to affect sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) levels. Overexpression of inhibitor-2 or treatment of cells with the GSK3 inhibitors lithium and SB216763 increased the levels of SERCA2. These results indicate that the protein phosphatase-1/inhibitor-2 complex differentially regulates GSK3 dephosphorylation induced by KCl and that GSK3 activity regulates SERCA2 levels

  16. Disturbance of DKK1 level is partly involved in survival of lung cancer cells via regulation of ROMO1 and γ-radiation sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In Gyu, E-mail: igkim@kaeri.re.kr [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, P.O. Box 105, Yuseong, Daejeon 305-600 (Korea, Republic of); Department of Radiation Biotechnology and Applied Radioisotope, University of Science and Technology (UST), 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Kim, Seo Yoen [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, P.O. Box 105, Yuseong, Daejeon 305-600 (Korea, Republic of); Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of); Kim, Hyun A; Kim, Jeong Yul [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, P.O. Box 105, Yuseong, Daejeon 305-600 (Korea, Republic of); Lee, Jae Ha; Choi, Soo Im [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, P.O. Box 105, Yuseong, Daejeon 305-600 (Korea, Republic of); Department of Radiation Biotechnology and Applied Radioisotope, University of Science and Technology (UST), 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Han, Jeong Ran; Kim, Kug Chan [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, P.O. Box 105, Yuseong, Daejeon 305-600 (Korea, Republic of); Cho, Eun Wie [Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of)

    2014-01-03

    Highlights: •DKK1 was expressed differently among non-small-cell lung cancer cell lines. •DKK1 negatively regulated ROMO1 gene expression. •Disturbance of DKK1 level induced the imbalance of cellular ROS. •DKK1/ROMO1-induced ROS imbalance is involved in cell survival in NSCLC. -- Abstract: Dickkopf1 (DKK1), a secreted protein involved in embryonic development, is a potent inhibitor of the Wnt signaling pathway and has been postulated to be a tumor suppressor or tumor promoter depending on the tumor type. In this study, we showed that DKK1 was expressed differently among non-small-cell lung cancer cell lines. The DKK1 expression level was much higher in A549 cells than in H460 cells. We revealed that blockage of DKK1 expression by silencing RNA in A549 cells caused up-regulation of intracellular reactive oxygen species (ROS) modulator (ROMO1) protein, followed by partial cell death, cell growth inhibition, and loss of epithelial–mesenchymal transition property caused by ROS, and it also increased γ-radiation sensitivity. DKK1 overexpression in H460 significantly inhibited cell survival with the decrease of ROMO1 level, which induced the decrease of cellular ROS. Thereafter, exogenous N-acetylcysteine, an antioxidant, or hydrogen peroxide, a pro-oxidant, partially rescued cells from death and growth inhibition. In each cell line, both overexpression and blockage of DKK1 not only elevated p-RB activation, which led to cell growth arrest, but also inactivated AKT/NF-kB, which increased radiation sensitivity and inhibited cell growth. This study is the first to demonstrate that strict modulation of DKK1 expression in different cell types partially maintains cell survival via tight regulation of the ROS-producing ROMO1 and radiation resistance.

  17. Budding yeast ATM/ATR control meiotic double-strand break (DSB levels by down-regulating Rec114, an essential component of the DSB-machinery.

    Directory of Open Access Journals (Sweden)

    Jesús A Carballo

    2013-06-01

    Full Text Available An essential feature of meiosis is Spo11 catalysis of programmed DNA double strand breaks (DSBs. Evidence suggests that the number of DSBs generated per meiosis is genetically determined and that this ability to maintain a pre-determined DSB level, or "DSB homeostasis", might be a property of the meiotic program. Here, we present direct evidence that Rec114, an evolutionarily conserved essential component of the meiotic DSB-machinery, interacts with DSB hotspot DNA, and that Tel1 and Mec1, the budding yeast ATM and ATR, respectively, down-regulate Rec114 upon meiotic DSB formation through phosphorylation. Mimicking constitutive phosphorylation reduces the interaction between Rec114 and DSB hotspot DNA, resulting in a reduction and/or delay in DSB formation. Conversely, a non-phosphorylatable rec114 allele confers a genome-wide increase in both DSB levels and in the interaction between Rec114 and the DSB hotspot DNA. These observations strongly suggest that Tel1 and/or Mec1 phosphorylation of Rec114 following Spo11 catalysis down-regulates DSB formation by limiting the interaction between Rec114 and DSB hotspots. We also present evidence that Ndt80, a meiosis specific transcription factor, contributes to Rec114 degradation, consistent with its requirement for complete cessation of DSB formation. Loss of Rec114 foci from chromatin is associated with homolog synapsis but independent of Ndt80 or Tel1/Mec1 phosphorylation. Taken together, we present evidence for three independent ways of regulating Rec114 activity, which likely contribute to meiotic DSBs-homeostasis in maintaining genetically determined levels of breaks.

  18. Budding Yeast ATM/ATR Control Meiotic Double-Strand Break (DSB) Levels by Down-Regulating Rec114, an Essential Component of the DSB-machinery

    Science.gov (United States)

    Carballo, Jesús A.; Panizza, Silvia; Serrentino, Maria Elisabetta; Johnson, Anthony L.; Geymonat, Marco; Borde, Valérie; Klein, Franz; Cha, Rita S.

    2013-01-01

    An essential feature of meiosis is Spo11 catalysis of programmed DNA double strand breaks (DSBs). Evidence suggests that the number of DSBs generated per meiosis is genetically determined and that this ability to maintain a pre-determined DSB level, or “DSB homeostasis”, might be a property of the meiotic program. Here, we present direct evidence that Rec114, an evolutionarily conserved essential component of the meiotic DSB-machinery, interacts with DSB hotspot DNA, and that Tel1 and Mec1, the budding yeast ATM and ATR, respectively, down-regulate Rec114 upon meiotic DSB formation through phosphorylation. Mimicking constitutive phosphorylation reduces the interaction between Rec114 and DSB hotspot DNA, resulting in a reduction and/or delay in DSB formation. Conversely, a non-phosphorylatable rec114 allele confers a genome-wide increase in both DSB levels and in the interaction between Rec114 and the DSB hotspot DNA. These observations strongly suggest that Tel1 and/or Mec1 phosphorylation of Rec114 following Spo11 catalysis down-regulates DSB formation by limiting the interaction between Rec114 and DSB hotspots. We also present evidence that Ndt80, a meiosis specific transcription factor, contributes to Rec114 degradation, consistent with its requirement for complete cessation of DSB formation. Loss of Rec114 foci from chromatin is associated with homolog synapsis but independent of Ndt80 or Tel1/Mec1 phosphorylation. Taken together, we present evidence for three independent ways of regulating Rec114 activity, which likely contribute to meiotic DSBs-homeostasis in maintaining genetically determined levels of breaks. PMID:23825959

  19. Disturbance of DKK1 level is partly involved in survival of lung cancer cells via regulation of ROMO1 and γ-radiation sensitivity

    International Nuclear Information System (INIS)

    Kim, In Gyu; Kim, Seo Yoen; Kim, Hyun A; Kim, Jeong Yul; Lee, Jae Ha; Choi, Soo Im; Han, Jeong Ran; Kim, Kug Chan; Cho, Eun Wie

    2014-01-01

    Highlights: •DKK1 was expressed differently among non-small-cell lung cancer cell lines. •DKK1 negatively regulated ROMO1 gene expression. •Disturbance of DKK1 level induced the imbalance of cellular ROS. •DKK1/ROMO1-induced ROS imbalance is involved in cell survival in NSCLC. -- Abstract: Dickkopf1 (DKK1), a secreted protein involved in embryonic development, is a potent inhibitor of the Wnt signaling pathway and has been postulated to be a tumor suppressor or tumor promoter depending on the tumor type. In this study, we showed that DKK1 was expressed differently among non-small-cell lung cancer cell lines. The DKK1 expression level was much higher in A549 cells than in H460 cells. We revealed that blockage of DKK1 expression by silencing RNA in A549 cells caused up-regulation of intracellular reactive oxygen species (ROS) modulator (ROMO1) protein, followed by partial cell death, cell growth inhibition, and loss of epithelial–mesenchymal transition property caused by ROS, and it also increased γ-radiation sensitivity. DKK1 overexpression in H460 significantly inhibited cell survival with the decrease of ROMO1 level, which induced the decrease of cellular ROS. Thereafter, exogenous N-acetylcysteine, an antioxidant, or hydrogen peroxide, a pro-oxidant, partially rescued cells from death and growth inhibition. In each cell line, both overexpression and blockage of DKK1 not only elevated p-RB activation, which led to cell growth arrest, but also inactivated AKT/NF-kB, which increased radiation sensitivity and inhibited cell growth. This study is the first to demonstrate that strict modulation of DKK1 expression in different cell types partially maintains cell survival via tight regulation of the ROS-producing ROMO1 and radiation resistance

  20. Elevated IGFBP3 levels in diabetic tears: a negative regulator of IGF-1 signaling in the corneal epithelium.

    Science.gov (United States)

    Wu, Yu-Chieh; Buckner, Benjamin R; Zhu, Meifang; Cavanagh, H Dwight; Robertson, Danielle M

    2012-04-01

    To determine the ratio of IGFBP3:IGF-1 in normal and diabetic human tears, and in telomerase-immortalized human corneal epithelial cells (hTCEpi) cultured under elevated glucose conditions and to correlate these changes with total and phosphorylated levels of IGF-1R. Tear samples were collected noninvasively from diabetic subjects and non-diabetic controls; corneal sensitivity was assessed using a Cochet-Bonnet Aesthesiometer. Conditioned media were collected following culture of hTCEpi cells in normal (5 mM) and elevated (25 mM) glucose conditions; mannitol was used as an osmotic control. IGFBP3, IGF-1, and phosphorylated IGF-1R levels were assessed by ELISA. IGFBP3 and IGF-1R mRNA were assessed by real-time polymerase chain reaction (PCR). Total and phosphorylated IGF-1R expression in whole cell lysates was assessed by western blot. There was a 2.8-fold increase in IGFBP3 in diabetic tears compared to non-diabetic controls (P=0.006); IGF-1 levels were not significantly altered. No difference in corneal sensitivity was detected between groups. The concentration of IGFBP3 in tears was independent of IGF-1. Consistent with human tear measurements in vivo, IGFBP3 secretion was increased 2.2 fold (Ptears compared to normal controls blocked phosphorylation of the IGF-1R by IGF-1 (Ptears may attenuate IGF-1R signaling in the diabetic cornea. A long-term increase in IGFBP3 may contribute to epithelial compromise and the pathogenesis of ocular surface complications reported in diabetes. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Strigolactone Levels in Dicot Roots Are Determined by an Ancestral Symbiosis-Regulated Clade of the PHYTOENE SYNTHASE Gene Family

    Directory of Open Access Journals (Sweden)

    Ron Stauder

    2018-03-01

    Full Text Available Strigolactones (SLs are apocarotenoid phytohormones synthesized from carotenoid precursors. They are produced most abundantly in roots for exudation into the rhizosphere to cope with mineral nutrient starvation through support of root symbionts. Abscisic acid (ABA is another apocarotenoid phytohormone synthesized in roots, which is involved in responses to abiotic stress. Typically low carotenoid levels in roots raise the issue of precursor supply for the biosynthesis of these two apocarotenoids in this organ. Increased ABA levels upon abiotic stress in Poaceae roots are known to be supported by a particular isoform of phytoene synthase (PSY, catalyzing the rate-limiting step in carotenogenesis. Here we report on novel PSY3 isogenes from Medicago truncatula (MtPSY3 and Solanum lycopersicum (SlPSY3 strongly expressed exclusively upon root interaction with symbiotic arbuscular mycorrhizal (AM fungi and moderately in response to phosphate starvation. They belong to a widespread clade of conserved PSYs restricted to dicots (dPSY3 distinct from the Poaceae-PSY3s involved in ABA formation. An ancient origin of dPSY3s and a potential co-evolution with the AM symbiosis is discussed in the context of PSY evolution. Knockdown of MtPSY3 in hairy roots of M. truncatula strongly reduced SL and AM-induced C13 α-ionol/C14 mycorradicin apocarotenoids. Inhibition of the reaction subsequent to phytoene synthesis revealed strongly elevated levels of phytoene indicating induced flux through the carotenoid pathway in roots upon mycorrhization. dPSY3 isogenes are coregulated with upstream isogenes and downstream carotenoid cleavage steps toward SLs (D27, CCD7, CCD8 suggesting a combined carotenoid/apocarotenoid pathway, which provides “just in time”-delivery of precursors for apocarotenoid formation.

  2. Alterations in glutathione levels and apoptotic regulators are associated with acquisition of arsenic trioxide resistance in multiple myeloma.

    Directory of Open Access Journals (Sweden)

    Shannon M Matulis

    Full Text Available Arsenic trioxide (ATO has been tested in relapsed/refractory multiple myeloma with limited success. In order to better understand drug mechanism and resistance pathways in myeloma we generated an ATO-resistant cell line, 8226/S-ATOR05, with an IC50 that is 2-3-fold higher than control cell lines and significantly higher than clinically achievable concentrations. Interestingly we found two parallel pathways governing resistance to ATO in 8226/S-ATOR05, and the relevance of these pathways appears to be linked to the concentration of ATO used. We found changes in the expression of Bcl-2 family proteins Bfl-1 and Noxa as well as an increase in cellular glutathione (GSH levels. At low, clinically achievable concentrations, resistance was primarily associated with an increase in expression of the anti-apoptotic protein Bfl-1 and a decrease in expression of the pro-apoptotic protein Noxa. However, as the concentration of ATO increased, elevated levels of intracellular GSH in 8226/S-ATOR05 became the primary mechanism of ATO resistance. Removal of arsenic selection resulted in a loss of the resistance phenotype, with cells becoming sensitive to high concentrations of ATO within 7 days following drug removal, indicating changes associated with high level resistance (elevated GSH are dependent upon the presence of arsenic. Conversely, not until 50 days without arsenic did cells once again become sensitive to clinically relevant doses of ATO, coinciding with a decrease in the expression of Bfl-1. In addition we found cross-resistance to melphalan and doxorubicin in 8226/S-ATOR05, suggesting ATO-resistance pathways may also be involved in resistance to other chemotherapeutic agents used in the treatment of multiple myeloma.

  3. Different roles of prepubertal and postpubertal germ cells and Sertoli cells in the regulation of serum inhibin B levels

    DEFF Research Database (Denmark)

    Andersson, A M; Müller, J; Skakkebaek, N E

    1998-01-01

    testis, intense immunostaining for the betaB-subunit was evident in germ cells from the pachytene spermatocyte to early spermatid stages and to a lesser degree in Leydig cells, but not in Sertoli cells or other stages of germ cells. Thus, surprisingly, in adult men the two subunits constituting inhibin B......-subunit. The correlation in adult men between serum inhibin B levels and spermatogenesis may be due to the fact that inhibin B in adult men is possibly a joint product of Sertoli cells and germ cells, including the stages from pachytene spermatocytes to early spermatids....

  4. Effects of RoHs and REACH regulations on firm-level production and export, and the role of global value chains : the cases of Malaysia and Vietnam

    OpenAIRE

    Otsuki, Tsunehiro; Honda, Keiichiro; Michida, Etsuyo; Nabeshima, Kaoru; Ueki, Yasushi

    2015-01-01

    This paper uses firm-level data to examine the impact of foreign chemical safety regulations such as RoHS and REACH on the production costs and export performance of firms in Malaysia and Vietnam. This paper also investigates the role of global value chains in enhancing the likelihood that a firm complies with RoHS and REACH. We find that in addition to the initial setup costs for compliance, EU RoHS (REACH) implementation imposes on firms additional variable production costs by requiring add...

  5. Role of geochemical factors in the assessment and regulation of geologic disposal of high-level radioactive waste

    International Nuclear Information System (INIS)

    O'Kelley, G.D.; Meyer, R.E.

    1984-03-01

    It is generally agreed that in a deep repository for high-level radioactive waste, the agent most likely to mobilize radionuclides and disperse them into the accessible environment is groundwater. Analyses of the performance of a high-level waste repository will require a detailed study of the chemical factors involved in the interaction of water-mobilized nuclides with the host rock. These chemical factors include sorption phenomena, redox processes, the roles of hydrolysis and complexation in the determination of speciation, solubility, and the formation of polymeric and colloidal forms of the nuclides. A discussion and review of these factors is given along with their pertinence to the migration of the nuclides and the development of computer codes for the prediction of this migration. Of particular interest are the formation of negatively charged species of the nuclides, which tend to exhibit very low adsorption, and the formation of insoluble products through redox processes. Knowledge of the different chemical factors must be used to postulate geochemical scenarios for the release of nuclides. Much of the chemistry of the nuclides is very sensitive to pH and redox conditions and, in general, increase of acidity and oxidizing power of the groundwater could have serious consequences with respect to mobilization of the nuclides. 33 references

  6. Positive and negative regulation of cell proliferation by E2F-1: influence of protein level and human papillomavirus oncoproteins

    DEFF Research Database (Denmark)

    Melillo, R M; Helin, K; Lowy, D R

    1994-01-01

    E2F-1 is a member of a family of transcription factors implicated in the activation of genes required for the progression through the S phase of the cell cycle. We have examined the biological activities of E2F-1 with short-term colony-forming assays and long-term immortalization assays. High...... to immortalize NHFKs, or by a transdominant p53 mutant. High levels of E2F-1 also inhibited growth of primary and established fibroblasts. The growth-inhibitory activity required the DNA binding function of E2F-1 but not its transactivation or pRB binding activities. A positive role for lower levels of E2F-1...... in NHFK immortalization was established by examining the ability of E2F-1 to complement HPV16 E7 mutants that were unable to cooperate with HPV16 E6 to immortalize NHFKs. Although E2F-1 was unable by itself to cooperate with E6, it did, in conjunction with E6, complement a p24GLY mutant of E7...

  7. Phosphatase Rtr1 Regulates Global Levels of Serine 5 RNA Polymerase II C-Terminal Domain Phosphorylation and Cotranscriptional Histone Methylation.

    Science.gov (United States)

    Hunter, Gerald O; Fox, Melanie J; Smith-Kinnaman, Whitney R; Gogol, Madelaine; Fleharty, Brian; Mosley, Amber L

    2016-09-01

    In eukaryotes, the C-terminal domain (CTD) of Rpb1 contains a heptapeptide repeat sequence of (Y1S2P3T4S5P6S7)n that undergoes reversible phosphorylation through the opposing action of kinases and phosphatases. Rtr1 is a conserved protein that colocalizes with RNA polymerase II (RNAPII) and has been shown to be important for the transition from elongation to termination during transcription by removing RNAPII CTD serine 5 phosphorylation (Ser5-P) at a selection of target genes. In this study, we show that Rtr1 is a global regulator of the CTD code with deletion of RTR1 causing genome-wide changes in Ser5-P CTD phosphorylation and cotranscriptional histone H3 lysine 36 trimethylation (H3K36me3). Using chromatin immunoprecipitation and high-resolution microarrays, we show that RTR1 deletion results in global changes in RNAPII Ser5-P levels on genes with different lengths and transcription rates consistent with its role as a CTD phosphatase. Although Ser5-P levels increase, the overall occupancy of RNAPII either decreases or stays the same in the absence of RTR1 Additionally, the loss of Rtr1 in vivo leads to increases in H3K36me3 levels genome-wide, while total histone H3 levels remain relatively constant within coding regions. Overall, these findings suggest that Rtr1 regulates H3K36me3 levels through changes in the number of binding sites for the histone methyltransferase Set2, thereby influencing both the CTD and histone codes. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  8. Ensuring fair levels of executive directors’ remuneration: Regulation and use of principles against the use of detailed legal rules in determining the most effective approach for setting executive pay levels. A discussion

    Directory of Open Access Journals (Sweden)

    Ewgeni Hersonski

    2012-10-01

    Full Text Available The purpose of this paper is to present arguments concerning the fair levels of executive directors’ remuneration. It is argued that principles are a better way to achieve this goal. However, we also find arguments in support of detailed legal rules when dealing with this matter. Since both methods have their pros and cons the paper delivers a balanced discussion and also outlines how the executive pay is currently regulated in the UK, the United States as well as on the global scale.

  9. Market, Regulation, Market, Regulation

    DEFF Research Database (Denmark)

    Frankel, Christian; Galland, Jean-Pierre

    2015-01-01

    barriers to trade in Europe, realized the free movement of products by organizing progressively several orders of markets and regulation. Based on historical and institutional documents, on technical publications, and on interviews, this article relates how the European Commission and the Member States had......This paper focuses on the European Regulatory system which was settled both for opening the Single Market for products and ensuring the consumers' safety. It claims that the New Approach and Standardization, and the Global Approach to conformity assessment, which suppressed the last technical...... alternatively recourse to markets and to regulations, at the three main levels of the New Approach Directives implementation. The article focuses also more specifically on the Medical Devices sector, not only because this New Approach sector has long been controversial in Europe, and has recently been concerned...

  10. Involvement of activated leukocytes in the regulation of plasma levels of acute phase proteins in microgravity simulation experiments

    Science.gov (United States)

    Larina, Olga; Bekker, Anna; Turin-Kuzmin, Alexey

    2016-07-01

    Earth-based studies of microgravity effects showed the induction of the mechanisms of acute phase reaction (APR). APR comprises the transition of stress-sensitive protein kinases of macrophages and other responsive cells into the active state and the phosphorylation of transcription factors which in turn stimulate the production of acute-phase reaction cytokines. Leukocyte activation is accompanied by the acceleration of the formation of oxygen radicals which can serve a functional indice of leukocyte cell state. The series of events at acute phase response result in selective changes in the synthesis of a number of secretory blood proteins (acute phase proteins, APPs) in liver cells thus contributing the recovery of homeostasis state in the organism. Earlier experiment with head-down tilt showed the increase in plasma concentrations of two cytokine mediators of acute phase response, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) being the outcome of the activation of producer cells, foremost, leukocytes. In experiment with 4-day dry immersion chemiluminescent (ChL) reply of the whole blood samples to a test stimulus were studied along with the measurements of plasma levels of APPs, namely, alpha1-antitrypsin (alpha1-AT), alpha1-acid glycoprotein (alpha1-AGP), alpha2-macroglobulin (alpha2-M), ceruloplasmin (Cer), haptoglobin (Hp), C3-complement component (C3), C-reactive protein (CRP). Eight individuals aged 21.2 ± 3.2 years were the test subjects in the investigation. Protein studies showed a noticeable increase in the mean plasma levels of all APPs measured in experiment thus producing the evidence of the activation of acute phase response mechanisms while individual patterns revealed variability during the immersion period. The overall trends were similar to these in the previous immersion series. The augment in the strength of signal in stimulated light emission tests was higher after 1- and 2-day of immersion exposure than before the

  11. The Wheat NAC Transcription Factor TaNAC2L Is Regulated at the Transcriptional and Post-Translational Levels and Promotes Heat Stress Tolerance in Transgenic Arabidopsis.

    Science.gov (United States)

    Guo, Weiwei; Zhang, Jinxia; Zhang, Ning; Xin, Mingming; Peng, Huiru; Hu, Zhaorong; Ni, Zhongfu; Du, Jinkun

    2015-01-01

    Heat stress poses a serious threat to global crop production. In efforts that aim to mitigate the adverse effects of heat stress on crops, a variety of genetic tools are being used to develop plants with improved thermotolerance. The characterization of important regulators of heat stress tolerance provides essential information for this aim. In this study, we examine the wheat (Triticum aestivum) NAC transcription factor gene TaNAC2L. High temperature induced TaNAC2L expression in wheat and overexpression of TaNAC2L in Arabidopsis thaliana enhanced acquired heat tolerance without causing obvious alterations in phenotype compared with wild type under normal conditions. TaNAC2L overexpression also activated the expression of heat-related genes in the transgenic Arabidopsis plants, suggesting that TaNAC2L may improve heat tolerance by regulating the expression of stress-responsive genes. Notably, TaNAC2L is also regulated at the post-translational level and might be degraded via a proteasome-mediated pathway. Thus, this wheat transcription factor may have potential uses in enhancing thermotolerance in crops.

  12. The Wheat NAC Transcription Factor TaNAC2L Is Regulated at the Transcriptional and Post-Translational Levels and Promotes Heat Stress Tolerance in Transgenic Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Weiwei Guo

    Full Text Available Heat stress poses a serious threat to global crop production. In efforts that aim to mitigate the adverse effects of heat stress on crops, a variety of genetic tools are being used to develop plants with improved thermotolerance. The characterization of important regulators of heat stress tolerance provides essential information for this aim. In this study, we examine the wheat (Triticum aestivum NAC transcription factor gene TaNAC2L. High temperature induced TaNAC2L expression in wheat and overexpression of TaNAC2L in Arabidopsis thaliana enhanced acquired heat tolerance without causing obvious alterations in phenotype compared with wild type under normal conditions. TaNAC2L overexpression also activated the expression of heat-related genes in the transgenic Arabidopsis plants, suggesting that TaNAC2L may improve heat tolerance by regulating the expression of stress-responsive genes. Notably, TaNAC2L is also regulated at the post-translational level and might be degraded via a proteasome-mediated pathway. Thus, this wheat transcription factor may have potential uses in enhancing thermotolerance in crops.

  13. Systems Level Analysis of Histone H3 Post-translational Modifications (PTMs) Reveals Features of PTM Crosstalk in Chromatin Regulation

    DEFF Research Database (Denmark)

    Schwämmle, Veit; Sidoli, Simone; Ruminowicz, Chrystian

    2016-01-01

    molecules contain multiple coexisting PTMs, some of which exhibit crosstalk, i.e. coordinated or mutually exclusive activities. Here, we present an integrated experimental and computational systems level molecular characterization of histone PTMs and PTM crosstalk. Using wild type and engineered mouse....... We characterized combinatorial PTM features across the four mESC lines and then applied statistical data analysis to predict crosstalk between histone H3 PTMs. We detected an overrepresentation of positive crosstalk (codependent marks) between adjacent mono-methylated and acetylated marks......, and negative crosstalk (mutually exclusive marks) among most of the seven characterized di- and tri-methylated lysine residues in the H3 tails. We report novel features of PTM interplay involving hitherto poorly characterized arginine methylation and lysine methylation sites, including H3R2me, H3R8me and H3K37...

  14. Regulation of c-myc and c-fos mRNA levels by polyomavirus: distinct roles for the capsid protein VP1 and the viral early proteins

    International Nuclear Information System (INIS)

    Zullo, J.; Stiles, C.D.; Garcea, R.L.

    1987-01-01

    The levels of c-myc, c-fos, and JE mRNAs accumulate in a biphasic pattern following infection of quiescent BALB/c 3T3 mouse cells with polyomavirus. Maximal levels of c-myc and c-fos mRNAs were seen within 1 hr and were nearly undetectable at 6 hr after infection. At 12 hr after infection mRNA levels were again maximal and remained elevated thereafter. Empty virions (capsids) and recombinant VP 1 protein, purified from Escherichia coli, induced the early but not the late phase of mRNA accumulation. Virions, capsids, and recombinant VP 1 protein stimulated [ 3 H]thymidine nuclear labeling and c-myc mRNA accumulation in a dose-responsive manner paralleling their affinity for the cell receptor for polyoma. The second phase of mRNA accumulation is regulated by the viral early gene products, as shown by polyomavirus early gene mutants and by a transfected cell line (336a) expressing middle tumor antigen upon glucocorticoid addition. These results suggest that polyomavirus interacts with the cell membrane at the onset of infection to increase the levels of mRNA for the cellular genes associated with cell competence for DNA replication, and subsequently these levels are maintained by the action of the early viral proteins

  15. Molecular basis for the regulation of hypoxia-inducible factor-1α levels by 2-deoxy-D-ribose.

    Science.gov (United States)

    Ikeda, Ryuji; Tabata, Sho; Tajitsu, Yusuke; Nishizawa, Yukihiko; Minami, Kentaro; Furukawa, Tatsuhiko; Yamamoto, Masatatsu; Shinsato, Yoshinari; Akiyama, Shin-Ichi; Yamada, Katsushi; Takeda, Yasuo

    2013-09-01

    The angiogenic factor, platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP), stimulates the chemotaxis of endothelial cells and confers resistance to apoptosis induced by hypoxia. 2-Deoxy-D-ribose, a degradation product of thymidine generated by TP enzymatic activity, inhibits the upregulation of hypoxia-inducible factor (HIF) 1α, BNIP3 and caspase-3 induced by hypoxia. In the present study, we investigated the molecular basis for the suppressive effect of 2-deoxy-D-ribose on the upregulation of HIF-1α. 2-Deoxy-D-ribose enhanced the interaction of HIF-1α and the von Hippel-Lindau (VHL) protein under hypoxic conditions. It did not affect the expression of HIF-1α, prolyl hydroxylase (PHD)1/2/3 and VHL mRNA under normoxic or hypoxic conditions, but enhanced the interaction of HIF-1α and PHD2 under hypoxic conditions. 2-Deoxy-D-ribose also increased the amount of hydroxy-HIF-1α in the presence of the proteasome inhibitor MG-132. The expression levels of TP are elevated in many types of malignant solid tumors and, thus, 2-deoxy-D-ribose generated by TP in these tumors may play an important role in tumor progression by preventing hypoxia-induced apoptosis.

  16. Iron-dependent regulation of hepcidin in Hjv-/- mice: evidence that hemojuvelin is dispensable for sensing body iron levels.

    Directory of Open Access Journals (Sweden)

    Konstantinos Gkouvatsos

    Full Text Available Hemojuvelin (Hjv is a bone morphogenetic protein (BMP co-receptor involved in the control of systemic iron homeostasis. Functional inactivation of Hjv leads to severe iron overload in humans and mice due to marked suppression of the iron-regulatory hormone hepcidin. To investigate the role of Hjv in body iron sensing, Hjv-/- mice and isogenic wild type controls were placed on a moderately low, a standard or a high iron diet for four weeks. Hjv-/- mice developed systemic iron overload under all regimens. Transferrin (Tf was highly saturated regardless of the dietary iron content, while liver iron deposition was proportional to it. Hepcidin mRNA expression responded to fluctuations in dietary iron intake, despite the absence of Hjv. Nevertheless, iron-dependent upregulation of hepcidin was more than an order of magnitude lower compared to that seen in wild type controls. Likewise, iron signaling via the BMP/Smad pathway was preserved but substantially attenuated. These findings suggest that Hjv is not required for sensing of body iron levels and merely functions as an enhancer for iron signaling to hepcidin.

  17. What is the contribution of two genetic variants regulating VEGF levels to type 2 diabetes risk and to microvascular complications?

    DEFF Research Database (Denmark)

    Bonnefond, Amélie; Saulnier, Pierre-Jean; Stathopoulou, Maria G

    2013-01-01

    Vascular endothelial growth factor (VEGF) is a key chemokine involved in tissue growth and organ repair processes, particularly angiogenesis. Elevated circulating VEGF levels are believed to play a role in type 2 diabetes (T2D) microvascular complications, especially diabetic retinopathy. Recently...... for diabetic nephropathy (N(cases)¿=¿1,242-N(controls)¿=¿860) and the other for diabetic retinopathy (N(cases)¿=¿1,336-N(controls)¿=¿1,231). The effects of each SNP on quantitative traits were analyzed in a French general population-based cohort (N¿=¿4,760) and two French T2D studies (N¿=¿3,480). SNP...... on diabetic microvascular complications or the variation in related traits in T2D patients.In spite of their impact on the variance in circulating VEGF, we did not find any association between SNPs rs6921438 and rs10738760, and the risk of T2D, diabetic nephropathy or retinopathy. The link between VEGF and T2...

  18. A history of trade routes and water-level regulation on waterways in Voyageurs National Park, Minnesota, USA

    Science.gov (United States)

    Christensen, Victoria G.; LaBounty, Andrew E.

    2018-01-01

    Unlike most national parks, main access to Voyageurs National Park is by boat. This remote system of interconnected waterways along the USA-Canada border was an important transportation route for thousands of years of American Indian occupation, leading up to and including the trade route of the voyageurs, or French-Canadian fur traders from around 1680 to 1870. The Ojibwe people collaborated with the voyageurs and the two cultures developed a trade network that continued to rely on these waterways. By the mid-1800s, European fashion changed, and the fur trade dwindled while the Ojibwe remained tied to the land and waters. The complexity of the waterways increased with the installation of dams on two of the natural lakes in the early 1900s. Modern water levels have affected—and in some cases destabilized—vulnerable landforms within the past century. The knowledge of these effects can be used by resource managers to weigh the consequences of hydrologic manipulation in Voyageurs National Park.

  19. Larval feeding duration affects ecdysteroid levels and nutritional reserves regulating pupal commitment in the yellow fever mosquito Aedes aegypti (Diptera: Culicidae).

    Science.gov (United States)

    Telang, Aparna; Frame, Laura; Brown, Mark R

    2007-03-01

    What little is known about the endocrine regulation of mosquito development suggests that models based on Lepidoptera and Drosophila may not apply. We report on basic parameters of larval development and the commitment to metamorphosis in the yellow fever mosquito Aedes aegypti that are affected by varying the length of feeding time for last instar larvae. A critical mass for pupal commitment was achieved after 24 h of feeding by last instars, also the age at which tissue production and hemolymph titers of ecdysteroids are increasing. A greater proportion of last instars successfully pupated and eclosed as adults as the length of their feeding time increased. Less than 24 h of feeding time resulted in last instars that were developmentally arrested; these larvae tolerated starvation conditions for up to 2 weeks and retained the capacity to pupate if re-fed. Starvation tolerance may be a common trait among container-inhabiting species, and this period is an important factor to be considered for vectorial capacity and control measures. To distinguish cues for metamorphosis related to a larva's nutritional status versus its age, newly molted last instars were fed for different periods of time but sampled at the same age; ecdysteroid levels, body mass and nutrient reserves were then measured for each group. Our data suggest that metamorphic capacity is dependent on a larva's nutritional condition and not just the age at which ecdysteroid titers increase. Last instars that have fed for a particular length of time may initiate their metamorphic molt when both threshold levels of nutrient reserves and ecdysteroid titer have been met. Future studies will lead to a conceptual model specific for the nutritional and hormonal regulation of mosquito post-embryonic development. This model should facilitate the exploitation of current and novel insect growth regulators that are among favored strategies for vector population suppression.

  20. Dlk1/FA1 Is a Novel Endocrine Regulator of Bone and Fat Mass and Its Serum Level Is Modulated By Growth Hormone

    DEFF Research Database (Denmark)

    Abdallah, B.M.; Ding, M.; Jensen, C.H.

    2007-01-01

    Fat and bone metabolism are two linked processes regulated by several hormonal factors. FA1 (fetal antigen 1) is the soluble form of dlk1 (delta like 1), which is a member of the Notch-Delta family. We have previously identified FA1 as a negative regulator of bone marrow mesenchymal stem cell...... differentiation. Here, we studied the effects of circulating FA1 on fat and bone mass in vivo by generating mice expressing high serum levels of FA1 (FA1-mice) using the hydrodynamic-based gene transfer procedure (HGTP). We found that increased serum FA1 levels led to a significant reduction in total body weight......, fat mass and bone mass in a dose-dependent manner. Reduced bone mass in FA1-mice was associated with the inhibition of mineral apposition rate and bone formation rates by 58% and 72% respectively. Since FA1 is co-localized with growth hormone (GH) in the pituitary gland, we explored the possible...

  1. Dlk1/FA1 is a novel endocrine regulator of bone and fat mass and its serum level is modulated by growth hormone

    DEFF Research Database (Denmark)

    Abdallah, Basem; Ding, Ming; Jensen, Charlotte H

    2007-01-01

    Fat and bone metabolism are two linked processes regulated by several hormonal factors. Fetal antigen 1 (FA1) is the soluble form of dlk1 (delta-like 1), which is a member of the Notch-Delta family. We previously identified FA1 as a negative regulator of bone marrow mesenchymal stem cell...... differentiation. Here, we studied the effects of circulating FA1 on fat and bone mass in vivo by generating mice expressing high serum levels of FA1 (FA1 mice) using the hydrodynamic-based gene transfer procedure. We found that increased serum FA1 levels led to a significant reduction in total body weight, fat...... mass, and bone mass in a dose-dependent manner. Reduced bone mass in FA1 mice was associated with the inhibition of mineral apposition rate and bone formation rates by 58 and 72%, respectively. Because FA1 is colocalized with GH in the pituitary gland, we explored the possible modulation of serum FA1...

  2. Adipocyte resistin mRNA levels are down-regulated by laparoscopic ovarian electrocautery in both obese and lean women with polycystic ovary syndrome.

    Science.gov (United States)

    Seow, Kok-Min; Juan, Chi-Chang; Ho, Low-Tone; Hsu, Yung-Pei; Lin, Yu-Hung; Huang, Lee-Wen; Hwang, Jiann-Loung

    2007-04-01

    The aim of this study was to investigate serum and adipocyte mRNA expression of resistin in lean and obese women with polycystic ovary syndrome (PCOS) before and 3 months after laparoscopic ovarian electrocauterization (LOE). Adipose tissue obtained from 12 women with PCOS (six obese and six lean, body mass index > 27 kg m(-1) as threshold point) before and after LOE was analysed. Gene expression of resistin was measured by semi-quantitative RT-PCR. Ten lean, age-matched healthy women served as controls. Both lean and obese women with PCOS had significantly higher fasting and 2 h insulin and homeostasis model insulin resistance index (HOMA(IR)) values and lower fasting glucose-to-insulin ratios (G(0)/I(0)) than did the controls. The serum levels of glucose and insulin and HOMA(IR) were significantly decreased, and the G(0)/I(0) ratio was significantly increased 3 months after LOE. No difference was found in serum resistin levels between controls and either obese or lean women with PCOS before LOE, nor between PCOS patients before and after LOE. However, resistin mRNA expression levels in both lean and obese women with PCOS before LOE were significantly higher than that in controls and were decreased significantly after LOE back to control levels. Local resistin activity may be actively involved in the pathogenesis of PCOS. LOE reduces insulin resistance and down-regulates resistin mRNA expression in lean and obese women with PCOS.

  3. Waterborne gemfibrozil challenges the hepatic antioxidant defense system and down-regulates peroxisome proliferator-activated receptor beta (PPARβ) mRNA levels in male goldfish (Carassius auratus)

    International Nuclear Information System (INIS)

    Mimeault, C.; Trudeau, V.L.; Moon, T.W.

    2006-01-01

    The lipid regulator gemfibrozil (GEM) is one of many human pharmaceuticals found in the aquatic environment. We previously demonstrated that GEM bioconcentrates in blood and reduces plasma testosterone levels in goldfish (Carassius auratus). In this study, we address the potential of an environmentally relevant waterborne concentration of GEM (1.5 μg/l) to induce oxidative stress in goldfish liver and whether this may be linked to GEM acting as a peroxisome proliferator (PP). We also investigate the autoregulation of the peroxisome proliferator-activated receptors (PPARs) as a potential index of exposure. The three PPAR subtypes (α, β, and γ) were amplified from goldfish liver cDNA. Goldfish exposed to a concentration higher (1500 μg/l) than environmentally relevant for 14 and 28 days significantly reduce hepatic PPARβ mRNA levels (p < 0.001). Levels of CYP1A1 mRNA were unchanged. GEM exposure significantly induced the antioxidant defense enzymes catalase (p < 0.001), glutathione peroxidase (p < 0.001) and glutathione-S-transferase (p = 0.006) but not acyl-CoA oxidase or glutathione reductase. As GEM exposure failed to increase levels of thiobarbituric reactive substances (TBARS), we conclude that a sub-chronic exposure to GEM upregulates the antioxidant defense status of the goldfish as an adaptive response to this human pharmaceutical

  4. Optogenetic Manipulation of Cyclic Di-GMP (c-di-GMP) Levels Reveals the Role of c-di-GMP in Regulating Aerotaxis Receptor Activity in Azospirillum brasilense.

    Science.gov (United States)

    O'Neal, Lindsey; Ryu, Min-Hyung; Gomelsky, Mark; Alexandre, Gladys

    2017-09-15

    Bacterial chemotaxis receptors provide the sensory inputs that inform the direction of navigation in changing environments. Recently, we described the bacterial second messenger cyclic di-GMP (c-di-GMP) as a novel regulator of a subclass of chemotaxis receptors. In Azospirillum brasilense , c-di-GMP binds to a chemotaxis receptor, Tlp1, and modulates its signaling function during aerotaxis. Here, we further characterize the role of c-di-GMP in aerotaxis using a novel dichromatic optogenetic system engineered for manipulating intracellular c-di-GMP levels in real time. This system comprises a red/near-infrared-light-regulated diguanylate cyclase and a blue-light-regulated c-di-GMP phosphodiesterase. It allows the generation of transient changes in intracellular c-di-GMP concentrations within seconds of irradiation with appropriate light, which is compatible with the time scale of chemotaxis signaling. We provide experimental evidence that binding of c-di-GMP to the Tlp1 receptor activates its signaling function during aerotaxis, which supports the role of transient changes in c-di-GMP levels as a means of adjusting the response of A. brasilense to oxygen gradients. We also show that intracellular c-di-GMP levels in A. brasilense change with carbon metabolism. Our data support a model whereby c-di-GMP functions to imprint chemotaxis receptors with a record of recent metabolic experience, to adjust their contribution to the signaling output, thus allowing the cells to continually fine-tune chemotaxis sensory perception to their metabolic state. IMPORTANCE Motile bacteria use chemotaxis to change swimming direction in response to changes in environmental conditions. Chemotaxis receptors sense environmental signals and relay sensory information to the chemotaxis machinery, which ultimately controls the swimming pattern of cells. In bacteria studied to date, differential methylation has been known as a mechanism to control the activity of chemotaxis receptors and

  5. Strigolactones in the Rhizobium-legume symbiosis: Stimulatory effect on bacterial surface motility and down-regulation of their levels in nodulated plants.

    Science.gov (United States)

    Peláez-Vico, María A; Bernabéu-Roda, Lydia; Kohlen, Wouter; Soto, María J; López-Ráez, Juan A

    2016-04-01

    Strigolactones (SLs) are multifunctional molecules acting as modulators of plant responses under nutrient deficient conditions. One of the roles of SLs is to promote beneficial association with arbuscular mycorrhizal (AM) fungi belowground under such stress conditions, mainly phosphorus shortage. Recently, a role of SLs in the Rhizobium-legume symbiosis has been also described. While SLs' function in AM symbiosis is well established, their role in the Rhizobium-legume interaction is still emerging. Recently, SLs have been suggested to stimulate surface motility of rhizobia, opening the possibility that they could also act as molecular cues. The possible effect of SLs in the motility in the alfalfa symbiont Sinorhizobium meliloti was investigated, showing that the synthetic SL analogue GR24 stimulates swarming motility in S. meliloti in a dose-dependent manner. On the other hand, it is known that SL production is regulated by nutrient deficient conditions and by AM symbiosis. Using the model alfalfa-S. meliloti, the impact of phosphorus and nitrogen deficiency, as well as of nodulation on SL production was also assessed. The results showed that phosphorus starvation promoted SL biosynthesis, which was abolished by nitrogen deficiency. In addition, a negative effect of nodulation on SL levels was detected, suggesting a conserved mechanism of SL regulation upon symbiosis establishment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Steady-state levels of G-protein beta-subunit expression are regulated by treatment of cells with bacterial toxins

    International Nuclear Information System (INIS)

    Watkins, D.C.; Northup, J.K.; Malbon, C.C.

    1987-01-01

    Cultures of 3T3-L1 cells were incubated with either 10 ng/ml cholera toxin or 10 ng/ml pertussis toxin from 4 days prior to the initiation of differentiation and throughout the subsequent incubation. Toxin concentrations were sufficient to completely prevent the labelling of alpha-subunits with [ 32 P]NAD + and pertussis toxin and to prevent by more than 90% the labelling with [ 32 P]NAD + and cholera toxin in membranes prepared from these cells. Neither toxin prevented the differentiation to the adipocyte phenotype. Neither toxin prevented the increases in the relative amounts of G-proteins which occur upon differentiation. Both toxins dramatically decreased the amount of beta-subunits. As measured by quantitative immunoblotting with antisera specific for both the 35 kDa and 36 kDa beta-subunits, levels of beta-subunit were decreased by more than 50% of steady-state level of control cells. Thus, bacterial toxins which modifies G-protein alpha-subunits are capable of modulating the levels of beta-subunits in vivo. The basis for the regulation of G-protein subunit expression by bacterial toxins is under study

  7. Levels of daily light doses under changed day-night cycles regulate temporal segregation of photosynthesis and N2 Fixation in the cyanobacterium Trichodesmium erythraeum IMS101.

    Science.gov (United States)

    Cai, Xiaoni; Gao, Kunshan

    2015-01-01

    While the diazotrophic cyanobacterium Trichodesmium is known to display inverse diurnal performances of photosynthesis and N2 fixation, such a phenomenon has not been well documented under different day-night (L-D) cycles and different levels of light dose exposed to the cells. Here, we show differences in growth, N2 fixation and photosynthetic carbon fixation as well as photochemical performances of Trichodesmium IMS101 grown under 12L:12D, 8L:16D and 16L:8D L-D cycles at 70 μmol photons m-2 s-1 PAR (LL) and 350 μmol photons m-2 s-1 PAR (HL). The specific growth rate was the highest under LL and the lowest under HL under 16L:8D, and it increased under LL and decreased under HL with increased levels of daytime light doses exposed under the different light regimes, respectively. N2 fixation and photosynthetic carbon fixation were affected differentially by changes in the day-night regimes, with the former increasing directly under LL with increased daytime light doses and decreased under HL over growth-saturating light levels. Temporal segregation of N2 fixation from photosynthetic carbon fixation was evidenced under all day-night regimes, showing a time lag between the peak in N2 fixation and dip in carbon fixation. Elongation of light period led to higher N2 fixation rate under LL than under HL, while shortening the light exposure to 8 h delayed the N2 fixation peaking time (at the end of light period) and extended it to night period. Photosynthetic carbon fixation rates and transfer of light photons were always higher under HL than LL, regardless of the day-night cycles. Conclusively, diel performance of N2 fixation possesses functional plasticity, which was regulated by levels of light energy supplies either via changing light levels or length of light exposure.

  8. Elevated level of human RPA interacting protein α (hRIPα) in cervical tumor cells is involved in cell proliferation through regulating RPA transport.

    Science.gov (United States)

    Namkoong, Sim; Lee, Eun-Ju; Jang, Ik-Soon; Park, Junsoo

    2012-10-19

    Replication protein A (RPA) is a eukaryotic single-stranded DNA binding protein that is essential for DNA replication, repair, and recombination, and human RPA interacting protein α (hRIPα) is the nuclear transporter of RPA. Here, we report the regulatory role of hRIPα protein in cell proliferation. Western blot analysis revealed that the level of hRIPα was frequently elevated in cervical tumors tissues and hRIPα knockdown by siRNA inhibited cellular proliferation through deregulation of the cell cycle. In addition, overexpression of hRIPα resulted in increased clonogenicity. These results indicate that hRIPα is involved in cell proliferation through regulation of RPA transport. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  9. Effects on DHEA levels by estrogen in rat astrocytes and CNS co-cultures via the regulation of CYP7B1-mediated metabolism

    DEFF Research Database (Denmark)

    Fex Svenningsen, Åsa; Wicher, Grzegorz; Lundqvist, Johan

    2011-01-01

    The neurosteroid dehydroepiandrosterone (DHEA) is formed locally in the CNS and has been implicated in several processes essential for CNS function, including control of neuronal survival. An important metabolic pathway for DHEA in the CNS involves the steroid hydroxylase CYP7B1. In previous...... studies, CYP7B1 was identified as a target for estrogen regulation in cells of kidney and liver. In the current study, we examined effects of estrogens on CYP7B1-mediated metabolism of DHEA in primary cultures of rat astrocytes and co-cultures of rat CNS cells. Astrocytes, which interact with neurons...... whereby estrogen can exert protective effects in the CNS may involve increase of the levels of DHEA by suppression of its metabolism....

  10. Sequences within the 5' untranslated region regulate the levels of a kinetoplast DNA topoisomerase mRNA during the cell cycle.

    Science.gov (United States)

    Pasion, S G; Hines, J C; Ou, X; Mahmood, R; Ray, D S

    1996-12-01

    Gene expression in trypanosomatids appears to be regulated largely at the posttranscriptional level and involves maturation of mRNA precursors by trans splicing of a 39-nucleotide miniexon sequence to the 5' end of the mRNA and cleavage and polyadenylation at the 3' end of the mRNA. To initiate the identification of sequences involved in the periodic expression of DNA replication genes in trypanosomatids, we have mapped splice acceptor sites in the 5' flanking region of the TOP2 gene, which encodes the kinetoplast DNA topoisomerase, and have carried out deletion analysis of this region on a plasmid-encoded TOP2 gene. Block deletions within the 5' untranslated region (UTR) identified two regions (-608 to -388 and -387 to -186) responsible for periodic accumulation of the mRNA. Deletion of one or the other of these sequences had no effect on periodic expression of the mRNA, while deletion of both regions resulted in constitutive expression of the mRNA throughout the cell cycle. Subcloning of these sequences into the 5' UTR of a construct lacking both regions of the TOP2 5' UTR has shown that an octamer consensus sequence present in the 5' UTR of the TOP2, RPA1, and DHFR-TS mRNAs is required for normal cycling of the TOP2 mRNA. Mutation of the consensus octamer sequence in the TOP2 5' UTR in a plasmid construct containing only a single consensus octamer and that shows normal cycling of the plasmid-encoded TOP2 mRNA resulted in substantial reduction of the cycling of the mRNA level. These results imply a negative regulation of TOP2 mRNA during the cell cycle by a mechanism involving redundant elements containing one or more copies of a conserved octamer sequence within the 5' UTR of TOP2 mRNA.

  11. IGF-1R Regulates the Extracellular Level of Active MMP-2, Pathological Neovascularization, and Functionality in Retinas of OIR Mouse Model.

    Science.gov (United States)

    Lorenc, Valeria E; Subirada Caldarone, Paula V; Paz, María C; Ferrer, Darío G; Luna, José D; Chiabrando, Gustavo A; Sánchez, María C

    2018-02-01

    In ischemic proliferative diseases such as retinopathies, persistent hypoxia leads to the release of numerous neovascular factors that participate in the formation of abnormal vessels and eventually cause blindness. The upregulation and activation of metalloproteinases (MMP-2 and MMP-9) represent a final common pathway in this process. Although many regulators of the neovascular process have been identified, the complete role of the insulin-like growth factor 1 (IGF-1) and its receptor (IGF-1R) appears to be significantly more complex. In this study, we used an oxygen-induced retinopathy (OIR) mouse model as well as an in vitro model of hypoxia to study the role of MMP-2 derived from Müller glial cells (MGCs) and its relation with the IGF-1/IGF-1R system. We demonstrated that MMP-2 protein expression increased in P17 OIR mice, which coincided with the active phase of the neovascular process. Also, glutamine synthetase (GS)-positive cells were also positive for MMP-2, whereas IGF-1R was expressed by GFAP-positive cells, indicating that both proteins were expressed in MGCs. In addition, in the OIR model a single intravitreal injection of the IGF-1R blocking antibody (αIR3) administered at P12 effectively prevented pathologic neovascularization, accelerated physiological revascularization, and improved retinal functionality at P17. Finally, in MGC supernatants, the blocking antibody abolished the IGF-1 effect on active MMP-2 under normoxic and hypoxic conditions without affecting the extracellular levels of pro-MMP-2. These results demonstrate, for the first time, that the IGF-1/IGF-1R system regulates active MMP-2 levels in MGCs, thus contributing to MEC remodeling during the retinal neovascular process.

  12. Monoamine oxidase B is elevated in Alzheimer disease neurons, is associated with γ-secretase and regulates neuronal amyloid β-peptide levels.

    Science.gov (United States)

    Schedin-Weiss, Sophia; Inoue, Mitsuhiro; Hromadkova, Lenka; Teranishi, Yasuhiro; Yamamoto, Natsuko Goto; Wiehager, Birgitta; Bogdanovic, Nenad; Winblad, Bengt; Sandebring-Matton, Anna; Frykman, Susanne; Tjernberg, Lars O

    2017-08-01

    MAO-B enhanced Aβ production. This study shows that MAO-B levels are increased not only in astrocytes but also in pyramidal neurons in AD brain. The study also suggests that MAO-B regulates Aβ production in neurons via γ-secretase and thereby provides a key to understanding the relationship between MAO-B and AD pathogenesis. Potentially, the γ-secretase/MAO-B association may be a target for reducing Aβ levels using protein-protein interaction breakers.

  13. Amelioration of ultraviolet-B-induced down-regulation of mRNA levels for chloroplast proteins, by high irradiance, is mediated by photosynthesis

    International Nuclear Information System (INIS)

    Mackerness, S.A. H.; Butt, P.J.; Jordan, B.R.; Thomas, B.

    1996-01-01

    The mechanism by which increasing photosynthetically active radiation (PAR) reduces the sensitivity of RNA transcripts to UV-B radiation was studied in pea (Pisum sativum L.). mRNA transcript levels for rbc S, rbc L, cab and psb A were measured over an 8 d experimental period in pea, plants supplemented with UV-B radiation under a range of conditions. Under low light (150 mu-mol m -2 s -1 ), UV-B resulted in a significant decline in the levels of transcripts for all four genes which was prevented by increasing the background irradiance to 350 mu-mol m -2 s -1 (high light) with white light from fluorescent lamps. Increasing CO 2 levels to give photosynthesis rates equivalent to the high light treatment partially protected rbc S and cab transcripts and fully protected rbc L transcripts but did not prevent visible injury. Increasing light with low pressure sodium lamps, which increase photosynthesis but are not effective for activation of the DNA repair enzyme, photolyase, gave results which were not significantly different from white fluorescent high light treatments. Protection by high light was lost in the presence of the photosynthesis inhibitors CCCP and DCMU. The UV-B induced increase in the expression of chalcone synthase (chs) genes was delayed by the treatments which increased photosynthesis rates and conferred protection. The results indicate that photosynthesis plays a key role in the amelioration of UV-B induced decline in mRNA levels for proteins. The minimal role of DNA repair by photolyase indicates that reduction in photosynthesis gene transcripts in response to UV-B represents a specific regulation rather than being a consequence of DNA damage. (author)

  14. Cross-Regulation between the phz1 and phz2 Operons Maintain a Balanced Level of Phenazine Biosynthesis in Pseudomonas aeruginosa PAO1.

    Directory of Open Access Journals (Sweden)

    Qinna Cui

    Full Text Available Gene duplication often provides selective advantages for the survival of microorganisms in adapting to varying environmental conditions. P. aeruginosa PAO1 possesses two seven-gene operons [phz1 (phzA1B1C1D1E1F1G1 and phz2 (phzA2B2C2D2E2F2G2] that are involved in the biosynthesis of phenazine-1-carboxylic acid and its derivatives. Although the two operons are highly homologous and their functions are well known, it is unclear how the two phz operons coordinate their expressions to maintain the phenazine biosynthesis. By constructing single and double deletion mutants of the two phz operons, we found that the phz1-deletion mutant produced the same or less amount of phenazine-1-carboxylic acid and pyocyanin in GA medium than the phz2-knockout mutant while the phz1-phz2 double knockout mutant did not produce any phenazines. By generating phzA1 and phzA2 translational and transcriptional fusions with a truncated lacZ reporter, we found that the expression of the phz1 operon increased significantly at the post-transcriptional level and did not alter at the transcriptional level in the absence of the phz2 operon. Surprisingly, the expression the phz2 operon increased significantly at the post-transcriptional level and only moderately at the transcriptional level in the absence of the phz1 operon. Our findings suggested that a complex cross-regulation existed between the phz1 and phz2 operons. By mediating the upregulation of one phz operon expression while the other was deleted, this crosstalk would maintain the homeostatic balance of phenazine biosynthesis in P. aeruginosa PAO1.

  15. Regulative environmental policy. Regulative Umweltpolitik

    Energy Technology Data Exchange (ETDEWEB)

    Goerlitz, A; Voigt, R [Universitaet der Bundeswehr Muenchen, Neubiberg (Germany, F.R.). Fakultaet fuer Sozialwissenschaften; eds.

    1991-01-01

    Regulative policy means those governmental attempts to steer the course of things which can fall back on a certain repertoire of instruments for actions in order to warrant the causal and temporal connection between the making available and the employment of means. The fact that environmental protection needs regulative policy is substantiated by the thesis that the market has failed; consequently only government can manage the public goods 'environment' in a suitable way, and it is a matter of fact that environmental protection at present is operated preferably via regulative policy. The problems of regulative enviromental policy are manifold. Its implementation often miscarries because of limited administrative resources on the one hand - making sufficient control impossible for instance -, and because of poor quality regulative instruments on the other hand. One way out would be to increase the efficiency of regulative policy by sophisticating judicial techniques. Other ways out point to the executing level and aim at improving implementation strategies or are concerned with post-regulative law. The latter refers to a new legal quality which demonstrates itself already in corporatistical crisis regulation or in induction programs such as pollution limits. A final way out favours deregulation strategies which includes the introduction of environmental levies or the allocation of environmental licences. An interdisciplinary discourse is to find out what would happen if these ways were taken. Pointers to solutions from varying scientific disciplines resulting from this discourse are to be found in this volume. (orig./HSCH).

  16. Risk Level Based Management System: a control banding model for occupational health and safety risk management in a highly regulated environment

    Energy Technology Data Exchange (ETDEWEB)

    Zalk, D; Kamerzell, R; Paik, S; Kapp, J; Harrington, D; Swuste, P

    2009-05-27

    The Risk Level Based Management System (RLBMS) is an occupational risk management (ORM) model that focuses occupational safety, hygeiene, and health (OSHH) resources on the highest risk procedures at work. This article demonstrates the model's simplicity through an implementation within a heavily regulated research institution. The model utilizes control banding strategies with a stratification of four risk levels (RLs) for many commonly performed maintenance and support activities, characterizing risk consistently for comparable tasks. RLBMS creates an auditable tracking of activities, maximizes OSHH professional field time, and standardizes documentation and control commensurate to a given task's RL. Validation of RLs and their exposure control effectiveness is collected in a traditional quantitative collection regime for regulatory auditing. However, qualitative risk assessment methods are also used within this validation process. Participatory approaches are used throughout the RLBMS process. Workers are involved in all phases of building, maintaining, and improving this model. This work participation also improves the implementation of established controls.

  17. Self-Regulated Assignment Attack Strategy: Evaluating the Effects of a Classroom-Level Intervention on Student Management of Curricular Activities in a Resource Context

    Science.gov (United States)

    Ness, Bryan M.; Sohlberg, McKay Moore

    2013-01-01

    The purpose of this study was to evaluate the impact of a classroom-based strategy instruction package grounded in self-regulated learning. The Self-Regulated Assignment Attack Strategy (SAAS) targeted self-regulation of assignment management and related academic-behavioral variables for 6th grade students in resource support classrooms. SAAS was…

  18. Centrobin-mediated Regulation of the Centrosomal Protein 4.1-associated Protein (CPAP) Level Limits Centriole Length during Elongation Stage*

    Science.gov (United States)

    Gudi, Radhika; Haycraft, Courtney J.; Bell, P. Darwin; Li, Zihai; Vasu, Chenthamarakshan

    2015-01-01

    Microtubule-based centrioles in the centrosome mediate accurate bipolar cell division, spindle orientation, and primary cilia formation. Cellular checkpoints ensure that the centrioles duplicate only once in every cell cycle and achieve precise dimensions, dysregulation of which results in genetic instability and neuro- and ciliopathies. The normal cellular level of centrosomal protein 4.1-associated protein (CPAP), achieved by its degradation at mitosis, is considered as one of the major mechanisms that limits centriole growth at a predetermined length. Here we show that CPAP levels and centriole elongation are regulated by centrobin. Exogenous expression of centrobin causes abnormal elongation of centrioles due to massive accumulation of CPAP in the cell. Conversely, CPAP was undetectable in centrobin-depleted cells, suggesting that it undergoes degradation in the absence of centrobin. Only the reintroduction of full-length centrobin, but not its mutant form that lacks the CPAP binding site, could restore cellular CPAP levels in centrobin-depleted cells, indicating that persistence of CPAP requires its interaction with centrobin. Interestingly, inhibition of the proteasome in centrobin-depleted cells restored the cellular and centriolar CPAP expression, suggesting its ubiquitination and proteasome-mediated degradation when centrobin is absent. Intriguingly, however, centrobin-overexpressing cells also showed proteasome-independent accumulation of ubiquitinated CPAP and abnormal, ubiquitin-positive, elongated centrioles. Overall, our results show that centrobin interacts with ubiquitinated CPAP and prevents its degradation for normal centriole elongation function. Therefore, it appears that loss of centrobin expression destabilizes CPAP and triggers its degradation to restrict the centriole length during biogenesis. PMID:25616662

  19. Nutrient-intake-level-dependent regulation of intestinal development in newborn intrauterine growth-restricted piglets via glucagon-like peptide-2.

    Science.gov (United States)

    Liu, J; Liu, Z; Gao, L; Chen, L; Zhang, H

    2016-10-01

    The objective of the present study was to investigate the intestinal development of newborn intrauterine growth-restricted (IUGR) piglets subjected to normal nutrient intake (NNI) or restricted nutrient intake (RNI). Newborn normal birth weight (NBW) and IUGR piglets were allotted to NNI or RNI levels for 4 weeks from day 8 postnatal. IUGR piglets receiving NNI had similar growth performance compared with that of NBW piglets. Small intestine length and villous height were greater in IUGR piglets fed the NNI than that of piglets fed the RNI. Lactase activity was increased in piglets fed the NNI compared with piglets fed the RNI. Absorptive function, represented by active glucose transport by the Ussing chamber method and messenger RNA (mRNA) expressions of two main intestinal glucose transporters, Na+-dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2), were greater in IUGR piglets fed the NNI compared with piglets fed the RNI regimen. The apoptotic process, characterized by caspase-3 activity (a sign of activated apoptotic cells) and mRNA expressions of p53 (pro-apoptotic), bcl-2-like protein 4 (Bax) (pro-apoptotic) and B-cell lymphoma-2 (Bcl-2) (anti-apoptotic), were improved in IUGR piglets fed the NNI regimen. To test the hypothesis that improvements in intestinal development of IUGR piglets fed NNI might be mediated through circulating glucagon-like peptide-2 (GLP-2), GLP-2 was injected subcutaneously to IUGR piglets fed the RNI from day 8 to day 15 postnatal. Although the intestinal development of IUGR piglets fed the RNI regimen was suppressed compared with those fed the NNI regimen, an exogenous injection of GLP-2 was able to bring intestinal development to similar levels as NNI-fed IUGR piglets. Collectively, our results demonstrate that IUGR neonates that have NNI levels could improve intestinal function via the regulation of GLP-2.

  20. The -271 G>A polymorphism of kinase insert domain-containing receptor gene regulates its transcription level in patients with non-small cell lung cancer

    International Nuclear Information System (INIS)

    An, She-Juan; Chen, Zhi-Hong; Lin, Qiu-Xiong; Su, Jian; Chen, Hua-Jun; Lin, Jia-Ying; Wu, Yi-Long

    2009-01-01

    Kinase insert domain-containing receptor (KDR) plays a critical role in the metastasis of cancer and is used as a molecular target in cancer therapy. We investigated the characteristics of the -271 G>A polymorphism of the KDR gene to gain information that may benefit the development of individualized therapies for patients with non-small cell lung cancer (NSCLC). The -271 G>A polymorphism of the KDR gene in 106 lung cancer patients and 203 healthy control individuals was analyzed by polymerase chain reaction (PCR) and DNA sequencing methods. Real-time quantitative PCR and immunohistochemical methods were used to evaluate KDR mRNA and protein expression levels, respectively, in frozen tumor specimens. The -271 G>A polymorphism was associated with the mRNA expression level of the KDR gene in tumor tissues (t = 2.178, P = 0.032, independent samples t-test). Compared with the AG/GG genotype, the AA genotype was associated with higher KDR mRNA expression in tumor tissues. We found no relationship between the genotype and the KDR protein expression level and no significant difference in the distribution of the KDR gene polymorphism genotypes between lung cancer patients and the control group (χ 2 = 1.269, P = 0.264, Fisher's exact test). This study is the first to show that the -271 G>A polymorphism of the KDR gene may be a functional polymorphism related to the regulation of gene transcription. These findings may have important implications for therapies targeting KDR in patients with NSCLC

  1. Alteration of cytochrome P450 1 regulation and HSP 70 level in brain of juvenile common carp (Cyprinus carpio) after chronic exposure to tributyltin.

    Science.gov (United States)

    Li, Zhi-Hua; Zhong, Li-Qiao; Wu, Yan-Hua; Mu, Wei-Na

    2016-02-01

    Tributyltin (TBT), a toxic contaminant in aquatic environments, has bio-accumulated in aquatic food webs throughout the world and can be found at toxic levels in some biota. However, the molecular mechanisms and effects of TBT are not fully understood. The aim of the present study was to investigate the effect of long-term exposure of TBT on cytochrome P450 (CYP450) 1 regulation and heat-shock proteins (HSPs) profiling in brain of freshwater teleost. The effects of long-term exposure to TBT on mRNA expression of cytochrome P450 (CYP450) 1 family genes and ethoxyresorufin O-deethylase (EROD) activity in the brain of common carp were evaluated, as well as HSP 70 level. Fish were exposed to sublethal concentrations of TBT (75 ng/L, 0.75 μg/L and 7.5 μg/L) for 15, 30, and 60 days. Based on the results, long-term exposure (more than 15 days) to TBT could lead to obvious physiological-biochemical responses (based on EROD activity, HSP 70 level and CYP450 1 family genes expression). The mRNA expression of CYP450 1 family genes (CYP1A, CYP1B, CYP1C1 and CYP1C2) suggested that CYP1A was to accommodate most EROD activity in fish, but other CYP450 forms also involved in this proceeding. Thus, the measured physiological responses in fish brain could provide useful information to better understand the mechanisms of TBT-induced bio-toxicity and could be used as potential biomarkers for monitoring the TBT pollution in the field.

  2. A Bi-Level Optimization Approach to Charging Load Regulation of Electric Vehicle Fast Charging Stations Based on a Battery Energy Storage System

    Directory of Open Access Journals (Sweden)

    Yan Bao

    2018-01-01

    Full Text Available Fast charging stations enable the high-powered rapid recharging of electric vehicles. However, these stations also face challenges due to power fluctuations, high peak loads, and low load factors, affecting the reliable and economic operation of charging stations and distribution networks. This paper introduces a battery energy storage system (BESS for charging load control, which is a more user-friendly approach and is more robust to perturbations. With the goals of peak-shaving, total electricity cost reduction, and minimization of variation in the state-of-charge (SOC range, a BESS-based bi-level optimization strategy for the charging load regulation of fast charging stations is proposed in this paper. At the first level, a day-ahead optimization strategy generates the optimal planned load curve and the deviation band to be used as a reference for ensuring multiple control objectives through linear programming, and even for avoiding control failure caused by insufficient BESS energy. Based on this day-ahead optimal plan, at a second level, real-time rolling optimization converts the control process to a multistage decision-making problem. The predictive control-based real-time rolling optimization strategy in the proposed model was used to achieve the above control objectives and maintain battery life. Finally, through a horizontal comparison of two control approaches in each case study, and a longitudinal comparison of the control robustness against different degrees of load disturbances in three cases, the results indicated that the proposed control strategy was able to significantly improve the charging load characteristics, even with large disturbances. Meanwhile, the proposed approach ensures the least amount of variation in the range of battery SOC and reduces the total electricity cost, which will be of a considerable benefit to station operators.

  3. Thyroid hormone receptor beta2 is strongly up-regulated at all levels of the hypothalamo-pituitary-thyroidal axis during late embryogenesis in chicken.

    Science.gov (United States)

    Grommen, Sylvia V H; Arckens, Lutgarde; Theuwissen, Tim; Darras, Veerle M; De Groef, Bert

    2008-03-01

    In this study, we tried to elucidate the changes in thyroid hormone (TH) receptor beta2 (TRbeta2) expression at the different levels of the hypothalamo-pituitary-thyroidal (HPT) axis during the last week of chicken embryonic development and hatching, a period characterized by an augmented activity of the HPT axis. We quantified TRbeta2 mRNA in retina, pineal gland, and the major control levels of the HPT axis - brain, pituitary, and thyroid gland - at day 18 of incubation, and found the most abundant mRNA content in retina and pituitary. Thyroidal TRbeta2 mRNA content increased dramatically between embryonic day 14 and 1 day post-hatch. In pituitary and hypothalamus, TRbeta2 mRNA expression rose gradually, in parallel with increases in plasma thyroxine concentrations. Using in situ hybridization, we have demonstrated the presence of TRbeta2 mRNA throughout the diencephalon and confirmed the elevation in TRbeta2 mRNA expression in the hypophyseal thyrotropes. In vitro incubation with THs caused a down-regulation of TRbeta2 mRNA levels in embryonic but not in post-hatch pituitaries. The observed expression patterns in pituitary and diencephalon may point to substantial changes in TRbeta2-mediated TH feedback active during the perinatal period. The strong rise in thyroidal TRbeta2 mRNA content could be indicative of an augmented modulation of thyroid development and/or function by THs toward and after hatching. Finally, THs proved to exert an age-dependent effect on pituitary TRbeta2 mRNA expression.

  4. Lamprey Prohibitin2 Arrest G2/M Phase Transition of HeLa Cells through Down-regulating Expression and Phosphorylation Level of Cell Cycle Proteins.

    Science.gov (United States)

    Shi, Ying; Guo, Sicheng; Wang, Ying; Liu, Xin; Li, Qingwei; Li, Tiesong

    2018-03-02

    Prohibitin 2(PHB2) is a member of the SFPH trans-membrane family proteins. It is a highly conserved and functionally diverse protein that plays an important role in preserving the structure and function of the mitochondria. In this study, the lamprey PHB2 gene was expressed in HeLa cells to investigate its effect on cell proliferation. The effect of Lm-PHB2 on the proliferation of HeLa cells was determined by treating the cells with pure Lm-PHB2 protein followed by MTT assay. Using the synchronization method with APC-BrdU and PI double staining revealed rLm-PHB2 treatment induced the decrease of both S phase and G0/G1 phase and then increase of G2/M phase. Similarly, cells transfected with pEGFP-N1-Lm-PHB2 also exhibited remarkable reduction in proliferation. Western blot and quantitative real-time PCR(qRT-PCR) assays suggested that Lm-PHB2 caused cell cycle arrest in HeLa cells through inhibition of CDC25C and CCNB1 expression. According to our western blot analysis, Lm-PHB2 was also found to reduce the expression level of Wee1 and PLK1 and the phosphorylation level of CCNB1, CDC25C and CDK1 in HeLa cells. Lamprey prohibitin 2 could arrest G2/M phase transition of HeLa cells through down-regulating expression and phosphorylation level of cell cycle proteins.

  5. Preliminary evidences of CCM operation and its down regulation in relation to increasing CO2 levels in natural phytoplankton assemblages from the coastal waters of Bay of Bengal

    Science.gov (United States)

    Biswas, Haimanti; Rahman Shaik, Aziz Ur; Bandyopadhyay, Debasmita

    2014-05-01

    Bay of Bengal (BoB), a low productive part of the North Indian Ocean, often possesses low CO2 levels in its surface water and diatoms dominate the phytoplankton communities. Virtually no studies are available from this area reporting how this diatom dominated phytoplankton community would respond any increase in dissolved CO2 levels either naturally or anthopogenically. In most of the marine phytoplankton, the inefficiency of the sole carbon fixing enzyme Rubisco necessitates the need of concentrating dissolved inorganic carbon (DIC) (mostly as HCO3) inside the cell in excess of the ambient water concentrations in order to maintain high rate of photosynthesis under low CO2 levels through an energy consuming carbon concentration mechanisms (CCMs). The ubiquitous enzyme carbonic anhydrase (CA) plays a vital role in CCMs by converting HCO3- to CO2 and usually utilizes the trace metal zinc (Zn) as a cofactor. However, it is evident in many marine phytoplankton species that with increasing external CO2 levels, CCMs can be down-regulated leading to energetic savings which can be reallocated to growth; although exceptions occur. Hence, in order to predict their responses to the projected changes, it is imperative to understand their carbon metabolism patterns. We have conducted a series of incubation experiments in microcosms with natural phytoplankton communities from the coastal waters of BoB under different CO2 levels. Our results revealed that the rate of net photosynthetic oxygen evolution and biomass build-up increased in response to increasing CO2 levels. The depletion in δ13CPOM values were more in the high CO2 treatments relative to the low CO2 treated cells (control), indicating that dissolved CO2 uptake was higher when CO2 levels were increased. When additional Zn was added to the low CO2 treated cells, net photosynthetic oxygen evolution rate was increased significantly than that of the untreated control. It is likely that upon the supply of Zn under low CO2

  6. MCG101-induced cancer anorexia-cachexia features altered expression of hypothalamic Nucb2 and Cartpt and increased plasma levels of cocaine- and amphetamine-regulated transcript peptides.

    Science.gov (United States)

    Burgos, Jonathan R; Iresjö, Britt-Marie; Smedh, Ulrika

    2016-04-01

    The aim of the present study was to explore central and peripheral host responses to an anorexia-cachexia producing tumor. We focused on neuroendocrine anorexigenic signals in the hypothalamus, brainstem, pituitary and from the tumor per se. Expression of mRNA for corticotropin-releasing hormone (CRH), cocaine- and amphetamine-regulated transcript (CART), nesfatin-1, thyrotropin (TSH) and the TSH receptor were explored. In addition, we examined changes in plasma TSH, CART peptides (CARTp) and serum amyloid P component (SAP). C57BL/6 mice were implanted with MCG101 tumors or sham-treated. A sham-implanted, pair‑fed (PF) group was included to delineate between primary tumor and secondary effects from reduced feeding. Food intake and body weight were measured daily. mRNA levels from microdissected mouse brain samples were assayed using qPCR, and plasma levels were determined using ELISA. MCG101 tumors expectedly induced anorexia and loss of body weight. Tumor-bearing (TB) mice exhibited an increase in nesfatin-1 mRNA as well as a decrease in CART mRNA in the paraventricular area (PVN). The CART mRNA response was secondary to reduced caloric intake whereas nesfatin-1 mRNA appeared to be tumor-specifically induced. In the pituitary, CART and TSH mRNA were upregulated in the TB and PF animals compared to the freely fed controls. Plasma levels for CARTp were significantly elevated in TB but not PF mice whereas levels of TSH were unaffected. The plasma CARTp response was correlated to the degree of inflammation represented by SAP. The increase in nesfatin-1 mRNA in the PVN highlights nesfatin-1 as a plausible candidate for causing tumor-induced anorexia. CART mRNA expression in the PVN is likely an adaptation to reduced caloric intake secondary to a cancer anorexia-cachexia syndrome (CACS)‑inducing tumor. The MCG101 tumor did not express CART mRNA, thus the elevation of plasma CARTp is host derived and likely driven by inflammation.

  7. Mechanisms that synergistically regulate η-secretase processing of APP and Aη-α protein levels: relevance to pathogenesis and treatment of Alzheimer's disease.

    Science.gov (United States)

    Ward, Joseph; Wang, Haizhi; Saunders, Aleister J; Tanzi, Rudolph E; Zhang, Can

    2017-02-01

    The pathophysiology of Alzheimer's disease (AD) is characterized by the formation of cerebral β-amyloid plaque from a small peptide amyloid-β (Aβ). Aβ is generated from the canonical amyloid-β precursor protein (APP) proteolysis pathway through β- and γ-secretases. Decreasing Aβ levels through targeting APP processing is a very promising direction in clinical trials for AD. A novel APP processing pathway was recently identified, in which η-secretase processing of APP occurs and results in the generation of the carboxy-terminal fragment-η (CTF-η or η-CTF) (Wang et al., 2015) and Aη-α peptide (Willem et al., 2015). η-Secretase processing of APP may be up-regulated by at least two mechanisms: either through inhibition of lysosomal-cathepsin degradation pathway (Wang et al., 2015) or through inhibition of BACE1 that competes with η-secretase cleavage of APP (Willem et al., 2015). A thorough characterization of η-processing of APP is critical for a better understanding of AD pathogenesis and insights into results of clinical trials of AD. Here we further investigated η-secretase processing of APP using well-characterized cell models of AD. We found that these two mechanisms act synergistically toward increasing η-secretase processing of APP and Aη-α levels. Furthermore, we evaluated the effects of several other known secretase modulators on η-processing of APP. The results of our study should advance the understanding of pathophysiology of AD, as well as enhance the knowledge in developing effective AD treatments or interventions related to η-secretase processing of APP.

  8. Glucagon-Like Peptide-1 Secreting Cell Function as well as Production of Inflammatory Reactive Oxygen Species Is Differently Regulated by Glycated Serum and High Levels of Glucose

    Directory of Open Access Journals (Sweden)

    Alessandra Puddu

    2014-01-01

    Full Text Available Glucagon-like peptide-1 (GLP-1, an intestinal hormone contributing to glucose homeostasis, is synthesized by proglucagon and secreted from intestinal neuroendocrine cells in response to nutrients. GLP-1 secretion is impaired in type 2 diabetes patients. Here, we aimed at investigating whether diabetic toxic products (glycated serum (GS or high levels of glucose (HG may affect viability, function, and insulin sensitivity of the GLP-1 secreting cell line GLUTag. Cells were cultured for 5 days in presence or absence of different dilutions of GS or HG. GS and HG (alone or in combination increased reactive oxygen species (ROS production and upregulated proglucagon mRNA expression as compared to control medium. Only HG increased total production and release of active GLP-1, while GS alone abrogated secretion of active GLP-1. HG-mediated effects were associated with the increased cell content of the prohormone convertase 1/3 (PC 1/3, while GS alone downregulated this enzyme. HG upregulated Glucokinase (GK and downregulated SYNTHAXIN-1. GS abrogated SYNTHAXIN-1 and SNAP-25. Finally, high doses of GS alone or in combination with HG reduced insulin-mediated IRS-1 phosphorylation. In conclusion, we showed that GS and HG might regulate different pathways of GLP-1 production in diabetes, directly altering the function of neuroendocrine cells secreting this hormone.

  9. Control Performance of General Electric Fuel and Torque Regulator Operating on T31-3 Turbine-Propeller Engine in Sea-Level Test Stand

    Science.gov (United States)

    Oppenheimer, Frank L.; Lazar, James

    1951-01-01

    A .General Electric fuel and torque regulator was tested in conjunction with a T31-3 turbine-propeller engine in the sea-level static test stand at the NACA Lewis laboratory. The engine and control were operated over the entire speed range: 11,000 rpm, nominal flight idle, to 13,000 rpm, full power. Steady-state and transient data were recorded and are presented with a description of the four control loops being used in the system. Results of this investigation indicated that single-lever control operation was satisfactory under conditions of test. Transient data presented showed that turbine-outlet temperature did overshoot maximum operating value on acceleration but that the time duration of overshoot did not exceed approximately 1 second. This temperature limiting resulted from a control on fuel flow as a function of engine speed. Speed and torque first reached their desired values 0.4 second from the time of change in power-setting lever position. Maximum speed overshoot was 3 percent.

  10. Competition between bank regulators

    OpenAIRE

    Schindler, Dirk; Eggert, Wolfgang

    2004-01-01

    This paper examines competition between bank regulators in open economies. We use a model where credit demand of firms is endogenous and show any tendency for downward competition in regulation policy is limited by the effect of regulation on profits of nonfinancial firms. Moreover, perfect mobility on loans and deposit markets fully eliminates the incentives of regulators to set bank regulation at ine±cient low levels.

  11. NORM regulations

    Energy Technology Data Exchange (ETDEWEB)

    Gray, P. [ed.

    1997-02-01

    The author reviews the question of regulation for naturally occuring radioactive material (NORM), and the factors that have made this a more prominent concern today. Past practices have been very relaxed, and have often involved very poor records, the involvment of contractors, and the disposition of contaminated equipment back into commercial service. The rationale behind the establishment of regulations is to provide worker protection, to exempt low risk materials, to aid in scrap recycling, to provide direction for remediation and to examine disposal options. The author reviews existing regulations at federal and state levels, impending legislation, and touches on the issue of site remediation and potential liabilities affecting the release of sites contaminated by NORM.

  12. m-Trifluoromethyl-diphenyl Diselenide Regulates Prefrontal Cortical MOR and KOR Protein Levels and Abolishes the Phenotype Induced by Repeated Forced Swim Stress in Mice.

    Science.gov (United States)

    Rosa, Suzan Gonçalves; Pesarico, Ana Paula; Martini, Franciele; Nogueira, Cristina Wayne

    2018-04-05

    The present study aimed to investigate the m-trifluoromethyl-diphenyl diselenide [(m-CF 3 -PhSe) 2 ] effects on prefrontal cortical MOR and KOR protein levels and phenotype induced by repeated forced swim stress (FSS) in mice. Adult Swiss mice were subjected to repeated FSS sessions, and after that, they performed the spontaneous locomotor/exploratory activity, tail suspension, and splash tests. (m-CF 3 -PhSe) 2 (0.1 to 5 mg/kg) was administered to mice 30 min before the first FSS session and 30 min before the subsequent repeated FSS. (m-CF 3 -PhSe) 2 abolished the phenotype induced by repeated FSS in mice. In addition, a single FSS session increased μ but reduced δ-opioid receptor contents, without changing the κ content. Mice subjected to repeated FSS had an increase in the μ content when compared to those of naïve group or subjected to single FSS. Repeated FSS induced an increase of δ-opioid receptor content compared to those mice subjected to single FSS. However, the δ-opioid receptor contents were lower than those found in the naïve group. The mice subjected to repeated FSS showed an increase in the κ-opioid receptor content when compared to that of the naïve mice. (m-CF 3 -PhSe) 2 regulated the protein contents of μ and κ receptors in mice subjected to repeated FSS. These findings demonstrate that (m-CF 3 -PhSe) 2 was effective to abolish the phenotype induced by FSS, which was accompanied by changes in the contents of cortical μ- and κ-opioid receptors.

  13. Hemoglobin LjGlb1-1 is involved in nodulation and regulates the level of nitric oxide in the Lotus japonicus-Mesorhizobium loti symbiosis.

    Science.gov (United States)

    Fukudome, Mitsutaka; Calvo-Begueria, Laura; Kado, Tomohiro; Osuki, Ken-Ichi; Rubio, Maria Carmen; Murakami, Ei-Ichi; Nagata, Maki; Kucho, Ken-Ichi; Sandal, Niels; Stougaard, Jens; Becana, Manuel; Uchiumi, Toshiki

    2016-09-01

    Leghemoglobins transport and deliver O2 to the symbiosomes inside legume nodules and are essential for nitrogen fixation. However, the roles of other hemoglobins (Hbs) in the rhizobia-legume symbiosis are unclear. Several Lotus japonicus mutants affecting LjGlb1-1, a non-symbiotic class 1 Hb, have been used to study the function of this protein in symbiosis. Two TILLING alleles with single amino acid substitutions (A102V and E127K) and a LORE1 null allele with a retrotransposon insertion in the 5'-untranslated region (96642) were selected for phenotyping nodulation. Plants of all three mutant lines showed a decrease in long infection threads and nodules, and an increase in incipient infection threads. About 4h after inoculation, the roots of mutant plants exhibited a greater transient accumulation of nitric oxide (NO) than did the wild-type roots; nevertheless, in vitro NO dioxygenase activities of the wild-type, A102V, and E127K proteins were similar, suggesting that the mutated proteins are not fully functional in vivo The expression of LjGlb1-1, but not of the other class 1 Hb of L. japonicus (LjGlb1-2), was affected during infection of wild-type roots, further supporting a specific role for LjGlb1-1. In conclusion, the LjGlb1-1 mutants reveal that this protein is required during rhizobial infection and regulates NO levels. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  14. THE INFLUENCE OF INTERACTIVE MULTIMEDIA AUDIO TELLING MACHINE (IMATE USE AND STUDENTS’ SELF REGU-LATED LEARNING LEVEL ON ENGLISH LANGUAGE GREET-INGS APPLICATION SKILLS (PENGARUH PENGGUNAAN INTERACTIVE MULTIMEDIA AU-DIO TELLING MACHINE (iMATE DAN TINGKAT SELF REGU-LATED LEARNING SISWA TERHADAP KEMAMPUAN MENERAP-KAN GREETINGS BAHASA INGGRIS

    Directory of Open Access Journals (Sweden)

    Muhammad Ridwan Sutisna

    2018-02-01

    Full Text Available Abstract. New trends of technology and also the higher needs of English proficiency have encouraged the quality improvent of English instructions. The aim of this research is to deter-mine the effect of Interactive Multimedia Audio Telling Machine (iMATE and self regulated learning level in English language greetings application skill of vocational school students. iMATE is an Interactive instructional media used in this research. While student’s self regulated learning is divided into high and low level. This research used experimental design. This re-search was held at SMK Pasundan 3 Bandung. Findings of this research were; (1 Generally students achieved better result when using iMATE. (2 There was an interaction between use of instructional media and students’ self regulated learning level. (3 Students with high self regu-lated learning achieved much better when using iMATE. (4 Students with low self regulated learning had a better result when not using iMATE. This Findings lead to the conclusion that students’ self regulated learning level may affect the succes of instructional media use, especially in teaching English language skills. Abstrak. Perkembangan teknologi dan kebutuhan akan kemampuan Bahasa Inggris yang lebih tinggi mendorong kualitas pembelajaran Bahasa Inggris juga mengalami perkem-bangan. Tujuan penelitian ini adalah untuk mengetahui pengaruh dari penggunaan Interactive Multimedia Audio Telling Machine (iMATE dan tingkat self regulated learning terhadap ke-mampuan menerapkan greetings Bahasa Inggris siswa SMK. iMATE adalah multimedia inter-aktif pembelajaran yang digunakan dalam penelitian ini. Siswa sebagai subjek penelitian dibagi kedalam dua kelompok yaitu yang memiliki tingkat self regulated learning yang tinggi dan ren-dah. Penelitian yang dilaksanakan di SMK Pasundan 3 Bandung ini menggunakan desain ek-sperimen. Temuan dari penelitian ini adalah (1 Secara umum siswa memperoleh hasil yang lebih baik dengan

  15. The effect of lipid regulation with atorvastatin on the blood lipid levels and carotid artery plaques in patients with atherosclerotic cerebral infarction

    Directory of Open Access Journals (Sweden)

    Shu XU

    2015-11-01

    Full Text Available Objective To analyze the effect of intensive lipid regulation treatment with atorvastatin on the blood lipid levels and carotid artery plaques in patients with atherosclerotic cerebral infarction.  Methods Ninety-two patients with atherosclerotic cerebral infarction were randomly divided into two groups: observation group (treated by atorvastatin calcium with the dosage of 20 mg/d, N = 46 and control group (treated by diet without lipid-rich food, N=46. Besides, other drugs given to the patients in two groups were the same. The blood lipid levels and the changes of carotid artery plaques in two groups were analyzed and compared before treatment and 3 months after treatment. Results After treatment, the concentrations of total cholesterol [TC, (4.23 ± 0.92 mmol/L vs (5.24 ± 0.68 mmol/L], triglyceride [TG, (2.46 ± 0.28 mmol/L vs (3.33 ± 0.47 mmol/L], low-density lipoprotein cholesterol [LDL-C, (2.52 ± 0.38 mmol/L vs (4.78 ± 0.86 mmol/L] in the patients of observation group were all decreased and significantly lower than those in the control group (P = 0.000, for all, and the concentration of high-density lipoprotein cholesterol [HDL-C, (1.13 ± 0.41 mmol/L vs (0.85 ± 0.32 mmol/L] in the patients of observation group was increased and significantly than that in the control group (P = 0.003. The carotid artery plaque size [(20.25 ± 0.32 mm2 vs (24.42 ± 10.33 mm2] and thickness [(0.59 ± 0.13 mm vs (1.93 ± 0.23 mm] of carotid artery plaques and intima?media thickness [IMT, (1.32 ± 0.67 mm vs (1.63 ± 0.56 mm] of common carotid artery (CCA in the patients of observation group were all significantly lower than those in patients in the control group (P = 0.000, 0.000, 0.010, respectively. Comparing serum alanine aminotransferase (ALT, aspartate aminotransferase (AST, creatine kinase (CK and creatinine (Cr levels after treatment with before treatment, there was no significant difference between 2 groups (P > 0.05, for all.  Conclusions

  16. An Assessment of the Stability and the Potential for In-Situ Synthesis of Regulated Organic Compounds in High Level Radioactive Waste Stored at Hanford, Richland, Washington

    Energy Technology Data Exchange (ETDEWEB)

    Wiemers, K.D.; Babad, H.; Hallen, R.T.; Jackson, L.P.; Lerchen, M.E.

    1999-01-04

    The stability assessment examined 269 non-detected regulated compounds, first seeking literature references of the stability of the compounds, then evaluating each compound based upon the presence of functional groups using professional judgment. Compounds that could potentially survive for significant periods in the tanks (>1 year) were designated as stable. Most of the functional groups associated with the regulated organic compounds were considered unstable under tank waste conditions. The general exceptions with respect to functional group stability are some simple substituted aromatic and polycyclic aromatic compounds that resist oxidation and the multiple substituted aliphatic and aromatic halides that hydrolyze or dehydrohalogenate slowly under tank waste conditions. One-hundred and eighty-one (181) regulated, organic compounds were determined as likely unstable in the tank waste environment.

  17. Reforming the Regulation of Trading Venues in the EU under the Proposed MiFID II – Levelling the Playing Field and Overcoming Fragmentation?

    DEFF Research Database (Denmark)

    Clausen, Nis Jul; Sørensen, Karsten Engsig

    2012-01-01

    The Directive on Markets in Financial Instruments (MiFID 2004), adopted in 2004, brought about substantial changes in the market. Competition between trading venues has increased and a substantial portion of trade in financial instruments has moved from regulated markets to other trading venues....... This has created an unlevel playing field between regulated markets on the one hand and other trading venues on the other. At the same time, the fragmentation of trade has led to problems for ensuring investor protection and market surveillance. The Commission has recently proposed a reform of the Mi......FID regime (MiFID II) to address these two problems. In this article there is an analysis of how and to what extent the proposed MiFID II will solve these problems. It is concluded that MiFID II will solve the problem of the unlevel playing field between regulated markets and multilateral trading facilities...

  18. An Assessment of the Stability and the Potential for In-Situ Synthesis of Regulated Organic Compounds in High Level Radioactive Waste Stored at Hanford, Richland, Washington

    International Nuclear Information System (INIS)

    Wiemers, K.D.; Babad, H.; Hallen, R.T.; Jackson, L.P.; Lerchen, M.E.

    1999-01-01

    The stability assessment examined 269 non-detected regulated compounds, first seeking literature references of the stability of the compounds, then evaluating each compound based upon the presence of functional groups using professional judgment. Compounds that could potentially survive for significant periods in the tanks (>1 year) were designated as stable. Most of the functional groups associated with the regulated organic compounds were considered unstable under tank waste conditions. The general exceptions with respect to functional group stability are some simple substituted aromatic and polycyclic aromatic compounds that resist oxidation and the multiple substituted aliphatic and aromatic halides that hydrolyze or dehydrohalogenate slowly under tank waste conditions. One-hundred and eighty-one (181) regulated, organic compounds were determined as likely unstable in the tank waste environment

  19. A complex regulatory network controls aerobic ethanol oxidation in Pseudomonas aeruginosa: indication of four levels of sensor kinases and response regulators.

    Science.gov (United States)

    Mern, Demissew S; Ha, Seung-Wook; Khodaverdi, Viola; Gliese, Nicole; Görisch, Helmut

    2010-05-01

    In addition to the known response regulator ErbR (former AgmR) and the two-component regulatory system EraSR (former ExaDE), three additional regulatory proteins have been identified as being involved in controlling transcription of the aerobic ethanol oxidation system in Pseudomonas aeruginosa. Two putative sensor kinases, ErcS and ErcS', and a response regulator, ErdR, were found, all of which show significant similarity to the two-component flhSR system that controls methanol and formaldehyde metabolism in Paracoccus denitrificans. All three identified response regulators, EraR (formerly ExaE), ErbR (formerly AgmR) and ErdR, are members of the luxR family. The three sensor kinases EraS (formerly ExaD), ErcS and ErcS' do not contain a membrane domain. Apparently, they are localized in the cytoplasm and recognize cytoplasmic signals. Inactivation of gene ercS caused an extended lag phase on ethanol. Inactivation of both genes, ercS and ercS', resulted in no growth at all on ethanol, as did inactivation of erdR. Of the three sensor kinases and three response regulators identified thus far, only the EraSR (formerly ExaDE) system forms a corresponding kinase/regulator pair. Using reporter gene constructs of all identified regulatory genes in different mutants allowed the hierarchy of a hypothetical complex regulatory network to be established. Probably, two additional sensor kinases and two additional response regulators, which are hidden among the numerous regulatory genes annotated in the genome of P. aeruginosa, remain to be identified.

  20. Genetic and systems level analysis of Drosophila sticky/citron kinase and dFmr1 mutants reveals common regulation of genetic networks

    Directory of Open Access Journals (Sweden)

    Zarnescu Daniela C

    2008-11-01

    Full Text Available Abstract Background In Drosophila, the genes sticky and dFmr1 have both been shown to regulate cytoskeletal dynamics and chromatin structure. These genes also genetically interact with Argonaute family microRNA regulators. Furthermore, in mammalian systems, both genes have been implicated in neuronal development. Given these genetic and functional similarities, we tested Drosophila sticky and dFmr1 for a genetic interaction and measured whole genome expression in both mutants to assess similarities in gene regulation. Results We found that sticky mutations can dominantly suppress a dFmr1 gain-of-function phenotype in the developing eye, while phenotypes produced by RNAi knock-down of sticky were enhanced by dFmr1 RNAi and a dFmr1 loss-of-function mutation. We also identified a large number of transcripts that were misexpressed in both mutants suggesting that sticky and dFmr1 gene products similarly regulate gene expression. By integrating gene expression data with a protein-protein interaction network, we found that mutations in sticky and dFmr1 resulted in misexpression of common gene networks, and consequently predicted additional specific phenotypes previously not known to be associated with either gene. Further phenotypic analyses validated these predictions. Conclusion These findings establish a functional link between two previously unrelated genes. Microarray analysis indicates that sticky and dFmr1 are both required for regulation of many developmental genes in a variety of cell types. The diversity of transcripts regulated by these two genes suggests a clear cause of the pleiotropy that sticky and dFmr1 mutants display and provides many novel, testable hypotheses about the functions of these genes. As both of these genes are implicated in the development and function of the mammalian brain, these results have relevance to human health as well as to understanding more general biological processes.

  1. Relation between Working Memory and Self-Regulation Capacities and the Level of Social Skills Acquisition in People with Moderate Intellectual Disability

    Science.gov (United States)

    Ducic, Bojan; Gligorovic, Milica; Kaljaca, Svetlana

    2018-01-01

    Background: Social competence deficit is one of the main characteristics of intellectual disability. The aim of this paper is to determine the influence of working memory (WM) and self-regulation (SR) on social skills in persons with moderate intellectual disability (MID). Method: The sample included 41 participants with MID, aged 14-21.…

  2. Use of the Lactococcal nisA Promoter To Regulate Gene Expression in Gram-Positive Bacteria : Comparison of Induction Level and Promoter Strength

    NARCIS (Netherlands)

    Eichenbaum, Zehava; Federle, Michael J.; Marra, Diana; Vos, Willem M. de; Kuipers, Oscar P.; Kleerebezem, Michiel; Scott, June R.

    1998-01-01

    We characterized the regulated activity of the lactococcal nisA promoter in strains of the gram-positive species Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, Enterococcus faecalis, and Bacillus subtilis. nisA promoter activity was dependent on the proteins NisR and

  3. The Use of Gestural Modes to Enhance Expressive Conducting at All Levels of Entering Behavior through the Use of Illustrators, Affect Displays and Regulators

    Science.gov (United States)

    Mathers, Andrew

    2009-01-01

    In this article, I discuss the use of illustrators, affect displays and regulators, which I consider to be non-verbal communication categories through which conductors can employ a more varied approach to body use, gesture and non-verbal communication. These categories employ the use of a conductor's hands and arms, face, eyes and body in a way…

  4. Isoforms of elongation factor eEF1A may be differently regulated at post-transcriptional level in breast cancer progression

    Directory of Open Access Journals (Sweden)

    Vislovukh A. A.

    2013-01-01

    Full Text Available Eukaryotic translation elongation factor 1A exists as two 98 % homologous isoforms: eEF1A1 (A1 and eEF1A2 (A2 which are tissue and development specific. Despite high homology in an open reading frame (ORF region, mRNAs coding for eEF1A1 and eEF1A2 are different in their untranslated regions (UTR, suggesting a possibility of their dissimilar post-transcriptional regulation. Aim. To analyze the existence of cis-acting motifs in the UTRs of EEF1A1/A2 mRNAs, to confirm the possibility of post-transcriptional control of eEF1A1 and eEF1A2 expression. Methods. An ensemble of bioinformatic methods was applied to predict regulatory motifs in the UTRs of EEF1A1/A2 mRNAs. Dual-luciferase reporter assay was employed to detect post-transcriptional regulation of eEF1A1/A2 expression. Results. Numerous regulatory motifs in the UTR of EEF1A1/A2 mRNAs were found bioinformatically. The experimental evidence was obtained for the existence of negative regulation of EEF1A1 and positive regulation of EEF1A2 mRNA in the model of breast cancer development. Conclusions. EEF1A1 and EEF1A2 mRNAs contain distinct motifs in the UTRs and are differently regulated in cancer suggesting the possibility of their control by different cellular signals.

  5. Regulating the Regulator

    Energy Technology Data Exchange (ETDEWEB)

    1992-08-26

    The article reports on a challenge to the UK electricity regulator to defend his record by the Coalition for Fair Electricity Regulation (COFFER). The challenge centres on whether the obligation for the regional electric companies (REC) to purchase power from the cheapest source is being enforced. This is related to the wider issue of whether the REC's support of combined-cycle gas turbine (CCGT) is economic. COFFER considers that uneconomic gas-fired power plants are being allowed to displace economic coal-fired stations. Aspects discussed include the background to the dispute and the costs of CCGT and coal fired power generation. 1 fig., 1 tab.

  6. Memories of Recent Life Events: Differences in Emotional Reactivity and Regulation of Individuals with High and Low Levels of Depressive Symptoms

    DEFF Research Database (Denmark)

    del Palacio Gonzalez, Adriana; Watson, Lynn Ann; Berntsen, Dorthe

    Existing studies investigating involuntary memories (IMs) in the context of depression extend their hypotheses from PTSD models. Findings suggest that the frequency and suppression of IMs are associated with depression. However, in order to fully understand the memory-mental health relationship......, it is of paramount importance to identify the centrality of events to an individual's identity, and potential differences between IMs and word-cued memories (i.e., voluntary). Method: Participants of this two-staged study were 205 non-clinical adults (Mage = 22.72, SD = 1.99). In Stage 1 participants completed...... questionnaires assessing depressive symptoms, emotion regulation, and recent positive and negative life events. Participants nominated the most and least central events to their identity. Emotion reactivity and regulation of IMs of both events were rated. In Stage 2, participants (n = 48) reporting low and high...

  7. Systems level analysis of two-component signal transduction systems in Erwinia amylovora: Role in virulence, regulation of amylovoran biosynthesis and swarming motility

    Directory of Open Access Journals (Sweden)

    Sundin George W

    2009-05-01

    Full Text Available Abstract Background Two-component signal transduction systems (TCSTs, consisting of a histidine kinase (HK and a response regulator (RR, represent a major paradigm for signal transduction in prokaryotes. TCSTs play critical roles in sensing and responding to environmental conditions, and in bacterial pathogenesis. Most TCSTs in Erwinia amylovora have either not been identified or have not yet been studied. Results We used a systems approach to identify TCST and related signal transduction genes in the genome of E. amylovora. Comparative genomic analysis of TCSTs indicated that E. amylovora TCSTs were closely related to those of Erwinia tasmaniensis, a saprophytic enterobacterium isolated from apple flowers, and to other enterobacteria. Forty-six TCST genes in E. amylovora including 17 sensor kinases, three hybrid kinases, 20 DNA- or ligand-binding RRs, four RRs with enzymatic output domain (EAL-GGDEF proteins, and two kinases were characterized in this study. A systematic TCST gene-knockout experiment was conducted, generating a total of 59 single-, double-, and triple-mutants. Virulence assays revealed that five of these mutants were non-pathogenic on immature pear fruits. Results from phenotypic characterization and gene expression experiments indicated that several groups of TCST systems in E. amylovora control amylovoran biosynthesis, one of two major virulence factors in E. amylovora. Both negative and positive regulators of amylovoran biosynthesis were identified, indicating a complex network may control this important feature of pathogenesis. Positive (non-motile, EnvZ/OmpR, negative (hypermotile, GrrS/GrrA, and intermediate regulators for swarming motility in E. amylovora were also identified. Conclusion Our results demonstrated that TCSTs in E. amylovora played major roles in virulence on immature pear fruit and in regulating amylovoran biosynthesis and swarming motility. This suggested presence of regulatory networks governing

  8. Systems-level approaches reveal conservation of trans-regulated genes in the rat and genetic determinants of blood pressure in humans

    Czech Academy of Sciences Publication Activity Database

    Langley, S. R.; Bottolo, L.; Kuneš, Jaroslav; Zicha, Josef; Zídek, Václav; Hubner, N.; Cook, S.A.; Pravenec, Michal; Aitman, T. J.; Petretto, E.

    2013-01-01

    Roč. 97, č. 4 (2013), s. 653-665 ISSN 0008-6363 R&D Projects: GA MŠk(CZ) LH11049; GA MŠk(CZ) LL1204; GA MŠk(CZ) 7E10067 Institutional support: RVO:67985823 Keywords : integrative genomics * expression QTLs * time series analysis * trans-acting regulation * genome-wide association studies Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.808, year: 2013

  9. NRC Task Force report on review of the Federal/State program for regulation of commercial low-level radioactive waste burial grounds. Analysis of public comments

    International Nuclear Information System (INIS)

    1977-09-01

    Correspondence after publication of NUREG-0217 in the Federal Register is listed by docket. A summary of the comments is given. Comments on the task force conclusions on federal/state roles, comprehensive regulator program, and need to study alternatives, provide adequate capacity, and avoid proliferation are analyzed. A breakdown of the comments of states, industry, and others on the task force conclusions and recommendations is tabulated

  10. Predicted RNA Binding Proteins Pes4 and Mip6 Regulate mRNA Levels, Translation, and Localization during Sporulation in Budding Yeast.

    Science.gov (United States)

    Jin, Liang; Zhang, Kai; Sternglanz, Rolf; Neiman, Aaron M

    2017-05-01

    In response to starvation, diploid cells of Saccharomyces cerevisiae undergo meiosis and form haploid spores, a process collectively referred to as sporulation. The differentiation into spores requires extensive changes in gene expression. The transcriptional activator Ndt80 is a central regulator of this process, which controls many genes essential for sporulation. Ndt80 induces ∼300 genes coordinately during meiotic prophase, but different mRNAs within the NDT80 regulon are translated at different times during sporulation. The protein kinase Ime2 and RNA binding protein Rim4 are general regulators of meiotic translational delay, but how differential timing of individual transcripts is achieved was not known. This report describes the characterization of two related NDT80 -induced genes, PES4 and MIP6 , encoding predicted RNA binding proteins. These genes are necessary to regulate the steady-state expression, translational timing, and localization of a set of mRNAs that are transcribed by NDT80 but not translated until the end of meiosis II. Mutations in the predicted RNA binding domains within PES4 alter the stability of target mRNAs. PES4 and MIP6 affect only a small portion of the NDT80 regulon, indicating that they act as modulators of the general Ime2/Rim4 pathway for specific transcripts. Copyright © 2017 American Society for Microbiology.

  11. The landsnail Cepaea nemoralis regulates internal Cd levels when fed on Cd-enriched stinging nettle (Urtica dioica) leaves at low, field-relevant concentrations

    International Nuclear Information System (INIS)

    Notten, M.J.M.; Oosthoek, A.J.P.; Rozema, J.; Aerts, R.

    2006-01-01

    We studied Cd accumulation in Cepaea nemoralis snails at low, but field-relevant Cd concentrations in the diet (Urtica dioica leaves). Six treatments of U. dioica plants were grown, resulting in leaf Cd concentrations between 0 and 2.6 μg g -1 dw. Seven snails per treatment were fed for 38 days. Leaf Cd concentrations did not affect food consumption rates, and consequently Cd intake rates increased with increasing leaf concentrations. No differences were detected among treatments in the final soft tissue Cd concentrations and body burdens in the snails. Regression analyses showed no positive relationship between either snail Cd concentrations or body burdens and total Cd intake. This suggests a regulation of internal Cd concentrations at low food Cd concentrations. Our data suggest that Cd excretion via the mucus plays a substantial role in this regulation, in addition to Cd excretion via the faeces. Snail shells were no sinks for Cd. - Cd excretion via the mucus plays a substantial role in the regulation of C. nemoralis soft tissue Cd concentrations at low, but field-relevant Cd concentrations in the food

  12. The landsnail Cepaea nemoralis regulates internal Cd levels when fed on Cd-enriched stinging nettle (Urtica dioica) leaves at low, field-relevant concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Notten, M.J.M. [Institute of Ecological Science, Department of Systems Ecology, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081 HV, Amsterdam (Netherlands)]. E-mail: martje.notten@ecology.falw.vu.nl; Oosthoek, A.J.P. [Institute of Ecological Science, Department of Systems Ecology, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081 HV, Amsterdam (Netherlands); Rozema, J. [Institute of Ecological Science, Department of Systems Ecology, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081 HV, Amsterdam (Netherlands); Aerts, R. [Institute of Ecological Science, Department of Systems Ecology, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081 HV, Amsterdam (Netherlands)

    2006-01-15

    We studied Cd accumulation in Cepaea nemoralis snails at low, but field-relevant Cd concentrations in the diet (Urtica dioica leaves). Six treatments of U. dioica plants were grown, resulting in leaf Cd concentrations between 0 and 2.6 {mu}g g{sup -1} dw. Seven snails per treatment were fed for 38 days. Leaf Cd concentrations did not affect food consumption rates, and consequently Cd intake rates increased with increasing leaf concentrations. No differences were detected among treatments in the final soft tissue Cd concentrations and body burdens in the snails. Regression analyses showed no positive relationship between either snail Cd concentrations or body burdens and total Cd intake. This suggests a regulation of internal Cd concentrations at low food Cd concentrations. Our data suggest that Cd excretion via the mucus plays a substantial role in this regulation, in addition to Cd excretion via the faeces. Snail shells were no sinks for Cd. - Cd excretion via the mucus plays a substantial role in the regulation of C. nemoralis soft tissue Cd concentrations at low, but field-relevant Cd concentrations in the food.

  13. Effectiveness of Ministry of Internal Affairs Regulation Number 15 Year 2008 about Mainstreaming Gender on Basic Education Level in the East Java, Indonesia

    Science.gov (United States)

    Handayani, Trisakti; Widodo, Wahyu

    2016-01-01

    General purpose of this research are: assessing the implementation of Permendagri no. 15 year 2008 about Gender Mainstreaming on Basic Education Levels in the East Java Province, analyze the problem of the implementation of Permendagri no. 15 year 2008 about Gender Mainstreaming on Basic Education Levels in the East Java Province and analyze the…

  14. Expression levels of hsc70 and hsp60 are developmentally regulated during B-cell maturation and not associated to childhood c-ALL at presentation or relapse

    DEFF Research Database (Denmark)

    Wehner, Peder Skov; Nielsen, Bendt; Hokland, Marianne

    2003-01-01

    ) or heat shock protein 60 (hsp60) contribute to B-cell differentiation and leukemogenesis. We compared the expression of these hsps in normal peripheral blood (PB) CD19+ B-cells, in pediatric bone marrow (BM) CD19+ CD10+ B-cell precursors (BCPs) from normal donors, and in BCPs from common acute......Heat shock proteins are potent regulators of apoptosis, and so they may also be involved in normal cellular differentiation and cancerogenesis. We used quantitative two-dimensional gel electrophoresis for determining whether either the constitutive chaperonic heat shock cognate protein 70 (hsc70...

  15. Effects of air transportation cause physiological and biochemical changes indicative of stress leading to regulation of chaperone expression levels and corticosterone concentration.

    Science.gov (United States)

    Shim, SunBo; Lee, SeHyun; Kim, ChuelKyu; Kim, ByoungGuk; Jee, SeungWan; Lee, SuHae; Sin, JiSoon; Bae, ChangJoon; Woo, Jong-Min; Cho, JungSik; Lee, EonPil; Choi, HaeWook; Kim, HongSung; Lee, JaeHo; Jung, YoungJin; Cho, ByungWook; Chae, KabRyong; Hwang, DaeYoun

    2009-01-01

    Laboratory animals generally experience numerous unfamiliar environmental and psychological influences such as noises, temperatures, handling, shaking, and smells during the process of air transportation. To investigate whether stress induced by air transportation affects stress-related factors in animals, the levels of hormone and chaperone protein were measured in several tissues of F344 rats transported for 13 h and not transported. Herein, we conclude that the levels of corticosterone, HSP70, and GRP78 were significantly increased in the transported group compare to not transported group, but they were rapidly restored to the not transported group level after a recovery period of one week. However, the magnitude of induction and restoration levels of these factors varied depending on the tissue type. Thus, these results suggest that air transportation should be considered for the improvement of laboratory animal health and to reduce the incidence of laboratory animal stress.

  16. Validity of the linear no-threshold (LNT) hypothesis in setting radiation protection regulations for the inhabitants in high level natural radiation areas of Ramsar, Iran

    International Nuclear Information System (INIS)

    Mortazavi, S.M.J.; Atefi, M.; Razi, Z.; Mortazavi Gh

    2010-01-01

    Some areas in Ramsar, a city in northern Iran, have long been known as inhabited areas with the highest levels of natural radiation. Despite the fact that the health effects of high doses of ionizing radiation are well documented, biological effects of above the background levels of natural radiation are still controversial and the validity of the LNT hypothesis in this area, has been criticized by many investigators around the world. The study of the health effects of high levels of natural radiation in areas such as Ramsar, help scientists to investigate the biological effects without the need for extrapolating the observations either from high doses of radiation to low dose region or from laboratory animals to humans. Considering the importance of these studies, National Radiation Protection Department (NRPD) of the Iranian Nuclear Regulatory Authority has started an integrative research project on the health effects of long-term exposure to high levels of natural radiation. This paper reviews findings of the studies conducted on the plants and humans living or laboratory animals kept in high level natural radiation areas of Ramsar. In human studies, different end points such as DNA damage, chromosome aberrations, blood cells and immunological alterations are discussed. This review comes to the conclusion that no reproducible detrimental health effect has been reported so far. In this paper the validity of LNT hypothesis in the assessment of the health effects of high levels of natural radiation is discussed. (author)

  17. Load regulating expansion fixture

    International Nuclear Information System (INIS)

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

    1998-01-01

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

  18. Alteration of serum thymus and activation-regulated chemokine level during biologic therapy for psoriasis: Possibility as a marker reflecting favorable response to anti-interleukin-17A agents.

    Science.gov (United States)

    Shibuya, Takashi; Honma, Masaru; Iinuma, Shin; Iwasaki, Takeshi; Takahashi, Hidetoshi; Ishida-Yamamoto, Akemi

    2018-06-01

    Biologics show great efficacy in treating psoriasis, a chronic inflammatory skin disease. The high cost and side-effects of biologics, dose-reduction, elongation of administration interval and suspension are possible options. However, there has been no reliable biomarker we can use when we consider these moderations in therapy. This study was conducted to test the possibility of using serum thymus and activation-regulated chemokine (TARC) level as an indicator for step down of biologic therapy. Serum TARC level was measured in 70 psoriatic patients at Asahikawa Medical University, and a correlation of TARC and severity of skin lesions was analyzed. Referring to serum TARC level, psoriatic patients can be divided into two groups. One is a population in which serum TARC level is positively correlated with severity of skin lesions, and the other is a population with low psoriatic severity and high TARC level. Serum TARC level was higher in the group that achieved PASI-clear with biologics than in the group which did not achieve PASI-clear. Among biologics, the group treated with secukinumab, an anti-interleukin (IL)-17A agent, showed significantly higher TARC level compared with the group treated with anti-tumor necrosis factor agents. In certain populations achieving PASI-clear, serum TARC level may be a potent marker reflecting better response to IL-17A inhibitors, and in this case step down of treatment for psoriasis is possible. © 2018 Japanese Dermatological Association.

  19. Building new WDM regulations for the Namibian tourism sector on factors influencing current water-management practices at the enterprise level

    Science.gov (United States)

    Schachtschneider, Klaudia

    Namibia's aridity is forcing its water sector to resort to new water resource management approaches, including water demand management (WDM). Such a change in management approach is facilitated through the country's opportunity at independence to rewrite and adapt its old policies, including those for water and tourism. Legal support for WDM through the Water Act and other sector-specific Acts is crucial to plan the practical implementation of WDM throughout the different water use sectors of Namibia. In order to be able to put the policy into practice, it is imperative to understand which factors motivate people to adopt WDM initiatives. Within the Namibian tourism industry three main factors have been identified which influence the water-management approaches at tourist facilities. This paper discusses how the water and tourism decision makers can consider these factors when developing new regulations to introduce WDM in the tourism sector.

  20. Energy regulation at EU level. The role of the European Commission and ACER in the context of REMIT; Energieregulierung auf Unionsebene. Die Rolle der Europaeischen Kommission und der ACER nach der REMIT-VO

    Energy Technology Data Exchange (ETDEWEB)

    Konar, Selma [Sozietaet Becker Buettner Held, Muenchen (Germany). Energie- und Infrastrukturrecht

    2015-03-15

    The regulatory act of promulgating REMIT, the Regulation on Wholesale Market Integrity and Transparency, has highlighted the commanding position of both the European Commission and ACER, the Agency for the Cooperation of Energy Regulators, in the regulation of energy affairs in the European Union. Furthermore it has led to major changes in how surveillance is organized at the national level. The first part of this publication is dedicated to the organization of market surveillance following the promulgation of REMIT. It depicts the tasks of the European Commission and ACER in this context. The Regulation has accorded the authorities a central role in managing the European Union's responsibilities with regard to energy wholesale trade. The act of delegating such far-reaching competence to the authorities deserves careful review however. The article shows how, given ACER's lack of practical experience in market surveillance, as well as its lack of human resources, the task of surveilling the European energy wholesale market confronts the agency with a significant challenge. How successfully the EU energy agency will master this challenge will depend on a number of different factors. Stringent requirements will be needed for the data registration offices in order to ensure optimal data processing. National authorities and supervisory bodies should be made to participate in the data monitoring process. ACER's efficiency in surveilling the market will furthermore depend decisively on its IT infrastructure.

  1. Efficiency of Iron-Based Oxy-Hydroxides in Removing Antimony from Groundwater to Levels below the Drinking Water Regulation Limits

    Directory of Open Access Journals (Sweden)

    Konstantinos Simeonidis

    2017-02-01

    Full Text Available This study evaluates the efficiency of iron-based oxy-hydroxides to remove antimony from groundwater to meet the requirements of drinking water regulations. Results obtained by batch adsorption experiments indicated that the qualified iron oxy-hydroxide (FeOOH, synthesized at pH 4 for maintaining a high positive charge density (2.5 mmol OH−/g achieved a residual concentration of Sb(III below the EU drinking water regulation limit of 5 μg/L by providing an adsorption capacity of 3.1 mg/g. This is more than twice greater compared either to similar commercial FeOOHs (GFH, Bayoxide or to tetravalent manganese feroxyhyte (Fe-MnOOH adsorbents. In contrast, all tested adsorbents failed to achieve a residual concentration below 5 μg/L for Sb(V. The higher efficiency of the qualified FeOOH was confirmed by rapid small-scale column tests, since an adsorption capacity of 3 mg Sb(III/g was determined at a breakthrough concentration of 5 μg/L. However, it completely failed to achieve Sb(V concentrations below 5 μg/L even at the beginning of the column experiments. The results of leaching tests classified the spent qualified FeOOH to inert wastes. Considering the rapid kinetics of this process (i.e., 85% of total removal was performed within 10 min, the developed qualified adsorbent may be promoted as a prospective material for point-of-use Sb(III removal from water in vulnerable communities, since the adsorbent’s cost was estimated to be close to 30 ± 3.4 €/103 m3 for every 10 μg Sb(III/L removed.

  2. Power-level regulation and simulation of nonlinear pressurized water reactor core with xenon oscillation using H-infinity loop shaping control

    Directory of Open Access Journals (Sweden)

    Li Gang

    2016-01-01

    Full Text Available This investigation is to solve the power-level control issue of a nonlinear pressurized water reactor core with xenon oscillations. A nonlinear pressurized water reactor core is modeled using the lumped parameter method, and a linear model of the core is then obtained through the small perturbation linearization way. The H∞loop shapingcontrolis utilized to design a robust controller of the linearized core model.The calculated H∞loop shaping controller is applied to the nonlinear core model. The nonlinear core model and the H∞ loop shaping controller build the nonlinear core power-level H∞loop shaping control system.Finally, the nonlinear core power-level H∞loop shaping control system is simulatedconsidering two typical load processes that are a step load maneuver and a ramp load maneuver, and simulation results show that the nonlinear control system is effective.

  3. Hydrogen sulfide regulates the levels of key metabolites and antioxidant defense system to counteract oxidative stress in pepper (Capsicum annuum L.) plants exposed to high zinc regime.

    Science.gov (United States)

    Kaya, Cengiz; Ashraf, Muhammad; Akram, Nudrat Aisha

    2018-02-21

    In the present experiment, we aimed to test the impact of hydrogen sulfide (H 2 S) on growth, key oxidant such as hydrogen peroxide, mineral elements, and antioxidative defense in Capia-type red sweet pepper (Capsicum annuum L.) plants subjected to high concentration of zinc (Zn). A factorial experiment was designed with two Zn levels (0.05 and 0.5 mM) and 0.2 mM sodium hydrosulfide (NaHS) as a donor of H 2 S supplied in combination plus nutrient solution through the root zone. High level of Zn led to reduce dry mass, chlorophyll pigments, fruit yield, leaf maximum fluorescence, and relative water content, but enhanced endogenous hydrogen peroxide (H 2 O 2 ), free proline, malondialdehyde (MDA), electrolyte leakage (EL), H 2 S, as well as the activities of peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD) enzymes. Exogenously applied NaHS significantly enhanced plant growth, fruit yield, water status, the levels of H 2 S and proline as well as the activities of different antioxidant enzymes, while it significantly suppressed EL, MDA, and H 2 O 2 contents in the pepper plants receiving low level Zn. NaHS application to the control plants did not significantly change all these parameters tested except the dry matter which increased significantly. High Zn regime led to increase intrinsic Zn levels in the leaves and roots, but it lowered leaf nitrogen (N), phosphorus (P), and iron (Fe) concentrations. However, NaHS reduces the Zn conc. and enhances Fe and N in leaf and root organs. It can be concluded that NaHS can mitigate the harmful effects of Zn on plant growth particularly by lowering the concentrations of H 2 O 2 , Zn, EL, and MDA, and enhancing the activities of enzymatic antioxidants and levels of essential nutrients in pepper plants.

  4. Melatonin mediated antidepressant-like effect in the hippocampus of chronic stress-induced depression rats: Regulating vesicular monoamine transporter 2 and monoamine oxidase A levels.

    Science.gov (United States)

    Stefanovic, Bojana; Spasojevic, Natasa; Jovanovic, Predrag; Jasnic, Nebojsa; Djordjevic, Jelena; Dronjak, Sladjana

    2016-10-01

    The hippocampus is sensitive to stress which activates norepinephrine terminals deriving from the locus coeruleus. Melatonin exerts positive effects on the hippocampal neurogenic process and on depressive-like behaviour. Thus, in the present study, an examination was made of the effect of chronic melatonin treatment on norepinephrine content, synthesis, uptake, vesicular transport and degradation in the hippocampus of rats exposed to CUMS. This entailed quantifying the norephinephrine, mRNA and protein levels of DBH, NET, VMAT 2, MAO-A and COMT. The results show that CUMS evoked prolonged immobility. Melatonin treatment decreased immobility in comparison with the placebo group, reflecting an antidepressant-like effect. Compared with the placebo group, a dramatic decrease in norepinephrine content, decreased VMAT2 mRNA and protein and increased MAO-A protein levels in the hippocampus of the CUMS rats were observed. However, no significant differences in the levels of DBH, NET, COMT mRNA and protein and MAO-A mRNA levels between the placebo and the stressed groups were found. The results showed the restorative effects of melatonin on the stress-induced decline in the norepinephrine content of the hippocampus. It was observed that melatonin treatment in the CUMS rats prevented the stress-induced decrease in VMAT2 mRNA and protein levels, whereas it reduced the increase of the mRNA of COMT and protein levels of MAO-A. Chronic treatment with melatonin failed to alter the gene expression of DBH or NET in the hippocampus of the CUMS rats. Additionally, the results show that melatonin enhances VMAT2 expression and norepinephrine storage, whilst it reduces norepinephrine degrading enzymes. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  5. Regulation of gas storages in Europe. The GGPSSO as an agreement in lieu of standard at EU level; Regulierung von Gasspeichern in Europa. Die GGPSSO als eine normersetzende Absprache auf der Ebene der Europaeischen Union

    Energy Technology Data Exchange (ETDEWEB)

    Barbknecht, Klaus-Dieter

    2012-07-01

    Since the enactment of the Gas Directive in 1998 demands have been raised at the European level for the regulation of privately owned installations used for the storage of natural gas (natural gas storages). In the time after 1998 regulatory codes both legislative and non-legislative governing the access of third parties to gas storages evolved at the European and, amongst others, German national level. The present study is dedicated to legal issues arising in this connection. It endeavours to provide an understanding of the GGPSSO, its legal nature and the significance of its regulations in the context of the European natural gas economy. For this purpose it briefly describes the economic and technical environment of this branch of industry as well as the legal framework within which it has evolved in the individual countries of the EU. It takes a close look at the necessity and possibilities of storing natural gas, the macroeconomic significance of this business for Europe, the products that result from the storage of natural gas and the private or public forms of organisation of the relevant corporations. These considerations provide indications regarding the special nature of certain regulations of the GGPSSO, particularly concerning the role of storage operators as administrators of private or public resources and the role of the regulatory authorities involved.

  6. Histone demethylase JMJD3 regulates CD11a expression through changes in histone H3K27 tri-methylation levels in CD4+ T cells of patients with systemic lupus erythematosus.

    Science.gov (United States)

    Yin, Heng; Wu, Haijing; Zhao, Ming; Zhang, Qing; Long, Hai; Fu, Siqi; Lu, Qianjin

    2017-07-25

    Aberrant CD11a overexpression in CD4+ T cells induces T cell auto-reactivity, which is an important factor for systemic lupus erythematosus (SLE) pathogenesis. Although many studies have focused on CD11a epigenetic regulation, little is known about histone methylation. JMJD3, as a histone demethylase, is capable of specifically removing the trimethyl group from the H3K27 lysine residue, triggering target gene activation. Here, we examined the expression and function of JMJD3 in CD4+ T cells from SLE patients. Significantly decreased H3K27me3 levels and increased JMJD3 binding were detected within the ITGAL (CD11a) promoter locus in SLE CD4+ T cells compared with those in healthy CD4+ T cells. Moreover, overexpressing JMJD3 through the transfection of pcDNA3.1-JMJD3 into healthy donor CD4+ T cells increased JMJD3 enrichment and decreased H3K27me3 enrichment within the ITGAL (CD11a) promoter and up-regulated CD11a expression, leading to T and B cell hyperactivity. Inhibition of JMJD3 via JMJD3-siRNA in SLE CD4+ T cells showed the opposite effects. These results demonstrated that histone demethylase JMJD3 regulates CD11a expression in lupus T cells by affecting the H3K27me3 levels in the ITGAL (CD11a) promoter region, and JMJD3 might thereby serve as a potential therapeutic target for SLE.

  7. Light and abiotic stresses regulate the expression of GDP-L-galactose phosphorylase and levels of ascorbic acid in two kiwifruit genotypes via light-responsive and stress-inducible cis-elements in their promoters.

    Science.gov (United States)

    Li, Juan; Liang, Dong; Li, Mingjun; Ma, Fengwang

    2013-09-01

    Ascorbic acid (AsA) plays an essential role in plants by protecting cells against oxidative damage. GDP-L-galactose phosphorylase (GGP) is the first committed gene for AsA synthesis. Our research examined AsA levels, regulation of GGP gene expression, and how these are related to abiotic stresses in two species of Actinidia (kiwifruit). When leaves were subjected to continuous darkness or light, ABA or MeJA, heat, or a hypoxic environment, we found some correlation between the relative levels of GGP mRNA and AsA concentrations. In transformed tobacco plants, activity of the GGP promoter was induced by all of these treatments. However, the degree of inducibility in the two kiwifruit species differed among the GGP promoter deletions. We deduced that the G-box motif, a light-responsive element, may have an important function in regulating GGP transcripts under various light conditions in both A. deliciosa and A. eriantha. Other elements such as ABRE, the CGTCA motif, and HSE might also control the promoter activities of GGP in kiwifruit. Altogether, these data suggest that GGP expression in the two kiwifruit species is regulated by light or abiotic stress via the relative cis-elements in their promoters. Furthermore, GGP has a critical role in modulating AsA concentrations in kiwifruit species under abiotic stresses.

  8. Avoidance-oriented students' development in motivation for maths, self-regulated learning behaviour and achievement: a person-centred study in the lowest level of secondary education

    NARCIS (Netherlands)

    Peetsma, T.; van der Veen, I.

    2013-01-01

    Performance-avoidance orientation has been found to undermine students’ academic motivation and achievement. Recognising groups of students with different levels and developments of performance-avoidance orientation makes it possible to try to intervene early in their school careers. In this study,

  9. LEVELS OF STATE REGULATION OF THE LEGAL STATUS OF THE DISPLACED PERSONS IN THE GOLD MINING INDUSTRY OF THE USSR (1930-1950

    Directory of Open Access Journals (Sweden)

    Kochegarova Elena Danilovna

    2013-04-01

    Full Text Available Repressive policy of the Soviet state remains one of the actual problems of Russian historical science. The peculiarities of the legal status of displaced persons, their contribution to the socio-economic development of certain regions, the use of labor by industry and government agencies deserve more attention. Purpose The purpose of this work is the analysis of public policy at different levels and reconstruction of the mechanism of development, adoption and implementation of government decisions in the employment of special group in the gold mining industry. Methodology The dialectical approach is a methodological basis of the research and was implemented through the principles of historicism, scientism, objectivity. Results General thrust of the state policy is determined by the directive of the central, regional and local authorities have particularized or duplicated relevant legal documents at higher levels. Dynamics of changes in the legal status of the displaced persons determined mutually exclusive trends: 1 the weakening or removal of restrictions, 2 toughening control. Priority in decisions belonged Party committees at all levels of management, while the real power had repressive authorities. The practical implementation of government decisions at the local level distorted and was adjusted based on personal or group interests. Practical implications The results can be used for further scientific development of the problem of forced migration.

  10. Regulation of levels of serum antibodies to ryegrass pollen allergen Lol pIV by an internal image anti-idiotypic monoclonal antibody.

    Science.gov (United States)

    Zhou, E M; Kisil, F T

    1995-03-01

    A murine monoclonal anti-idiotypic antibody (anti-Id), designated B1/1, was produced against an idiotope of a murine antibody (mAb91), which recognizes the epitope, site A, of allergen Lol pIV, one of the major groups of allergens in ryegrass (Lolium perenne) pollen. The ability of B1/1 to modulate the antibody responses to Lol pIV was investigated in murine model systems. In the first system, B1/1-keyhole limpet haemocyanin (KLH) conjugate was administered to treat three different strains of mice (C57BL/6, BALB/c and C3H). In the second and third model systems, a solution of B1/1 in phosphate-buffered saline (PBS) was used to treat syngeneic BALB/c mice at various doses and time intervals, respectively. The treatment with either form of B1/1, administered at doses ranging from 100 ng to 100 micrograms mouse, resulted in a reduction of the levels of the antibodies to Lol pIV. In particular, the level of IgE antibodies to Lol pIV was greatly reduced. The administration of a single intravenous (i.v.) injection of a solution of B1/1 8 weeks prior to the challenge with Lol pIV was still effective in reducing the level of antibodies to the allergen. Moreover, the level of antibodies to Lol pIV that expressed the idiotope mAb91 was also markedly decreased. By contrast, it was observed that the level of antibodies to Lol pIV in mice pretreated with B1/1 in PBS at a dose of 10 ng/mouse increased (albeit slightly) compared to that in mice treated with control mAb. These experimental models lend themselves for investigating the mechanism(s) by which an anti-Id modulates antibody responses to a grass pollen allergen.

  11. The tyrosine phosphatase SHP-1 regulates hypoxia inducible factor-1α (HIF-1α protein levels in endothelial cells under hypoxia.

    Directory of Open Access Journals (Sweden)

    Stefan K Alig

    Full Text Available The tyrosine phosphatase SHP-1 negatively influences endothelial function, such as VEGF signaling and reactive oxygen species (ROS formation, and has been shown to influence angiogenesis during tissue ischemia. In ischemic tissues, hypoxia induced angiogenesis is crucial for restoring oxygen supply. However, the exact mechanism how SHP-1 affects endothelial function during ischemia or hypoxia remains unclear. We performed in vitro endothelial cell culture experiments to characterize the role of SHP-1 during hypoxia.SHP-1 knock-down by specific antisense oligodesoxynucleotides (AS-Odn increased cell growth as well as VEGF synthesis and secretion during 24 hours of hypoxia compared to control AS-Odn. This was prevented by HIF-1α inhibition (echinomycin and apigenin. SHP-1 knock-down as well as overexpression of a catalytically inactive SHP-1 (SHP-1 CS further enhanced HIF-1α protein levels, whereas overexpression of a constitutively active SHP-1 (SHP-1 E74A resulted in decreased HIF-1α levels during hypoxia, compared to wildtype SHP-1. Proteasome inhibition (MG132 returned HIF-1α levels to control or wildtype levels respectively in these cells. SHP-1 silencing did not alter HIF-1α mRNA levels. Finally, under hypoxic conditions SHP-1 knock-down enhanced intracellular endothelial reactive oxygen species (ROS formation, as measured by oxidation of H2-DCF and DHE fluorescence.SHP-1 decreases half-life of HIF-1α under hypoxic conditions resulting in decreased cell growth due to diminished VEGF synthesis and secretion. The regulatory effect of SHP-1 on HIF-1α stability may be mediated by inhibition of endothelial ROS formation stabilizing HIF-1α protein. These findings highlight the importance of SHP-1 in hypoxic signaling and its potential as therapeutic target in ischemic diseases.

  12. Severity of the aggression/anxiety-depression/attention child behavior checklist profile discriminates between different levels of deficits in emotional regulation in youth with attention-deficit hyperactivity disorder.

    Science.gov (United States)

    Biederman, Joseph; Petty, Carter R; Day, Helen; Goldin, Rachel L; Spencer, Thomas; Faraone, Stephen V; Surman, Craig B H; Wozniak, Janet

    2012-04-01

    We examined whether severity scores (1 SD vs 2 SDs) of a unique profile of the Child Behavior Checklist (CBCL) consisting of the Anxiety/Depression, Aggression, and Attention (AAA) scales would help differentiate levels of deficits in children with attention-deficit hyperactivity disorder (ADHD). Subjects were 197 children with ADHD and 224 without ADHD. We defined deficient emotional self-regulation (DESR) as an aggregate cutoff score of >180 but siblings. In contrast, the CBCL-DESR was associated with higher rates of comorbid disruptive behavior, anxiety disorders, and impaired interpersonal functioning compared with other ADHD children. Severity scores of the AAA CBCL profiles can help distinguish 2 groups of emotional regulation problems in children with ADHD.

  13. Identification of a c-Jun N-terminal kinase-2-dependent signal amplification cascade that regulates c-Myc levels in ras transformation

    DEFF Research Database (Denmark)

    Mathiasen, D.P.; Egebjerg, C.; Andersen, S.H.

    2012-01-01

    are essential for ras transformation. Previous studies show that ERK-mediated serine 62 phosphorylation protects c-Myc from proteasomal degradation. ERK is, however, not alone sufficient to stabilize c-Myc but requires the cooperation of cancerous inhibitor of protein phosphatase 2A (CIP2A), an oncogene...... that counteracts protein phosphatase 2A-mediated dephosphorylation of c-Myc. Here we show that JNK2 regulates Cip2a transcription via ATF2. ATF2 and c-Myc cooperate to activate the transcription of ATF3. Remarkably, not only ectopic JNK2, but also ectopic ATF2, CIP2A, c-Myc and ATF3 are sufficient to rescue...... the defective ras transformation of JNK2-deficient cells. Thus, these data identify the key signal converging point of JNK2 and ERK pathways and underline the central role of CIP2A in ras transformation.Oncogene advance online publication, 27 June 2011; doi:10.1038/onc.2011.230....

  14. The type II cGMP dependent protein kinase regulates GluA1 levels at the plasma membrane of developing cerebellar granule cells

    Science.gov (United States)

    Incontro, Salvatore; Ciruela, Francisco; Ziff, Edward; Hofmann, Franz; Sánchez-Prieto, José; Torres, Magdalena

    2014-01-01

    Trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is regulated by specific interactions with other proteins and by post-translational mechanisms, such as phosphorylation. We have found that the type II cGMP-dependent protein kinase (cGKII) phosphorylates GluA1 (formerly GluR1) at S845, augmenting the surface expression of AMPARs at both synaptic and extrasynaptic sites. Activation of cGKII by 8-Br-cGMP enhances the surface expression of GluA1, whereas its inhibition or suppression effectively diminished the expression of this protein at the cell surface. In granule cells, NMDA receptor activation (NMDAR) stimulates nitric oxide and cGMP production, which in turn activates cGKII and induces the phosphorylation of GluA1, promoting its accumulation in the plasma membrane. GluA1 is mainly incorporated into calcium permeable AMPARs as exposure to 8-Br-cGMP or NMDA activation enhanced AMPA-elicited calcium responses that are sensitive to NASPM inhibition. We summarize evidence for an increase of calcium permeable AMPA receptors downstream of NMDA receptor activation that might be relevant for granule cell development and plasticity. PMID:23545413

  15. Relation between working memory and self-regulation capacities and the level of social skills acquisition in people with moderate intellectual disability.

    Science.gov (United States)

    Dučić, Bojan; Gligorović, Milica; Kaljača, Svetlana

    2018-03-01

    Social competence deficit is one of the main characteristics of intellectual disability. The aim of this paper is to determine the influence of working memory (WM) and self-regulation (SR) on social skills in persons with moderate intellectual disability (MID). The sample included 41 participants with MID, aged 14-21. Memorizing animals and maze tasks were used for WM assessment. SR skills were assessed by the Behavioral Multitask Batteries. Social skills were rated by the Socialization subscale from the Adaptive Behavior Assessment System II, which consists of two parts. Social skills part could mainly be predicted from SR scores (β = -.441), followed by WM (β = .390) and IQ score (β = .382). Only WM score (β = .494) had a predictive value for Leisure time part. As WM had a greater influence on social skills, incorporating WM training into programmes for improving social skills in persons with MID should be considered. © 2017 John Wiley & Sons Ltd.

  16. Fibroblast Growth Factor (FGF) 23 Regulates the Plasma Levels of Parathyroid Hormone In Vivo Through the FGF Receptor in Normocalcemia, But Not in Hypocalcemia

    DEFF Research Database (Denmark)

    Mace, Maria L; Gravesen, Eva; Nordholm, Anders

    2018-01-01

    hypocalcemia. We demonstrated that FGF23 rapidly inhibited PTH secretion and that this effect was completely blocked by inhibition of the FGF receptor. Furthermore, inhibition of the FGF receptor by itself significantly increased PTH levels, indicating that FGF23 has a suppressive tonus on the parathyroid...... gland's PTH secretion. In acute hypocalcemia, there was no effect of either recombinant FGF23 or FGF receptor inhibition on the physiological response to the low ionized calcium levels. In conclusion, FGF23 has an inhibitory tonus on PTH secretion in normocalcemia and signals through the FGF receptor....... In acute hypocalcemia, when increased PTH secretion is needed to restore the calcium homeostasis, this inhibitory effect of FGF23 is abolished....

  17. Octopamine regulates antennal sensory neurons via daytime-dependent changes in cAMP and IP3 levels in the hawkmoth Manduca sexta.

    Directory of Open Access Journals (Sweden)

    Thomas Schendzielorz

    Full Text Available The biogenic amine octopamine (OA mediates reward signals in olfactory learning and memory as well as circadian rhythms of sleep and activity. In the crepuscular hawkmoth Manduca sexta, OA changed pheromone detection thresholds daytime-dependently, suggesting that OA confers circadian control of olfactory transduction. Thus, with enzyme-linked immunosorbent assays we searched hawkmoth antennae for daytime-dependent changes in the concentration of OA and its respective second messengers. Antennal stimulation with OA raised cAMP- and IP3 levels. Furthermore, antennae expressed daytime-dependent changes in the concentration of OA, with maxima at Zeitgebertime (ZT 20 when moths were active and also maximal concentrations of cAMP occurred. Maximal IP3 levels at ZT 18 and 23 correlated with maximal flight activity of male moths, while minimal IP3 levels at dusk correlated with peaks of feeding activity. Half maximal effective concentration (EC50 for activation of the OA-receptor decreased during the moth's activity phase suggesting daytime-dependent changes in OA receptor sensitivity. With an antiserum against tyramine, the precursor of OA, two centrifugal neurons were detected projecting out into the sensory cell layer of the antenna, possibly mediating more rapid stimulus-dependent OA actions. Indeed, in fast kinetic assays OA receptor stimulation increased cAMP concentrations within 50 msec. Thus, we hypothesize that fast, stimulus-dependent centrifugal control of OA-release in the antenna occurs. Additional slow systemic OA actions might be based upon circadian release of OA into the hemolymph mediating circadian rhythms of antennal second messenger levels. The resulting rhythms of odor sensitivity are suggested to underlie circadian rhythms in odor-mediated behavior.

  18. Paclitaxel-resistant HeLa cells have up-regulated levels of reactive oxygen species and increased expression of taxol resistance gene 1.

    Science.gov (United States)

    Bi, Wenxiang; Wang, Yuxia; Sun, Gaoying; Zhang, Xiaojin; Wei, Yongqing; Li, Lu; Wang, Xiaoyuan

    2014-07-01

    This study is to establish a paclitaxel (PTX)-resistant human cervical carcinoma HeLa cell line (HeLa/PTX) and to investigate its redox characteristics and the expression of taxol resistance gene 1 (Txr1). HeLa cells were treated with PTX and effects of PTX on cell proliferation were detected through cell counting and the MTT assay. Levels of cellular reactive oxygen species (ROS), reduced glutathione (GSH), and oxidized glutathione (GSSG) as well as the ratio of GSH to GSSG were measured by the 2,7-difluorescein diacetate (DCFH-DA) method and the 5,5'dithiobis(2-nitrobenzoic acid) (DTNB) method. Activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined by the nitrite formation method, the molybdate colorimetric method, and the DTNB colorimetric method, respectively. The level of Txr1 mRNA was determined by real-time PCR. Compared with the regular HeLa cells, HeLa/PTX cells were larger in size and had more cytoplasmic granules. The population doubling time for HeLa/PTX cells was 1.32 times of that of HeLa cells (PHeLa/PTX cells showed stronger resistance to PTX than HeLa cells with a resistance index of 122.69. HeLa/PTX cells had higher levels of ROS (PHeLa cells. HeLa/PTX cells, with higher levels of ROS and Txr1 mRNA expression, are more resistant to PTX than HeLa cells.

  19. Regulation of breeding behavior: do energy-demanding periods induce a change in prolactin or corticosterone baseline levels in the common tern (Sterna hirundo)?

    Science.gov (United States)

    Riechert, Juliane; Chastel, Olivier; Becker, Peter H

    2014-01-01

    Hormones are involved in reproductive decisions, linking environmental cues and body condition and adapting behavior. Mass loss is often accompanied by decreased prolactin and increased corticosterone concentrations, influencing incubation and brooding behavior and ultimately triggering nest desertion. Using blood-sucking bugs (Dipetalogaster maxima), we measured baseline prolactin, corticosterone, and ketone body values in incubating common terns (Sterna hirundo) between 2006 and 2009 during energy-demanding periods: 50 pairs were sampled hungry (after an incubation bout) and again fed (after foraging). In a second approach, we sampled 57 other pairs (experienced and inexperienced birds) three times over their individual breeding period, because reproduction, especially chick rearing, is a very energy-demanding process. In line with the common physiological pattern of fasting, we found significantly lower baseline prolactin values in hungry terns, which were negatively related to mass loss over the incubation bout, whereas corticosterone and ketone body levels were marginally increased. Compared to that in the incubation phase, the prolactin level dropped after hatching of chicks in inexperienced birds, perhaps indicating lower parental expenditure. Corticosterone, on the other hand, increased after hatching in males, probably linked to higher foraging activity, as males mainly deliver food during the first days. These energy-demanding periods clearly influenced hormones and ketone bodies, maybe reinforced by the low energy margin of this small seabird species, but energy reserves were not depleted to a level affecting behavior or reproductive success.

  20. Relevance of biotic pathways to the long-term regulation of nuclear-waste disposal. Topical report on reference western arid low-level sites

    International Nuclear Information System (INIS)

    McKenzie, D.H.; Cadwell, L.L.; Eberhardt, L.E.; Kennedy, W.E. Jr.; Peloquin, R.A.; Simmons, M.A.

    1982-10-01

    The purpose of the work reported here was to develop an order of magnitude estimate for the potential dose to man resulting from biotic transport mechanisms at a reference western arid low-level waste site. A description of the reference site is presented that includes the waste inventories, site characteristics and biological communities. Parameter values for biotic transport processes are based on data reported in current literature. Transport and exposure scenarios are developed for assessing biotic transport during 100 years following site closure. Calculations of radionuclide decay and waste container decomposition are made to estimate the quantities available for biotic transport. Dose to a man occupying the reference site following the 100 years of biotic transport are calculated. These dose estimates are compared to dose estimates for the intruder-agricultural scenario reported in the DEIS for 10 CFR 61 (NRC). Dose to man estimates as a result of biotic transport are estimated to be of the same order of magnitude as the dose resulting from the more commonly evaluated human intrusion scenario. The reported lack of potential importance of biotic transport at low-level waste sites in earlier assessment studies is not confirmed by the findings presented in this report. These results indicate that biotic transport has the potential to influence low-level waste site performance. Through biotic transport, radionuclides may be moved to locations where they can enter exposure pathways to man

  1. Methyl salicylate-induced arginine catabolism is associated with up-regulation of polyamine and nitric oxide levels and improves chilling tolerance in cherry tomato fruit.

    Science.gov (United States)

    Zhang, Xinhua; Shen, Lin; Li, Fujun; Meng, Demei; Sheng, Jiping

    2011-09-14

    The effects of methyl salicylate (MeSA) on chilling injury (CI) and gene expression levels, enzyme activities, and metabolites related to arginine catabolism in cherry tomato fruit were investigated. Freshly harvested fruits were treated with 0.05 mM MeSA vapor at 20 °C for 12 h and then stored at 2 °C for up to 28 days. MeSA reduced CI and enhanced the accumulation of putrescine, spermidine, and spermine, which was associated with increased gene expression levels and activities of arginase, arginine decarboxylase, and ornithine decarboxylase at most sampling times. MeSA also increased nitric oxide synthase activity, which at least partly contributed to the increased nitric oxide content. The results indicate that MeSA activates the different pathways of arginine catabolism in cold-stored fruit and that the reduction in CI by MeSA may be due to the coordinated metabolism of arginine and the increase in polyamines and nitric oxide levels.

  2. Supplementation of branched-chain amino acids in protein-restricted diets modulates the expression levels of amino acid transporters and energy metabolism associated regulators in the adipose tissue of growing pigs

    Directory of Open Access Journals (Sweden)

    Yinghui Li

    2016-03-01

    Full Text Available This experiment was conducted to investigate the effects of branched-chain amino acids (BCAA supplemented in protein-restricted diets on the growth performance and the expression profile of amino acid transporters and energy metabolism related regulators in the white adipose tissue (WAT of different regional depots including dorsal subcutaneous adipose (DSA and abdominal subcutaneous adipose (ASA. A total of 24 crossbred barrows (7.40 ± 0.70 kg were randomly divided into 4 groups and were fed the following isocaloric diets for 33 days: 1 a recommended adequate protein diet (AP, 20% CP, as a positive control; 2 a low protein diet (LP, 17% CP; 3 the LP diet supplemented with BCAA (LP + B, 17% CP to reach the same level of the AP diet group; 4 the LP diet supplemented with 2 times the amount of BCAA (LP + 2B, 17% CP. The daily gain and daily feed intake of the LP diet group were the lowest among all the treatments (P  0.05. Moreover, BCAA supplementation down-regulated the expression levels of amino acid transporters including L-type amino acid transporter 1 and sodium-coupled neutral amino acid transporter 2 in DSA, but up-regulated the expression level of L-type amino acid transporter 4 in ASA (P < 0.05. Meanwhile, the energy sensor AMP-activated protein kinase α was activated in the DSA of pigs fed LP diet and in the ASA of the pigs fed AP or LP + 2B diets (P < 0.05. The mRNA expression profile of the selected mitochondrial component and mitochondrial biogenesis associated regulators in DSA and ASA also responded differently to dietary BCAA supplementation. These results suggested that the growth performance of growing pigs fed protein restricted diets supplemented with BCAA could catch up to that of the pigs fed AP diets. The results also partly demonstrated that the regulation mechanisms of BCAA are different in the adipose tissues of different depots.

  3. The importance of regulation of blood glucose levels through activation of peripheral 5'-AMP-activated protein kinase on ischemic neuronal damage.

    Science.gov (United States)

    Harada, Shinichi; Fujita-Hamabe, Wakako; Tokuyama, Shogo

    2010-09-10

    5'-AMP-activated protein kinase (AMPK) is a serine/threonine kinase that plays a key role in energy homeostasis. Recently, it was reported that centrally activated AMPK is involved in the development of ischemic neuronal damage, while the effect of peripherally activated AMPK on ischemic neuronal damage is not known. In addition, we have previously reported that the development of post-ischemic glucose intolerance could be one of the triggers for the aggravation of neuronal damage. In this study, we focused on effect of activation of peripheral or central AMPK on the development of ischemic neuronal damage. Male ddY mice were subjected to 2 h of middle cerebral artery occlusion (MCAO). Neuronal damage was estimated by histological and behavioral analysis after MCAO. In the liver and skeletal muscle, AMPK activity was not affected by MCAO. But, application of intraperitoneal metformin (250 mg/kg), an AMPK activator, significantly suppressed the development of post-ischemic glucose intolerance and ischemic neuronal damage without alteration of central AMPK activity. On the other hand, application of intracerebroventricular metformin (25, 100 microg/mouse) significantly exacerbated the development of neuronal damage observed on day 1 after MCAO, in a dose-dependent manner. These effects were significantly blocked by compound C, a specific AMPK inhibitor. These results suggest that central AMPK was activated by ischemic stress per se, however, peripheral AMPK was not altered. Furthermore, the regulation of post-ischemic glucose intolerance by activation of peripheral AMPK is of assistance for the suppression of cerebral ischemic neuronal damage. 2010 Elsevier B.V. All rights reserved.

  4. On Variations in the Level of PER in Glial Clocks of Drosophila Optic Lobe and Its Negative Regulation by PDF Signaling.

    Science.gov (United States)

    Górska-Andrzejak, Jolanta; Chwastek, Elżbieta M; Walkowicz, Lucyna; Witek, Kacper

    2018-01-01

    We show that the level of the core protein of the circadian clock Period (PER) expressed by glial peripheral oscillators depends on their location in the Drosophila optic lobe. It appears to be controlled by the ventral lateral neurons (LNvs) that release the circadian neurotransmitter Pigment Dispersing Factor (PDF). We demonstrate that glial cells of the distal medulla neuropil (dMnGl) that lie in the vicinity of the PDF-releasing terminals of the LNvs possess receptors for PDF (PDFRs) and express PER at significantly higher level than other types of glia. Surprisingly, the amplitude of PER molecular oscillations in dMnGl is increased twofold in PDF-free environment, that is in Pdf 0 mutants. The Pdf 0 mutants also reveal an increased level of glia-specific protein REPO in dMnGl. The photoreceptors of the compound eye (R-cells) of the PDF-null flies, on the other hand, exhibit de-synchrony of PER molecular oscillations, which manifests itself as increased variability of PER-specific immunofluorescence among the R-cells. Moreover, the daily pattern of expression of the presynaptic protein Bruchpilot (BRP) in the lamina terminals of the R-cells is changed in Pdf 0 mutant. Considering that PDFRs are also expressed by the marginal glia of the lamina that surround the R-cell terminals, the LNv pacemakers appear to be the likely modulators of molecular cycling in the peripheral clocks of both the glial cells and the photoreceptors of the compound eye. Consequently, some form of PDF-based coupling of the glial clocks and the photoreceptors of the eye with the central LNv pacemakers must be operational.

  5. Up-regulation of serum periostin and squamous cell carcinoma antigen levels in infants with acute bronchitis due to respiratory syncytial virus

    Directory of Open Access Journals (Sweden)

    Hiroaki Nakamura

    2018-04-01

    Full Text Available Background: Periostin and squamous cell carcinoma antigen (SCCA are involved in the pathogenesis of asthma. Acute bronchitis due to respiratory syncytial virus (RSV infection during infancy exhibits an asthma-like pathogenesis, suggesting that it may be associated with the subsequent development of asthma. However, the mechanism by which RSV infection leads to development of asthma has not yet been fully elucidated. Methods: Infants younger than 36 months were enrolled and classified into three groups. Group I included patients hospitalized with RSV-induced bronchitis. These patients were further stratified into two sub-groups according to whether the criteria for the modified Asthma Predictive Index (mAPI had been met: Group I consisted of mAPI (+ and mAPI (− patients; Group II included patients with food allergy as a positive control group; and Group III included children with no allergy as a negative control group. Serum periostin and SCCA levels were measured in the groups. This study was registered as a clinical trial (UMIN000012339. Results: We enrolled 14 subjects in Group I mAPI (+, 22 in Group I mAPI (−, 18 in Group II, and 18 in Group III. In Group I, the serum periostin and SCCA levels were significantly higher during the acute phase compared with the recovery phase. However, no significant differences were found between Group I mAPI (+ and mAPI (−. Conclusions: The serum periostin and SCCA levels increased during acute RSV bronchitis. Both periostin and SCCA may play a role in the pathogenesis of acute bronchitis due to RSV. Keywords: Infants, Periostin, Respiratory syncytial virus, Squamous cell carcinoma antigen, T-helper 2 cell cytokines

  6. Geranyl acetate esterase controls and regulates the level of geraniol in lemongrass (Cymbopogon flexuosus Nees ex Steud.) mutant cv. GRL-1 leaves.

    Science.gov (United States)

    Ganjewala, Deepak; Luthra, Rajesh

    2009-01-01

    Essential oil isolated from lemongrass (Cymbopogon flexuosus) mutant cv. GRL-1 leaves is mainly composed of geraniol (G) and geranyl acetate (GA). The proportion of G and GA markedly fluctuates during leaf development. The proportions of GA and G in the essential oil recorded at day 10 after leaf emergence were approximately 59% and approximately 33% respectively. However, the level of GA went down from approximately 59 to approximately 3% whereas the level of G rose from approximately 33 to approximately 91% during the leaf growth period from day 10 to day 50. However, the decline in the level of GA was most pronounced in the early (day 10 to day 30) stage of leaf growth. The trend of changes in the proportion of GA and G has clearly indicated the role of an esterase that must be involved in the conversion of GA to G during leaf development. We isolated an esterase from leaves of different ages that converts GA into G and has been given the name geranyl acetate esterase (GAE). The GAE activity markedly varied during the leaf development cycle; it was closely correlated with the monoterpene (GA and G) composition throughout leaf development. GAE appeared as several isoenzymes but only three (GAE-I, GAE-II, and GAE-III) of them had significant GA cleaving activity. The GAE isoenzymes pattern was greatly influenced by the leaf developmental stages and so their GA cleaving activities. Like the GAE activity, GAE isoenzyme patterns were also found to be consistent with the monoterpene (GA and G) composition. GAE had an optimum pH at 8.5 and temperature at 30 degrees C. Besides GAE, a compound with phosphatase activity capable of hydrolyzing geranyl diphosphate (GPP) to produce geraniol has also been isolated.

  7. Framework for combining REACH and national regulations to obtain equal protection levels of human health and the environment in different countries - Comparative study of Denmark and Korea

    DEFF Research Database (Denmark)

    Lee, Jihyun; Pedersen, Anders Branth; Thomsen, Marianne

    2013-01-01

    The aim of this paper is to present a conceptual framework for a systems approach to protect the environment and human health by taking into account differences in the cumulative risks of total human exposure in a territorial context. To this end the measures that are available and that can...... compound, the territorial differences in background exposure to endocrine and neurological interfering stressors were modelled. It is concluded that the different territorial soil and air lead pollution levels contribute differently to the total childhood lead exposure in the two countries. As such...

  8. Relevance of biotic pathways to the long-term regulation of nuclear waste disposal. Topical report on reference eastern humid low-level sites

    International Nuclear Information System (INIS)

    McKenzie, D.H.; Cadwell, L.L.; Eberhardt, L.E.; Kennedy, W.E. Jr.; Peloquin, R.A.; Simmons, M.A.

    1983-01-01

    The purpose of the work reported here was to develop an order-of-magnitude estimate for the potential dose to man resulting from biotic transport mechanisms at a humid reference low-level waste site in the eastern US. A description of the reference site is presented that includes the waste inventories, site characteristics and biological communites. Parameter values for biotic transport processes are based on data reported in current literature. Transport and exposure scenarios are developed for assessing biotic transport during 500 years following site closure. Calculations of radionuclide decay and waste container decomposition are made to estimate the quantities available for biotic transport. Doses to man are calculated for the biological transport of radionucludes at the reference site after loss of institutional control. These dose estimates are compared to dose estimates we calculated for the intruder-agricultural scenarios reported in the DEIS for 10 CFR 61 (NRC). Dose to man estimates as a result of cumulative biotic transport are calculated to be of the same order-of-magnitude as the dose resulting from the more commonly evaluated human intrusion scenario. The reported lack of potential importance of biotic transport at low-level waste sites in earlier assessment studies is not confirmed by findings presented in this report. Through biotic transport, radionuclides can be moved to locations where they can enter exposure pathways to man

  9. Thioredoxin-1 promotes survival in cells exposed to S-nitrosoglutathione: Correlation with reduction of intracellular levels of nitrosothiols and up-regulation of the ERK1/2 MAP Kinases

    International Nuclear Information System (INIS)

    Arai, Roberto J.; Ogata, Fernando T.; Batista, Wagner L.; Masutani, Hiroshi; Yodoi, Junji; Debbas, Victor; Augusto, Ohara; Stern, Arnold; Monteiro, Hugo P.

    2008-01-01

    Accumulating evidence indicates that post-translational protein modifications by nitric oxide and its derived species are critical effectors of redox signaling in cells. These protein modifications are most likely controlled by intracellular reductants. Among them, the importance of the 12 kDa dithiol protein thioredoxin-1 (TRX-1) has been increasingly recognized. However, the effects of TRX-1 in cells exposed to exogenous nitrosothiols remain little understood. We investigated the levels of intracellular nitrosothiols and survival signaling in HeLa cells over-expressing TRX-1 and exposed to S-nitrosoglutahione (GSNO). A role for TRX-1 expression on GSNO catabolism and cell viability was demonstrated by the concentration-dependent effects of GSNO on decreasing TRX-1 expression, activation of caspase-3, and increasing cell death. The over-expression of TRX-1 in HeLa cells partially attenuated caspase-3 activation and enhanced cell viability upon GSNO treatment. This was correlated with reduction of intracellular levels of nitrosothiols and increasing levels of nitrite and nitrotyrosine. The involvement of ERK, p38 and JNK pathways were investigated in parental cells treated with GSNO. Activation of ERK1/2 MAP kinases was shown to be critical for survival signaling. In cells over-expressing TRX-1, basal phosphorylation levels of ERK1/2 MAP kinases were higher and further increased after GSNO treatment. These results indicate that the enhanced cell viability promoted by TRX-1 correlates with its capacity to regulate the levels of intracellular nitrosothiols and to up-regulate the survival signaling pathway mediated by the ERK1/2 MAP kinases

  10. Comparison of national programs and regulations for the management of spent fuel and disposal of high-level waste in seven countries

    International Nuclear Information System (INIS)

    Numark, N.J.; Mattson, R.J.; Gaunt, J.

    1986-01-01

    This paper describes programs and regulatory requirements affecting the management of spent fuel and disposal of high-level radioactive waste in seven nations with large nuclear power programs. The comparison is intended to illustrate that the range of spent fuel management options is influenced by certain technical and political constraints. It begins by providing overall nuclear fuel cycle facts for each country, including nuclear generating capacities, rates of spent fuel discharge, and policies on spent fuel reprocessing. Spent fuel storage techniques and reprocessing activities are compared in light of constraints such as fuel type. Waste disposal investigations are described, including a summary of the status of regulatory developments affecting repository siting and disposal. A timeline is provided to illustrate the principle milestones in spent fuel management and waste disposal in each country. Finally, policies linking nuclear power licensing and development to nuclear waste management milestones and RandD progress are discussed

  11. Co-operative intermolecular kinetics of 2-oxoglutarate dependent dioxygenases may be essential for system-level regulation of plant cell physiology.

    Science.gov (United States)

    Kundu, Siddhartha

    2015-01-01

    Can the stimulus-driven synergistic association of 2-oxoglutarate dependent dioxygenases be influenced by the kinetic parameters of binding and catalysis?In this manuscript, I posit that these indices are necessary and specific for a particular stimulus, and are key determinants of a dynamic clustering that may function to mitigate the effects of this trigger. The protein(s)/sequence(s) that comprise this group are representative of all major kingdoms of life, and catalyze a generic hydroxylation, which is, in most cases accompanied by a specialized conversion of the substrate molecule. Iron is an essential co-factor for this transformation and the response to waning levels is systemic, and mandates the simultaneous participation of molecular sensors, transporters, and signal transducers. Here, I present a proof-of-concept model, that an evolving molecular network of 2OG-dependent enzymes can maintain iron homeostasis in the cytosol of root hair cells of members of the family Gramineae by actuating a non-reductive compensatory chelation by the phytosiderophores. Regression models of empirically available kinetic data (iron and alpha-ketoglutarate) were formulated, analyzed, and compared. The results, when viewed in context of the superfamily responding as a unit, suggest that members can indeed, work together to accomplish system-level function. This is achieved by the establishment of transient metabolic conduits, wherein the flux is dictated by kinetic compatibility of the participating enzymes. The approach adopted, i.e., predictive mathematical modeling, is integral to the hypothesis-driven acquisition of experimental data points and, in association with suitable visualization aids may be utilized for exploring complex plant biochemical systems.

  12. 12/15 Lipoxygenase regulation of colorectal tumorigenesis is determined by the relative tumor levels of its metabolite 12-HETE and 13-HODE in animal models.

    Science.gov (United States)

    Chang, Jian; Jiang, Li; Wang, Yinqiu; Yao, Bing; Yang, Shilin; Zhang, Bixiang; Zhang, Ming-Zhi

    2015-02-20

    Colorectal cancer (CRC) continues to be a major cause of morbidity and mortality. The arachidonic acid (AA) pathway and linoleic acid (LA) pathway have been implicated as important contributors to CRC development and growth. Human 15-lipoxygenase 1 (15-LOX-1) converts LA to anti-tumor 13-S-hydroxyoctadecadienoic acid (13-HODE)and 15-LOX-2 converts AA to 15-hydroxyeicosatetraenoic acid (15-HETE). In addition, human 12-LOX metabolizes AA to pro-tumor 12-HETE. In rodents, the function of 12-LOX and 15-LOX-1 and 15-LOX-2 is carried out by a single enzyme, 12/15-LOX. As a result, conflicting conclusions concerning the role of 12-LOX and 15-LOX have been obtained in animal studies. In the present studies, we determined that PD146176, a selective 15-LOX-1 inhibitor, markedly suppressed 13-HODE generation in human colon cancer HCA-7 cells and HCA-7 tumors, in association with increased tumor growth. In contrast, PD146176 treatment led to decreases in 12-HETE generation in mouse colon cancer MC38 cells and MC38 tumors, in association with tumor inhibition. Surprisingly, deletion of host 12/15-LOX alone led to increased MC38 tumor growth, in association with decreased tumor 13-HODE levels, possibly due to inhibition of 12/15-LOX activity in stroma. Therefore, the effect of 12/15-LOX on colorectal tumorigenesis in mouse models could be affected by tumor cell type (human or mouse), relative 12/15 LOX activity in tumor cells and stroma as well as the relative tumor 13-HODE and 12-HETE levels.

  13. Dietary Lipid Sources Influence Fatty Acid Composition in Tissue of Large Yellow Croaker (Larmichthys crocea by Regulating Triacylglycerol Synthesis and Catabolism at the Transcriptional Level.

    Directory of Open Access Journals (Sweden)

    Hong Qiu

    Full Text Available An 8-week feeding trial was conducted to evaluate the effects of dietary lipid sources on growth performance, fatty acid composition, rate-limiting enzyme activities and gene expression related to lipid metabolism in large yellow croaker (Larmichthys crocea. Five iso-nitrogenous and iso-lipidic experimental diets were formulated to contain different lipid sources, such as fish oil (FO, soybean oil (SO, linseed oil (LO, rapeseed oil (RO and peanut oil (PO, respectively. Triplicate groups of 50 fish (initial weight 13.77±0.07g were stocked in 15 floating net cages (1.5m×1.5m×2.0m. Fish fed the diets containing RO and LO had lower weight gain and specific growth rates than those fed the FO, SO and PO diets. Survival, feed efficiency, protein efficiency ratio, hepatosomatic index, viscerasomatic index and condition factor were not significantly affected by different dietary lipid sources. Fish fed the diet containing FO had higher lipid content in whole body compared with the other groups, whereas fish fed the SO diet had the lowest muscle lipid content. Fatty acid profiles of muscle and liver reflected the fatty acid composition of the diets. Plasma glucose, triglyceride, and the enzymatic activity of aspartate aminotransferase and alanine aminotransferase were significantly influenced by different dietary lipid sources, while total protein, cholesterol, superoxide dismutase or malondialdehyde in plasma were not affected by the different dietary lipid sources. Fish fed the LO diet had lower adipose triglyceride lipase and fatty acid synthase activities in liver than those fed the diets containing FO and RO, while the LO diet resulted in the highest hepatic carnitine palmitoultransferase-1 activity. Hepatic gene relative expression of adipose triglyceride lipase and carnitine palmitoyltransferase-1 in fish fed PO diet was significantly higher than all other groups, whereas fish fed the SO and LO diets had lower relative expression levels of

  14. Topical application of recombinant platelet-derived growth factor increases the rate of healing and the level of proteins that regulate this response.

    Science.gov (United States)

    Gowda, Santosh; Weinstein, David A; Blalock, Timothy D; Gandhi, Kavita; Mast, Bruce A; Chin, Gloria; Schultz, Gregory S

    2015-10-01

    A bipedicle ischaemic rat skin flap model was used to study the effects of daily topical applications of platelet-derived growth factor (PDGF) on the healing of ischaemic wounds. Levels of tumour necrosis factor-alpha (TNFA), interleukin 1-beta (IL1B) and both the latent and active forms of matrix metalloproteinase 2 (MMP2) and 9 (MMP9) were measured. Full-thickness wounds were made on a total of 72 adult male Sprague-Dawley rats. Each group of 18 rats with normal and ischaemic wounds received either vehicle or 0·01% recombinant PDGF-BB. Additional applications were made on the wounds on a daily basis. Wound areas were measured at 0, 1, 3, 5, 7 9 and 13 days after wounding. Ischaemia caused a delay in wound healing as well as an increase in TNFA, IL1B and both the pro and active forms of MMP2 and MMP9. PDGF accelerated the rate of wound healing in both normal and ischaemic wounds and negated the effect of ischaemia. PDGF reduced the TNFA concentration in both normal and ischaemic wounds, and the rate of wound healing closely resembled the pattern of TNFA protein expression. PDGF also reduced both the magnitude and duration of the increases in IL1B and both the pro and active forms of MMP2 and MMP9 induced by ischaemia. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  15. Induction of rabbit lung cytochrome P450 prostaglandin in omega-hyroxylase during pregnancy: evidence for regulation at the genetic level

    International Nuclear Information System (INIS)

    Master, B.S.S.; Muerhoff, A.S.; Jackson, V.; Williams, D.E.; Waterman, M.R.; Johnson, E.F.

    1986-01-01

    The induction of a cytochrome P450 prostaglandin omega-hydroxylase (P450/sub PG omega/) isolated from pregnant rabbit lung has been shown by Western blots to be concomitant with an increase in the amount of P450 protein. Peaks in enzyme activity and P450/sub PG omega/ protein occur between the 20th and 28th days of gestation with increases of more than 100-fold compared to nonpregnant rabbits. To elucidate the mechanisms controlling induction, total cellular RNA was extracted from rabbit lungs at various days of gestation, translated in vitro using 35 S-met, and the newly synthesized P450/sub PG omega/ immunoprecipitated from the lysate. Utilizing an immunopurified goat IgG to P450/sub PG omega/, immunopellets of in vitro translation reactions charged with RNA from lungs at 6,11,19,22,25, or 28-days gestation were isolated. A single band corresponding to P450/sub PG omega/ was seen in autoradiographs of SDS-PAGE gels containing these immunopellets, but no band was visible in lanes containing immunopellets from reactions charged with RNA from nonpregnant or 1-day post-partum animals. The gestational time-dependent increase in in vitro-translated P450/sub PG omega/ suggests that control of its induction during pregnancy is at the transcriptional level. A monoclonal antibody to the P450/sub PG omega/ has been produced for the isolation of the P450/sub PG omega/ mRNA for cDNA production

  16. Co-operative intermolecular kinetics of 2-oxoglutarate dependent dioxygenases may be essential for system-level regulation of plant cell physiology

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    Siddhartha eKundu

    2015-07-01

    Full Text Available Chlorosis, a common manifestation of Fe-deficiency in plants occurs in soils with an alkaline pH and/or a high concentration of calcium carbonate (calcareous, and is an important cause of depressed yield. The core premise of this work is the notion that the response to waning ferrous iron in the cytosol of graminaceous root cells is a well orchestrated pathophysiological event, wherein the principal co-ordinator is not restricted to a single protein, but is an assortment of enzymes. The 2OG-dependent sequences comprise members present in all major kingdoms of life, and catalyze the release of carbon dioxide and succinic acid from 2-oxoglutarate, and the hydroxylation of a substrate molecule. This generic reaction is, in most cases accompanied by a specialized conversion of the product. Here, I present a model of iron deficiency sensing and response actuation in the root cells of graminaceous crops. This hypothesis is centered on the rationale that, iron is an essential co-factor for the catalytic process, and therefore, declining cytosolic levels of this micronutrient could trigger compensatory measures. Regression models of empirically available kinetic data for iron and alpha-ketoglutarate were formulated, analysed, and compared. The results, when viewed in the context of the superfamily responding as a unit to this abiotic stressor, suggest that the 2OG-sequences can indeed, work together to mitigate the effects of this noxious stimulus.

  17. IL-4 and IL-13 mediated down-regulation of CD8 expression levels can dampen anti-viral CD8⁺ T cell avidity following HIV-1 recombinant pox viral vaccination.

    Science.gov (United States)

    Wijesundara, Danushka K; Jackson, Ronald J; Tscharke, David C; Ranasinghe, Charani

    2013-09-23

    We have shown that mucosal HIV-1 recombinant pox viral vaccination can induce high, avidity HIV-specific CD8(+) T cells with reduced interleukin (IL)-4 and IL-13 expression compared to, systemic vaccine delivery. In the current study how these cytokines act to regulate anti-viral CD8(+) T, cell avidity following HIV-1 recombinant pox viral prime-boost vaccination was investigated. Out of a panel of T cell avidity markers tested, only CD8 expression levels were found to be enhanced on, KdGag197-205 (HIV)-specific CD8(+) T cells obtained from IL-13(-/-), IL-4(-/-) and signal transducer and, activator of transcription of 6 (STAT6)(-/-) mice compared to wild-type (WT) controls following, vaccination. Elevated CD8 expression levels in this instance also correlated with polyfunctionality, (interferon (IFN)-γ, tumour necorsis factor (TNF)-α and IL-2 production) and the avidity of HIVspecific CD8(+) T cells. Furthermore, mucosal vaccination and vaccination with the novel adjuvanted IL-13 inhibitor (i.e. IL-13Rα2) vaccines significantly enhanced CD8 expression levels on HIV-specific CD8(+), T cells, which correlated with avidity. Using anti-CD8 antibodies that blocked CD8 availability on CD8(+), T cells, it was established that CD8 played an important role in increasing HIV-specific CD8(+) T cell avidity and polyfunctionality in IL-4(-/-), IL-13(-/-) and STAT6(-/-) mice compared to WT controls, following vaccination. Collectively, our data demonstrate that IL-4 and IL-13 dampen CD8 expression levels on anti-viral CD8(+) T cells, which can down-regulate anti-viral CD8(+) T cell avidity and, polyfunctionality following HIV-1 recombinant pox viral vaccination. These findings can be exploited to, design more efficacious vaccines not only against HIV-1, but many chronic infections where high, avidity CD8(+) T cells help protection. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Intracellular cholesterol level regulates sensitivity of glioblastoma cells against temozolomide-induced cell death by modulation of caspase-8 activation via death receptor 5-accumulation and activation in the plasma membrane lipid raft.

    Science.gov (United States)

    Yamamoto, Yutaro; Tomiyama, Arata; Sasaki, Nobuyoshi; Yamaguchi, Hideki; Shirakihara, Takuya; Nakashima, Katsuhiko; Kumagai, Kosuke; Takeuchi, Satoru; Toyooka, Terushige; Otani, Naoki; Wada, Kojiro; Narita, Yoshitaka; Ichimura, Koichi; Sakai, Ryuichi; Namba, Hiroki; Mori, Kentaro

    2018-01-01

    Development of resistance against temozolomide (TMZ) in glioblastoma (GBM) after continuous treatment with TMZ is one of the critical problems in clinical GBM therapy. Intracellular cholesterol regulates cancer cell biology, but whether intracellular cholesterol is involved in TMZ resistance of GBM cells remains unclear. The involvement of intracellular cholesterol in acquired resistance against TMZ in GBM cells was investigated. Intracellular cholesterol levels were measured in human U251 MG cells with acquired TMZ resistance (U251-R cells) and TMZ-sensitive control U251 MG cells (U251-Con cells), and found that the intracellular cholesterol level was significantly lower in U251-R cells than in U251-Con cells. In addition, treatment by intracellular cholesterol remover, methyl-beta cyclodextrin (MβCD), or intracellular cholesterol inducer, soluble cholesterol (Chol), regulated TMZ-induced U251-Con cell death in line with changes in intracellular cholesterol level. Involvement of death receptor 5 (DR5), a death receptor localized in the plasma membrane, was evaluated. TMZ without or with MβCD and/or Chol caused accumulation of DR5 into the plasma membrane lipid raft and formed a complex with caspase-8, an extrinsic caspase cascade inducer, reflected in the induction of cell death. In addition, treatment with caspase-8 inhibitor or knockdown of DR5 dramatically suppressed U251-Con cell death induced by combination treatment with TMZ, MβCD, and Chol. Combined treatment of Chol with TMZ reversed the TMZ resistance of U251-R cells and another GBM cell model with acquired TMZ resistance, whereas clinical antihypercholesterolemia agents at physiological concentrations suppressed TMZ-induced cell death of U251-Con cells. These findings suggest that intracellular cholesterol level affects TMZ treatment of GBM mediated via a DR5-caspase-8 mechanism. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Acetylcholine receptor (AChR) clustering is regulated both by glycogen synthase kinase 3β (GSK3β)-dependent phosphorylation and the level of CLIP-associated protein 2 (CLASP2) mediating the capture of microtubule plus-ends.

    Science.gov (United States)

    Basu, Sreya; Sladecek, Stefan; Pemble, Hayley; Wittmann, Torsten; Slotman, Johan A; van Cappellen, Wiggert; Brenner, Hans-Rudolf; Galjart, Niels

    2014-10-31

    The postsynaptic apparatus of the neuromuscular junction (NMJ) traps and anchors acetylcholine receptors (AChRs) at high density at the synapse. We have previously shown that microtubule (MT) capture by CLASP2, a MT plus-end-tracking protein (+TIP), increases the size and receptor density of AChR clusters at the NMJ through the delivery of AChRs and that this is regulated by a pathway involving neuronal agrin and several postsynaptic kinases, including GSK3. Phosphorylation by GSK3 has been shown to cause CLASP2 dissociation from MT ends, and nine potential phosphorylation sites for GSK3 have been mapped on CLASP2. How CLASP2 phosphorylation regulates MT capture at the NMJ and how this controls the size of AChR clusters are not yet understood. To examine this, we used myotubes cultured on agrin patches that induce AChR clustering in a two-dimensional manner. We show that expression of a CLASP2 mutant, in which the nine GSK3 target serines are mutated to alanine (CLASP2-9XS/9XA) and are resistant to GSK3β-dependent phosphorylation, promotes MT capture at clusters and increases AChR cluster size, compared with myotubes that express similar levels of wild type CLASP2 or that are noninfected. Conversely, myotubes expressing a phosphomimetic form of CLASP2 (CLASP2-8XS/D) show enrichment of immobile mutant CLASP2 in clusters, but MT capture and AChR cluster size are reduced. Taken together, our data suggest that both GSK3β-dependent phosphorylation and the level of CLASP2 play a role in the maintenance of AChR cluster size through the regulated capture and release of MT plus-ends. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Subcellular location of Arabidopsis thaliana subfamily a1 β-galactosidases and developmental regulation of transcript levels of their coding genes.

    Science.gov (United States)

    Moneo-Sánchez, María; Izquierdo, Lucía; Martín, Ignacio; Labrador, Emilia; Dopico, Berta

    2016-12-01

    The aim of this work is to gain insight into the six members of the a1 subfamily of the β-galactosidases (BGAL) from Arabidopsis thaliana. First, the subcellular location of all these six BGAL proteins from a1 subfamily has been established in the cell wall by the construction of transgenic plants producing the enhanced green fluorescent protein (eGFP) fused to the BGAL proteins. BGAL12 is also located in the endoplasmic reticulum. Our study of the AtBGAL transcript accumulation along plant development indicated that all AtBGAL transcript appeared in initial stages of development, both dark- and light-grown seedlings, being AtBGAL1, AtBGAL2 and AtBGAL3 transcripts the predominant ones in the latter condition, mainly in the aerial part and with levels decreasing with age. The high accumulation of transcript of AtBGAL4 in basal internodes and in leaves at the end of development, and their strong increase after treatment both with BL and H 3 BO 3 point to an involvement of BGAL4 in cell wall changes leading to the cease of elongation and increased rigidity. The changes of AtBGAL transcript accumulation in relation to different stages and conditions of plant development, suggest that each of the different gene products have a plant-specific function and provides support for the proposed function of the subfamily a1 BGAL in plant cell wall remodelling for cell expansion or for cell response to stress conditions. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  1. Increased serum IL-6 level time-dependently regulates hyperalgesia and spinal mu opioid receptor expression during CFA-induced arthritis.

    Science.gov (United States)

    Tekieh, E; Zaringhalam, Jalal; Manaheji, H; Maghsoudi, N; Alani, B; Zardooz, H

    2011-01-01

    Interleukin (IL)-6 is known to cause pro- and anti-inflammatory effects during different stages of inflammation. Recent therapeutic investigations have focused on treatment of various inflammatory disorders with anti-cytokine substances. As a result, the aim of this study was to further elucidate the influence of IL-6 in hyperalgesia and edema during different stages of Complete Freund's Adjuvant (CFA)-induced arthritis (AA) in male Wistar rats. AA was induced by a single subcutaneous injection of CFA into the rats' hindpaw. Anti-IL-6 was administered either daily or weekly during the 21 days of study. Spinal mu opioid receptor (mOR) expression was detected by Western blotting. Daily and weekly treatment with an anti-IL-6 antibody significantly decreased paw edema in the AA group compared to the AA control group. Additionally, daily and weekly anti-IL-6 administration significantly reduced hyperalgesia on day 7 in the AA group compared to the AA control group; however, there were significant increases in hyperalgesia in the antibody-treated group on days 14 and 21 compared to the AA control group. IL-6 antibody-induced increases in hyperalgesia on the 14 th and 21 st days after CFA injection correlated with a time-dependent, significant reduction in spinal mOR expression during anti-IL-6 treatment. Our study confirmed the important time-dependent relationship between serum IL-6 levels and hyperalgesia during AA. These results suggest that the stages of inflammation in AA must be considered for anti-hyperalgesic and anti-inflammatory interventions via anti-IL-6 antibody treatment.

  2. The signaling mechanisms of hippocampal endoplasmic reticulum stress affecting neuronal plasticity-related protein levels in high fat diet-induced obese rats and the regulation of aerobic exercise.

    Science.gov (United States)

    Cai, Ming; Wang, Hong; Li, Jing-Jing; Zhang, Yun-Li; Xin, Lei; Li, Feng; Lou, Shu-Jie

    2016-10-01

    High fat diet (HFD)-induced obesity has been shown to reduce the levels of neuronal plasticity-related proteins, specifically brain-derived neurotrophic factor (BDNF) and synaptophysin (SYN), in the hippocampus. However, the underlying mechanisms are not fully clear. Endoplasmic reticulum stress (ERS) has been reported to play a key role in regulating gene expression and protein production by affecting stress signaling pathways and ER functions of protein folding and post-translational modification in peripheral tissues of obese rodent models. Additionally, HFD that is associated with hyperglycemia could induce hippocampal ERS, thus impairing insulin signaling and cognitive health in HFD mice. One goal of this study was to determine whether hyperglycemia and hyperlipidemia could cause hippocampal ERS in HFD-induced obese SD rats, and explore the potential mechanisms of ERS regulating hippocampal BDNF and SYN proteins production. Additionally, although regular aerobic exercise could reduce central inflammation and elevate hippocampal BDNF and SYN levels in obese rats, the regulated mechanisms are poorly understood. Nrf2-HO-1 pathways play roles in anti-ERS, anti-inflammation and anti-apoptosis in peripheral tissues. Therefore, the other goal of this study was to determine whether aerobic exercise could activate Nrf2-HO-1 in hippocampus to alleviate obesity-induced hippocampal ERS, which would lead to increased BDNF and SYN levels. Male SD rats were fed on HFD for 8weeks to establish the obese model. Then, 8weeks of aerobic exercise treadmill intervention was arranged for the obese rats. Results showed that HFD-induced obesity caused hyperglycemia and hyperlipidemia, and significantly promoted hippocampal glucose transporter 3 (GLUT3) and fatty acid transport protein 1 (FATP1) protein expression. These results were associated with the activation of hippocampal ERS and ERS-mediated apoptosis. At the same time, we found that excessive hippocampal ERS not only

  3. Impact of gene variants on sex-specific regulation of human Scavenger receptor class B type 1 (SR-BI expression in liver and association with lipid levels in a population-based study

    Directory of Open Access Journals (Sweden)

    Barrett-Connor Elizabeth

    2010-01-01

    Full Text Available Abstract Background Several studies have noted that genetic variants of SCARB1, a lipoprotein receptor involved in reverse cholesterol transport, are associated with serum lipid levels in a sex-dependent fashion. However, the mechanism underlying this gene by sex interaction has not been explored. Methods We utilized both epidemiological and molecular methods to study how estrogen and gene variants interact to influence SCARB1 expression and lipid levels. Interaction between 35 SCARB1 haplotype-tagged polymorphisms and endogenous estradiol levels was assessed in 498 postmenopausal Caucasian women from the population-based Rancho Bernardo Study. We further examined associated variants with overall and SCARB1 splice variant (SR-BI and SR-BII expression in 91 human liver tissues using quantitative real-time PCR. Results Several variants on a haplotype block spanning intron 11 to intron 12 of SCARB1 showed significant gene by estradiol interaction affecting serum lipid levels, the strongest for rs838895 with HDL-cholesterol (p = 9.2 × 10-4 and triglycerides (p = 1.3 × 10-3 and the triglyceride:HDL cholesterol ratio (p = 2.7 × 10-4. These same variants were associated with expression of the SR-BI isoform in a sex-specific fashion, with the strongest association found among liver tissue from 52 young women Conclusions Estrogen and SCARB1 genotype may act synergistically to regulate expression of SCARB1 isoforms and impact serum levels of HDL cholesterol and triglycerides. This work highlights the importance of considering sex-dependent effects of gene variants on serum lipid levels.

  4. Increased toll-like receptors and p53 levels regulate apoptosis and angiogenesis in non-muscle invasive bladder cancer: mechanism of action of P-MAPA biological response modifier

    International Nuclear Information System (INIS)

    Garcia, Patrick Vianna; Seiva, Fábio Rodrigues Ferreira; Carniato, Amanda Pocol; Mello Júnior, Wilson de; Duran, Nelson; Macedo, Alda Maria; Oliveira, Alexandre Gabarra de; Romih, Rok; Nunes, Iseu da Silva; Nunes, Odilon da Silva; Fávaro, Wagner José

    2016-01-01

    The new modalities for treating patients with non-muscle invasive bladder cancer (NMIBC) for whom BCG (Bacillus Calmette-Guerin) has failed or is contraindicated are recently increasing due to the development of new drugs. Although agents like mitomycin C and BCG are routinely used, there is a need for more potent and/or less-toxic agents. In this scenario, a new perspective is represented by P-MAPA (Protein Aggregate Magnesium-Ammonium Phospholinoleate-Palmitoleate Anhydride), developed by Farmabrasilis (non-profit research network). This study detailed and characterized the mechanisms of action of P-MAPA based on activation of mediators of Toll-like Receptors (TLRs) 2 and 4 signaling pathways and p53 in regulating angiogenesis and apoptosis in an animal model of NMIBC, as well as, compared these mechanisms with BCG treatment. Our results demonstrated the activation of the immune system by BCG (MyD88-dependent pathway) resulted in increased inflammatory cytokines. However, P-MAPA intravesical immunotherapy led to distinct activation of TLRs 2 and 4-mediated innate immune system, resulting in increased interferons signaling pathway (TRIF-dependent pathway), which was more effective in the NMIBC treatment. Interferon signaling pathway activation induced by P-MAPA led to increase of iNOS protein levels, resulting in apoptosis and histopathological recovery. Additionally, P-MAPA immunotherapy increased wild-type p53 protein levels. The increased wild-type p53 protein levels were fundamental to NO-induced apoptosis and the up-regulation of BAX. Furthermore, interferon signaling pathway induction and increased p53 protein levels by P-MAPA led to important antitumor effects, not only suppressing abnormal cell proliferation, but also by preventing continuous expansion of tumor mass through suppression of angiogenesis, which was characterized by decreased VEGF and increased endostatin protein levels. Thus, P-MAPA immunotherapy could be considered an important therapeutic

  5. Increased toll-like receptors and p53 levels regulate apoptosis and angiogenesis in non-muscle invasive bladder cancer: mechanism of action of P-MAPA biological response modifier.

    Science.gov (United States)

    Garcia, Patrick Vianna; Seiva, Fábio Rodrigues Ferreira; Carniato, Amanda Pocol; de Mello Júnior, Wilson; Duran, Nelson; Macedo, Alda Maria; de Oliveira, Alexandre Gabarra; Romih, Rok; Nunes, Iseu da Silva; Nunes, Odilon da Silva; Fávaro, Wagner José

    2016-07-07

    The new modalities for treating patients with non-muscle invasive bladder cancer (NMIBC) for whom BCG (Bacillus Calmette-Guerin) has failed or is contraindicated are recently increasing due to the development of new drugs. Although agents like mitomycin C and BCG are routinely used, there is a need for more potent and/or less-toxic agents. In this scenario, a new perspective is represented by P-MAPA (Protein Aggregate Magnesium-Ammonium Phospholinoleate-Palmitoleate Anhydride), developed by Farmabrasilis (non-profit research network). This study detailed and characterized the mechanisms of action of P-MAPA based on activation of mediators of Toll-like Receptors (TLRs) 2 and 4 signaling pathways and p53 in regulating angiogenesis and apoptosis in an animal model of NMIBC, as well as, compared these mechanisms with BCG treatment. Our results demonstrated the activation of the immune system by BCG (MyD88-dependent pathway) resulted in increased inflammatory cytokines. However, P-MAPA intravesical immunotherapy led to distinct activation of TLRs 2 and 4-mediated innate immune system, resulting in increased interferons signaling pathway (TRIF-dependent pathway), which was more effective in the NMIBC treatment. Interferon signaling pathway activation induced by P-MAPA led to increase of iNOS protein levels, resulting in apoptosis and histopathological recovery. Additionally, P-MAPA immunotherapy increased wild-type p53 protein levels. The increased wild-type p53 protein levels were fundamental to NO-induced apoptosis and the up-regulation of BAX. Furthermore, interferon signaling pathway induction and increased p53 protein levels by P-MAPA led to important antitumor effects, not only suppressing abnormal cell proliferation, but also by preventing continuous expansion of tumor mass through suppression of angiogenesis, which was characterized by decreased VEGF and increased endostatin protein levels. Thus, P-MAPA immunotherapy could be considered an important therapeutic

  6. La autorregulación a nivel social desde una perspectiva cibernético axiológica. Social level self regulation from a cybernetic and axiological point of view.

    Directory of Open Access Journals (Sweden)

    Arturo José Sánchez Hernández

    2006-04-01

    Full Text Available El autor comienza explicando el origen del término cibernética y su relación con la teoría de los valores ético-morales. Mas adelante conceptúa los términos: sistema, autorregulación, adaptación, equilibrio, homeostasis, entropía, eficacia y eficiencia. Continúa dando respuesta a la interrogante: ¿Cómo se efectúa la autorregulación a nivel social?, explicando los elementos que participan en la misma. Por último argumenta las características que esta debe tener para que sea correcta desde el punto de vista ético-moralThe author begins explaining the origin of the term cybernetics and its relationship with the ethical -moral values theory. Alter that he defines the terms: system, self-regulation, adaptation, balance, homeostasis, entropy, effectiveness and efficiency. He continues giving answers to the question: How is self-regulation made at social level? Explaining the elements that participate in it. Lastly he argues the characteristics that it should have so that  it be correct from the ethical-moral point of view

  7. Radiation regulation

    International Nuclear Information System (INIS)

    Braithwaite, J.; Grabosky, P.

    1985-01-01

    The five main areas of radiation regulation considered are radiation exposure in the mining of uranium and other minerals, exposure in the use of uranium in nuclear reactors, risks in the transport of radioactive materials and hazards associated with the disposal of used materials. In Australia these problems are regulated by mines departments, the Australian Atomic Energy Commission and radiation control branches in state health departments. Each of these instutional areas of regulation is examined

  8. Up-regulated EMMPRIN/CD147 protein expression might play a role in colorectal carcinogenesis and its subsequent progression without an alteration of its glycosylation and mRNA level.

    Science.gov (United States)

    Zheng, Hua-chuan; Wang, Wei; Xu, Xiao-yan; Xia, Pu; Yu, Miao; Sugiyama, Toshiro; Takano, Yasuo

    2011-04-01

    Extracellular matrix metalloproteinase inducer (EMMPRIN) was reported to involve in the invasion and metastasis of malignancies by regulating the expression of vascular endothelial growth factor (VEGF) in stromal and cancer cells. The study aimed to clarify the role of EMMPRIN expression in tumorigenesis and progression of colorectal carcinomas (CRC). EMMPRIN expression was examined on tissue microarray containing colorectal carcinomas, adenoma and non-neoplastic mucosa (NNM) by immunohistochemistry and in situ hybridization (ISH). Colorectal carcinoma cell lines (DLD-1, HCT-15, SW480 and WiDr) and tissues were studied for EMMPRIN expression by Western blot or RT-PCR, followed by sequencing. All carcinoma cell lines showed EMMPRIN expression at both mRNA and protein levels. Two synonymous mutations were found in carcinoma cell lines at codon109 (GCT → GCC: Ala) or 179 (GAT → GAC: Asp). Frozen CRC tissues displayed higher EMMPRIN expression than paired NNM (P EMMPRIN expression was immunohistochemically stronger in colorectal high-grade adenoma, adenocarcinoma and metastatic carcinoma than non-neoplastic superficial epithelium and low-grade adenoma (P 0.05). Immunohistochemically, EMMPRIN expression was positively correlated with tumor size, depth of invasion, vascular or lymphatic invasion, grade of infiltration (INF), ki-67 and VEGF expression of CRCs (P EMMPRIN expression in CRCs (P EMMPRIN protein expression might contribute to colorectal carcinogenesis without the alteration of its glycosylation and mRNA level. Aberrant EMMPRIN protein expression might promote growth or invasion of CRCs possibly through increased ki-67 expression and inducible angiogenesis via up-regulating VEGF expression.

  9. The power of regulation

    International Nuclear Information System (INIS)

    Lewis, M.G.

    1995-01-01

    Slides accompanying a presentation at The Power of Change Conference in Vancouver, BC in April 1995 about regulations affecting the power industry were presented. Issues addressed included customer choice, incentive regulation changes (price-caps, revenue sharing and pricing flexibility), the reactions of Canadian industry to regulatory changes, and anticipated reactions of the financial markets to changes in regulations. The potential effects of competition and changes that will create competition were discussed. The level of readiness of Canadian financial, ownership and regulatory bodies was discussed. The needs and expectations of investors from a new regulatory regime were quesstimated. Possible alternatives to the present regulatory framework were suggested

  10. Protein-Enriched Liquid Preloads Varying in Macronutrient Content Modulate Appetite and Appetite-Regulating Hormones in Healthy Adults.

    Science.gov (United States)

    Dougkas, Anestis; Östman, Elin

    2016-03-01

    Dietary protein is considered the most satiating macronutrient, yet there is little evidence on whether the effects observed are attributable to the protein or to the concomitant manipulation of carbohydrates and fat. The aim was to examine the effect of consumption of preloads varying in macronutrient content on appetite, energy intake, and biomarkers of satiety. Using a randomized, within-subjects, 2-level factorial design, 36 adults [mean ± SD age: 27 ± 5 y; body mass index (in kg/m(2)): 24.3 ± 1.6) received a breakfast consisting of 1 of 7 isovolumetric (670 mL) and isoenergetic (2100 kJ) liquid preloads matched for energy density and sensory properties but with different macronutrient composition (levels: 9%, 24%, or 40% of energy from protein combined with a carbohydrate-to-fat ratio of 0.4, 2, or 3.6, respectively). Appetite ratings and blood samples were collected and assessed at baseline and every 30 and 60 min, respectively, until a lunch test meal, which participants consumed ad libitum, was served 3.5 h after breakfast. Prospective consumption was 12% lower after intake of the high-protein (40%)/3.6 carbohydrate:fat preload than after intake of the low-protein (9%)/0.4 carbohydrate:fat preload (P = 0.02) solely because of the increased protein, irrespective of the manipulation of the other macronutrients. Most appetite ratings tended to be suppressed (13%) with increasing protein content of the preloads (P appetite than did carbohydrates and fat. Modulating the nutritional profile of a meal by replacing fat with protein can influence appetite in healthy adults. This trial was registered at www.clinicaltrials.gov as NCT01849302. © 2016 American Society for Nutrition.

  11. Serum Levels of IL-1β, IL-6, TGF-β, and MMP-9 in Patients Undergoing Carotid Artery Stenting and Regulation of MMP-9 in a New In Vitro Model of THP-1 Cells Activated by Stenting

    Directory of Open Access Journals (Sweden)

    Rongrong Zhang

    2015-01-01

    Full Text Available Inflammation plays an important role in the pathophysiological process after carotid artery stenting (CAS. Monocyte is a significant source of inflammatory cytokines in vascular remodeling. Telmisartan could reduce inflammation. In our study, we first found that, after CAS, the serum IL-1β, IL-6, TGF-β, and MMP-9 levels were significantly increased, but only MMP-9 level was elevated no less than 3 months. Second, we established a new in vitro model, where THP-1 monocytes were treated with the supernatants of human umbilical vein endothelial cells (HUVECs that were scratched by pipette tips, which mimics monocytes activated by mechanical injury of stenting. The treatment enhanced THP-1 cell adhesion, migration and invasion ability, and the phosphorylation of ERK1/2 and Elk-1 and MMP-9 expression were significantly increased. THP-1 cells pretreated with PD98095 (ERK1/2 inhibitor attenuated the phosphorylation of ERK1/2 and Elk-1 and upregulation of MMP-9, while pretreatment with telmisartan merely decreased the phosphorylation of Elk-1 and MMP-9 expression. These results suggested that IL-1β, IL-6, TGF-β, and MMP-9 participate in the pathophysiological process after CAS. Our new in vitro model mimics monocytes activated by stenting. MMP-9 expression could be regulated through ERK1/2/Elk-1 pathway, and the protective effects of telmisartan after stenting are partly attributed to its MMP-9 inhibition effects via suppression of Elk-1.

  12. Hypermethylation of MIR21 in CD4+ T cells from patients with relapsing-remitting multiple sclerosis associates with lower miRNA-21 levels and concomitant up-regulation of its target genes

    KAUST Repository

    Ruhrmann, Sabrina

    2017-08-02

    Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system caused by genetic and environmental factors. DNA methylation, an epigenetic mechanism that controls genome activity, may provide a link between genetic and environmental risk factors.We sought to identify DNA methylation changes in CD4+ T cells in patients with relapsing-remitting (RR-MS) and secondary-progressive (SP-MS) disease and healthy controls (HC).We performed DNA methylation analysis in CD4+ T cells from RR-MS, SP-MS, and HC and associated identified changes with the nearby risk allele, smoking, age, and gene expression.We observed significant methylation differences in the VMP1/MIR21 locus, with RR-MS displaying higher methylation compared to SP-MS and HC. VMP1/MIR21 methylation did not correlate with a known MS risk variant in VMP1 or smoking but displayed a significant negative correlation with age and the levels of mature miR-21 in CD4+ T cells. Accordingly, RR-MS displayed lower levels of miR-21 compared to SP-MS, which might reflect differences in age between the groups, and healthy individuals and a significant enrichment of up-regulated miR-21 target genes.Disease-related changes in epigenetic marking of MIR21 in RR-MS lead to differences in miR-21 expression with a consequence on miR-21 target genes.

  13. The international radioactive transportation regulations: A model for national regulations

    International Nuclear Information System (INIS)

    Pope, R.B.; Rawl, R.R.

    1990-06-01

    The International Atomic Energy Agency's (IAEA) Regulations for the Safe Transport of Radioactive Material, Safety Series No. 6 (herein after denoted as the ''International Regulations'') serve as the model for the regulations for individual countries and international modal organizations controlling the packaging and transportation of radioactive materials. The purpose of this paper is to outline the background and history of the International Regulations, the general principles behind the requirements of the International Regulations, the structure and general contents of the latest edition of the International Regulations, and the roles of various international bodies in the development and implementation of the International Regulations and the current status of regulatory and supportive document development at both the international and domestic level. This review will provide a basis for users and potential users to better understand the source and application of the International Regulations. 1 tab

  14. Impact of Rye Kernel-Based Evening Meal on Microbiota Composition of Young Healthy Lean Volunteers With an Emphasis on Their Hormonal and Appetite Regulations, and Blood Levels of Brain-Derived Neurotrophic Factor

    Directory of Open Access Journals (Sweden)

    Olena Prykhodko

    2018-05-01

    Full Text Available Rye kernel bread (RKB evening meals improve glucose tolerance, enhance appetite regulation and increase satiety in healthy volunteers. These beneficial effects on metabolic responses have been shown to be associated with increased gut fermentation. The present study aimed to elucidate if RKB evening meals may cause rapid alterations in microbiota composition that might be linked to metabolic-, immune-, and appetite- parameters. Gut-brain axis interaction was also studied by relating microbiota composition to amount of brain-derived neurotrophic factor (BDNF in blood plasma. Nineteen healthy volunteers, ten women and nine men aged 22–29 years, BMI < 25 (NCT02093481 participated in the study performed in a crossover design. Each person was assigned to either white wheat bread (WWB or RKB intake as a single evening meal or three consecutive evenings. Stool and blood samples as well as subjective appetite ratings were obtained the subsequent morning after each test occasion, resulting in four independent collections per participant (n = 76. DNA was extracted from the fecal samples and V4 hypervariable region of the bacterial 16S rRNA genes was sequenced using next generation sequencing technology. Higher abundance of Prevotella and Faecalibacterium with simultaneous reduction of Bacteroides spp. were observed after RKB meals compared to WWB. The associations between metabolic test variables and microbiota composition showed a positive correlation between Bacteroides and adiponectin levels, whereas only Prevotella genus was found to have positive association with plasma levels of BDNF. These novel findings in gut-brain interactions might be of importance, since decreased levels of BDNF, that plays an essential role in brain function, contribute to the pathogenesis of several major neurodisorders, including Alzheimer's. Thus, daily consumption of Faecalibacterium- and/or Prevotella-favoring meals should be investigated further for their potential to

  15. Closeout technical report for DOE award number DE-FG02-97ER62332 [Nitrogen budget under elevated CO{sub 2} levels: regulation by absorption and assimilation

    Energy Technology Data Exchange (ETDEWEB)

    BassiriRad, Hormoz; Gutschick, Vincent

    2001-10-01

    This entire project was conducted between 1995 and 1999, during which two postdocs and numerous undergraduate students received training in research. Furthermore, the funds from this grant contributed either totally or partially to the publication of 14 refereed journal articles. The focus of this research was to investigate plant nitrogen budget under elevated CO{sub 2} concentration. Of particular interest were the following: (1) Does elevated CO{sub 2} increase root carbohydrate availability? (2) Does such an enhancement increase kinetics of root nitrogen acquisition? (3) Does the effect on kinetics differ between NH{sub 4}{sup +} and NO{sub 3}{sup -}? (4) If there are interspecific differences in (1)-(3), could those variations lead to changes in community composition? This report shows that, although root carbohydrate availability often increases in response to elevated CO{sub 2}, such an increase is neither necessary nor directly related to changes in root N uptake kinetics . The data also show that, depending on species, the effects of elevated CO{sub 2} on root nitrogen uptake kinetics ranges from down regulation to no changes to up regulation. Furthermore, the effects on NH{sub 4}{sup +} are not always similar to the effects on NO{sub 3}{sup -}. Perhaps the most critical finding is the fact that in many instances a change in root N uptake kinetics alone does not provide a reliable prediction of plant N acquisition in response to elevated CO{sub 2}. It is shown that a better examination of whether plant N uptake responds to CO{sub 2} level and whether such a response can be scaled up to community level processes would require integration of knowledge of other root system characteristics. For example, it is well established that mycorrhizal fungi are important regulators of plant N uptake. The data suggest that, while elevated CO{sub 2} affects root N uptake capacity, this effect is highly dependent on the type and level of the mycorrhizal infection. Another

  16. Time- and dose-dependent differential regulation of copper-zinc superoxide dismutase and manganese superoxide dismutase enzymatic activity and mRNA level by vitamin E in rat blood cells.

    Science.gov (United States)

    Hajiani, Maliheh; Razi, Farideh; Golestani, Aboualfazl; Frouzandeh, Mehdi; Owji, Ali Akbar; Khaghani, Shahnaz; Ghannadian, Naghmeh; Shariftabrizi, Ahmad; Pasalar, Parvin

    2012-01-01

    Vitamin E is the most important lipid-soluble antioxidant. Recently, it has been proposed as a gene regulator, and its gene modulation effects have been observed at different levels of gene expression and cell signaling. This study was performed to investigate the effects of vitamin E on the activity and expression of the most important endogenous antioxidant enzyme, superoxide dismutase (SOD), in rat plasma. Twenty-eight male Sprauge-Dawley rats were divided into four groups: control group and three dosing groups. The control group received the vehicle (liquid paraffin), and the dosing groups received twice-weekly intraperitoneal injections of 10, 30, and 100 mg/kg of vitamin E ((±)-α-Tocopherol) for 6 weeks. Quantitative real-time reverse transcription-polymerase chain reaction and enzyme assays were used to assess the levels of Cu/Zn-SOD and Mn-SOD mRNA and enzyme activity levels in blood cells at 0, 2, 4, and 6 weeks following vitamin E administration. Catalase enzyme activity and total antioxidant capacity were also assessed in plasma at the same time intervals. Mn-SOD activity was significantly increased in the 100 and 30 mg/kg dosing groups after 4 and 6 weeks, with corresponding significant increase in their mRNA levels. Cu/Zn-SOD activity was not significantly changed in response to vitamin E administration at any time points, whereas Cu/Zn-SOD mRNA levels were significantly increased after longer time points with high doses (30 and 100 mg/kg) of vitamin E. Catalase enzyme activity was transiently but significantly increased after 4 weeks of vitamin E treatment in 30 and 100 mg/kg dosing groups. Total antioxidant status was significantly increased after 4 and 6 weeks in the 100 mg/kg dosing group. Only the chronic administration of higher doses of alpha-tocopherol is associated with the increased activity and expression of Mn-SOD in rats. Cu/Zn-SOD activity and expression does not dramatically change in response to vitamin E.

  17. Skeletal Muscle Estrogen Receptor Activation in Response to Eccentric Exercise Up-Regulates Myogenic-Related Gene Expression Independent of Differing Serum Estradiol Levels Occurring during the Human Menstrual Cycle.

    Science.gov (United States)

    Haines, Mackenzie; McKinley-Barnard, Sarah K; Andre, Thomas L; Gann, Josh J; Hwang, Paul S; Willoughby, Darryn S

    2018-03-01

    This study sought to determine if the differences in serum estradiol we have previously observed to occur during the mid-follicular (MF) and mid-luteal (ML) phases of the female menstrual cycle could be attributed to estrogen-induced receptor activation and subsequent effects on myogenic-related genes which may otherwise impact muscle regeneration in response to eccentric exercise. Twenty-two physically-active females (20.9 ± 1.4 years, 63.5 ± 9.0 kg, 1.65 ± 0.08 m) underwent an eccentric exercise bout of the knee extensors during the MF and ML phases of their 28-day menstrual cycle. Prior to (PRE), at 6 (6HRPOST), and 24 (24HRPOST) hours post-exercise for each session, participants had muscle biopsies obtained. Skeletal muscle estradiol and estrogen receptor-α (ER-α) content and ER-DNA binding were determined with ELISA. Real-time PCR was used to assess ER-α, Myo-D, and cyclin D1 mRNA expression. Data were analyzed utilizing a 2 x 3 repeated measures univariate analyses of variance (ANOVA) for each criterion variable (p ≤ .05). Skeletal muscle estradiol levels were not significantly impacted by either menstrual phase (p > 0.05); however, both ER-α mRNA and protein were significantly increased during MF (p < 0.05). ER-DNA binding and Myo-D mRNA expression increased significantly in both menstrual phases in response to exercise but were not different from one another; however, cyclin D1 mRNA expression was significantly greater during MF. This study demonstrates that skeletal muscle ER-α activation in response to eccentric exercise up-regulates myogenic-related gene expression independent of serum estradiol levels occurring during the human menstrual cycle.

  18. Fast Green FCF Alleviates Pain Hypersensitivity and Down-Regulates the Levels of Spinal P2X4 Expression and Pro-inflammatory Cytokines in a Rodent Inflammatory Pain Model

    Directory of Open Access Journals (Sweden)

    Fang Xu

    2018-05-01

    Full Text Available Fast Green FCF (FGF, a biocompatible dye, recently drew attention as a potential drug to treat amyloid-deposit diseases due to its effects against amyloid fibrillogenesis in vitro and a high degree of safety. However, its role in inflammatory pain is unknown. Our study aimed to investigate the effect of FGF in the inflammatory pain model induced by complete Freund’s adjuvant (CFA and to identify the associated mechanisms. We found that systemic administration of FGF reversed mechanical and thermal pain hypersensitivity evoked by CFA in a dose-dependent manner. FGF treatment decreased purinergic spinal P2X4 expression in the spinal cord of CFA-inflamed mice. FGF also down-regulated spinal and peripheral pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β, and interleukin-6 (IL-6], but did not alter the spinal level of nerve growth factor (NGF or brain-derived neurotrophic factor (BDNF. In conclusion, our results suggest the potential of FGF for controlling the progress of inflammatory pain.

  19. Nondissipative optimum charge regulator

    Science.gov (United States)

    Rosen, R.; Vitebsky, J. N.

    1970-01-01

    Optimum charge regulator provides constant level charge/discharge control of storage batteries. Basic power transfer and control is performed by solar panel coupled to battery through power switching circuit. Optimum controller senses battery current and modifies duty cycle of switching circuit to maximize current available to battery.

  20. Fisheries regulation

    DEFF Research Database (Denmark)

    Jensen, Frank; Frost, Hans Staby; Abildtrup, Jens

    2017-01-01

    Economists normally claim that a stock externality arises within fisheries because each individual fisherman does not take the effect on stock size into account when making harvest decisions. Due to the stock externality, it is commonly argued that fisheries regulation is necessary, but regulatory...... decisions are complicated by a tremendous amount of uncertainty and asymmetric information. This paper provides an overview of selected parts of the literature on the regulation of fisheries under uncertainty and asymmetric information, and possible areas for future research are identified. Specifically...

  1. French regulations

    International Nuclear Information System (INIS)

    Ballereau, P.

    1998-01-01

    In this issue are given the new French regulations relative to radiation protection of temporary personnel, the licensing to release gaseous and liquid wastes and the licensing granted to thirty two laboratories using beta and gamma decay radioisotopes. (N.C.)

  2. Understanding Regulation of Metabolism through Feasibility Analysis

    NARCIS (Netherlands)

    Nikerel, I.E.; Berkhout, J.; Hu, F.; Teusink, B.; Reinders, M.J.T.; De Ridder, D.

    2012-01-01

    Understanding cellular regulation of metabolism is a major challenge in systems biology. Thus far, the main assumption was that enzyme levels are key regulators in metabolic networks. However, regulation analysis recently showed that metabolism is rarely controlled via enzyme levels only, but

  3. High glucose enhances cAMP level and extracellular signal-regulated kinase phosphorylation in Chinese hamster ovary cell: Usage of Br-cAMP in foreign protein β-galactosidase expression.

    Science.gov (United States)

    Lin, Hsiao-Hsien; Lee, Tsung-Yih; Liu, Ting-Wei; Tseng, Ching-Ping

    2017-07-01

    Glucose is a carbon source for Chinese hamster ovary (CHO) cell growth, while low growth rate is considered to enhance the production of recombinant proteins. The present study reveals that glucose concentrations higher than 1 g/L reduce the growth rate and substantially increase in cAMP (∼300%) at a high glucose concentration (10 g/L). High glucose also enhances the phosphorylation of extracellular signal-regulated kinase (ERK) and p27 kip by Western blot analysis. To determine whether the phosphorylation of ERK is involved in the mechanism, a cyclic-AMP dependent protein kinase A (PKA) inhibitor (H-8) or MEK (MAPKK) inhibitor (PD98059) was added to block ERK phosphorylation. We show that both the high glucose-induced ERK phosphorylation and growth rate return to baseline levels. These results suggest that the cAMP/PKA and MAP signaling pathways are involved in the abovementioned mechanism. Interestingly, the direct addition of 8-bromo-cAMP (Br-cAMP), a membrane-permeable cAMP analog, can mimic the similar effects produced by high glucose. Subsequently Br-cAMP could induce β-galactosidase (β-Gal) recombinant protein expression by 1.6-fold. Furthermore, Br-cAMP can additionally enhance the β-Gal production (from 2.8- to 4.5-fold) when CHO cells were stimulated with glycerol, thymidine, dimethyl sulfoxide, pentanoic acid, or sodium butyrate. Thus, Br-cAMP may be used as an alternative agent in promoting foreign protein expression for CHO cells. Copyright © 2017. Published by Elsevier B.V.

  4. Genome-Scale Co-Expression Network Comparison across Escherichia coli and Salmonella enterica Serovar Typhimurium Reveals Significant Conservation at the Regulon Level of Local Regulators Despite Their Dissimilar Lifestyles

    Science.gov (United States)

    Zarrineh, Peyman; Sánchez-Rodríguez, Aminael; Hosseinkhan, Nazanin; Narimani, Zahra; Marchal, Kathleen; Masoudi-Nejad, Ali

    2014-01-01

    Availability of genome-wide gene expression datasets provides the opportunity to study gene expression across different organisms under a plethora of experimental conditions. In our previous work, we developed an algorithm called COMODO (COnserved MODules across Organisms) that identifies conserved expression modules between two species. In the present study, we expanded COMODO to detect the co-expression conservation across three organisms by adapting the statistics behind it. We applied COMODO to study expression conservation/divergence between Escherichia coli, Salmonella enterica, and Bacillus subtilis. We observed that some parts of the regulatory interaction networks were conserved between E. coli and S. enterica especially in the regulon of local regulators. However, such conservation was not observed between the regulatory interaction networks of B. subtilis and the two other species. We found co-expression conservation on a number of genes involved in quorum sensing, but almost no conservation for genes involved in pathogenicity across E. coli and S. enterica which could partially explain their different lifestyles. We concluded that despite their different lifestyles, no significant rewiring have occurred at the level of local regulons involved for instance, and notable conservation can be detected in signaling pathways and stress sensing in the phylogenetically close species S. enterica and E. coli. Moreover, conservation of local regulons seems to depend on the evolutionary time of divergence across species disappearing at larger distances as shown by the comparison with B. subtilis. Global regulons follow a different trend and show major rewiring even at the limited evolutionary distance that separates E. coli and S. enterica. PMID:25101984

  5. Exploring individual cognitions, self-regulation skills, and environmental-level factors as mediating variables of two versions of a Web-based computer-tailored nutrition education intervention aimed at adults: A randomized controlled trial.

    Science.gov (United States)

    Springvloet, Linda; Lechner, Lilian; Candel, Math J J M; de Vries, Hein; Oenema, Anke

    2016-03-01

    This study explored whether the determinants that were targeted in two versions of a Web-based computer-tailored nutrition education intervention mediated the effects on fruit, high-energy snack, and saturated fat intake among adults who did not comply with dietary guidelines. A RCT was conducted with a basic (tailored intervention targeting individual cognitions and self-regulation), plus (additionally targeting environmental-level factors), and control group (generic nutrition information). Participants were recruited from the general Dutch adult population and randomly assigned to one of the study groups. Online self-reported questionnaires assessed dietary intake and potential mediating variables (behavior-specific cognitions, action- and coping planning, environmental-level factors) at baseline and one (T1) and four (T2) months post-intervention (i.e. four and seven months after baseline). The joint-significance test was used to establish mediating variables at different time points (T1-mediating variables - T2-intake; T1-mediating variables - T1-intake; T2-mediating variables - T2-intake). Educational differences were examined by testing interaction terms. The effect of the plus version on fruit intake was mediated (T2-T2) by intention and fruit availability at home and for high-educated participants also by attitude. Among low/moderate-educated participants, high-energy snack availability at home mediated (T1-T1) the effect of the basic version on high-energy snack intake. Subjective norm mediated (T1-T1) the effect of the basic version on fat intake among high-educated participants. Only some of the targeted determinants mediated the effects of both intervention versions on fruit, high-energy snack, and saturated fat intake. A possible reason for not finding a more pronounced pattern of mediating variables is that the educational content was tailored to individual characteristics and that participants only received feedback for relevant and not for all

  6. Contract & agency labour: beyond self-regulation?

    OpenAIRE

    Cotton, Elizabeth

    2010-01-01

    A paper about the regulation of contract labour. Academic and legal aspects as well as case studies of global union federation work to organise and regulate contract labour in Thailand, Pakistan, Colombia, South Korea and at international level.

  7. Regulating Internalities

    OpenAIRE

    Sunstein, Cass Robert; Allcott, Hunt

    2015-01-01

    This paper offers a framework for regulating internalities. Using a simple economic model, we provide four principles for designing and evaluating behaviorally-motivated policy. We then outline rules for determining which contexts reliably reflect true preferences and discuss empirical strategies for measuring internalities. As a case study, we focus on energy efficiency policy, including Corporate Average Fuel Economy (CAFE) standards and appliance and lighting energy efficiency standards.

  8. Post-translational regulation enables robust p53 regulation.

    Science.gov (United States)

    Shin, Yong-Jun; Chen, Kai-Yuan; Sayed, Ali H; Hencey, Brandon; Shen, Xiling

    2013-08-30

    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. 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. Our analyses suggest that the p53-Mdm2 feedback favors regulatory mechanisms that provide the optimal trade-offs for dynamic control.

  9. REGULATION OF NATIONAL QUALIFICATIONS SYSTEMS

    Directory of Open Access Journals (Sweden)

    Anna A. Muravyeva

    2014-01-01

    Full Text Available The paper looks into the diverse aspects of qualifications system regulation, designed for balancing the supply and demand in the labor and educational service markets. Both the objects and mechanisms of such regulation are described. Special attention is given to institutions, involved in regulation of qualifications, and their jurisdiction. Another emphasis is on the industry-related regulation of qualifications which proved to be effective both on the national and European level. Such structures were first established on the national levels to regulate the qualifications and ensure their comparability and compatibility, given the economic globalization and growing labor and academic mobility. The author points out the role of the ministries of education and labor in maintaining a steady qualifications system, and outlines the positive experience of Great Britain using the industry councils for continuing development of qualifications system.

  10. Human telomerase activity regulation

    OpenAIRE

    Wojtyla, Aneta; Gladych, Marta; Rubis, Blazej

    2010-01-01

    Telomerase has been recognized as a relevant factor distinguishing cancer cells from normal cells. Thus, it has become a very promising target for anticancer therapy. The cell proliferative potential can be limited by replication end problem, due to telomeres shortening, which is overcome in cancer cells by telomerase activity or by alternative telomeres lengthening (ALT) mechanism. However, this multisubunit enzymatic complex can be regulated at various levels, including expression control b...

  11. Environmental Regulation

    Data.gov (United States)

    Kansas Data Access and Support Center — KR305b 1994 coverage, used to support water quality programs, references water quality use designations and support levels. The KR305b 1994 coverage is available for...

  12. Effectiveness of the Self-Regulation eHealth Intervention "MyPlan1.0." on Physical Activity Levels of Recently Retired Belgian Adults: A Randomized Controlled Trial

    Science.gov (United States)

    Van Dyck, Delfien; Plaete, Jolien; Cardon, Greet; Crombez, Geert; De Bourdeaudhuij, Ilse

    2016-01-01

    The study purpose was to test the effectiveness of the self-regulation eHealth intervention "MyPlan1.0." to increase physical activity (PA) in recently retired Belgian adults. This study was a randomized controlled trial with three points of follow-up/modules (baseline to 1-week to 1-month follow-up). In total, 240 recently retired…

  13. Nuclear regulation

    International Nuclear Information System (INIS)

    1990-04-01

    Because of an accidental release in 1986 of low-level waste stored at the Wright-Patterson Air Force Base, Ohio, several individuals inhaled small amounts of a radioactive substance. GAO examined the Nuclear Regulatory Commission's oversight of the Department of Defense's use, handling, and disposal of radioactive material and found that no comprehensive DOD waste disposal program exists and none of the three services knows the full extent of its low-level radioactive waste disposal problems. Throughout the 1980s, the Army and the Air Force had, on occasion, been banned from disposal sites for failing to comply with federal and state requirements. By December 1992, two of the three sites now used by DOD to disposed of waste will close, and only a limited number of new sites may be available for several years. In the interim, DID will pay substantial surcharges to dispose of waste. After January 1993, DOD will have to comply with disposal requirements for as many as 16 sites or store waste on-site pending the availability of new sites. This report discusses how GAO believes DOD needs to take full advantage of the time between now and January 1993 to establish a low-level radioactive waste disposal program. DOD also needs to work with other federal agencies, compacts, and states to determine the feasibility of dedicating a portion of one or more disposal sites for the government's use

  14. The genetic variation rs6903956 in the novel androgen-dependent tissue factor pathway inhibitor regulating protein (ADTRP) gene is not associated with levels of plasma coagulation factors in the Singaporean Chinese

    OpenAIRE

    Chang, Xuling; Chin, Hui-Lin; Quek, Swee-Chye; Goh, Daniel Y. T.; Dorajoo, Rajkumar; Friedlander, Yechiel; Heng, Chew-Kiat

    2017-01-01

    Background Genome-wide association study (GWAS) has reported that rs6903956 within the first intron of androgen-dependent tissue factor pathway inhibitor (TFPI) regulating protein (ADTRP) gene is associated with coronary artery disease (CAD) risk in the Chinese population. Although ADTRP is believed to be involved in the upregulation of TFPI, the underlying mechanism involved is largely unknown. This study investigated the association of rs6903956 with plasma Factor VII coagulant activity (FV...

  15. Markets, religion, regulation

    DEFF Research Database (Denmark)

    Fischer, Johan

    2016-01-01

    Most recent scholarship on moral economies or religious markets argues for the compatibility of economies/markets and religious practices in particular national or regional contexts. However, over the last couple of decades or so religious markets have entered a new phase characterized by new forms...... of regulation, certification and standardization on a global scale. Building on research on global kosher (a Hebrew term meaning “fit” or “proper”), halal (an Arabic word that literally means “permissible” or “lawful”) and Hindu vegetarianism this paper argues that these economies or markets to a large extent...... are conditioned by and themselves condition forms of transnational governmentality, that is, new and often overlapping practices of government and grassroots politics. I explore religious economies and markets at three interrelated levels of the social scale: state and non-state regulation, the marketplace...

  16. PPARγ regulates exocrine pancreas lipase.

    Science.gov (United States)

    Danino, Hila; Naor, Ronny Peri-; Fogel, Chen; Ben-Harosh, Yael; Kadir, Rotem; Salem, Hagit; Birk, Ruth

    2016-12-01

    Pancreatic lipase (triacylglycerol lipase EC 3.1.1.3) is an essential enzyme in hydrolysis of dietary fat. Dietary fat, especially polyunsaturated fatty acids (PUFA), regulate pancreatic lipase (PNLIP); however, the molecular mechanism underlying this regulation is mostly unknown. As PUFA are known to regulate expression of proliferator-activated receptor gamma (PPARγ), and as we identified in-silico putative PPARγ binding sites within the putative PNLIP promoter sequence, we hypothesized that PUFA regulation of PNLIP might be mediated by PPARγ. We used in silico bioinformatics tools, reporter luciferase assay, PPARγ agonists and antagonists, PPARγ overexpression in exocrine pancreas AR42J and primary cells to study PPARγ regulation of PNLIP. Using in silico bioinformatics tools we mapped PPARγ binding sites (PPRE) to the putative promoter region of PNLIP. Reporter luciferase assay in AR42J rat exocrine pancreas acinar cells transfected with various constructs of the putative PNLIP promoter showed that PNLIP transcription is significantly enhanced by PPARγ dose-dependently, reaching maximal levels with multi PPRE sites. This effect was significantly augmented in the presence of PPARγ agonists and reduced by PPARγ antagonists or mutagenesis abrogating PPRE sites. Over-expression of PPARγ significantly elevated PNLIP transcript and protein levels in AR42J cells and in primary pancreas cells. Moreover, PNLIP expression was up-regulated by PPARγ agonists (pioglitazone and 15dPGJ2) and significantly down-regulated by PPARγ antagonists in non-transfected rat exocrine pancreas AR42J cell line cells. PPARγ transcriptionally regulates PNLIP gene expression. This transcript regulation resolves part of the missing link between dietary PUFA direct regulation of PNLIP. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Hygienic regulation of ionizing radiations

    International Nuclear Information System (INIS)

    Saurov, M.M.

    1984-01-01

    Modern state of the problem on hygienic regulation of ionizing radiations is considered. Concepts and principles of the regulation based on risk concept are presented according to ICRP 26 and 27. Two types of risk are designated: ''absolute'' and ''relative'' ones. The concept of acceptable risk on the basis of cost - benefit ratio is substantiated. Special attention is paid to the principle of accounting the complex of health signs, when determining radiation hazard. To determine the level of permissible risk and permissible dose to population the concept of ''inadmissibility of s-tatistically significant risk'' has been developed. Standards, regulating population doses in the USSR, which are valid nowadays, are considered

  18. To regulate or not to regulate?

    Energy Technology Data Exchange (ETDEWEB)

    Mason, G.; Wrixon, A. [IAEA, Vienna (Austria)

    2006-07-01

    Full text of publication follows: In Hamlet famous soliloquy to be or not to be, he wrestles with the perennial human problem of choosing the right course of action in difficult circumstances. In recent years, we have witnessed a cast of thousands playing out a long-running scene that seems to echo Hamlet dilemma on a rather more prosaic level. When is it necessary to apply regulations to the control of exposure to ionizing radiation and when is regulatory control not warranted? This seemingly straightforward question has brought out the philosopher, ethician, lawyer, pragmatist, orator in simple radiation protection folk and has led to passionate debate on numerous occasions. This paper attempts an answer based on a review of recent developments. For deciding when to apply regulatory controls, several concepts have evolved over time, including exemption of practices and sources, exclusion of exposures and clearance of materials. These have different origins, purposes and characteristics. Exemption and clearance have often been associated with triviality of risk, while exclusion has been related to un-amenability of control. For each concept, criteria have been developed to assist the regulator in reaching a decision, but there has much disputation over numerical values. This paper briefly reviews and analyses recent developments and attempts to clarify the problem from first principles. The conclusion is that the underlying issue in each case is to determine when regulatory controls become unwarranted: that is, when the societal resources expended in applying them and complying with them would be disproportionate to any benefit they might bring. This is a natural extension of the principle of optimization of protection to the regulatory control of protection, in the context of exposure to radiation at very low levels. It also reflects common expectations of good governance: wise management of finite societal resources and avoidance of unwarranted controls on

  19. To regulate or not to regulate?

    International Nuclear Information System (INIS)

    Mason, G.; Wrixon, A.

    2006-01-01

    Full text of publication follows: In Hamlet famous soliloquy to be or not to be, he wrestles with the perennial human problem of choosing the right course of action in difficult circumstances. In recent years, we have witnessed a cast of thousands playing out a long-running scene that seems to echo Hamlet dilemma on a rather more prosaic level. When is it necessary to apply regulations to the control of exposure to ionizing radiation and when is regulatory control not warranted? This seemingly straightforward question has brought out the philosopher, ethician, lawyer, pragmatist, orator in simple radiation protection folk and has led to passionate debate on numerous occasions. This paper attempts an answer based on a review of recent developments. For deciding when to apply regulatory controls, several concepts have evolved over time, including exemption of practices and sources, exclusion of exposures and clearance of materials. These have different origins, purposes and characteristics. Exemption and clearance have often been associated with triviality of risk, while exclusion has been related to un-amenability of control. For each concept, criteria have been developed to assist the regulator in reaching a decision, but there has much disputation over numerical values. This paper briefly reviews and analyses recent developments and attempts to clarify the problem from first principles. The conclusion is that the underlying issue in each case is to determine when regulatory controls become unwarranted: that is, wh