KAJIAN PENERAPAN GOOD MANUFACTURING PRACTICE (GMP DI INDUSTRI RAJUNGAN PT.KELOLA MINA LAUT MADURA

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Bhiaztika Ristyanadi

2016-11-01

Full Text Available Good manufacturing practice is the first step implementation of food safety regulation. PT. Kelola Mina Laut is one of chilled sea crab producers in Madura. It has four branches in Madura,those are in Tanjung Bumi, Noreh, Sampang, and Lobuk. The objective of this research is to assess the effectiveness GMP in four branches of PT. Kelola Mina Laut. The research  uses field observation, data analysis and GMP development as the method. Based on GMP analysis, four branches of PT. Kelola Mina Laut appear to have a cummulative score between 337-369, in which Lobuk has the highest score. Therefore, it can be concluded that PT. Kelola Mina Laut has applied most of GMP elements

C-di-GMP regulates antimicrobial peptide resistance in Pseudomonas aeruginosa

DEFF Research Database (Denmark)

Chua, Song Lin; Tan, Sean Yang-Yi; Rybtke, Morten Theil

2013-01-01

Bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) is an intracellular second messenger which controls the life styles of many bacteria. A high intracellular level of c-di-GMP induces a biofilm lifestyle, whereas a low intracellular level of c-di-GMP stimulates dispersal of biofilms and promotes...... a planktonic lifestyle. Here, we used expression of different reporters to show that planktonic cells (PCells), biofilm cells (BCells) and cells dispersed from biofilms (DCells) had distinct intracellular c-di-GMP levels. Proteomics analysis showed that the low intracellular c-di-GMP level of DCells induced...... the expression of proteins required for the virulence and development of antimicrobial peptide resistance in P. aeruginosa. In accordance, P. aeruginosa cells with low c-di-GMP levels were found to be more resistant to colistin than P. aeruginosa cells with high c-di-GMP levels. This contradicts the current...

Guanylin peptides: cyclic GMP signaling mechanisms

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Forte L.R.

1999-01-01

Full Text Available Guanylate cyclases (GC serve in two different signaling pathways involving cytosolic and membrane enzymes. Membrane GCs are receptors for guanylin and atriopeptin peptides, two families of cGMP-regulating peptides. Three subclasses of guanylin peptides contain one intramolecular disulfide (lymphoguanylin, two disulfides (guanylin and uroguanylin and three disulfides (E. coli stable toxin, ST. The peptides activate membrane receptor-GCs and regulate intestinal Cl- and HCO3- secretion via cGMP in target enterocytes. Uroguanylin and ST also elicit diuretic and natriuretic responses in the kidney. GC-C is an intestinal receptor-GC for guanylin and uroguanylin, but GC-C may not be involved in renal cGMP pathways. A novel receptor-GC expressed in the opossum kidney (OK-GC has been identified by molecular cloning. OK-GC cDNAs encode receptor-GCs in renal tubules that are activated by guanylins. Lymphoguanylin is highly expressed in the kidney and heart where it may influence cGMP pathways. Guanylin and uroguanylin are highly expressed in intestinal mucosa to regulate intestinal salt and water transport via paracrine actions on GC-C. Uroguanylin and guanylin are also secreted from intestinal mucosa into plasma where uroguanylin serves as an intestinal natriuretic hormone to influence body Na+ homeostasis by endocrine mechanisms. Thus, guanylin peptides control salt and water transport in the kidney and intestine mediated by cGMP via membrane receptors with intrinsic guanylate cyclase activity.

Multiple Degradation Pathways of Chemoattractant Mediated Cyclic GMP Accumulation in Dictyostelium

NARCIS (Netherlands)

Haastert, Peter J.M. van; Lookeren Campagne, Michiel M. van; Kesbeke, Fanja

1983-01-01

Chemoattractants induce a transient accumulation of cGMP levels in Dictyostelium. Intracellular cGMP levels reach a peak at 10 s and prestimulated cGMP levels are recovered at about 30 s. Intracellular and extracellular cGMP levels were detected simultaneously after stimulation of D. lacteum cells

Environmental Monitoring Trendy Study for cGMP Tc-99m Production at Nuclear Malaysia for the Year 2014

International Nuclear Information System (INIS)

Bohari Yaacob; Manisah Saedon; Fazliana Mohd Saaya

2015-01-01

Nuclear Malaysia is engaged to produce quality promising Tc-99m generator for the medical usage which is carried out at the production area of block 21, compromise of grade A, C and D clean room. This study applies to the trending of the environmental monitoring of the clean room for the year 2014 in order to ensure that the clean room complies with the cGMP requirement in term of environmental specification which is room temperature, relative humidity, room pressure and particle count. The room temperature specification is 22±2 degree Celsius and result showed that both preparation and pharmaceutical room are within the limit. But it was found that the result from gowning and degowning room temperature was more than 24 degree Celsius. Whereby, result for average percentage relative humidity of the gowning, preparation, pharmaceutical and degowning rooms were found 51 %.±7, 60 %±4, 61 %±5, 61 %±5 and 58 %±4 respectively are out off the range (< 60 %). The target level of pressure differential for all rooms is 1.5 mmH 2 O and only pharmaceutical room was found not within the target with the reading of 3.3 mmH 2 O±0.5. Result for 16 location showed that particle counts which particles size 5.0 μm were within the limit namely ≤ 2000/ m 3 except location number 21 and 18 in the pharmaceutical room and location number 23 in the degowning rooms were exceeding more than 2000/ m 3 for the month of July 2014. However results for all location particles size of 0.5 μm, were within specification (≤350000/ m 3 ). All location of all rooms with class C grade is within limit that is < 50 CFU of microbiology growth except location number 8, 9 and 10 of preparation room whereby this location is a class A grade. Generally, the environmental monitoring result for the clean room are satisfactory for the year 2014 since all the final product of all batches has passed the sterility and endotoxin test. In conclusion, Malaysian Nuclear Agency had fulfills the cGMP requirement

Correlative intravital imaging of cGMP signals and vasodilation in mice

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Martin eThunemann

2014-10-01

Full Text Available Cyclic guanosine monophosphate (cGMP is an important signaling molecule and drug target in the cardiovascular system. It is well known that stimulation of the vascular nitric oxide (NO-cGMP pathway results in vasodilation. However, the spatiotemporal dynamics of cGMP signals themselves and the cGMP concentrations within specific cardiovascular cell types in health, disease, and during pharmacotherapy with cGMP-elevating drugs are largely unknown. To facilitate the analysis of cGMP signaling in vivo, we have generated transgenic mice that express fluorescence resonance energy transfer (FRET-based cGMP sensor proteins. Here, we describe two models of intravital FRET/cGMP imaging in the vasculature of cGMP sensor mice: (1 epifluorescence-based ratio imaging in resistance-type vessels of the cremaster muscle and (2 ratio imaging by multiphoton microscopy within the walls of subcutaneous blood vessels accessed through a dorsal skinfold chamber. Both methods allow simultaneous monitoring of NO-induced cGMP transients and vasodilation in living mice. Detailed protocols of all steps necessary to perform and evaluate intravital imaging experiments of the vasculature of anesthetized mice including surgery, imaging, and data evaluation are provided. An image segmentation approach is described to estimate FRET/cGMP changes within moving structures such as the vessel wall during vasodilation. The methods presented herein should be useful to visualize cGMP or other biochemical signals that are detectable with FRET-based biosensors, such as cyclic adenosine monophosphate or Ca2+, and to correlate them with respective vascular responses. With further refinement and combination of transgenic mouse models and intravital imaging technologies, we envision an exciting future, in which we are able to ‘watch’ biochemistry, (patho physiology, and pharmacotherapy in the context of a living mammalian organism.

Quality Risk Management: Putting GMP Controls First.

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O'Donnell, Kevin; Greene, Anne; Zwitkovits, Michael; Calnan, Nuala

2012-01-01

This paper presents a practical way in which current approaches to quality risk management (QRM) may be improved, such that they better support qualification, validation programs, and change control proposals at manufacturing sites. The paper is focused on the treatment of good manufacturing practice (GMP) controls during QRM exercises. It specifically addresses why it is important to evaluate and classify such controls in terms of how they affect the severity, probability of occurrence, and detection ratings that may be assigned to potential failure modes or negative events. It also presents a QRM process that is designed to directly link the outputs of risk assessments and risk control activities with qualification and validation protocols in the GMP environment. This paper concerns the need for improvement in the use of risk-based principles and tools when working to ensure that the manufacturing processes used to produce medicines, and their related equipment, are appropriate. Manufacturing processes need to be validated (or proven) to demonstrate that they can produce a medicine of the required quality. The items of equipment used in such processes need to be qualified, in order to prove that they are fit for their intended use. Quality risk management (QRM) tools can be used to support such qualification and validation activities, but their use should be science-based and subject to as little subjectivity and uncertainty as possible. When changes are proposed to manufacturing processes, equipment, or related activities, they also need careful evaluation to ensure that any risks present are managed effectively. This paper presents a practical approach to how QRM may be improved so that it better supports qualification, validation programs, and change control proposals in a more scientific way. This improved approach is based on the treatment of what are called good manufacturing process (GMP) controls during those QRM exercises. A GMP control can be considered

Purification and characterization of cGMP binding protein-phosphodiesterase from rat lung

International Nuclear Information System (INIS)

Francis, S.H.; Walseth, T.F.; Corbin, J.D.

1986-01-01

The cGMP binding protein-phosphodiesterase (cG-BPP) with a phosphodiesterase specific activity of 7 μM/min/mg has been purified from rat lung by sequential chromatography on DEAE-cellulose, Blue-Sepharose, zinc chelate affinity adsorbent and HPLC-DEAE. Migration of the major band on SDS-PAGE corresponds to a MW of ∼93,000. Both cGMP phosphodiesterase activity and cGMP binding from the HPLC-DEAE profile correlate with this band. Since the authors previous work has determined the native MW to be ∼177,000, this suggests a dimeric structure comprised of two 93,000 MW subunits for the rat lung cG-BPP. At low cGMP concentrations, cGMP binding is stimulated ∼20-fold by histone and ∼5-fold by 3-isobutyl-1-methylxanthine(IBMX). The purified protein has one component of cGMP dissociation with a rate constant of 0.045/min. Photolysis of the purified protein in the presence of 32 P-cGMP labels the 93,000 MW band and this labeling is increased by IBMX, indicating that the 93,000 MW band is a subunit of the cGMP-BPP. This implies that the enzyme preparation is nearly homogeneous, a conclusion also supported by a minimum [ 3 H]-cGMP binding stoichiometry of 0.5 mol per 93,000 subunit. An additional protein band with a MW of ∼90,000 also occurs in these preparations which exhibits behavior similar to the 93,000 MW protein. N 2 -Hexyl-cGMP inhibits phosphodiesterase activity by competing with cGMP for hydrolysis at the catalytic site but not at the binding site. N 2 -Hexyl cGMP actually increases cGMP binding. This provides the first evidence that cGMP binding is increased by compounds hydrolyzed at the catalytic site. This interaction between the binding and phosphodiesterase sites could be important in the regulation of the functions of these sites in vivo

Good Manufacturing Practices (GMP) manufacturing of advanced therapy medicinal products: a novel tailored model for optimizing performance and estimating costs.

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Abou-El-Enein, Mohamed; Römhild, Andy; Kaiser, Daniel; Beier, Carola; Bauer, Gerhard; Volk, Hans-Dieter; Reinke, Petra

2013-03-01

Advanced therapy medicinal products (ATMP) have gained considerable attention in academia due to their therapeutic potential. Good Manufacturing Practice (GMP) principles ensure the quality and sterility of manufacturing these products. We developed a model for estimating the manufacturing costs of cell therapy products and optimizing the performance of academic GMP-facilities. The "Clean-Room Technology Assessment Technique" (CTAT) was tested prospectively in the GMP facility of BCRT, Berlin, Germany, then retrospectively in the GMP facility of the University of California-Davis, California, USA. CTAT is a two-level model: level one identifies operational (core) processes and measures their fixed costs; level two identifies production (supporting) processes and measures their variable costs. The model comprises several tools to measure and optimize performance of these processes. Manufacturing costs were itemized using adjusted micro-costing system. CTAT identified GMP activities with strong correlation to the manufacturing process of cell-based products. Building best practice standards allowed for performance improvement and elimination of human errors. The model also demonstrated the unidirectional dependencies that may exist among the core GMP activities. When compared to traditional business models, the CTAT assessment resulted in a more accurate allocation of annual expenses. The estimated expenses were used to set a fee structure for both GMP facilities. A mathematical equation was also developed to provide the final product cost. CTAT can be a useful tool in estimating accurate costs for the ATMPs manufactured in an optimized GMP process. These estimates are useful when analyzing the cost-effectiveness of these novel interventions. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

The brassinosteroid receptor BRI1 can generate cGMP enabling cGMP-dependent downstream signaling

CSIR Research Space (South Africa)

Wheeler, J

2017-06-01

Full Text Available ) with the ll PickUp Injection mode using the loading pump at 15 ll min�1 flow rate for 3 min. Samples were then loaded on a RSLC, 75 lm 9 500 mm, nanoVi- per, C18, 2 lm, 100 �A column (Acclaim, PepMap) retrofitted to an EASY-spray source with a flow rate of 300... receptor BRI1 can generate cGMP enabling cGMP-dependent downstream signaling Janet I. Wheeler1,2,†, Aloysius Wong3,4, Claudius Marondedze3,5, Arnoud J. Groen5, Lusisizwe Kwezi1,6, Lubna Freihat1, Jignesh Vyas1, Misjudeen A. Raji7, Helen R. Irving1...

BolA Is Required for the Accurate Regulation of c-di-GMP, a Central Player in Biofilm Formation.

Science.gov (United States)

Moreira, Ricardo N; Dressaire, Clémentine; Barahona, Susana; Galego, Lisete; Kaever, Volkhard; Jenal, Urs; Arraiano, Cecília M

2017-09-19

mechanisms to cope with environmental stresses. BolA-like proteins are widely conserved from prokaryotes to eukaryotes, and in Escherichia coli , in addition to its pleiotropic effects, this protein plays a determinant role in bacterial motility and biofilm formation regulation. Similarly, the bacterial second messenger c-di-GMP is a molecule with high importance in coordinating the switch between planktonic and sessile life in bacteria. Here we have unravelled the importance of accurate regulation of cross-talk between BolA and c-di-GMP for a proper response in the regulation of these bacterial lifestyles. This finding underlines the complexity of bacterial cell regulation, revealing the existence of one additional tool for fine-tuning such important cellular molecular mechanisms. The relationship between BolA and c-di-GMP gives new perspectives regarding biofilm formation and opens the possibility to extend our studies to other organisms with relevance for human health. Copyright © 2017 Moreira et al.

Cyclic GMP alters Ca exchange in vascular smooth muscle

International Nuclear Information System (INIS)

Magliola, L.; Bailey, B.; Jones, A.W.

1986-01-01

Contraction and 42 K efflux from vascular smooth muscle stimulated either by norepinephrine (NE) or by K-depolarization is dependent on an increase in cytosolic Ca concentration. The purpose of this study was to determine if cyclic GMP (cGMP) inhibited these processes and if inhibition was secondary to the action of cGMP on Ca movements. Basal cGMP content of rat aorta was 1.2 fmol/mg wet wt. Sodium nitroprusside (NP) increased cGMP ∼2-fold at 1 nM and ∼750-fold at 1 μM with no effect on cAMP levels. A 5 min pretreatment with NP (1 μM) completely prevented tension development induced by 3 μM NE. The same concentration of NP also inhibited NE-stimulated 42 K and 45 Ca efflux > 90 and > 80%, respectively. Removal of NP in the continued presence of NE (3 μM) caused recovery of the 42 K efflux response to ∼75% of control with a half-time of ∼2.5 min. NP (1 μM) also caused a rapid relaxation of aorta contracted with 3 μM NE and a loss of the 42 K efflux response with half-times of 2-3 min. In contrast, 100 μM NP produced only a 50% inhibition of contraction induced by high K (55 mM). Also, NP (1 μM) inhibited K-stimulated 42 K efflux only ∼25%. These results demonstrate both a concentration- and a time-dependent relationship between increases in cGMP induced by NP and decreases in NE-stimulated contraction, 42 K and 45 Ca effluxes. They also indicate that the sensitivity of NE-induced contraction and 42 K efflux to NP is greater than that induced by high K. These studies suggest that cGMP modulates the control sites for Ca exchange in the plasma membrane and sarcoplasmic reticulum

The role of cGMP as a mediator of lipolysis in bovine oocytes and its effects on embryo development and cryopreservation.

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Kátia R L Schwarz

Full Text Available This study aimed to determine the influence of cyclic guanosine 3'5'-monophosphate (cGMP and cGMP-dependent kinase (PKG during in vitro maturation (IVM on lipolysis-related parameters in bovine cumulus-oocyte complexes (COCs, and on embryo development and cryosurvival. COCs were matured with cGMP/PKG modulators and assessed for metaphase II rates (MII, cGMP levels, lipid content in oocytes (OO, transcript abundance for genes involved in lipolysis (ATGL and lipid droplets (PLIN2 in cumulus cells (CC and OO, and presence of phosphorylated (active hormone sensitive lipase (HSLser563 in OO. Embryo development, lipid contents and survival to vitrification were also assessed. Phosphodiesterase 5 inhibition (PDE5; cGMP-hydrolyzing enzyme with 10-5M sildenafil (SDF during 24 h IVM increased cGMP in COCs (56.9 vs 9.5 fMol/COC in untreated controls, p<0.05 and did not affect on maturation rate (84.3±6.4% MII. Fetal calf serum (FCS in IVM medium decreased cGMP in COCs compared to bovine serum albumin (BSA + SDF (19.6 vs 66.5 fMol/COC, respectively, p<0.05. FCS increased lipid content in OO (40.1 FI, p<0.05 compared to BSA (34.6 FI, while SDF decreased (29.8 and 29.6 FI, with BSA or FCS, respectively p<0.05. PKG inhibitor (KT5823 reversed this effect (38.9 FI, p<0.05. ATGL and PLIN2 transcripts were detected in CC and OO, but were affected by cGMP and PKG only in CC. HSLser563 was detected in OO matured with or without modulators. Reduced lipid content in embryos were observed only when SDF was added during IVM and IVC (27.6 FI compared to its use in either or none of the culture periods (34.2 FI, p<0.05. Survival to vitrification was unaffected by SDF. In conclusion, cGMP and PKG are involved in lipolysis in OO and possibly in CC and embryos; serum negatively affects this pathway, contributing to lipid accumulation, and cGMP modulation may reduce lipid contents in oocytes and embryos, but without improving embryo cryotolerance.

The Oxidative Stress Agent Hypochlorite Stimulates c-di-GMP Synthesis and Biofilm Formation in Pseudomonas aeruginosa

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Nikola Strempel

2017-11-01

Full Text Available The opportunistic human pathogen Pseudomonas aeruginosa is able to survive under a variety of often harmful environmental conditions due to a multitude of intrinsic and adaptive resistance mechanisms, including biofilm formation as one important survival strategy. Here, we investigated the adaptation of P. aeruginosa PAO1 to hypochlorite (HClO, a phagocyte-derived host defense compound and frequently used disinfectant. In static biofilm assays, we observed a significant enhancement in initial cell attachment in the presence of sublethal HClO concentrations. Subsequent LC-MS analyses revealed a strong increase in cyclic-di-GMP (c-di-GMP levels suggesting a key role of this second messenger in HClO-induced biofilm development. Using DNA microarrays, we identified a 26-fold upregulation of ORF PA3177 coding for a putative diguanylate cyclase (DGC, which catalyzes the synthesis of the second messenger c-di-GMP – an important regulator of bacterial motility, sessility and persistence. This DGC PA3177 was further characterized in more detail demonstrating its impact on P. aeruginosa motility and biofilm formation. In addition, cell culture assays attested a role for PA3177 in the response of P. aeruginosa to human phagocytes. Using a subset of different mutants, we were able to show that both Pel and Psl exopolysaccharides are effectors in the PA3177-dependent c-di-GMP network.

Luteinizing hormone signaling phosphorylates and activates the cyclic GMP phosphodiesterase PDE5 in mouse ovarian follicles, contributing an additional component to the hormonally induced decrease in cyclic GMP that reinitiates meiosis.

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Egbert, Jeremy R; Yee, Siu-Pok; Jaffe, Laurinda A

2018-03-01

Prior to birth, oocytes within mammalian ovarian follicles initiate meiosis, but then arrest in prophase until puberty, when with each reproductive cycle, one or more follicles are stimulated by luteinizing hormone (LH) to resume meiosis in preparation for fertilization. Within preovulatory follicles, granulosa cells produce high levels of cGMP, which diffuses into the oocyte to maintain meiotic arrest. LH signaling restarts meiosis by rapidly lowering the levels of cGMP in the follicle and oocyte. Part of this decrease is mediated by the dephosphorylation and inactivation the NPR2 guanylyl cyclase in response to LH, but the mechanism for the remainder of the cGMP decrease is unknown. At least one cGMP phosphodiesterase, PDE5, is activated by LH signaling, which would contribute to lowering cGMP. PDE5 exhibits increased cGMP-hydrolytic activity when phosphorylated on serine 92, and we recently demonstrated that LH signaling phosphorylates PDE5 on this serine and increases its activity in rat follicles. To test the extent to which this mechanism contributes to the cGMP decrease that restarts meiosis, we generated a mouse line in which serine 92 was mutated to alanine (Pde5-S92A), such that it cannot be phosphorylated. Here we show that PDE5 phosphorylation is required for the LH-induced increase in cGMP-hydrolytic activity, but that this increase has only a modest effect on the LH-induced cGMP decrease in mouse follicles, and does not affect the timing of meiotic resumption. Though we show that the activation of PDE5 is among the mechanisms contributing to the cGMP decrease, these results suggest that another cGMP phosphodiesterase is also activated by LH signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

cGMP-phosphodiesterase inhibition enhances photic responses and synchronization of the biological circadian clock in rodents.

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Santiago A Plano

Full Text Available The master circadian clock in mammals is located in the hypothalamic suprachiasmatic nuclei (SCN and is synchronized by several environmental stimuli, mainly the light-dark (LD cycle. Light pulses in the late subjective night induce phase advances in locomotor circadian rhythms and the expression of clock genes (such as Per1-2. The mechanism responsible for light-induced phase advances involves the activation of guanylyl cyclase (GC, cGMP and its related protein kinase (PKG. Pharmacological manipulation of cGMP by phosphodiesterase (PDE inhibition (e.g., sildenafil increases low-intensity light-induced circadian responses, which could reflect the ability of the cGMP-dependent pathway to directly affect the photic sensitivity of the master circadian clock within the SCN. Indeed, sildenafil is also able to increase the phase-shifting effect of saturating (1200 lux light pulses leading to phase advances of about 9 hours, as well as in C57 a mouse strain that shows reduced phase advances. In addition, sildenafil was effective in both male and female hamsters, as well as after oral administration. Other PDE inhibitors (such as vardenafil and tadalafil also increased light-induced phase advances of locomotor activity rhythms and accelerated reentrainment after a phase advance in the LD cycle. Pharmacological inhibition of the main downstream target of cGMP, PKG, blocked light-induced expression of Per1. Our results indicate that the cGMP-dependent pathway can directly modulate the light-induced expression of clock-genes within the SCN and the magnitude of light-induced phase advances of overt rhythms, and provide promising tools to design treatments for human circadian disruptions.

Reduced intracellular c-di-GMP content increases expression of quorum sensing-regulated genes in Pseudomonas aeruginosa

DEFF Research Database (Denmark)

Chua, Song Lin; Liu, Yang; Li, Yingying

2017-01-01

Cyclic-di-GMP (c-di-GMP) is an intracellular secondary messenger which controls the biofilm life cycle in many bacterial species. High intracellular c-di-GMP content enhances biofilm formation via the reduction of motility and production of biofilm matrix, while low c-di-GMP content in biofilm...... cells leads to increased motility and biofilm dispersal. While the effect of high c-di-GMP levels on bacterial lifestyles is well studied, the physiology of cells at low c-di-GMP levels remains unclear. Here, we showed that Pseudomonas aeruginosa cells with high and low intracellular c-di-GMP contents...... possessed distinct transcriptome profiles. There were 535 genes being upregulated and 432 genes downregulated in cells with low c-di-GMP, as compared to cells with high c-di-GMP. Interestingly, both rhl and pqs quorum-sensing (QS) operons were expressed at higher levels in cells with low intracellular c-di-GMP...

A cyclic GMP signalling module that regulates gliding motility in a malaria parasite.

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Robert W Moon

2009-09-01

Full Text Available The ookinete is a motile stage in the malaria life cycle which forms in the mosquito blood meal from the zygote. Ookinetes use an acto-myosin motor to glide towards and penetrate the midgut wall to establish infection in the vector. The regulation of gliding motility is poorly understood. Through genetic interaction studies we here describe a signalling module that identifies guanosine 3', 5'-cyclic monophosphate (cGMP as an important second messenger regulating ookinete differentiation and motility. In ookinetes lacking the cyclic nucleotide degrading phosphodiesterase delta (PDEdelta, unregulated signalling through cGMP results in rounding up of the normally banana-shaped cells. This phenotype is suppressed in a double mutant additionally lacking guanylyl cyclase beta (GCbeta, showing that in ookinetes GCbeta is an important source for cGMP, and that PDEdelta is the relevant cGMP degrading enzyme. Inhibition of the cGMP-dependent protein kinase, PKG, blocks gliding, whereas enhanced signalling through cGMP restores normal gliding speed in a mutant lacking calcium dependent protein kinase 3, suggesting at least a partial overlap between calcium and cGMP dependent pathways. These data demonstrate an important function for signalling through cGMP, and most likely PKG, in dynamically regulating ookinete gliding during the transmission of malaria to the mosquito.

c-di-GMP is an Effective Immunomodulator and Vaccine Adjuvant Against Pneumococcal Infection

Science.gov (United States)

Ogunniyi, Abiodun D.; Paton, James C.; Kirby, Alun C.; McCullers, Jonathan A.; Cook, Jan; Hyodo, Mamoru; Hayakawa, Yoshihiro; Karaolis, David K. R.

2009-01-01

Cyclic diguanylate (c-di-GMP) is a unique bacterial intracellular signaling molecule capable of stimulating enhanced protective innate immunity against various bacterial infections. The effects of intranasal pretreatment with c-di-GMP, or intraperitoneal coadministration of c-di-GMP with the pneumolysin toxoid (PdB) or PspA before pneumococcal challenge, was investigated in mice. We found that c-di-GMP had no significant direct short-term effect on the growth rate of S. pneumoniae either in vitro or in vivo. However, intranasal pretreatment of mice with c-di-GMP resulted in significant decrease in bacterial load in lungs and blood after serotypes 2 and 3 challenge, and significant decrease in lung titers after serotype 4 challenge. Potential cellular mediators of these enhanced protective responses were identified in lungs and draining lymph nodes. Intraperitoneal coadministration of c-di-GMP with PdB or PspA before challenge resulted in significantly higher antigen-specific antibody titers and increased survival of mice, compared to that obtained with alum adjuvant. These findings demonstrate that local or systemic c-di-GMP administration stimulates innate and adaptive immunity against invasive pneumococcal disease. We propose that c-di-GMP can be used as an effective broad spectrum immunomodulator and vaccine adjuvant to prevent infectious diseases. PMID:18640167

Diguanylate cyclase null mutant reveals that C-Di-GMP pathway regulates the motility and adherence of the extremophile bacterium Acidithiobacillus caldus.

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Matías Castro

Full Text Available An understanding of biofilm formation is relevant to the design of biological strategies to improve the efficiency of the bioleaching process and to prevent environmental damages caused by acid mine/rock drainage. For this reason, our laboratory is focused on the characterization of the molecular mechanisms involved in biofilm formation in different biomining bacteria. In many bacteria, the intracellular levels of c-di-GMP molecules regulate the transition from the motile planktonic state to sessile community-based behaviors, such as biofilm development, through different kinds of effectors. Thus, we recently started a study of the c-di-GMP pathway in several biomining bacteria including Acidithiobacillus caldus. C-di-GMP molecules are synthesized by diguanylate cyclases (DGCs and degraded by phosphodiesterases (PDEs. We previously reported the existence of intermediates involved in c-di-GMP pathway from different Acidithiobacillus species. Here, we report our work related to At. caldus ATCC 51756. We identified several putative-ORFs encoding DGC and PDE and effector proteins. By using total RNA extracted from At. caldus cells and RT-PCR, we demonstrated that these genes are expressed. We also demonstrated the presence of c-di-GMP by mass spectrometry and showed that genes for several of the DGC enzymes were functional by heterologous genetic complementation in Salmonella enterica serovar Typhimurium mutants. Moreover, we developed a DGC defective mutant strain (Δc1319 that strongly indicated that the c-di-GMP pathway regulates the swarming motility and adherence to sulfur surfaces by At. caldus. Together, our results revealed that At. caldus possesses a functional c-di-GMP pathway which could be significant for ores colonization during the bioleaching process.

c-di-GMP Regulates Various Phenotypes and Insecticidal Activity of Gram-Positive Bacillus thuringiensis

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Yang Fu

2018-02-01

Full Text Available C-di-GMP has been well investigated to play significant roles in the physiology of many Gram-negative bacteria. However, its effect on Gram-positive bacteria is less known. In order to more understand the c-di-GMP functions in Gram-positive bacteria, we have carried out a detailed study on the c-di-GMP-metabolizing enzymes and their physiological functions in Bacillus thuringiensis, a Gram-positive entomopathogenic bacterium that has been applied as an insecticide successfully. We performed a systematic study on the ten putative c-di-GMP-synthesizing enzyme diguanylate cyclases (DGCs and c-di-GMP-degrading enzyme phosphodiesterases (PDEs in B. thuringiensis BMB171, and artificially elevated the intracellular c-di-GMP level in BMB171 by deleting one or more pde genes. We found increasing level of intracellular c-di-GMP exhibits similar activities as those in Gram-negative bacteria, including altered activities in cell motility, biofilm formation, and cell-cell aggregation. Unexpectedly, we additionally found a novel function exhibited by the increasing level of c-di-GMP to promote the insecticidal activity of this bacterium against Helicoverpa armigera. Through whole-genome transcriptome profile analyses, we found that 4.3% of the B. thuringiensis genes were differentially transcribed when c-di-GMP level was increased, and 77.3% of such gene products are involved in some regulatory pathways not reported in other bacteria to date. In summary, our study represents the first comprehensive report on the c-di-GMP-metabolizing enzymes, their effects on phenotypes, and the transcriptome mediated by c-di-GMP in an important Gram-positive bacterium.

Regulation of the Na(+)-K(+)-2Cl(-) cotransporter by cGMP/cGMP-dependent protein kinase I after furosemide administration.

Science.gov (United States)

Limmer, Franziska; Schinner, Elisabeth; Castrop, Hayo; Vitzthum, Helga; Hofmann, Franz; Schlossmann, Jens

2015-10-01

Sodium chloride reabsorption in the thick ascending limb of the loop of Henle is mediated by the Na(+)-K(+)-2Cl(-) cotransporter (NKCC2). The loop diuretic furosemide is a potent inhibitor of NKCC2. However, less is known about the mechanism regulating the electrolyte transporter. Considering the well-established effects of nitric oxide on NKCC2 activity, cGMP is likely involved in this regulation. cGMP-dependent protein kinase I (cGKI; PKGI) is a cGMP target protein that phosphorylates different substrates after activation through cGMP. We investigated the potential correlation between the cGMP/cGKI pathway and NKCC2 regulation. We treated wild-type (wt) and cGKIα-rescue mice with furosemide. cGKIα-rescue mice expressed cGKIα only under the control of the smooth muscle-specific transgelin (SM22) promoter in a cGKI deficient background. Furosemide treatment increased the urine excretion of sodium and chloride in cGKIα-rescue mice compared to that in wt mice. We analyzed the phosphorylation of NKCC2 by western blotting and immunostaining using the phosphospecific antibody R5. The administration of furosemide significantly increased the phosphorylated NKCC2 signal in wt but not in cGKIα-rescue mice. NKCC2 activation led to its phosphorylation and membrane translocation. To examine whether cGKI was involved in this process, we analyzed vasodilator-stimulated phosphoprotein, which is phosphorylated by cGKI. Furosemide injection resulted in increased vasodilator-stimulated phosphoprotein phosphorylation in wt mice. We hypothesize that furosemide administration activated cGKI, leading to NKCC2 phosphorylation and membrane translocation. This cGKI-mediated pathway could be a mechanism to compensate for the inhibitory effect of furosemide on NKCC2. © 2015 FEBS.

Identification, activity and disulfide connectivity of C-di-GMP regulating proteins in Mycobacterium tuberculosis.

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Kajal Gupta

2010-11-01

Full Text Available C-di-GMP, a bacterial second messenger plays a key role in survival and adaptation of bacteria under different environmental conditions. The level of c-di-GMP is regulated by two opposing activities, namely diguanylate cyclase (DGC and phosphodiesterase (PDE-A exhibited by GGDEF and EAL domain, respectively in the same protein. Previously, we reported a bifunctional GGDEF-EAL domain protein, MSDGC-1 from Mycobacterium smegmatis showing both these activities (Kumar and Chatterji, 2008. In this current report, we have identified and characterized the homologous protein from Mycobacterium tuberculosis (Rv 1354c named as MtbDGC. MtbDGC is also a bifunctional protein, which can synthesize and degrade c-di-GMP in vitro. Further we expressed Mtbdgc in M. smegmatis and it was able to complement the MSDGC-1 knock out strain by restoring the long term survival of M. smegmatis. Another protein Rv 1357c, named as MtbPDE, is an EAL domain protein and degrades c-di-GMP to pGpG in vitro. Rv1354c and 1357c have seven cysteine amino acids in their sequence, distributed along the full length of the protein. Disulfide bonds play an important role in stabilizing protein structure and regulating protein function. By proteolytic digestion and mass spectrometric analysis of MtbDGC, connectivity between cysteine pairs Cys94-Cys584, Cys2-Cys479 and Cys429-Cys614 was determined, whereas the third cysteine (Cys406 from N terminal was found to be free in MtbDGC protein, which was further confirmed by alkylation with iodoacetamide labeling. Bioinformatics modeling investigations also supported the pattern of disulfide connectivity obtained by Mass spectrometric analysis. Cys406 was mutated to serine by site directed mutagenesis and the mutant MtbC406S was not found to be active and was not able to synthesize or degrade c-di-GMP. The disulfide connectivity established here would help further in understanding the structure - function relationship in MtbDGC.

Clinical application of combined detection of serum hs-CRP, GMP-140 and cTnI in patients with coronary heart diseases

International Nuclear Information System (INIS)

Qin Jibao; Wu Zhaozeng

2010-01-01

Objective: To explore the clinical significance of changes of serum hs-CRP, GMP-140 and cTnI levels in patients with coronary heart diseases. Methods: Serum GMP-140 (with RIA), cTnI (with ELISA) and hs-CRP (with immuno turbidity method) levels were determined in 91 patients with coronary heart diseases (42 SAP, 34UAP, 15AMI) and 35 controls. Results: Serum hs-CRP, GMP-140, cTnI levels in patients with coronary heart diseases were significantly higher than those in controls (P <0.01). Among the patients with of coronary heart diseases, the magnitude of changes of the levels of serum hs-CRP, GMP-140 and cTnI levels in AMI and UAP groups were significantly larger than those in SAP group (P < 0.05). Serum hs-CRP levels were positively correlated with serum GMP-140 and cTnI levels (r = 0.6214, 0.6023, P < 0.01). Conclusion: Serum hs-CRP, GMP140 and cTnI levels were closely related to the diseases process of coronary heart diseases and were of great clinical importance for assessment of the disease and outcome prediction. (authors)

The cyclic-di-GMP signaling pathway in the Lyme disease spirochete, Borrelia burgdorferi

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Elizabeth A. Novak

2014-05-01

Full Text Available In nature, the Lyme disease spirochete Borrelia burgdorferi cycles between the unrelated environments of the Ixodes tick vector and mammalian host. In order to survive transmission between hosts, B. burgdorferi must be able to not only detect changes in its environment, but also rapidly and appropriately respond to these changes. One manner in which this obligate parasite regulates and adapts to its changing environment is through cyclic-di-GMP (c-di-GMP signaling. c-di-GMP has been shown to be instrumental in orchestrating the adaptation of B. burgdorferi to the tick environment. B. burgdorferi possesses only one set of c-di-GMP-metabolizing genes (one diguanylate cyclase and two distinct phosphodiesterases and one c-di-GMP-binding PilZ-domain protein designated as PlzA. While studies in the realm of c-di-GMP signaling in B. burgdorferi have exploded in the last few years, there are still many more questions than answers. Elucidation of the importance of c-di-GMP signaling to B. burgdorferi may lead to the identification of mechanisms that are critical for the survival of B. burgdorferi in the tick phase of the enzootic cycle as well as potentially delineate a role (if any c-di-GMP may play in the transmission and virulence of B. burgdorferi during the enzootic cycle, thereby enabling the development of effective drugs for the prevention and/or treatment of Lyme disease.

A study on relations between the levels of GMP-140 and microangiopathy in NIDDM

International Nuclear Information System (INIS)

Du Tongxin; Wang Zizheng; Shi Hongzhen

1995-01-01

The relations between the level of GMP-140 and microangiopathy in NIDDM for earlier diagnosis or better treatment are investigated, the level of GMP-140 in both platelet and plasma was measured. The level of GMP-140 in both platelet and plasma in 104 cases with NIDDM (55 with and 49 without microagiopathy) and 38 controls were assayed by RIA and also simultaneously with direct platelet count. The level of GMP-140 in both platelet and plasma in NIDDM was remarkably higher than that in controls (P 1 = 0.69, r 2 = 0.75). No differences existed in platelet count between NIDDM and controls. The level of GMP-140 and ophthalmoscopic study had no change after decreasing the concentration of blood glucose (<7.8 mmol/L) and administrating aspirin for 6 months. Microangiopathy in NIDDM had close relation with platelet function and the level of GMP-140

Gauging and visualizing c-di-GMP levels in pseudomonas aeruginosa using fluorescence-based biosensors

DEFF Research Database (Denmark)

Rybtke, Morten; Chua, Song Lin; Yam, Joey Kuok Hoong

2017-01-01

Recent research has shown that the molecule c-di-GMP is an important second messenger regulating various functions in bacteria. In particular, the implication of c-di-GMP as a positive regulator of adhesion and biofilm formation has gained momentum as a highly relevant research topic, as detailed...... knowledge about the underlying regulatory mechanisms may enable the development of measures to control biofilms in both industrial and medical settings. Accordingly, it is in many cases of interest to measure the c-di-GMP level in bacteria under specific conditions or in specific mutant strains. We have...... developed a collection of fluorescence-based c-di-GMP biosensors capable of gauging the c-di-GMP level in Pseudomonas aeruginosa and closely related bacteria. Here, we describe protocols for the use of these biosensors in gauging and visualizing cellular c-di-GMP levels of P. aeruginosa both in in vitro...

Cyclic GMP protects human macrophages against peroxynitrite-induced apoptosis.

Science.gov (United States)

Shaw, Catherine A; Webb, David J; Rossi, Adriano G; Megson, Ian L

2009-05-07

Nitric oxide (NO) can be both pro- and anti-apoptotic in various cell types, including macrophages. This apparent paradox may result from the actions of NO-related species generated in the microenvironment of the cell, for example the formation of peroxynitrite (ONOO-). In this study we have examined the ability of NO and ONOO- to evoke apoptosis in human monocyte-derived macrophages (MDMvarphi), and investigated whether preconditioning by cyclic guanosine monophosphate (cGMP) is able to limit apoptosis in this cell type. Characterisation of the NO-related species generated by (Z)-1- [2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA/NO) and 1,2,3,4-oxatriazolium, 5-amino-3-(3,4-dichlorophenyl)-, chloride (GEA-3162) was performed by electrochemistry using an isolated NO electrode and electron paramagnetic resonance (EPR) spectrometry. Mononuclear cells were isolated from peripheral blood of healthy volunteers and cultured to allow differentiation into MDMvarphi. Resultant MDMvarphi were treated for 24 h with DETA/NO (100 - 1000 muM) or GEA-3162 (10 - 300 muM) in the presence or absence of BAY 41-2272 (1 muM), isobutylmethylxanthine (IBMX; 1 muM), 1H- [1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ; 20 muM) or 8-bromo-cGMP (1 mM). Apoptosis in MDMvarphi was assessed by flow cytometric analysis of annexin V binding in combination with propidium iodide staining. Electrochemistry and EPR revealed that DETA/NO liberated free NO radical, whilst GEA-3162 concomitantly released NO and O2-, and is therefore a ONOO- generator. NO (DETA/NO) had no effect on cell viability, but ONOO- (GEA-3162) caused a concentration-dependent induction of apoptosis in MDMvarphi. Preconditioning of MDMvarphi with NO in combination with the phosphodiesterase inhibitor, 3-Isobutyl-1-methylxanthine (IBMX), or the NO-independent stimulator of soluble guanylate cyclase, BAY 41-2272, significantly attenuated ONOO--induced apoptosis in a cGMP-dependent manner. These results

Cyclic GMP protects human macrophages against peroxynitrite-induced apoptosis

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Rossi Adriano G

2009-05-01

Full Text Available Abstract Background Nitric oxide (NO can be both pro- and anti-apoptotic in various cell types, including macrophages. This apparent paradox may result from the actions of NO-related species generated in the microenvironment of the cell, for example the formation of peroxynitrite (ONOO-. In this study we have examined the ability of NO and ONOO- to evoke apoptosis in human monocyte-derived macrophages (MDMϕ, and investigated whether preconditioning by cyclic guanosine monophosphate (cGMP is able to limit apoptosis in this cell type. Methods Characterisation of the NO-related species generated by (Z-1- [2-(2-aminoethyl-N-(2-ammonioethylamino]diazen-1-ium-1,2-diolate (DETA/NO and 1,2,3,4-oxatriazolium, 5-amino-3-(3,4-dichlorophenyl-, chloride (GEA-3162 was performed by electrochemistry using an isolated NO electrode and electron paramagnetic resonance (EPR spectrometry. Mononuclear cells were isolated from peripheral blood of healthy volunteers and cultured to allow differentiation into MDMϕ. Resultant MDMϕ were treated for 24 h with DETA/NO (100 – 1000 μM or GEA-3162 (10 – 300 μM in the presence or absence of BAY 41–2272 (1 μM, isobutylmethylxanthine (IBMX; 1 μM, 1H- [1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ; 20 μM or 8-bromo-cGMP (1 mM. Apoptosis in MDMϕ was assessed by flow cytometric analysis of annexin V binding in combination with propidium iodide staining. Results Electrochemistry and EPR revealed that DETA/NO liberated free NO radical, whilst GEA-3162 concomitantly released NO and O2-, and is therefore a ONOO- generator. NO (DETA/NO had no effect on cell viability, but ONOO- (GEA-3162 caused a concentration-dependent induction of apoptosis in MDMϕ. Preconditioning of MDMϕ with NO in combination with the phosphodiesterase inhibitor, 3-Isobutyl-1-methylxanthine (IBMX, or the NO-independent stimulator of soluble guanylate cyclase, BAY 41–2272, significantly attenuated ONOO--induced apoptosis in a cGMP-dependent manner

Intercellular signaling via cyclic GMP diffusion through gap junctions restarts meiosis in mouse ovarian follicles.

Science.gov (United States)

Shuhaibar, Leia C; Egbert, Jeremy R; Norris, Rachael P; Lampe, Paul D; Nikolaev, Viacheslav O; Thunemann, Martin; Wen, Lai; Feil, Robert; Jaffe, Laurinda A

2015-04-28

Meiosis in mammalian oocytes is paused until luteinizing hormone (LH) activates receptors in the mural granulosa cells of the ovarian follicle. Prior work has established the central role of cyclic GMP (cGMP) from the granulosa cells in maintaining meiotic arrest, but it is not clear how binding of LH to receptors that are located up to 10 cell layers away from the oocyte lowers oocyte cGMP and restarts meiosis. Here, by visualizing intercellular trafficking of cGMP in real-time in live follicles from mice expressing a FRET sensor, we show that diffusion of cGMP through gap junctions is responsible not only for maintaining meiotic arrest, but also for rapid transmission of the signal that reinitiates meiosis from the follicle surface to the oocyte. Before LH exposure, the cGMP concentration throughout the follicle is at a uniformly high level of ∼2-4 μM. Then, within 1 min of LH application, cGMP begins to decrease in the peripheral granulosa cells. As a consequence, cGMP from the oocyte diffuses into the sink provided by the large granulosa cell volume, such that by 20 min the cGMP concentration in the follicle is uniformly low, ∼100 nM. The decrease in cGMP in the oocyte relieves the inhibition of the meiotic cell cycle. This direct demonstration that a physiological signal initiated by a stimulus in one region of an intact tissue can travel across many layers of cells via cyclic nucleotide diffusion through gap junctions could provide a general mechanism for diverse cellular processes.

8-Nitro-cGMP promotes bone growth through expansion of growth plate cartilage.

Science.gov (United States)

Hoshino, Marie; Kaneko, Kotaro; Miyamoto, Yoichi; Yoshimura, Kentaro; Suzuki, Dai; Akaike, Takaaki; Sawa, Tomohiro; Ida, Tomoaki; Fujii, Shigemoto; Ihara, Hideshi; Tanaka, Junichi; Tsukuura, Risa; Chikazu, Daichi; Mishima, Kenji; Baba, Kazuyoshi; Kamijo, Ryutaro

2017-09-01

In endochondral ossification, growth of bones occurs at their growth plate cartilage. While it is known that nitric oxide (NO) synthases are required for proliferation of chondrocytes in growth plate cartilage and growth of bones, the precise mechanism by which NO facilitates these process has not been clarified yet. C-type natriuretic peptide (CNP) also positively regulate elongation of bones through expansion of the growth plate cartilage. Both NO and CNP are known to use cGMP as the second messenger. Recently, 8-nitro-cGMP was identified as a signaling molecule produced in the presence of NO in various types of cells. Here, we found that 8-nitro-cGMP is produced in proliferating chondrocytes in the growth plates, which was enhanced by CNP, in bones cultured ex vivo. In addition, 8-nitro-cGMP promoted bone growth with expansion of the proliferating zone as well as increase in the number of proliferating cells in the growth plates. 8-Nitro-cGMP also promoted the proliferation of chondrocytes in vitro. On the other hand, 8-bromo-cGMP enhanced the growth of bones with expansion of hypertrophic zone of the growth plates without affecting either the width of proliferating zone or proliferation of chondrocytes. These results indicate that 8-nitro-cGMP formed in growth plate cartilage accelerates chondrocyte proliferation and bone growth as a downstream molecule of NO. Copyright © 2017. Published by Elsevier Inc.

Novel cyclic di-GMP effectors of the YajQ protein family control bacterial virulence.

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Shi-qi An

2014-10-01

Full Text Available Bis-(3',5' cyclic di-guanylate (cyclic di-GMP is a key bacterial second messenger that is implicated in the regulation of many critical processes that include motility, biofilm formation and virulence. Cyclic di-GMP influences diverse functions through interaction with a range of effectors. Our knowledge of these effectors and their different regulatory actions is far from complete, however. Here we have used an affinity pull-down assay using cyclic di-GMP-coupled magnetic beads to identify cyclic di-GMP binding proteins in the plant pathogen Xanthomonas campestris pv. campestris (Xcc. This analysis identified XC_3703, a protein of the YajQ family, as a potential cyclic di-GMP receptor. Isothermal titration calorimetry showed that the purified XC_3703 protein bound cyclic di-GMP with a high affinity (K(d∼2 µM. Mutation of XC_3703 led to reduced virulence of Xcc to plants and alteration in biofilm formation. Yeast two-hybrid and far-western analyses showed that XC_3703 was able to interact with XC_2801, a transcription factor of the LysR family. Mutation of XC_2801 and XC_3703 had partially overlapping effects on the transcriptome of Xcc, and both affected virulence. Electromobility shift assays showed that XC_3703 positively affected the binding of XC_2801 to the promoters of target virulence genes, an effect that was reversed by cyclic di-GMP. Genetic and functional analysis of YajQ family members from the human pathogens Pseudomonas aeruginosa and Stenotrophomonas maltophilia showed that they also specifically bound cyclic di-GMP and contributed to virulence in model systems. The findings thus identify a new class of cyclic di-GMP effector that regulates bacterial virulence.

Amyloid-β Peptide Is Needed for cGMP-Induced Long-Term Potentiation and Memory.

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Palmeri, Agostino; Ricciarelli, Roberta; Gulisano, Walter; Rivera, Daniela; Rebosio, Claudia; Calcagno, Elisa; Tropea, Maria Rosaria; Conti, Silvia; Das, Utpal; Roy, Subhojit; Pronzato, Maria Adelaide; Arancio, Ottavio; Fedele, Ernesto; Puzzo, Daniela

2017-07-19

High levels of amyloid-β peptide (Aβ) have been related to Alzheimer's disease pathogenesis. However, in the healthy brain, low physiologically relevant concentrations of Aβ are necessary for long-term potentiation (LTP) and memory. Because cGMP plays a key role in these processes, here we investigated whether the cyclic nucleotide cGMP influences Aβ levels and function during LTP and memory. We demonstrate that the increase of cGMP levels by the phosphodiesterase-5 inhibitors sildenafil and vardenafil induces a parallel release of Aβ due to a change in the approximation of amyloid precursor protein (APP) and the β-site APP cleaving enzyme 1. Moreover, electrophysiological and behavioral studies performed on animals of both sexes showed that blocking Aβ function, by using anti-murine Aβ antibodies or APP knock-out mice, prevents the cGMP-dependent enhancement of LTP and memory. Our data suggest that cGMP positively regulates Aβ levels in the healthy brain which, in turn, boosts synaptic plasticity and memory. SIGNIFICANCE STATEMENT Amyloid-β (Aβ) is a key pathogenetic factor in Alzheimer's disease. However, low concentrations of endogenous Aβ, mimicking levels of the peptide in the healthy brain, enhance hippocampal long-term potentiation (LTP) and memory. Because the second messenger cGMP exerts a central role in LTP mechanisms, here we studied whether cGMP affects Aβ levels and function during LTP. We show that cGMP enhances Aβ production by increasing the APP/BACE-1 convergence in endolysosomal compartments. Moreover, the cGMP-induced enhancement of LTP and memory was disrupted by blockade of Aβ, suggesting that the physiological effect of the cyclic nucleotide on LTP and memory is dependent upon Aβ. Copyright © 2017 the authors 0270-6474/17/376926-12$15.00/0.

Good manufacturing practice (GMP) compliance in the biologics sector: plasma fractionation.

Science.gov (United States)

Ways, J P; Preston, M S; Baker, D; Huxsoll, J; Bablak, J

1999-12-01

The U.S. blood supply is the safest it has ever been. Due to blood safety and the introduction of viral inactivation/clearance technologies, protein therapies derived from human blood have also in recent years had a history of product safety. Nevertheless, since 1995, the plasma-fractionation industry has experienced increased compliance-related actions by the Food and Drug Administration (FDA), as shown by a substantive increase in the number of FDA 483 inspectional observations, FDA warning letters and other FDA regulatory action. An evaluation of these trends shows that they reflect the implementation by the FDA of increased inspectional interest in the plasma-fractionation industry and an evolution of inspectional practices and standards of current good manufacturing practice (cGMP). Plasma fractionators have responded to FDA actions by carefully evaluating and addressing each inspectional observation, assessing impact to product and taking appropriate actions, including corrective actions to prevent future occurrence. They have made major investments in facilities, quality systems, personnel and training to meet the evolving standards of cGMP and in an effort to implement these standards systemically. Through industry associations, manufacturers have further enhanced product safety by adopting additional voluntary standards for plasma to prevent the entry of potentially unsuitable plasma into the production process. The industry remains committed to application of cGMP and to working with the FDA in further evolution of these standards while striving to assure a continued supply of safe, pure and effective plasma-derived therapies.

The Cyclic AMP-Vfr Signaling Pathway in Pseudomonas aeruginosa Is Inhibited by Cyclic Di-GMP

DEFF Research Database (Denmark)

Almblad, Henrik; Harrison, Joe J; Rybtke, Morten

2015-01-01

infection give rise to rugose small colony variants (RSCVs), which are hyper-biofilm-forming mutants that commonly possess mutations that increase production of the biofilm-promoting secondary messenger cyclic di-GMP (c-di-GMP). We show that RSCVs display a decreased production of acute virulence factors...... as a direct result of elevated c-di-GMP content. Overproduction of c-di-GMP causes a decrease in the transcription of virulence factor genes that are regulated by the global virulence regulator Vfr. The low level of Vfr-dependent transcription is caused by a low level of its coactivator, cyclic AMP (c......AMP), which is decreased in response to a high level of c-di-GMP. Mutations that cause reversion of the RSCV phenotype concomitantly reactivate Vfr-cAMP signaling. Attempts to uncover the mechanism underlying the observed c-di-GMP-mediated lowering of cAMP content provided evidence that it is not caused...

Acute stress-induced antinociception is cGMP-dependent but heme oxygenase-independent

International Nuclear Information System (INIS)

Carvalho-Costa, P.G.; Branco, L.G.S.; Leite-Panissi, C.R.A.

2014-01-01

Endogenous carbon monoxide (CO), which is produced by the enzyme heme oxygenase (HO), participates as a neuromodulator in physiological processes such as thermoregulation and nociception by stimulating the formation of 3′,5′-cyclic guanosine monophosphate (cGMP). In particular, the acute physical restraint-induced fever of rats can be blocked by inhibiting the enzyme HO. A previous study reported that the HO-CO-cGMP pathway plays a key phasic antinociceptive role in modulating noninflammatory acute pain. Thus, this study evaluated the involvement of the HO-CO-cGMP pathway in antinociception induced by acute stress in male Wistar rats (250-300 g; n=8/group) using the analgesia index (AI) in the tail flick test. The results showed that antinociception induced by acute stress was not dependent on the HO-CO-cGMP pathway, as neither treatment with the HO inhibitor ZnDBPG nor heme-lysinate altered the AI. However, antinociception was dependent on cGMP activity because pretreatment with the guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) blocked the increase in the AI induced by acute stress

Acute stress-induced antinociception is cGMP-dependent but heme oxygenase-independent

Energy Technology Data Exchange (ETDEWEB)

Carvalho-Costa, P.G. [Programa de Graduação em Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Branco, L.G.S. [Departamento de Morfologia, Fisiologia e Patologia Básica, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Leite-Panissi, C.R.A. [Programa de Graduação em Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Departamento de Morfologia, Fisiologia e Patologia Básica, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

2014-09-19

Endogenous carbon monoxide (CO), which is produced by the enzyme heme oxygenase (HO), participates as a neuromodulator in physiological processes such as thermoregulation and nociception by stimulating the formation of 3′,5′-cyclic guanosine monophosphate (cGMP). In particular, the acute physical restraint-induced fever of rats can be blocked by inhibiting the enzyme HO. A previous study reported that the HO-CO-cGMP pathway plays a key phasic antinociceptive role in modulating noninflammatory acute pain. Thus, this study evaluated the involvement of the HO-CO-cGMP pathway in antinociception induced by acute stress in male Wistar rats (250-300 g; n=8/group) using the analgesia index (AI) in the tail flick test. The results showed that antinociception induced by acute stress was not dependent on the HO-CO-cGMP pathway, as neither treatment with the HO inhibitor ZnDBPG nor heme-lysinate altered the AI. However, antinociception was dependent on cGMP activity because pretreatment with the guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) blocked the increase in the AI induced by acute stress.

Physiological and Molecular Effects of the Cyclic Nucleotides cAMP and cGMP on Arabidopsis thaliana

KAUST Repository

Herrera, Natalia M.

2012-12-01

The cyclic nucleotide monophosphates (CNs), cAMP and cGMP, are second messengers that participate in the regulation of development, metabolism and adaptive responses. In plants, CNs are associated with the control of pathogen responses, pollen tube orientation, abiotic stress response, membrane transport regulation, stomatal movement and light perception. In this study, we hypothesize that cAMP and cGMP promote changes in the transcription level of genes related to photosynthesis, high light and membrane transport in Arabidopsis thaliana leaves and, that these changes at the molecular level can have functional biological consequences. For this reason we tested if CNs modulate the photosynthetic rate, responses to high light and root ion transport. Real time quantitative PCR was used to assess transcription levels of selected genes and infrared gas analyzers coupled to fluorescence sensors were used to measure the photosynthetic parameters. We present evidence that both cAMP and cGMP modulate foliar mRNA levels early after stimulation. The two CNs trigger different responses indicating that the signals have specificity. A comparison of proteomic and transcriptional changes suggest that both transcriptional and post-transcriptional mechanisms are modulated by CNs. cGMP up-regulates the mRNA levels of components of the photosynthesis and carbon metabolism. However, neither cAMP nor cGMP trigger differences in the rate of carbon assimilation, maximum efficiency of the photosystem II (PSII), or PSII operating efficiency. It was also demonstrated that CN regulate the expression of its own targets, the cyclic nucleotide gated channels - CNGC. Further studies are needed to identify the components of the signaling transduction pathway that mediate cellular changes and their respective regulatory and/or signaling roles.

Cyclic GMP-AMP Displays Mucosal Adjuvant Activity in Mice

OpenAIRE

Škrnjug, Ivana; Guzmán, Carlos Alberto; Ruecker, Christine

2014-01-01

The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP) after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice....

Implementation of good manufacturing practices (GMP) on human blood irradiation

International Nuclear Information System (INIS)

Boghi, Claudio; Napolitano, Celia M.; Ferreira, Danilo C.; Rela, Paulo Roberto; Zarate, Herman S.

2007-01-01

The irradiation of human blood is used to avoid the TA-GVHD (transfusion-associated graft-versus-host-disease), a rare but devastating adverse effect of leukocytes present in blood components for a immuno-competent transfusion recipients. Usually this irradiation practice is performed to a physical elimination of lymphocytes. The implementation of the GMP will assure that the properly dose in a range of 25 Gy to 50 Gy will be delivered to the blood in the bag collected in a blood tissue bank. The studies to establish the GMP were developed under the guidelines of the standard ISO 11137 - Sterilization of health care products - Requirements for validation and routine control - Radiation sterilization. In this work, two dosimetric systems were used for dose mapping during the studies of irradiator qualification, loading pattern, irradiation process validation and auditing. The CaSO 4 : Dy dosimeter presented difficulties concerning to uncertainty on dose measurement, stability, trace ability and calibration system. The PMMA and gafchromic dosimetric systems have shown a better performance and were adopted on establishment of GMP procedures. The irradiation tests have been done using a Gammacell 220 Irradiator. The developed GMP can be adapted for different types of gamma irradiators, allowing to set up a quality assurance program for blood irradiation. (author)

Implementation of good manufacturing practices (GMP) on human blood irradiation

Energy Technology Data Exchange (ETDEWEB)

Boghi, Claudio; Napolitano, Celia M.; Ferreira, Danilo C.; Rela, Paulo Roberto [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)]. E-mails: cboghi@uol.com.br; cmnapoli@ipen.br; dancarde@ig.com.br; prela@ipen.br; Zarate, Herman S. [Comission Chilena de Energia Nuclear, Santiago (Chile)]. E-mail: hzarate@cchen.cl

2007-07-01

The irradiation of human blood is used to avoid the TA-GVHD (transfusion-associated graft-versus-host-disease), a rare but devastating adverse effect of leukocytes present in blood components for a immuno-competent transfusion recipients. Usually this irradiation practice is performed to a physical elimination of lymphocytes. The implementation of the GMP will assure that the properly dose in a range of 25 Gy to 50 Gy will be delivered to the blood in the bag collected in a blood tissue bank. The studies to establish the GMP were developed under the guidelines of the standard ISO 11137 - Sterilization of health care products - Requirements for validation and routine control - Radiation sterilization. In this work, two dosimetric systems were used for dose mapping during the studies of irradiator qualification, loading pattern, irradiation process validation and auditing. The CaSO{sub 4}: Dy dosimeter presented difficulties concerning to uncertainty on dose measurement, stability, trace ability and calibration system. The PMMA and gafchromic dosimetric systems have shown a better performance and were adopted on establishment of GMP procedures. The irradiation tests have been done using a Gammacell 220 Irradiator. The developed GMP can be adapted for different types of gamma irradiators, allowing to set up a quality assurance program for blood irradiation. (author)

Good manufacturing practices (GMP utilized on human blood irradiation process

Directory of Open Access Journals (Sweden)

Cláudio Boghi

2008-01-01

Full Text Available Irradiation of human blood is used to avoid the TA-GVHD (transfusion-associated graft-versus-host-disease, a rare but devastating adverse effect of leukocytes present in blood components for immunocompetent transfusion recipients. Usually this irradiation practice is performed to a physical elimination of lymphocytes. The implementation of the GMP will assure that the properly dose in a range of 25Gy to 50Gy will be delivered to the blood in the bag collected in a blood tissue bank. The studies to establish the GMP were developed under the guidelines of the standard ISO 11137 - Sterilization of health care products - Requirements for validation and routine control - Radiation sterilization. In this work, two dosimetric systems were used for dose mapping during the studies of irradiator qualification, loading pattern, irradiation process validation and auditing. The CaSO4: Dy dosimeter presented difficulties concerning to uncertainty on dose measurement, stability, trace ability and calibration system. The PMMA and gafchromic dosimetric systems have shown a better performance and were adopted on establishment of GMP procedures. The irradiation tests have been done using a Gammacell 220 Irradiator. The developed GMP can be adapted for different types of gamma irradiators, allowing to set up a quality assurance program for blood irradiation.

Implementation of Good Maufacturing Practices (GMP) in the Kitchen Hospital

OpenAIRE

Sari, Fitria Novita

2016-01-01

Abstract: Food safety is one of the important thing in public health improvement in Indonesia. Hospitals are required to keep food safety for patients by conducting the principle Good Manufacturing Practices (GMP). The purpose of this research to -identify the application of GMP in Installation Nutrition Hospital. Design of this study was using descriptive research in observational method with cross sectional design. Variables the treatment were the physical building, utility, equipment, stor...

Modulation of cGMP by human HO-1 retrovirus gene transfer in pulmonary microvessel endothelial cells.

Science.gov (United States)

Abraham, Nader G; Quan, Shuo; Mieyal, Paul A; Yang, Liming; Burke-Wolin, Theresa; Mingone, Christopher J; Goodman, Alvin I; Nasjletti, Alberto; Wolin, Michael S

2002-11-01

Carbon monoxide (CO) stimulates guanylate cyclase (GC) and increases guanosine 3',5'-cyclic monophosphate (cGMP) levels. We transfected rat-lung pulmonary endothelial cells with a retrovirus-mediated human heme oxygenase (hHO)-1 gene. Pulmonary cells that expressed hHO-1 exhibited a fourfold increase in HO activity associated with decreases in the steady-state levels of heme and cGMP without changes in soluble GC (sGC) and endothelial nitric oxide synthase (NOS) proteins or basal nitrite production. Heme elicited significant increases in CO production and intracellular cGMP levels in both pulmonary endothelial and pulmonary hHO-1-expressing cells. N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS, significantly decreased cGMP levels in heme-treated pulmonary endothelial cells but not heme-treated hHO-1-expressing cells. In the presence of exogenous heme, CO and cGMP levels in hHO-1-expressing cells exceeded the corresponding levels in pulmonary endothelial cells. Acute exposure of endothelial cells to SnCl2, which is an inducer of HO-1, increased cGMP levels, whereas chronic exposure decreased heme and cGMP levels. These results indicate that prolonged overexpression of HO-1 ultimately decreases sGC activity by limiting the availability of cellular heme. Heme activates sGC and enhances cGMP levels via a mechanism that is largely insensitive to NOS inhibition.

The participation of elevated levels of cyclic GMP in the recovery from radiation-induced mitotic delay

International Nuclear Information System (INIS)

Daniel, J.W.; Oleinick, N.L.

1984-01-01

The levels of cyclic AMP and cyclic GMP have been measured in Physarum plasmodia before and after treatment with gamma-radiation, 2 mM caffeine, or combinations of the two agents compared to the length of the radiation-induced mitotic delay. Caffeine alone produces a rapid transient elevation of cyclic AMP and a slower delayed elevation of cyclic GMP. Irradiation elicits an immediate transient increase in cyclic AMP and a later cyclic GMP increase which accompanies or precedes the delayed mitosis. A composite pattern is produced by combinations of radiation and caffeine, a distinctive feature of which is an elevated level of cyclic GMP near the time of the radiation-delayed and caffeine-promoted mitosis. With pretreatment by caffeine, the least radiation-induced mitotic delay occurs when plasmodia are irradiated during the caffeine-elicited increase in cyclic GMP. The plasmodium becomes refractory to the reduction of mitotic delay by caffeine at approximately the time it becomes refractory to the further elevation of cyclic GMP by caffeine. The data support a role for cyclic AMP in the onset of and for cyclic GMP in the recovery from mitotic delay induced by ionizing radiation. (author)

The anti-cancerous drug doxorubicin decreases the c-di-GMP content in Pseudomonas aeruginosa but promotes biofilm formation

DEFF Research Database (Denmark)

Groizeleau, Julie; Rybtke, Morten; Andersen, Jens Bo

2016-01-01

Current antibiotic treatments are insufficient in eradicating bacterial biofilms, which represent the primary cause of chronic bacterial infections. Thus, there is an urgent need for new strategies to eradicate biofilm infections. The second messenger c-di-GMP is a positive regulator of biofilm...... formation in many clinically relevant bacteria. It is hypothesized that drugs lowering the intracellular level of c-di-GMP will force biofilm bacteria into a more treatable planktonic lifestyle. To identify compounds capable of lowering c-di-GMP levels in Pseudomonas aeruginosa, we screened 5000 compounds...... for their potential c-di-GMP-lowering effect using a recently developed c-di-GMP biosensor strain. Our screen identified the anti-cancerous drug doxorubicin as a potent c-di-GMP inhibitor. In addition, the drug decreased the transcription of many biofilm-related genes. However, despite its effect on the c-di-GMP...

Auxin-induced nitric oxide, cGMP and gibberellins were involved in the gravitropism

Science.gov (United States)

Cai, Weiming; Hu, Liwei; Hu, Xiangyang; Cui, Dayong; Cai, Weiming

Gravitropism is the asymmetric growth or curvature of plant organs in response to gravistimulation. There is a complex signal transduction cascade which involved in the differential growth of plants in response to changes in the gravity vector. The role of auxin in gravitropism has been demonstrated by many experiments, but little is known regarding the molecular details of such effects. In our studies before, mediation of the gravitropic bending of soybean roots and rice leaf sheath bases by nitric oxide, cGMP and gibberellins, are induced by auxin. The asymmetrical distribution of nitric oxide, cGMP and gibberellins resulted from the asymmetrical synthesis of them in bending sites. In soybean roots, inhibitions of NO and cGMP synthesis reduced differential NO and cGMP accumulation respectively, which both of these effects can lead to the reduction of gravitropic bending. Gibberellin-induced OsXET, OsEXPA4 and OsRWC3 were also found involved in the gravitropic bending. These data indicated that auxin-induced nitric oxide, cGMP and gibberellins were involved in the gravitropism. More experiments need to prove the more detailed mechanism of them.

Complex regulatory network encompassing the Csr, c-di-GMP and motility systems of Salmonella Typhimurium.

Science.gov (United States)

Jonas, Kristina; Edwards, Adrianne N; Ahmad, Irfan; Romeo, Tony; Römling, Ute; Melefors, Ojar

2010-02-01

Bacterial survival depends on the ability to switch between sessile and motile lifestyles in response to changing environmental conditions. In many species, this switch is governed by (3'-5')-cyclic-diguanosine monophosphate (c-di-GMP), a signalling molecule, which is metabolized by proteins containing GGDEF and/or EAL domains. Salmonella Typhimurium contains 20 such proteins. Here, we show that the RNA-binding protein CsrA regulates the expression of eight genes encoding GGDEF, GGDEF-EAL and EAL domain proteins. CsrA bound directly to the mRNA leaders of five of these genes, suggesting that it may regulate these genes post-transcriptionally. The c-di-GMP-specific phosphodiesterase STM3611, which reciprocally controls flagella function and production of biofilm matrix components, was regulated by CsrA binding to the mRNA, but was also indirectly regulated by CsrA through the FlhDC/FliA flagella cascade and STM1344. STM1344 is an unconventional (c-di-GMP-inactive) EAL domain protein, recently identified as a negative regulator of flagella gene expression. Here, we demonstrate that CsrA directly downregulates expression of STM1344, which in turn regulates STM3611 through fliA and thus reciprocally controls motility and biofilm factors. Altogether, our data reveal that the concerted and complex regulation of several genes encoding GGDEF/EAL domain proteins allows CsrA to control the motility-sessility switch in S. Typhimurium at multiple levels.

The role of cGMP hydrolysing phosphodiesterases 1 and 5 in cerebral artery dilatation

DEFF Research Database (Denmark)

Kruuse, Christina; Rybalkin, S D; Khurana, T S

2001-01-01

The aim was to investigate the presence and activity of cGMP hydrolysing phosphodiesterases in guinea pig basilar arteries and the effect of selective and non-selective phosphodiesterase inhibitors on cerebral artery dilatation involving the nitric oxide (NO)-guanosine cyclic 3'5-monophosphate (cGMP...... a close relation to the nitric oxide-cGMP pathway. The responses to zaprinast and dipyridamole, however, were not only moderately affected, but also restored by sodium nitroprusside (0.1 microM) pretreatment. At high concentrations, the dilatory effects of zaprinast and dipyridamole were partly caused...... by cGMP-independent mechanisms. Targeting the phosphodiesterases present in cerebral arteries, with selective inhibitors or activators of phosphodiesterase, may be a possible new way of treating cerebrovascular disease....

Effects of the NO/soluble guanylate cyclase/cGMP system on the functions of human platelets.

Science.gov (United States)

Makhoul, Stephanie; Walter, Elena; Pagel, Oliver; Walter, Ulrich; Sickmann, Albert; Gambaryan, Stepan; Smolenski, Albert; Zahedi, René P; Jurk, Kerstin

2018-06-01

Platelets are circulating sentinels of vascular integrity and are activated, inhibited, or modulated by multiple hormones, vasoactive substances or drugs. Endothelium- or drug-derived NO strongly inhibits platelet activation via activation of the soluble guanylate cyclase (sGC) and cGMP elevation, often in synergy with cAMP-elevation by prostacyclin. However, the molecular mechanisms and diversity of cGMP effects in platelets are poorly understood and sometimes controversial. Recently, we established the quantitative human platelet proteome, the iloprost/prostacyclin/cAMP/protein kinase A (PKA)-regulated phosphoproteome, and the interactions of the ADP- and iloprost/prostacyclin-affected phosphoproteome. We also showed that the sGC stimulator riociguat is in vitro a highly specific inhibitor, via cGMP, of various functions of human platelets. Here, we review the regulatory role of the cGMP/protein kinase G (PKG) system in human platelet function, and our current approaches to establish and analyze the phosphoproteome after selective stimulation of the sGC/cGMP pathway by NO donors and riociguat. Present data indicate an extensive and diverse NO/riociguat/cGMP phosphoproteome, which has to be compared with the cAMP phosphoproteome. In particular, sGC/cGMP-regulated phosphorylation of many membrane proteins, G-proteins and their regulators, signaling molecules, protein kinases, and proteins involved in Ca 2+ regulation, suggests that the sGC/cGMP system targets multiple signaling networks rather than a limited number of PKG substrate proteins. Copyright © 2018 Elsevier Inc. All rights reserved.

Free and total GMP (glycomacropeptide contents of milk during bovine lactation Variação dos teores de GMP (glicomacropeptídeo livre e total no leite bovino durante a lactação

Directory of Open Access Journals (Sweden)

Andréa Maria Furlanetti

2003-12-01

Full Text Available Individual milk samples taken every two weeks from parturition to the end of lactation from 34 animals of three different herds and breeds were analyzed for free-GMP. A milk pool of each herd was analyzed for free and total GMP (released from k-casein by the action of rennin and the data were correlated with sanitary conditions of animal and udder, phase of lactation and milk production. Most udder problems were concentrated near parturition, with few and spaced occurrences of clinical mastitis. The Californian Mastitis Test (CMT results showed oscillations compatible with the phases of lactation period and environmental conditions. The widest variations in free-GMP occurred as a function of lactation period and as a consequence of clinical or subclinical mastitis. Higher levels were observed at the beginning of lactation (5.87mg L-1 of sialic acid, becoming normal with mean values of about 3.30mg L-1 at the end of the second month, and increasing again during the final third of lactation. On average, the same trends were observed for total GMP released by commercial rennet, beginning with slightly high values (35.59mg L-1, becoming normal by the sixth month with values close to 27.15mg L-1, and rising gradually up to the end of lactation, with 58.35mg L-1 of sialic acid. These results prove to be useful for the correct interpretation of tests applied to milk selection with respect to proteolytic status or even to restrain frauds by the addition of whey to milk.Amostras quinzenais, desde o parto até o final do período de lactação, obtidas de 34 vacas de três diferentes raças e propriedades, foram analisadas quanto à presença de GMP livre. Um "pool" das amostras quinzenais de cada rebanho foi analisada tanto para o conteúdo de GMP livre quanto para o GMP total (liberado da k-caseína pela ação da renina, correlacionando-os com as condições sanitárias do animal e do úbere, à fase da lactação e à produção de leite. A maioria

A cGMP kinase mutant with increased sensitivity to the protein kinase inhibitor peptide PKI(5-24).

Science.gov (United States)

Ruth, P; Kamm, S; Nau, U; Pfeifer, A; Hofmann, F

1996-01-01

Synthetic peptides corresponding to the active domain of the heat-stable inhibitor protein PKI are very potent inhibitors of cAMP-dependent protein kinase, but are extremely weak inhibitors of cGMP-dependent protein kinase. In this study, we tried to confer PKI sensitivity to cGMP kinase by site-directed mutagenesis. The molecular requirements for high affinity inhibition by PKI were deduced from the crystal structure of the cAMP kinase/PKI complex. A prominent site of interaction are residues Tyr235 and Phe239 in the catalytic subunit, which from a sandwich-like structure with Phe10 of the PKI(5-24) peptide. To increase the sensitivity for PKI, the cGMP kinase codons at the corresponding sites, Ser555 and Ser559, were changed to Tyr and Phe. The mutant cGMP kinase was stimulated half maximally by cGMP at 3-fold higher concentrations (240 nM) than the wild type (77 nM). Wild type and mutant cGMP kinase did not differ significantly in their Km and Vmax for three different substrate peptides. The PKI(5-24) peptide inhibited phosphotransferase activity of the mutant cGMP kinase with higher potency than that of wild type, with Ki values of 42 +/- .3 microM and 160 +/- .7 microM, respectively. The increased affinity of the mutant cGMP kinase was specific for the PKI(5-24) peptide. Mutation of the essential Phe10 in the PKI(5-24) sequence to an Ala yielded a peptide that inhibited mutant and wild type cGMP kinase with similar potency, with Ki values of 160 +/- 11 and 169 +/- 27 microM, respectively. These results suggest that the mutations Ser555Tyr and Ser559Phe are required, but not sufficient, for high affinity inhibition of cGMP kinase by PKI.

Radioimmunoassay for platelet activation specific protein GMP-140 on the platelet surface and in plasma

International Nuclear Information System (INIS)

Wu Guoxin; Li Jianyong; Ruan Changgeng

1991-08-01

Using monoclonal antibody (McAb) SZ-51 which is specific for an alpha-granule membrane protein (GMP-140) on the surface of human activated platelets, the platelet GMP-140 expression in fixed whole blood was measured by direct radioimmunoassay and GMP-140 microparticles in plasma was measured by sandwich method. The GMP-140 molecules per platelet or milliliter (mL) were calculated for the following subjects; acute myocardial infarction; cerebro thrombosis; diabetic mellitus; asthma attack; epidemic hemorrhagic fever etc.. By comparing with the concentration of thromboxane B 2 (TXB 2 ) and von Willebrand factor (vWF) in plasma, it is confirmed that the measurement of GMP-140 molecules is better than that of TXB 2 and vWF. It is a sensitive and specific method for evaluating the platelet activation degree in vivo. The establishment of this method will be useful to diagnosing the thrombotic disorders and studying the pathogenesis of some other diseases

Atrial natriuretic peptide receptor heterogeneity and effects on cyclic GMP accumulation

International Nuclear Information System (INIS)

Leitman, D.C.

1988-01-01

The effects of atrial natriuretic peptide (ANP), oxytocin (OT) and vasopressin (AVP) on guanylate cyclase activity and cyclic GMP accumulation were examined, since these hormones appear to be intimately associated with blood pressure and intravascular volume homeostasis. ANP was found to increase cyclic GMP accumulation in ten cell culture systems, which were derived from blood vessels, adrenal cortex, kidney, lung, testes and mammary gland. ANP receptors were characterized in intact cultured cells using 125 I-ANP 8-33 . Specific 125 I-ANP binding was saturable and of high affinity. Scratchard analysis of the binding data for all cell types exhibited a straight line, indicating that these cells possessed a single class of binding sites. Despite the presence of linear Scatchard plots, these studies demonstrated that cultured cells possess two functionally and physically distinct ANP-binding sites. Most of the ANP-binding sites in cultured cells have a molecular size of 66,000 daltons under reducing conditions. The identification of cultured cell types in which hormones (ANP and oxytocin) regulate guanylate cyclase activity and increase cyclic GMP synthesis will provide valuable systems to determine the mechanisms of hormone-receptor coupling to guanylate cyclase and the cellular processes regulated by cyclic GMP

Receptors and cGMP signalling mechanism for E. coli enterotoxin in opossum kidney

International Nuclear Information System (INIS)

Forte, L.R.; Krause, W.J.; Freeman, R.H.

1988-01-01

Receptors for the heat-stable enterotoxin produced by Escherichia coli were found in the kidney and intestine of the North American opossum and in cultured renal cell lines. The enterotoxin markedly increased guanosine 3',5'-cyclic monophosphate (cGMP) production in slices of kidney cortex and medulla, in suspensions of intestinal mucosa, and in the opossum kidney (OK) and rat kangaroo kidney (PtK-2) cell lines. In contrast, atrial natriuretic factor elicited much smaller increases in cGMP levels of kidney, intestine, or cultured kidney cell lines. The enterotoxin receptors in OK cells had a molecular mass of approximately 120 kDa when measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of receptors crosslinked with 125 I-enterotoxin. The occurrence of receptors for the E. coli peptide in OK implies that these receptors may be involved in the regulation of renal tubular function in the opossum. E. coli enterotoxin caused a much larger increase in urine cGMP excretion than did atrial natriuretic factor when these peptides were injected intravenously into opossums. However, atrial natriuretic factor elicited a marked diuresis, natriuresis, and increased urinary excretion of calcium, phosphate, potassium, and magnesium. In contrast, the enterotoxin did not acutely influence OK fluid and electrolyte excretion. Thus the substantial increase in cGMP synthesis produced by the bacterial peptide in OK cortex and medulla in vitro and the increased renal excretion of cGMP in vivo were not associated with changes in electrolyte or water excretion. Whether cGMP represents a second messenger molecule in the kidney is an interesting question that was raised but not answered in this series of experiments

Differential control of Yersinia pestis biofilm formation in vitro and in the flea vector by two c-di-GMP diguanylate cyclases.

Directory of Open Access Journals (Sweden)

Yi-Cheng Sun

2011-04-01

Full Text Available Yersinia pestis forms a biofilm in the foregut of its flea vector that promotes transmission by flea bite. As in many bacteria, biofilm formation in Y. pestis is controlled by intracellular levels of the bacterial second messenger c-di-GMP. Two Y. pestis diguanylate cyclase (DGC enzymes, encoded by hmsT and y3730, and one phosphodiesterase (PDE, encoded by hmsP, have been shown to control biofilm production in vitro via their opposing c-di-GMP synthesis and degradation activities, respectively. In this study, we provide further evidence that hmsT, hmsP, and y3730 are the only three genes involved in c-di-GMP metabolism in Y. pestis and evaluated the two DGCs for their comparative roles in biofilm formation in vitro and in the flea vector. As with HmsT, the DGC activity of Y3730 depended on a catalytic GGDEF domain, but the relative contribution of the two enzymes to the biofilm phenotype was influenced strongly by the environmental niche. Deletion of y3730 had a very minor effect on in vitro biofilm formation, but resulted in greatly reduced biofilm formation in the flea. In contrast, the predominant effect of hmsT was on in vitro biofilm formation. DGC activity was also required for the Hms-independent autoaggregation phenotype of Y. pestis, but was not required for virulence in a mouse model of bubonic plague. Our results confirm that only one PDE (HmsP and two DGCs (HmsT and Y3730 control c-di-GMP levels in Y. pestis, indicate that hmsT and y3730 are regulated post-transcriptionally to differentially control biofilm formation in vitro and in the flea vector, and identify a second c-di-GMP-regulated phenotype in Y. pestis.

The crucial role of cyclic GMP in the eclosion hormone mediated signal transduction in the silkworm metamorphoses.

Science.gov (United States)

Shibanaka, Y; Hayashi, H; Okada, N; Fujita, N

1991-10-31

The signal transduction of the peptide, eclosion hormone, in the silkworm Bombyx mori appears to be mediated via the second messenger cyclic GMP throughout their life cycle. Injection of 8-bromo-cGMP induced the ecdysis behavior in pharate adults with similar latency to eclosion hormone-induced ecdysis; the moulting occurred 50-70 min after the injection. The potency of 8Br-cGMP was 10(2) fold higher than that of cGMP and the efficacy was increased by the co-injection of the phosphodiesterase inhibitor IBMX. On the other hand, in the silkworm pupal ecdysis the eclosion hormone and also 8Br-cGMP induced the moulting behavior in a dose-dependent manner. The adult development of the ability to respond to 8Br-cGMP took place concomitantly with the response to the eclosion hormone. Both the developmental time courses were shifted by a shift of light and dark cycles. Accordingly, the sensitivities to the peptide and cyclic nucleotide developed correspondently under the light and dark circadian rhythm. Thus throughout the silkworm life cycle, eclosion hormone is effective to trigger the ecdysis behavior and cGMP plays a crucial role as the second messenger in the eclosion hormone-mediated signal transduction.

BolA Is Required for the Accurate Regulation of c-di-GMP, a Central Player in Biofilm Formation

OpenAIRE

Moreira, Ricardo N.; Dressaire, Clémentine; Barahona, Susana; Galego, Lisete; Kaever, Volkhard; Jenal, Urs; Arraiano, Cecília M.

2017-01-01

The bacterial second messenger cyclic dimeric GMP (c-di-GMP) is a nearly ubiquitous intracellular signaling molecule involved in the transition from the motile to the sessile/biofilm state in bacteria. C-di-GMP regulates various cellular processes, including biofilm formation, motility, and virulence. BolA is a transcription factor that promotes survival in different stresses and is also involved in biofilm formation. Both BolA and c-di-GMP participate in the regulation of motility mechanisms...

C-di-GMP regulates Pseudomonas aeruginosa stress response to tellurite during both planktonic and biofilm modes of growth

DEFF Research Database (Denmark)

Chua, Song Lin; Sivakumar, Krishnakumar; Rybtke, Morten Levin

2015-01-01

tellurite (TeO3(2-)) exposure induced the intracellular content of the secondary messenger cyclic di-GMP (c-di-GMP) of Pseudomonas aeruginosa. Two diguanylate cyclases (DGCs), SadC and SiaD, were responsible for the increased intracellular content of c-di-GMP. Enhanced c-di-GMP levels by TeO3(2-) further...... increased P. aeruginosa biofilm formation and resistance to TeO3(2-). P. aeruginosa ΔsadCΔsiaD and PAO1/p(lac)-yhjH mutants with low intracellular c-di-GMP content were more sensitive to TeO3(2-) exposure and had low relative fitness compared to the wild-type PAO1 planktonic and biofilm cultures exposed...... to TeO3(2-). Our study provided evidence that c-di-GMP level can play an important role in mediating stress response in microbial communities during both planktonic and biofilm modes of growth....

GMP-140 binds to a glycoprotein receptor on human neutrophils: Evidence for a lectin-like interaction

International Nuclear Information System (INIS)

Moore, K.L.; Varki, A.; McEver, R.P.

1991-01-01

GMP-140 is a rapidly inducible receptor for neutrophils and monocytes expressed on activated platelets and endothelial cells. It is a member of the selectin family of lectin-like cell surface molecules that mediate leukocyte adhesion. We used a radioligand binding assay to characterize the interaction of purified GMP-140 with human neutrophils. Unstimulated neutrophils rapidly bound [125I]GMP-140 at 4 degrees C, reaching equilibrium in 10-15 min. Binding was Ca2+ dependent, reversible, and saturable at 3-6 nM free GMP-140 with half-maximal binding at approximately 1.5 nM. Receptor density and apparent affinity were not altered when neutrophils were stimulated with 4 beta-phorbol 12-myristate 13-acetate. Treatment of neutrophils with proteases abolished specific binding of [125I]GMP-140. Binding was also diminished when neutrophils were treated with neuraminidase from Vibrio cholerae, which cleaves alpha 2-3-, alpha 2-6-, and alpha 2-8-linked sialic acids, or from Newcastle disease virus, which cleaves only alpha 2-3- and alpha 2-8-linked sialic acids. Binding was not inhibited by an mAb to the abundant myeloid oligosaccharide, Lex (CD15), or by the neoglycoproteins Lex-BSA and sialyl-Lex-BSA. We conclude that neutrophils constitutively express a glycoprotein receptor for GMP-140, which contains sialic acid residues that are essential for function. These findings support the concept that GMP-140 interacts with leukocytes by a lectin-like mechanism

Cohesive Properties of the Caulobacter crescentus Holdfast Adhesin Are Regulated by a Novel c-di-GMP Effector Protein

Directory of Open Access Journals (Sweden)

Kathrin S. Sprecher

2017-03-01

Full Text Available When encountering surfaces, many bacteria produce adhesins to facilitate their initial attachment and to irreversibly glue themselves to the solid substrate. A central molecule regulating the processes of this motile-sessile transition is the second messenger c-di-GMP, which stimulates the production of a variety of exopolysaccharide adhesins in different bacterial model organisms. In Caulobacter crescentus, c-di-GMP regulates the synthesis of the polar holdfast adhesin during the cell cycle, yet the molecular and cellular details of this control are currently unknown. Here we identify HfsK, a member of a versatile N-acetyltransferase family, as a novel c-di-GMP effector involved in holdfast biogenesis. Cells lacking HfsK form highly malleable holdfast structures with reduced adhesive strength that cannot support surface colonization. We present indirect evidence that HfsK modifies the polysaccharide component of holdfast to buttress its cohesive properties. HfsK is a soluble protein but associates with the cell membrane during most of the cell cycle. Coincident with peak c-di-GMP levels during the C. crescentus cell cycle, HfsK relocalizes to the cytosol in a c-di-GMP-dependent manner. Our results indicate that this c-di-GMP-mediated dynamic positioning controls HfsK activity, leading to its inactivation at high c-di-GMP levels. A short C-terminal extension is essential for the membrane association, c-di-GMP binding, and activity of HfsK. We propose a model in which c-di-GMP binding leads to the dispersal and inactivation of HfsK as part of holdfast biogenesis progression.

[The Contribution of GMP-grade Hospital Preparation to Translational Research].

Science.gov (United States)

Yonezawa, Atsushi; Kajiwara, Moto; Minami, Ikuko; Omura, Tomohiro; Nakagawa, Shunsaku; Matsubara, Kazuo

2015-01-01

Translational research is important for applying the outcomes of basic research studies to practical medical treatments. In exploratory early-phase clinical trials for an innovative therapy, researchers should generally manufacture investigational agents by themselves. To provide investigational agents with safety and high quality in clinical studies, appropriate production management and quality control are essential. In the Department of Pharmacy of Kyoto University Hospital, a manufacturing facility for sterile drugs was established, independent of existing manufacturing facilities. Manuals on production management and quality control were developed according to Good Manufacturing Practices (GMP) for Investigational New Drugs (INDs). Advanced clinical research has been carried out using investigational agents manufactured in our facility. These achievements contribute to both the safety of patients and the reliability of clinical studies. In addition, we are able to do licensing-out of our technique for the manufacture of investigational drugs. In this symposium, we will introduce our GMP grade manufacturing facility for sterile drugs and discuss the role of GMP grade hospital preparation in translational research.

High-throughput screening for compounds that modulate the cellular c-di-GMP level in bacteria

DEFF Research Database (Denmark)

Groizeleau, Julie; Andersen, Jens Bo; Givskov, Michael

2017-01-01

. The secondary messenger c-di-GMP is a positive regulator of biofilm formation in many clinically relevant bacteria, and it is assumed that drugs that lower the intracellular level of c-di-GMP will force biofilm bacteria into a more treatable planktonic lifestyle. We describe a protocol for high......-throughput screening of chemical libraries for compounds that lower the c-di-GMP level in bacteria, and potentially can serve as lead compounds in the development of novel biofilm dismantling drugs....

Molecular properties of mammalian proteins that interact with cGMP: protein kinases, cation channels, phosphodiesterases, and multi-drug anion transporters.

Science.gov (United States)

Francis, Sharron H; Blount, Mitsi A; Zoraghi, Roya; Corbin, Jackie D

2005-09-01

Cyclic GMP is a critical second messenger signaling molecule in many mammalian cell types. It is synthesized by a family of guanylyl cyclases that is activated in response to stimuli from hormones such as natriuretic peptides, members of the guanylin family, and chemical stimuli including nitric oxide and carbon monoxide. The resulting elevation of cGMP modulates myriad physiological processes. Three major groups of cellular proteins bind cGMP specifically at allosteric sites; interaction of cGMP with these sites modulates the activities and functions of other domains within these protein groups to bring about physiological effects. These proteins include the cyclic nucleotide (cN)-dependent protein kinases, cN-gated cation channels, and cGMP-binding phosphodiesterases (PDE). Cyclic GMP also interacts with the catalytic sites of many cN PDEs and with some members of the multi-drug anion transporter family (MRPs) which can extrude nucleotides from cells. The allosteric cN-binding sites in the kinases and the cN-gated channels are evolutionarily and biochemically related, whereas the allosteric cGMP-binding sites in PDEs (also known as GAF domains), the catalytic sites of PDEs , and the ligand-binding sites in the MRPs are evolutionarily and biochemically distinct from each other and from those in the kinase and channel families. The sites that interact with cGMP within each of these groups of proteins have unique properties that provide for cGMP binding. Within a given cell, cGMP can potentially interact with members of all these groups of proteins if they are present. The relative abundance and affinities of these various cGMP-binding sites in conjunction with their subcellular compartmentation, proximity to cyclases and PDEs, and post-translational modification contribute importantly in determining the impact of these respective proteins to cGMP signaling within a particular cell.

[Aging reduces contents of endogenous CO, cAMP and cGMP in rat penile tissues].

Science.gov (United States)

Qin, Wen-Bo; Wang, Shu-Qiu; Li, Ming; Kang, Yu-Ming; Gui, Shi-Liang; Chi, Bao-Jin

2009-02-01

To explore the relationship of aging with the changes of endogenous carbon monoxide (CO), cGMP and cAMP contents in the penile tissues of rats. Twenty-four male rats were equally divided into an 8-month, a 16-month and a 24-month group, and their penile erection was detected by injecting apomorphine, their penile cavernous body harvested, and the contents of CO, cAPM and cGMP detected by improved dual wavelength spectrophotometry. The contents of CO, cAPM and cGMP were reduced with the increase of age, with statistically significant differences between the three age groups (P < 0.01). Aging significantly decreased the contents of CO, cAMP and cGMP in the penile tissues of the rats, which suggests that aging might play an important role in erectile dysfunction.

Stimulation of cyclic GMP efflux in human melanocytes by hypergravity generated by centrifugal acceleration

NARCIS (Netherlands)

Ivanova, Krassimira; Zadeh, Nahid Hamidi; Block, Ingrid; Das, Pranab K.; Gerzer, Rupert

2004-01-01

Gravity alteration (micro- and hypergravity) is known to influence cell functions. As guanosine 3',5'-cyclic monophosphate (cGMP) plays an important role in human melanocyte functions and different guanylyl cyclase isoforms are responsible for cGMP synthesis in human non-metastatic and metastatic

Interactions in the aqueous phase and adsorption at the air-water interface of caseinoglycomacropeptide (GMP) and beta-lactoglobulin mixed systems.

Science.gov (United States)

Martinez, María J; Sánchez, Cecilio Carrera; Patino, Juan M Rodríguez; Pilosof, Ana M R

2009-01-01

The aim of this work was to study the interactions and adsorption of caseinoglycomacropeptide (GMP) and GMP:beta-lactoglobulin (beta-lg) mixed system in the aqueous phase and at the air-water interface. The existence of associative interactions between GMP and beta-lg in the aqueous phase was investigated by dynamic light scattering, differential scanning calorimetry (DSC), fluorometry and native PAGE-electrophoresis. The surface pressure isotherm and the static and dynamic surface pressure were determined by tensiometry and surface dilatational properties. The results showed that GMP presented higher surface activity than beta-lg at a concentration of 4%wt but beta-lg showed higher film forming ability. In the mixed systems beta-lg dominated the static and dynamic surface pressure and the rheological properties of interfacial films suggesting that beta-lg hinders GMP adsorption because, in simple competition, GMP should dominate because of its higher surface activity. The surface predominance of beta-lg can be attributed to binding of GMP to beta-lg in the aqueous phase that prevents GMP adsorption on its own.

Gibberellic acid and cGMP-dependent transcriptional regulation in arabidopsis thaliana

KAUST Repository

Bastian, René

2010-03-01

An ever increasing amount of transcriptomic data and analysis tools provide novel insight into complex responses of biological systems. Given these resources we have undertaken to review aspects of transcriptional regulation in response to the plant hormone gibberellic acid (GA) and its second messenger guanosine 3\\',5\\'-cyclic monophosphate (cGMP) in Arabidopsis thaliana, both wild type and selected mutants. Evidence suggests enrichment of GA-responsive (GARE) elements in promoters of genes that are transcriptionally upregulated in response to cGMP but downregulated in a GA insensitive mutant (ga1-3). In contrast, in the genes upregulated in the mutant, no enrichment in the GARE is observed suggesting that GARE motifs are diagnostic for GA-induced and cGMP-dependent transcriptional upregulation. Further, we review how expression studies of GA-dependent transcription factors and transcriptional networks based on common promoter signatures derived from ab initio analyses can contribute to our understanding of plant responses at the systems level. © 2010 Landes Bioscience.

3',5'-Cyclic diguanylic acid (c-di-GMP) inhibits basal and growth factor-stimulated human colon cancer cell proliferation

International Nuclear Information System (INIS)

Karaolis, David K.R.; Cheng, Kunrong; Lipsky, Michael; Elnabawi, Ahmed; Catalano, Jennifer; Hyodo, Mamoru; Hayakawa, Yoshihiro; Raufman, Jean-Pierre

2005-01-01

The novel cyclic dinucleotide, 3',5'-cyclic diguanylic acid, cGpGp (c-di-GMP), is a naturally occurring small molecule that regulates important signaling mechanisms in prokaryotes. Recently, we showed that c-di-GMP has 'drug-like' properties and that c-di-GMP treatment might be a useful antimicrobial approach to attenuate the virulence and pathogenesis of Staphylococcus aureus and prevent or treat infection. In the present communication, we report that c-di-GMP (≤50 μM) has striking properties regarding inhibition of cancer cell proliferation in vitro. c-di-GMP inhibits both basal and growth factor (acetylcholine and epidermal growth factor)-induced cell proliferation of human colon cancer (H508) cells. Toxicity studies revealed that exposure of normal rat kidney cells and human neuroblastoma cells to c-di-GMP at biologically relevant doses showed no lethal cytotoxicity. Cyclic dinucleotides, such as c-di-GMP, represent an attractive and novel 'drug-platform technology' that can be used not only to develop new antimicrobial agents, but also to develop novel therapeutic agents to prevent or treat cancer

Supercritical fluid chromatography for GMP analysis in support of pharmaceutical development and manufacturing activities.

Science.gov (United States)

Hicks, Michael B; Regalado, Erik L; Tan, Feng; Gong, Xiaoyi; Welch, Christopher J

2016-01-05

Supercritical fluid chromatography (SFC) has long been a preferred method for enantiopurity analysis in support of pharmaceutical discovery and development, but implementation of the technique in regulated GMP laboratories has been somewhat slow, owing to limitations in instrument sensitivity, reproducibility, accuracy and robustness. In recent years, commercialization of next generation analytical SFC instrumentation has addressed previous shortcomings, making the technique better suited for GMP analysis. In this study we investigate the use of modern SFC for enantiopurity analysis of several pharmaceutical intermediates and compare the results with the conventional HPLC approaches historically used for analysis in a GMP setting. The findings clearly illustrate that modern SFC now exhibits improved precision, reproducibility, accuracy and robustness; also providing superior resolution and peak capacity compared to HPLC. Based on these findings, the use of modern chiral SFC is recommended for GMP studies of stereochemistry in pharmaceutical development and manufacturing. Copyright © 2015 Elsevier B.V. All rights reserved.

cGMP Signaling in the Cardiovascular System—The Role of Compartmentation and Its Live Cell Imaging

Science.gov (United States)

Bork, Nadja I.; Nikolaev, Viacheslav O.

2018-01-01

The ubiquitous second messenger 3′,5′-cyclic guanosine monophosphate (cGMP) regulates multiple physiologic processes in the cardiovascular system. Its intracellular effects are mediated by stringently controlled subcellular microdomains. In this review, we will illustrate the current techniques available for real-time cGMP measurements with a specific focus on live cell imaging methods. We will also discuss currently accepted and emerging mechanisms of cGMP compartmentation in the cardiovascular system. PMID:29534460

Cyclic GMP-AMP Containing Mixed Phosphodiester Linkages Is An Endogenous High Affinity Ligand for STING

OpenAIRE

Zhang, Xu; Shi, Heping; Wu, Jiaxi; Zhang, Xuewu; Sun, Lijun; Chen, Chuo; Chen, Zhijian J.

2013-01-01

The presence of microbial or self DNA in the cytoplasm of mammalian cells is a danger signal detected by the DNA sensor cyclic-GMP-AMP (cGAMP) synthase (cGAS), which catalyzes the production of cGAMP that in turn serves as a second messenger to activate innate immune responses. Here we show that endogenous cGAMP in mammalian cells contains two distinct phosphodiester linkages, one between 2′-OH of GMP and 5′-phosphate of AMP, and the other between 3′-OH of AMP and 5′-phosphate of GMP. This mo...

A cyclic GMP-dependent calcium-activated chloride current in smooth-muscle cells from rat mesenteric resistance arteries

DEFF Research Database (Denmark)

Matchkov, Vladimir; Aalkjær, Christian; Nilsson, Holger

2004-01-01

We have previously demonstrated the presence of a cyclic GMP (cGMP)-dependent calcium-activated inward current in vascular smooth-muscle cells, and suggested this to be of importance in synchronizing smooth-muscle contraction. Here we demonstrate the characteristics of this current. Using......M) in the pipette solution. The current was found to be a calcium-activated chloride current with an absolute requirement for cyclic GMP (EC50 6.4 microM). The current could be activated by the constitutively active subunit of PKG. Current activation was blocked by the protein kinase G antagonist Rp-8-Br-PET-cGMP...... differed from those of the calcium-activated chloride current in pulmonary myocytes, which was cGMP-independent, exhibited a high sensitivity to inhibition by niflumic acid, was unaffected by zinc ions, and showed outward current rectification as has previously been reported for this current. Under...

Understanding the link between GMP and dough: from glutenin particles in flour towards developed dough

NARCIS (Netherlands)

Don, C.; Lichtendonk, W.J.; Plijter, J.J.; Hamer, R.J.

2003-01-01

Clear correlations exist for glutenin macropolymer (GMP) quantity and rheological properties vs. wheat quality and dough rheological properties, but real insight in understanding these links is still missing. The observation that GMP consists of glutenin particles opens up new possibilities to

Understanding the link between GMP and dough: From glutenin particles in flour towards developed dough

NARCIS (Netherlands)

Don, C.; Lichtendonk, W.J.; Plijter, J.J.; Hamer, R.J.

2003-01-01

Clear correlations exist for glutenin macropolymer (GMP) quantity and rheological properties vs. wheat quality and dough rheological properties, but real insight in understanding these links is still missing. The observation that GMP consists of glutenin particles opens up new possibilities to

Thrombin has biphasic effects on the nitric oxide-cGMP pathway in endothelial cells and contributes to experimental pulmonary hypertension.

Directory of Open Access Journals (Sweden)

Katrin F Nickel

Full Text Available BACKGROUND: A potential role for coagulation factors in pulmonary arterial hypertension has been recently described, but the mechanism of action is currently not known. Here, we investigated the interactions between thrombin and the nitric oxide-cGMP pathway in pulmonary endothelial cells and experimental pulmonary hypertension. PRINCIPAL FINDINGS: Chronic treatment with the selective thrombin inhibitor melagatran (0.9 mg/kg daily via implanted minipumps reduced right ventricular hypertrophy in the rat monocrotaline model of experimental pulmonary hypertension. In vitro, thrombin was found to have biphasic effects on key regulators of the nitric oxide-cGMP pathway in endothelial cells (HUVECs. Acute thrombin stimulation led to increased expression of the cGMP-elevating factors endothelial nitric oxide synthase (eNOS and soluble guanylate cyclase (sGC subunits, leading to increased cGMP levels. By contrast, prolonged exposition of pulmonary endothelial cells to thrombin revealed a characteristic pattern of differential expression of the key regulators of the nitric oxide-cGMP pathway, in which specifically the factors contributing to cGMP elevation (eNOS and sGC were reduced and the cGMP-hydrolyzing PDE5 was elevated (qPCR and Western blot. In line with the differential expression of key regulators of the nitric oxide-cGMP pathway, a reduction of cGMP by prolonged thrombin stimulation was found. The effects of prolonged thrombin exposure were confirmed in endothelial cells of pulmonary origin (HPAECs and HPMECs. Similar effects could be induced by activation of protease-activated receptor-1 (PAR-1. CONCLUSION: These findings suggest a link between thrombin generation and cGMP depletion in lung endothelial cells through negative regulation of the nitric oxide-cGMP pathway, possibly mediated via PAR-1, which could be of relevance in pulmonary arterial hypertension.

Evaluation of GMP-compliant culture media for in vitro expansion of human bone marrow mesenchymal stromal cells.

Science.gov (United States)

Wuchter, Patrick; Vetter, Marcel; Saffrich, Rainer; Diehlmann, Anke; Bieback, Karen; Ho, Anthony D; Horn, Patrick

2016-06-01

Mesenchymal stromal cells (MSCs) from human bone marrow serve as a resource for cell-based therapies in regenerative medicine. Clinical applications require standardized protocols according to good manufacturing practice (GMP) guidelines. Donor variability as well as the intrinsic heterogeneity of MSC populations must be taken into consideration. The composition of the culture medium is a key factor in successful MSC expansion. The aim of this study was to comparatively assess the efficiency of xeno-free human platelet lysate (HPL)-based cell expansion with two commercially available media-StemPro MSC SFM CTS (for human ex vivo tissue and cell culture processing applications) and MSCGM (non-GMP-compliant, for research only)-in an academic setting as the first optimization step toward GMP-compliant manufacturing. We report the feasibility of MSC expansion up to the yielded cell number with all three media. MSCs exhibited the typical fibroblastoid morphology, with distinct differences in cell size depending on the medium. The differentiation capacity and characteristic immunophenotype were confirmed for all MSC populations. Proliferation was highest using StemPro MSC SFM CTS, whereas HPL medium was more cost-effective and its composition could be adjusted individually according to the respective needs. In summary, we present a comprehensive evaluation of GMP-compatible culture media for MSC expansion. Both StemPro and HPL medium proved to be suitable for clinical application and allowed sufficient cell proliferation. Specific differences were observed and should be considered according to the intended use. This study provides a detailed cost analysis and tools that may be helpful for the establishment of GMP-compliant MSC expansion. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

78 FR 13081 - Draft Environmental Impact Statement for General Management Plan, Everglades National Park, Florida

Science.gov (United States)

2013-02-26

... visitor use in the Park. The GMP will provide updated management direction for the entire park. The EEWS....YP0000] Draft Environmental Impact Statement for General Management Plan, Everglades National Park... the General Management Plan (GMP) and East Everglades Wilderness Study (EEWS) for Everglades National...

Opposing actions of dibutyryl cyclic AMP and GMP on temperature in conscious guinea-pigs

Science.gov (United States)

Kandasamy, S. B.; Williaes, B. A.

1983-01-01

It is shown that the intracerebroventricular administration of dibutyryl cyclic AMP (Db-cAMP) induced hyperthermia in guinea pigs which was not mediated through prostaglandins or norepinephrine since a prostaglandin synthesis inhibitor and an alpha-adrenergic receptor blocking agent did not antagonize the hyperthermia. However, the hyperthermic response to Db-cAMP was attenuated by the central administration of a beta-adrenergic receptor antagonist, which indicates that cAMP may be involved, through beta-adrenergic receptors, in the central regulation of heat production and conservation. The central administration of Db-cGMP produced hypothermia which was not mediated via histamine H1 or H2 receptors and serotonin. The antagonism of hypothermia induced by Db-cGMP and acetylcholine + physostigmine by central administration of a cholinergic muscarine receptor antagonist and not by a cholinergic nicotinic receptor antagonist suggests that cholinoceptive neurons and endogenous cGMP may regulate heat loss through cholinergic muscarine receptors. It is concluded that these results indicate a regulatory role in thermoregulation provided by a balance between opposing actions of cAMP and cGMP in guinea pigs.

cGMP-dependent protein kinase I, the circadian clock, sleep and learning

OpenAIRE

Feil, Robert; Hölter, Sabine M; Weindl, Karin; Wurst, Wolfgang; Langmesser, Sonja; Gerling, Andrea; Feil, Susanne; Albrecht, Urs

2009-01-01

The second messenger cGMP controls cardiovascular and gastrointestinal homeostasis in mammals. However, its physiological relevance in the nervous system is poorly understood.1 Now, we have reported that the cGMP-dependent protein kinase type I (PRKG1) is implicated in the regulation of the timing and quality of sleep and wakefulness.2 Prkg1 mutant mice showed altered distribution of sleep and wakefulness as well as reduction in rapid-eye-movement sleep (REMS) duration and in non-REMS consoli...

Cyclic di-GMP is essential for the survival of the lyme disease spirochete in ticks.

Directory of Open Access Journals (Sweden)

Ming He

2011-06-01

Full Text Available Cyclic dimeric GMP (c-di-GMP is a bacterial second messenger that modulates many biological processes. Although its role in bacterial pathogenesis during mammalian infection has been documented, the role of c-di-GMP in a pathogen's life cycle within a vector host is less understood. The enzootic cycle of the Lyme disease pathogen Borrelia burgdorferi involves both a mammalian host and an Ixodes tick vector. The B. burgdorferi genome encodes a single copy of the diguanylate cyclase gene (rrp1, which is responsible for c-di-GMP synthesis. To determine the role of c-di-GMP in the life cycle of B. burgdorferi, an Rrp1-deficient B. burgdorferi strain was generated. The rrp1 mutant remains infectious in the mammalian host but cannot survive in the tick vector. Microarray analyses revealed that expression of a four-gene operon involved in glycerol transport and metabolism, bb0240-bb0243, was significantly downregulated by abrogation of Rrp1. In vitro, the rrp1 mutant is impaired in growth in the media containing glycerol as the carbon source (BSK-glycerol. To determine the contribution of the glycerol metabolic pathway to the rrp1 mutant phenotype, a glp mutant, in which the entire bb0240-bb0243 operon is not expressed, was generated. Similar to the rrp1 mutant, the glp mutant has a growth defect in BSK-glycerol medium. In vivo, the glp mutant is also infectious in mice but has reduced survival in ticks. Constitutive expression of the bb0240-bb0243 operon in the rrp1 mutant fully rescues the growth defect in BSK-glycerol medium and partially restores survival of the rrp1 mutant in ticks. Thus, c-di-GMP appears to govern a catabolic switch in B. burgdorferi and plays a vital role in the tick part of the spirochetal enzootic cycle. This work provides the first evidence that c-di-GMP is essential for a pathogen's survival in its vector host.

Regulation of Burkholderia cenocepacia biofilm formation by RpoN and the c-di-GMP effector BerB

DEFF Research Database (Denmark)

Fazli, Mustafa; Rybtke, Morten Levin; Steiner, Elisabeth

2017-01-01

Knowledge about the molecular mechanisms that are involved in the regulation of biofilm formation is essential for the development of biofilm-control measures. It is well established that the nucleotide second messenger cyclic diguanosine monophosphate (c-di-GMP) is a positive regulator of biofilm...... formation in many bacteria, but more knowledge about c-di-GMP effectors is needed. We provide evidence that c-di-GMP, the alternative sigma factor RpoN (σ54), and the enhancer-binding protein BerB play a role in biofilm formation of Burkholderia cenocepacia by regulating the production of a biofilm......-stabilizing exopolysaccharide. Our findings suggest that BerB binds c-di-GMP, and activates RpoN-dependent transcription of the berA gene coding for a c-di-GMP-responsive transcriptional regulator. An increased level of the BerA protein in turn induces the production of biofilm-stabilizing exopolysaccharide in response to high...

Molecular Analysis of Sensory Axon Branching Unraveled a cGMP-Dependent Signaling Cascade.

Science.gov (United States)

Dumoulin, Alexandre; Ter-Avetisyan, Gohar; Schmidt, Hannes; Rathjen, Fritz G

2018-04-24

Axonal branching is a key process in the establishment of circuit connectivity within the nervous system. Molecular-genetic studies have shown that a specific form of axonal branching—the bifurcation of sensory neurons at the transition zone between the peripheral and the central nervous system—is regulated by a cyclic guanosine monophosphate (cGMP)-dependent signaling cascade which is composed of C-type natriuretic peptide (CNP), the receptor guanylyl cyclase Npr2, and cGMP-dependent protein kinase Iα (cGKIα). In the absence of any one of these components, neurons in dorsal root ganglia (DRG) and cranial sensory ganglia no longer bifurcate, and instead turn in either an ascending or a descending direction. In contrast, collateral axonal branch formation which represents a second type of axonal branch formation is not affected by inactivation of CNP, Npr2, or cGKI. Whereas axon bifurcation was lost in mouse mutants deficient for components of CNP-induced cGMP formation; the absence of the cGMP-degrading enzyme phosphodiesterase 2A had no effect on axon bifurcation. Adult mice that lack sensory axon bifurcation due to the conditional inactivation of Npr2-mediated cGMP signaling in DRG neurons demonstrated an altered shape of sensory axon terminal fields in the spinal cord, indicating that elaborate compensatory mechanisms reorganize neuronal circuits in the absence of bifurcation. On a functional level, these mice showed impaired heat sensation and nociception induced by chemical irritants, whereas responses to cold sensation, mechanical stimulation, and motor coordination are normal. These data point to a critical role of axon bifurcation for the processing of acute pain perception.

Molecular Analysis of Sensory Axon Branching Unraveled a cGMP-Dependent Signaling Cascade

Directory of Open Access Journals (Sweden)

Alexandre Dumoulin

2018-04-01

Full Text Available Axonal branching is a key process in the establishment of circuit connectivity within the nervous system. Molecular-genetic studies have shown that a specific form of axonal branching—the bifurcation of sensory neurons at the transition zone between the peripheral and the central nervous system—is regulated by a cyclic guanosine monophosphate (cGMP-dependent signaling cascade which is composed of C-type natriuretic peptide (CNP, the receptor guanylyl cyclase Npr2, and cGMP-dependent protein kinase Iα (cGKIα. In the absence of any one of these components, neurons in dorsal root ganglia (DRG and cranial sensory ganglia no longer bifurcate, and instead turn in either an ascending or a descending direction. In contrast, collateral axonal branch formation which represents a second type of axonal branch formation is not affected by inactivation of CNP, Npr2, or cGKI. Whereas axon bifurcation was lost in mouse mutants deficient for components of CNP-induced cGMP formation; the absence of the cGMP-degrading enzyme phosphodiesterase 2A had no effect on axon bifurcation. Adult mice that lack sensory axon bifurcation due to the conditional inactivation of Npr2-mediated cGMP signaling in DRG neurons demonstrated an altered shape of sensory axon terminal fields in the spinal cord, indicating that elaborate compensatory mechanisms reorganize neuronal circuits in the absence of bifurcation. On a functional level, these mice showed impaired heat sensation and nociception induced by chemical irritants, whereas responses to cold sensation, mechanical stimulation, and motor coordination are normal. These data point to a critical role of axon bifurcation for the processing of acute pain perception.

The NO/cGMP pathway inhibits transient cAMP signals through the activation of PDE2 in striatal neurons

Directory of Open Access Journals (Sweden)

Marina ePolito

2013-11-01

Full Text Available The NO-cGMP signaling plays an important role in the regulation of striatal function although the mechanisms of action of cGMP specifically in medium spiny neurons (MSNs remain unclear. Using genetically encoded fluorescent biosensors, including a novel Epac-based sensor (EPAC-SH150 with increased sensitivity for cAMP, we analyze the cGMP response to NO and whether it affected cAMP/PKA signaling in MSNs. The Cygnet2 sensor for cGMP reported large responses to NO donors in both striatonigral and striatopallidal MSNs, and this cGMP signal was controlled partially by PDE2. At the level of cAMP brief forskolin stimulations produced transient cAMP signals which differed between D1 and D2 medium spiny neurons. NO inhibited these cAMP transients through cGMP-dependent PDE2 activation, an effect that was translated and magnified downstream of cAMP, at the level of PKA. PDE2 thus appears as a critical effector of NO which modulates the post-synaptic response of MSNs to dopaminergic transmission.

Plasma levels of cAMP, cGMP and CGRP in sildenafil-induced headache

DEFF Research Database (Denmark)

Kruuse, Christina Rostrup; Frandsen, E; Schifter, S

2004-01-01

Sildenafil, a selective inhibitor of the cyclic guanosine monophosphate (cGMP) degrading phosphodiestrase 5 (PDE5), induced migraine without aura in 10 of 12 migraine patients and in healthy subjects it induced significantly more headache than placebo. The aim of the present study was to determine...... whether the pain-inducing effects of sildenafil would be reflected in plasma levels of important signalling molecules in migraine: cGMP, cyclic adenosine monophosphate (cAMP) and calcitonin gene-related peptide (CGRP). Ten healthy subjects (four women, six men) and 12 patients (12 women) suffering from...... migraine without aura were included in two separate double-blind, placebo-controlled, cross-over studies in which placebo or sildenafil 100 mg was administered orally. Plasma levels of CGRP, cAMP and cGMP were determined in blood from the antecubital vein. Despite the ability of sildenafil to induce...

Effect on Antibody and T-Cell Responses of Mixing Five GMP-Produced DNA Plasmids and Administration With Plasmid Expressing GM-CSF

National Research Council Canada - National Science Library

Sedegah, M; Charoenvit, Y; Aguiar, J; Sacci, J; Hedstrom, R; Kumar, S; Belmonte, A; Lanar, DE; Jones, TR; Abot, E

2004-01-01

.... In preparation for a clinical trial, we assessed the immunogenicity of GMP-produced plasmids encoding five Plasmodium falciparum proteins, PfCSP, PfSSP2, PfEXP1, PfLSA1, and PfLSA3, given as a mixture, or alone...

Developing a tool for the preparation of GMP audit of pharmaceutical contract manufacturer.

Science.gov (United States)

Linna, Anu; Korhonen, Mirka; Mannermaa, Jukka-Pekka; Airaksinen, Marja; Juppo, Anne Mari

2008-06-01

Outsourcing is rapidly growing in the pharmaceutical industry. When the manufacturing activities are outsourced, control of the product's quality has to be maintained. One way to confirm contract manufacturer's GMP (Good Manufacturing Practice) compliance is auditing. Audits can be supported for instance by using GMP questionnaires. The objective of this study was to develop a tool for the audit preparation of pharmaceutical contract manufacturers and to validate its contents by using Delphi method. At this phase of the study the tool was developed for non-sterile finished product contract manufacturers. A modified Delphi method was used with expert panel consisting of 14 experts from pharmaceutical industry, authorities and university. The content validity of the developed tool was assessed by a Delphi questionnaire round. The response rate in Delphi questionnaire round was 86%. The tool consisted of 103 quality items, from which 90 (87%) achieved the pre-defined agreement rate level (75%). Thirteen quality items which did not achieve the pre-defined agreement rate were excluded from the tool. The expert panel suggested only minor changes to the tool. The results show that the content validity of the developed audit preparation tool was good.

Single amino acids in the carboxyl terminal domain of aquaporin-1 contribute to cGMP-dependent ion channel activation

Directory of Open Access Journals (Sweden)

Yool Andrea J

2003-10-01

Full Text Available Abstract Background Aquaporin-1 (AQP1 functions as an osmotic water channel and a gated cation channel. Activation of the AQP1 ion conductance by intracellular cGMP was hypothesized to involve the carboxyl (C- terminus, based on amino acid sequence alignments with cyclic-nucleotide-gated channels and cGMP-selective phosphodiesterases. Results Voltage clamp analyses of human AQP1 channels expressed in Xenopus oocytes demonstrated that the nitric oxide donor, sodium nitroprusside (SNP; 3–14 mM activated the ionic conductance response in a dose-dependent manner. Block of soluble guanylate cyclase prevented the response. Enzyme immunoassays confirmed a linear dose-dependent relationship between SNP and the resulting intracellular cGMP levels (up to 1700 fmol cGMP /oocyte at 14 mM SNP. Results here are the first to show that the efficacy of ion channel activation is decreased by mutations of AQP1 at conserved residues in the C-terminal domain (aspartate D237 and lysine K243. Conclusions These data support the idea that the limited amino acid sequence similarities found between three diverse classes of cGMP-binding proteins are significant to the function of AQP1 as a cGMP-gated ion channel, and provide direct evidence for the involvement of the AQP1 C-terminal domain in cGMP-mediated ion channel activation.

Changes of platelet GMP-140 in diabetic nephropathy and its multi-factor regression analysis

International Nuclear Information System (INIS)

Wang Zizheng; Du Tongxin; Wang Shukui

2001-01-01

The relation of platelet GMP-140 and its related factors with diabetic nephropathy was studied. 144 patients of diabetic mellitus without nephropathy (group without DN, mean suffering duration of 25.5 +- 18.6 months); 80 with diabetic nephropathy (group DN, mean suffering duration of 58.7 +- 31.6 months) and 50 normal controls were chosen in the research. Platelet GMP-140, plasma α 1 -MG, β 2 -MG, and 24 hour urine albumin (ALB), IgG, α 1 -MG, β 2 -MG were detected by RIA, while HBA 1 C via chromatographic separation and FBG, PBG, Ch, TG, HDL, FG via biochemical methods. All the data had been processed with software on computer with t-test and linear regression, and multi-factor analysis were done also. The levels of platelet GMP-140, FG, DBP, TG, HBA 1 C and PBG in group DN were significantly higher than those of group without DN and normal control (P 0.05), while they were higher than those of normal controls. Multi-factor analysis of platelet GMP-140 with TG, DBP and HBA 1 C were performed in 80 patients with DN (P 1 C are the independent factors enhancing the activation of platelets. The disturbance of lipid metabolism in type II diabetic mellitus may also enhance the activation of platelets. Elevation of blood pressure may accelerate the initiation and deterioration of DN in which change of platelet GMP-140 is an independent factor. Elevation of HBA 1 C and blood glucose are related closely to the diabetic nephropathy

Nicorandil directly and cyclic GMP-dependently opens K+ channels in human bypass grafts

Directory of Open Access Journals (Sweden)

Marija Marinko

2015-06-01

Full Text Available As we previously demonstrated the role of different K+ channels in the action of nicorandil on human saphenous vein (HSV and human internal mammary artery (HIMA, this study aimed to analyse the contribution of the cGMP pathway in nicorandil-induced vasorelaxation and to determine the involvement of cGMP in the K+ channel-activating effect of nicorandil. An inhibitor of soluble guanylate cyclase (GC, ODQ, significantly inhibited nicorandil-induced relaxation, while ODQ plus glibenclamide, a selective ATP-sensitive K+ (KATP channel inhibitor, produced a further inhibition of both vessels. In HSV, ODQ in combination with 4-aminopyridine, a blocker of voltage-gated K+ (KV channels, did not modify the concentration-response to nicorandil compared with ODQ, whereas in HIMA, ODQ plus iberiotoxin, a selective blocker of large-conductance Ca2+-activated K+ (BKCa channels, produced greater inhibition than ODQ alone. We showed that the cGMP pathway plays a significant role in the vasorelaxant effect of nicorandil on HSV and HIMA. It seems that nicorandil directly opens KATP channels in both vessels and BKCa channels in HIMA, although it is possible that stimulation of GC contributes to KATP channels activation in HIMA. Contrary, the activation of KV channels in HSV is probably due to GC activation and increased levels of cGMP.

Simulation of an Aspheric Glass Lens Forming Behavior in Progressive GMP Process

International Nuclear Information System (INIS)

Chang, Sung Ho; Lee, Young Min; Kang, Jeong Jin; Hong, Seok Kwan; Shin, Gwang Ho; Heo, Young Moo; Jung, Tae Sung

2007-01-01

Recently, GMP(Glass Molding Press) process is mainly used to produce aspheric glass lenses. Because glass lens is heated at high temperature above Tg (Transformation Temperature) for forming the glass, the quality of aspheric glass lens is deteriorated by residual stresses which are generated in a aspheric glass lens after forming. In this study, as a fundamental study to develop the mold for progressive GMP process, we conducted a aspheric glass lens forming simulation. Prior to a aspheric glass lens forming simulation, compression and thermal conductivity tests were carried out to obtain mechanical and thermal properties of K-PBK40 which is newly developed material for precision molding, and flow characteristics of K-PBK40 were obtained at high temperature. Then, using the flow characteristics obtained, compression simulation was carried out and compared with the experimental result for the purpose of verifying the obtained flow characteristics. Finally, a glass lens press simulation in progressive GMP process was carried out and we could forecast the shape of deformed glass lenses and residual stresses contribution in the structure of deformed glass lenses after forming

Magnesium Lithospermate B, an Active Extract of Salvia miltiorrhiza, Mediates sGC/cGMP/PKG Translocation in Experimental Vasospasm

Directory of Open Access Journals (Sweden)

Chih-Zen Chang

2014-01-01

Full Text Available Background. Soluble guanylyl cyclases (sGCs and Ras homolog gene family, member A (rhoA/Ras homolog gene family kinase(rho-kinase plays a role in vascular smooth muscle relaxation in subarachnoid hemorrhage (SAH. It is of interest to examine the effect of MLB on rhoA/ROCK and sGC/cGMP/PKG expression. Methods. A rodent SAH model was employed. Tissue samples were for sGCα1, sGCβ1, PKG, rhoA, ROCK (Western blot, and cGMP (ELISA measurement. Results. MLB morphologically improved convolution of the internal elastic lamina, distortion of endothelial wall, and necrosis of the smooth muscle in the SAH rats. Expressed cGMP, sGCα1, sGCβ1, and PKG in the SAH groups were reduced (P<0.01, and MLB precondition significantly induced cGMP, sGCα1, sGCβ1, and PKG. L-NAME reversed the vasodilation effect of MLB, reduced the bioexpression of PKG and cGMP (P<0.01, and tends to reduce sGCα1 level and induce rhoA, ROCK level in MLB precondition + SAH groups. Conclusion. These results demonstrate that sGC/cGMP/PKG and NO/ET pathways play pivotal roles in SAH-induced vasospasm. Through activating sGC/cGMP/PKG pathway and partially by inactivating rho-kinase in a NO-dependent mechanism, MLB shows promise to be an effective strategy for the treatment of this disease entity.

Design of GMP compliance radiopharmaceutical production facility in MINT

International Nuclear Information System (INIS)

Anwar Abd Rahman; Shaharum Ramli; M Rizal Mamat Ibrahim; Rosli Darmawan; Yusof Azuddin Ali; Jusnan Hashim

2005-01-01

In 1985, MINT built the only radiopharmaceutical production facility in Malaysia. The facility was designed based on IAEA (International Atomic Energy Agency) standard guidelines which provide radiation safety to the staff and the surrounding environment from radioactive contamination. Since 1999, BPFK (Biro Pengawalan Farmaseutikal Kebangsaan) has used the guidelines from Pharmaceutical Inspection Convention Scheme (PICS) to meet the requirements of the Good Manufacturing Practice (GMP) for Pharmaceutical Products. In the guidelines, the pharmaceutical production facility shall be designed based on clean room environment. In order to design a radiopharmaceutical production facility, it is important to combine the concept of radiation safety and clean room to ensure that both requirements from GMP and IAEA are met. The design requirement is necessary to set up a complete radiopharmaceutical production facility, which is safe, has high production quality and complies with the Malaysian and International standards. (Author)

Inhibition of excitatory synaptic transmission in the trigeminal motor nucleus by the nitric oxide-cyclic GMP signaling pathway.

Science.gov (United States)

Pose, Inés; Silveira, Valentina; Morales, Francisco R

2011-06-01

Nitric oxide (NO) and cyclic GMP (cGMP) suppressed glutamatergic synaptic transmission to trigeminal motoneurons in brain stem slices of neonatal rats. Histological studies showed guanylate cyclase (GC) containing fibers in the trigeminal motor pool. Glutamatergic excitatory postsynaptic currents (EPSCs) were recorded from neonatal trigeminal motoneurons in response to stimulation of the supratrigeminal nucleus (SuV). The NO donors DETA/NONOate (DETA/NO), at a concentration which released 275.1 nM of NO, and Spermine/NONOate (Sper/NO) reduced the amplitude of the EPSC to 52.7±0.6% and 60.1±10.8% of control values, respectively. These actions were not blocked by the GC inhibitors, ODQ or NS-2028. However, in the presence of YC-1 or BAY41-2272, modulators of GC that act as NO sensitizers, lower and otherwise ineffective concentrations of DETA/NO induced a reduction of the EPSC to 60.6±5.2%. Moreover, NO effects were mimicked by 8BrcGMP and by Zaprinast, an inhibitor of Phosphodiesterase 5. Glutamatergic currents evoked by exogenous glutamate were not reduced by DETA/NO nor 8BrcGMP. Paired-pulse facilitation was increased by NO donors. Under "minimal stimulation" conditions NO donors and cGMP increased the failure rate of evoked EPSCs. Protein kinase inhibitors antagonized cGMP effects. The results suggest that NO, through the synthesis of cGMP, presynaptically inhibits glutamatergic synaptic transmission on trigeminal motoneurons. We propose that NO has complex actions on motor pools; specific studies are needed to elucidate their physiological significance in the behaving animal. Copyright © 2011 Elsevier B.V. All rights reserved.

cGMP-Phosphodiesterase Inhibition Prevents Hypoxia-Induced Cell Death Activation in Porcine Retinal Explants.

Directory of Open Access Journals (Sweden)

Lorena Olivares-González

Full Text Available Retinal hypoxia and oxidative stress are involved in several retinal degenerations including diabetic retinopathy, glaucoma, central retinal artery occlusion, or retinopathy of prematurity. The second messenger cyclic guanosine monophosphate (cGMP has been reported to be protective for neuronal cells under several pathological conditions including ischemia/hypoxia. The purpose of this study was to evaluate whether the accumulation of cGMP through the pharmacological inhibition of phosphodiesterase (PDE with Zaprinast prevented retinal degeneration induced by mild hypoxia in cultures of porcine retina. Exposure to mild hypoxia (5% O2 for 24h reduced cGMP content and induced retinal degeneration by caspase dependent and independent (PARP activation mechanisms. Hypoxia also produced a redox imbalance reducing antioxidant response (superoxide dismutase and catalase activities and increasing superoxide free radical release. Zaprinast reduced mild hypoxia-induced cell death through inhibition of caspase-3 or PARP activation depending on the cell layer. PDE inhibition also ameliorated the effects of mild hypoxia on antioxidant response and the release of superoxide radical in the photoreceptor layer. The use of a PKG inhibitor, KT5823, suggested that cGMP-PKG pathway is involved in cell survival and antioxidant response. The inhibition of PDE, therefore, could be useful for reducing retinal degeneration under hypoxic/ischemic conditions.

Development of GMP-1 a molecular chaperone network modulator protecting mitochondrial function and its assessment in fly and mice models of Alzheimer's disease.

Science.gov (United States)

Pavlov, Pavel F; Hutter-Paier, Birgit; Havas, Daniel; Windisch, Manfred; Winblad, Bengt

2018-04-27

Mitochondrial dysfunction is an early feature of Alzheimer's disease (AD) and may play an important role in the pathogenesis of disease. It has been shown that amyloid beta peptide (Aβ) and amyloid precursor protein (APP) interact with mitochondria contributing to the mitochondrial dysfunction in AD. Prevention of abnormal protein targeting to mitochondria can protect normal mitochondrial function, increase neuronal survival and at the end, ameliorate symptoms of AD and other neurodegenerative disorders. First steps of mitochondrial protein import are coordinated by molecular chaperones Hsp70 and Hsp90 that bind to the newly synthesized mitochondria-destined proteins and deliver them to the protein import receptors on the surface of organelle. Here, we have described the development of a novel compound named GMP-1 that disrupts interactions between Hsp70/Hsp90 molecular chaperones and protein import receptor Tom70. GMP-1 treatment of SH-SY5Y cells results in decrease in mitochondria-associated APP and protects SH-SY5Y cells from toxic effect of Aβ 1-42 exposure. Experiments in drosophila and mice models of AD demonstrated neuroprotective effect of GMP-1 treatment, improvement in memory and behaviour tests as well as restoration of mitochondrial function. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

The environmental impacts of windpower development in Vermont: A policy analyses

Energy Technology Data Exchange (ETDEWEB)

Goodman, N. [Univ. of Vermont, Burlington, CT (United States)

1997-12-31

In the spring of 1996, construction of a six-megawatt wind power facility commenced on a mountain ridge in the town of Searsburgh in southern Vermont. While this process marked the beginning of physical development on the ridge, Green Mountain Power Corporation (GMP) had been planning the process for over 25 years. From wind speed data collection in 1971, to site selection, and environmental studies still ongoing, GMP has sought to increase their renewable energy portfolio by bringing wind power to the state of Vermont. While on the surface, wind power appears to be relatively pollution free, producing no emissions, it should be noted that there are environmental impacts associated with wind power and these would have to be addressed before any substantial development could occur. But how would this happen in Vermont? Power generating facilities are not subject to the Act 250 process; rather they require certification from the Public Service Board (P.S.B.). As the project progressed, questions arose over just how the process would adequately address the environmental impacts associated with developing a remote ridge in southern Vermont. In preparing for and participating in the certification process, GMP identified several environmental impact issues in need of investigation. GMP initiated studies in several fields and hired consultants to investigate these issues with the hope that they would not serve as an impediment to their project. Preliminary analysis revealed the need for in-depth studies in four specific impact areas, including aesthetics, critical wildlife habitat, noise and avian studies. While all participants in the process do not share the same concerns, different stakeholders have raised enough questions to justify a critical look at the certification process.

Cyclic GMP-mediated memory enhancement in the object recognition test by inhibitors of phosphodiesterase-2 in mice.

Science.gov (United States)

Lueptow, Lindsay M; Zhan, Chang-Guo; O'Donnell, James M

2016-02-01

Cyclic nucleotide phosphodiesterase-2 (PDE2) is a potential therapeutic target for the treatment of cognitive dysfunction. Using the object recognition test (ORT), this study assessed the effects of two PDE2 inhibitors, Bay 60-7550 and ND7001, on learning and memory, and examined underlying mechanisms. To assess the role of PDE2 inhibition on phases of memory, Bay 60-7550 (3 mg/kg) was administered: 30 min prior to training; 0, 1, or 3 h after training; or 30 min prior to recall testing. To assess cyclic nucleotide involvement in PDE2 inhibitor-enhanced memory consolidation, either the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 20 mg/kg; intraperitoneal (IP)), soluble guanylyl cyclase inhibitor 1H-[-1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ; 20 mg/kg; IP), protein kinase G inhibitor KT5823 (2.5 μg; intracerebroventricular (ICV)), or protein kinase A inhibitor H89 (1 μg; ICV) was administered 30 min prior to the PDE2 inhibitor Bay 60-7550 (3 mg/kg) or ND7001 (3 mg/kg). Changes in the phosphorylation of 3'5'-cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) at Ser-133 and vasodilator-stimulated phosphoprotein (VASP) at Ser-239 were determined to confirm activation of cAMP and 3'5'-cyclic guanosine monophosphate (cGMP) signaling. Bay 60-7550 (3 mg/kg) enhanced memory of mice in the ORT when given 30 min prior to training, immediately after training, or 30 min prior to recall. Inhibitors of the cGMP pathway blocked the memory-enhancing effects of both Bay 60-7550 (3 mg/kg) and ND7001 (3 mg/kg) on early consolidation processes. Bay 60-7550 (3 mg/kg) enhanced phosphorylation of CREB and VASP, both targets of cGMP-dependent protein kinase (PKG). These results confirm a potential of PDE2, or components of its signaling pathway, as a therapeutic target for drug discovery focused on restoring memory function.

Time-dependent inhibitory effects of cGMP-analogues on thrombin-induced platelet-derived microparticles formation, platelet aggregation, and P-selectin expression

International Nuclear Information System (INIS)

Nygaard, Gyrid; Herfindal, Lars; Kopperud, Reidun; Aragay, Anna M.; Holmsen, Holm; Døskeland, Stein Ove; Kleppe, Rune; Selheim, Frode

2014-01-01

Highlights: • We investigated the impact of cyclic nucleotide analogues on platelet activation. • Different time dependence were found for inhibition of platelet activation. • Additive effect was found using PKA- and PKG-activating analogues. • Our results may explain some of the discrepancies reported for cNMP signalling. - Abstract: In platelets, nitric oxide (NO) activates cGMP/PKG signalling, whereas prostaglandins and adenosine signal through cAMP/PKA. Cyclic nucleotide signalling has been considered to play an inhibitory role in platelets. However, an early stimulatory effect of NO and cGMP-PKG signalling in low dose agonist-induced platelet activation have recently been suggested. Here, we investigated whether different experimental conditions could explain some of the discrepancy reported for platelet cGMP-PKG-signalling. We treated gel-filtered human platelets with cGMP and cAMP analogues, and used flow cytometric assays to detect low dose thrombin-induced formation of small platelet aggregates, single platelet disappearance (SPD), platelet-derived microparticles (PMP) and thrombin receptor agonist peptide (TRAP)-induced P-selectin expression. All four agonist-induced platelet activation phases were blocked when platelets were costimulated with the PKG activators 8-Br-PET-cGMP or 8-pCPT-cGMP and low-doses of thrombin or TRAP. However, extended incubation with 8-Br-PET-cGMP decreased its inhibition of TRAP-induced P-selectin expression in a time-dependent manner. This effect did not involve desensitisation of PKG or PKA activity, measured as site-specific VASP phosphorylation. Moreover, PKG activators in combination with the PKA activator Sp-5,6-DCL-cBIMPS revealed additive inhibitory effect on TRAP-induced P-selectin expression. Taken together, we found no evidence for a stimulatory role of cGMP/PKG in platelets activation and conclude rather that cGMP/PKG signalling has an important inhibitory function in human platelet activation

Structural Basis for the Catalytic Mechanism of DncV, Bacterial Homolog of Cyclic GMP-AMP Synthase.

Science.gov (United States)

Kato, Kazuki; Ishii, Ryohei; Hirano, Seiichi; Ishitani, Ryuichiro; Nureki, Osamu

2015-05-05

Cyclic dinucleotides (CDNs) play key roles as second messengers and signaling molecules in bacteria and metazoans. The newly identified dinucleotide cyclase in Vibrio cholerae (DncV) produces three different CDNs containing two 3'-5' phosphodiester bonds, and its predominant product is cyclic GMP-AMP, whereas mammalian cyclic GMP-AMP synthase (cGAS) produces only cyclic GMP-AMP containing mixed 2'-5' phosphodiester bonds. We report the crystal structures of V. cholerae and Escherichia coli DncV in complex with various nucleotides in the pre-reaction states. The high-resolution structures revealed that DncV preferably recognizes ATP and GTP as acceptor and donor nucleotides, respectively, in the first nucleotidyl transfer reaction. Considering the recently reported intermediate structures, our pre-reaction state structures provide the precise mechanism of 3'-5' linked cyclic AMP-GMP production in bacteria. A comparison with cGAS in the pre-reaction states suggests that the orientation of the acceptor nucleotide primarily determines the distinct linkage specificities between DncV and cGAS. Copyright © 2015 Elsevier Ltd. All rights reserved.

The role of cGMP signalling in regulating life cycle progression of Plasmodium.

OpenAIRE

Hopp, CS; Bowyer, PW; Baker, DA

2012-01-01

The 3′-5′-cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is the main mediator of cGMP signalling in the malaria parasite. This article reviews the role of PKG in Plasmodium falciparum during gametogenesis and blood stage schizont rupture, as well as the role of the Plasmodium berghei orthologue in ookinete differentiation and motility, and liver stage schizont development. The current views on potential effector proteins downstream of PKG and the mechanisms that may regu...

The role of cGMP signalling in regulating life cycle progression of Plasmodium.

Science.gov (United States)

Hopp, Christine S; Bowyer, Paul W; Baker, David A

2012-08-01

The 3'-5'-cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is the main mediator of cGMP signalling in the malaria parasite. This article reviews the role of PKG in Plasmodium falciparum during gametogenesis and blood stage schizont rupture, as well as the role of the Plasmodium berghei orthologue in ookinete differentiation and motility, and liver stage schizont development. The current views on potential effector proteins downstream of PKG and the mechanisms that may regulate cyclic nucleotide levels are presented. Copyright © 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

PDE1A inhibition elicits cGMP-dependent relaxation of rat mesenteric arteries

DEFF Research Database (Denmark)

Khammy, Makhala Michell; Dalsgaard, Thomas; Larsen, Peter Hjorringgaard

2017-01-01

(EC50 = 32 nM). Inhibition of NOS with L-NAME, soluble GC with ODQ, or PKG with Rp-8-Br-PET-cGMP all attenuated PDE1 inhibition-induced relaxation, whereas PKA inhibition with H89 had no effect. CONCLUSION AND IMPLICATIONS: Pde1a was the dominant PDE1 isoform present in VSMC and relaxation mediated...... by PDE1A-inhibition was predominantly driven by enhanced cGMP signalling. These results imply that isoform-selective PDE1 inhibitors are powerful investigative tools allowing examination of physiological and pathological roles of PDE1 isoforms....

Cyclic GMP-AMP displays mucosal adjuvant activity in mice.

Directory of Open Access Journals (Sweden)

Ivana Škrnjug

Full Text Available The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice. A characteristic of the cGAMP-induced immune response is the slightly reduced induction of interleukin-17 as a hallmark of Th17 activity--a distinct feature that is not observed with other cyclic di-nucleotide adjuvants. We further characterize the innate immune stimulation activity in vitro on murine bone marrow-derived dendritic cells and human dendritic cells. The observed results suggest the consideration of cGAMP as a candidate mucosal adjuvant for human vaccines.

Cyclic GMP-AMP displays mucosal adjuvant activity in mice.

Science.gov (United States)

Škrnjug, Ivana; Guzmán, Carlos Alberto; Rueckert, Christine; Ruecker, Christine

2014-01-01

The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP) after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice. A characteristic of the cGAMP-induced immune response is the slightly reduced induction of interleukin-17 as a hallmark of Th17 activity--a distinct feature that is not observed with other cyclic di-nucleotide adjuvants. We further characterize the innate immune stimulation activity in vitro on murine bone marrow-derived dendritic cells and human dendritic cells. The observed results suggest the consideration of cGAMP as a candidate mucosal adjuvant for human vaccines.

Environmental impact assessment report

Energy Technology Data Exchange (ETDEWEB)

Jung, K. J.; Paik, S. T.; Chung, U. S.; Jung, K. H.; Park, S. K.; Lee, D. G.; Kim, H. R.; Kim, J. K.; Yang, S. H.; Lee, B. J.; Kim, E. H.; Choi, K. S

2000-10-01

This report is the revised Environmental Impact Assessment Report which was made and submitted as one of the license documents for TRIGA Research Reactor D and D Project. The Environmental Impact Assessment Report includes introduction of decommissioning plan, status of reactors and environmental impact of surroundings. Also it was assessed and analyzed on radioactivity for environment, and the plan was established to minimize radioactive material release. Finally environmental monitoring plan was established to confirm whether contaminated or not from radioactivity during decommissioning period. According to the assessment results, the risk of excess exposure will be not on environment and public. The first Environmental Impact Assessment Report was submitted to the government for the license and reviewed by Korea Institute of Nuclear Safety. The first Report was revised including answers for the questions arising from review process.

Antidepressant-like properties of sildenafil in a genetic rat model of depression: Role of cholinergic cGMP-interactions

DEFF Research Database (Denmark)

Liebenberg, Nico; Brink, Christiaan; Brand, Linda

2008-01-01

Background: The N-methyl-D-aspartate (NMDA)/nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway has been implicated in the neurobiology of depression. Recently we suggested a possible complex interaction between the cholinergic and NO-cGMP pathways in the antidepressant-like response....... Conclusions: Using a genetic animal model of depression, we have confirmed the antidepressant-like property of sildenafil following “unmasking” by concomitant block of muscarinic receptors. These findings hint at a novel interaction between the cGMP and cholinergic systems in depression, and suggest...

Extracellular Protein Kinase A Modulates Intracellular Calcium/Calmodulin-Dependent Protein Kinase II, Nitric Oxide Synthase, and the Glutamate-Nitric Oxide-cGMP Pathway in Cerebellum. Differential Effects in Hyperammonemia.

Science.gov (United States)

Cabrera-Pastor, Andrea; Llansola, Marta; Felipo, Vicente

2016-12-21

Extracellular protein kinases, including cAMP-dependent protein kinase (PKA), modulate neuronal functions including N-methyl-d-aspartate (NMDA) receptor-dependent long-term potentiation. NMDA receptor activation increases calcium, which binds to calmodulin and activates nitric oxide synthase (NOS), increasing nitric oxide (NO), which activates guanylate cyclase, increasing cGMP, which is released to the extracellular fluid, allowing analysis of this glutamate-NO-cGMP pathway in vivo by microdialysis. The function of this pathway is impaired in hyperammonemic rats. The aims of this work were to assess (1) whether the glutamate-NO-cGMP pathway is modulated in cerebellum in vivo by an extracellular PKA, (2) the role of phosphorylation and activity of calcium/calmodulin-dependent protein kinase II (CaMKII) and NOS in the pathway modulation by extracellular PKA, and (3) whether the effects are different in hyperammonemic and control rats. The pathway was analyzed by in vivo microdialysis. The role of extracellular PKA was analyzed by inhibiting it with a membrane-impermeable inhibitor. The mechanisms involved were analyzed in freshly isolated cerebellar slices from control and hyperammonemic rats. In control rats, inhibiting extracellular PKA reduces the glutamate-NO-cGMP pathway function in vivo. This is due to reduction of CaMKII phosphorylation and activity, which reduces NOS phosphorylation at Ser1417 and NOS activity, resulting in reduced guanylate cyclase activation and cGMP formation. In hyperammonemic rats, under basal conditions, CaMKII phosphorylation and activity are increased, increasing NOS phosphorylation at Ser847, which reduces NOS activity, guanylate cyclase activation, and cGMP. Inhibiting extracellular PKA in hyperammonemic rats normalizes CaMKII phosphorylation and activity, NOS phosphorylation, NOS activity, and cGMP, restoring normal function of the pathway.

Aging has the opposite effect on cAMP and cGMP circadian variations in rat Leydig cells.

Science.gov (United States)

Baburski, Aleksandar Z; Sokanovic, Srdjan J; Andric, Silvana A; Kostic, Tatjana S

2017-05-01

The Leydig cell physiology displays a circadian rhythm driven by a complex interaction of the reproductive axis hormones and circadian system. The final output of this regulatory process is circadian pattern of steroidogenic genes expression and testosterone production. Aging gradually decreases robustness of rhythmic testosterone secretion without change in pattern of LH secretion. Here, we analyzed effect of aging on circadian variation of cAMP and cGMP signaling in Leydig cells. Results showed opposite effect of aging on cAMP and cGMP daily variation. Reduced amplitude of cAMP circadian oscillation was probably associated with changed expression of genes involved in cAMP production (increased circadian pattern of Adcy7, Adcy9, Adcy10 and decreased Adcy3); cAMP degradation (increased Pde4a, decreased Pde8b, canceled rhythm of Pde4d, completely reversed circadian pattern of Pde7b and Pde8a); and circadian expression of protein kinase A subunits (Prkac/PRKAC and Prkar2a). Aging stimulates expression of genes responsible for cGMP production (Nos2, Gucy1a3 and Gucy1b3/GUCYB3) and degradation (Pde5a, Pde6a and Pde6h) but the overall net effect is elevation of cGMP circadian oscillations in Leydig cells. In addition, the expression of cGMP-dependent kinase, Prkg1/PRKG1 is up-regulated. It seems that aging potentiate cGMP- and reduce cAMP-signaling in Leydig cells. Since both signaling pathways affect testosterone production and clockwork in the cells, further insights into these signaling pathways will help to unravel disorders linked to the circadian timing system, aging and reproduction.

cGMP signalling : different ways to create a pathway

NARCIS (Netherlands)

Roelofs, Jeroen; Smith, Janet L.; Haastert, Peter J.M. van

Recently, a novel cGMP signalling cascade was uncovered in Dictyostelium, a eukaryote that diverged from the lineage leading to metazoa after plants and before yeast. In both Dictyostelium and metazoa, the ancient cAMP-binding (cNB) motif of bacterial CAP has been modified and assembled with other

In vitro and in vivo generation and characterization of Pseudomonas aeruginosa biofilm-dispersed cells via c-di-GMP manipulation

DEFF Research Database (Denmark)

Chua, Song Lin; Hultqvist, Louise D; Yuan, Mingjun

2015-01-01

Bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) is a global secondary bacterial messenger that controls the formation of drug-resistant multicellular biofilms. Lowering the intracellular c-di-GMP content can disperse biofilms, and it is proposed as a biofilm eradication strategy...... biofilms by reducing the intracellular c-di-GMP content through modulation of phosphodiesterases (PDEs). Unlike conventional protocols that demonstrate biofilm dispersal by biomass quantification, our protocols enable physiological characterization of the dispersed cells. Biomarkers of dispersed cells...

Gametogenesis in malaria parasites is mediated by the cGMP-dependent protein kinase.

Directory of Open Access Journals (Sweden)

Louisa McRobert

2008-06-01

Full Text Available Malaria parasite transmission requires differentiation of male and female gametocytes into gametes within a mosquito following a blood meal. A mosquito-derived molecule, xanthurenic acid (XA, can trigger gametogenesis, but the signalling events controlling this process in the human malaria parasite Plasmodium falciparum remain unknown. A role for cGMP was revealed by our observation that zaprinast (an inhibitor of phosphodiesterases that hydrolyse cGMP stimulates gametogenesis in the absence of XA. Using cGMP-dependent protein kinase (PKG inhibitors in conjunction with transgenic parasites expressing an inhibitor-insensitive mutant PKG enzyme, we demonstrate that PKG is essential for XA- and zaprinast-induced gametogenesis. Furthermore, we show that intracellular calcium (Ca2+ is required for differentiation and acts downstream of or in parallel with PKG activation. This work defines a key role for PKG in gametogenesis, elucidates the hierarchy of signalling events governing this process in P. falciparum, and demonstrates the feasibility of selective inhibition of a crucial regulator of the malaria parasite life cycle.

Specific GMP guidelines for radiopharmaceutical products

International Nuclear Information System (INIS)

2000-01-01

These guidelines are intended to complement those provided in ''Good manufacturing practices for pharmaceutical products'', as well as the GMP for sterile pharmaceutical products. The regulatory procedures necessary to control radiopharmaceutical products are in large part determined by the sources of products and methods of manufacture. Manufacturing procedures within the scope of these guidelines include: preparation of radiopharmaceuticals in hospital radiopharmacies, preparation of radiopharmaceuticals in centralized radiopharmacies, production of radiopharmaceuticals in nuclear centres, institutes or industrial manufacturers, preparation and production of radiopharmaceuticals in Positron Emission Tomography (PET) centres

Clearance of Pseudomonas aeruginosa Foreign-Body Biofilm Infections through Reduction of the Cyclic Di-GMP Level in the Bacteria

DEFF Research Database (Denmark)

Christensen, Louise D.; van Gennip, Maria; Rybtke, Morten Theil

2013-01-01

Opportunistic pathogenic bacteria can engage in biofilm-based infections that evade immune responses and develop into chronic conditions. Because conventional antimicrobials cannot efficiently eradicate biofilms, there is an urgent need to develop alternative measures to combat biofilm infections....... It has recently been established that the secondary messenger cyclic diguanosine monophosphate (c-di-GMP) functions as a positive regulator of biofilm formation in several different bacteria. In the present study we investigated whether manipulation of the c-di-GMP level in bacteria potentially can...... be used for biofilm control in vivo. We constructed a Pseudomonas aeruginosa strain in which a reduction in the c-di-GMP level can be achieved via induction of the Escherichia coli YhjH c-di-GMP phosphodiesterase. Initial experiments showed that induction of yhjH expression led to dispersal...

Now that you want to take your HIV/AIDS vaccine/biological product research concept into the clinic: what are the "cGMP"?

Science.gov (United States)

Sheets, Rebecca L; Rangavajhula, Vijaya; Pullen, Jeffrey K; Butler, Chris; Mehra, Vijay; Shapiro, Stuart; Pensiero, Michael

2015-04-08

The Division of AIDS Vaccine Research Program funds the discovery and development of HIV/AIDS vaccine candidates. Basic researchers, having discovered a potential vaccine in the laboratory, next want to take that candidate into the clinic to test the concept in humans, to see if it translates. Many of them have heard of "cGMP" and know that they are supposed to make a "GMP product" to take into the clinic, but often they are not very familiar with what "cGMP" means and why these good practices are so important. As members of the Vaccine Translational Research Branch, we frequently get asked "can't we use the material we made in the lab in the clinic?" or "aren't Phase 1 studies exempt from cGMP?" Over the years, we have had many experiences where researchers or their selected contract manufacturing organizations have not applied an appropriate degree of compliance with cGMP suitable for the clinical phase of development. We share some of these experiences and the lessons learned, along with explaining the importance of cGMP, just what cGMP means, and what they can assure, in an effort to de-mystify this subject and facilitate the rapid and safe translational development of HIV vaccines. Published by Elsevier Ltd.

Identification of the gamma subunit-interacting residues on photoreceptor cGMP phosphodiesterase, PDE6alpha '.

Science.gov (United States)

Granovsky, A E; Artemyev, N O

2000-12-29

Photoreceptor cGMP phosphodiesterase (PDE6) is the effector enzyme in the G protein-mediated visual transduction cascade. In the dark, the activity of PDE6 is shut off by the inhibitory gamma subunit (Pgamma). Chimeric proteins between cone PDE6alpha' and cGMP-binding and cGMP-specific PDE (PDE5) have been constructed and expressed in Sf9 cells to study the mechanism of inhibition of PDE6 catalytic activity by Pgamma. Substitution of the segment PDE5-(773-820) by the corresponding PDE6alpha'-(737-784) sequence in the wild-type PDE5 or in a PDE5/PDE6alpha' chimera containing the catalytic domain of PDE5 results in chimeric enzymes capable of inhibitory interaction with Pgamma. The catalytic properties of the chimeric PDEs remained similar to those of PDE5. Ala-scanning mutational analysis of the Pgamma-binding region, PDE6alpha'-(750-760), revealed PDE6alpha' residues essential for the interaction. The M758A mutation markedly impaired and the Q752A mutation moderately impaired the inhibition of chimeric PDE by Pgamma. The analysis of the catalytic properties of mutant PDEs and a model of the PDE6 catalytic domain suggest that residues Met(758) and Gln(752) directly bind Pgamma. A model of the PDE6 catalytic site shows that PDE6alpha'-(750-760) forms a loop at the entrance to the cGMP-binding pocket. Binding of Pgamma to Met(758) would effectively block access of cGMP to the catalytic cavity, providing a structural basis for the mechanism of PDE6 inhibition.

Cumulative Impact Assessment: Approaching Environmental Capacity in Development Area Using Environmental Impact Assessment Information

Science.gov (United States)

Cho, N.; Lee, M. J.; Maeng, J. H.

2017-12-01

Environmental impact assessment estimates the impact of development as a business unit and establishes mitigation plan. If the development is done, its economic effects can spread to the nearby areas. So that various developments can be distributed at different time intervals. The impact of the new developments can be combined with existing environmental impacts and can have a larger impact. That is, Cumulative impact assessment is needed to consider the environmental capacity of the Nearby area. Cumulative impact assessments require policy tools such as environmental impact assessment information and cumulative impact estimation models. In Korea, environmental information (water quality, air quality, etc.) of the development site is measured for environmental impact assessment and monitored for a certain period (generally 5 years) after the project. In addition, by constructing the environmental information as a spatial database, it is possible to express the environmental impact on a regional basis spatially and to intuitively use it for development site selection. Utilizing a composite model of environmental impact assessment information and Remote Sensing data for cumulative impact estimation, That can be used as a policy decision support tool that provides quantitative information for development area management, such as time series effect and sprawl phenomenon.

Differential Contribution of the Guanylyl Cyclase-Cyclic GMP-Protein Kinase G Pathway to the Proliferation of Neural Stem Cells Stimulated by Nitric Oxide

Directory of Open Access Journals (Sweden)

Bruno P. Carreira

2012-02-01

Full Text Available Nitric oxide (NO is an important inflammatory mediator involved in the initial boost in the proliferation of neural stem cells following brain injury. However, the mechanisms underlying the proliferative effect of NO are still unclear. The aim of this work was to investigate whether cyclic GMP (cGMP and the cGMP-dependent kinase (PKG are involved in the proliferative effect triggered by NO in neural stem cells. For this purpose, cultures of neural stem cells isolated from the mouse subventricular zone (SVZ were used. We observed that long-term exposure to the NO donor (24 h, NOC-18, increased the proliferation of SVZ cells in a cGMP-dependent manner, since the guanylate cyclase inhibitor, ODQ, prevented cell proliferation. Similarly to NOC-18, the cGMP analogue, 8-Br-cGMP, also increased cell proliferation. Interestingly, shorter exposures to NO (6 h increased cell proliferation in a cGMP-independent manner via the ERK/MAP kinase pathway. The selective inhibitor of PKG, KT5823, prevented the proliferative effect induced by NO at 24 h but not at 6 h. In conclusion, the proliferative effect of NO is initially mediated by the ERK/MAPK pathway, and at later stages by the GC/cGMP/PKG pathway. Thus, our work shows that NO induces neural stem cell proliferation by targeting these two pathways in a biphasic manner.

Differential Regulation of cGMP Signaling in Human Melanoma Cells at Altered Gravity: Simulated Microgravity Down-Regulates Cancer-Related Gene Expression and Motility

Science.gov (United States)

Ivanova, Krassimira; Eiermann, Peter; Tsiockas, Wasiliki; Hemmersbach, Ruth; Gerzer, Rupert

2018-03-01

Altered gravity is known to affect cellular function by changes in gene expression and cellular signaling. The intracellular signaling molecule cyclic guanosine-3',5'-monophosphate (cGMP), a product of guanylyl cyclases (GC), e.g., the nitric oxide (NO)-sensitive soluble GC (sGC) or natriuretic peptide-activated GC (GC-A/GC-B), is involved in melanocyte response to environmental stress. NO-sGC-cGMP signaling is operational in human melanocytes and non-metastatic melanoma cells, whereas up-regulated expression of GC-A/GC-B and inducible NO synthase (iNOS) are found in metastatic melanoma cells, the deadliest skin cancer. Here, we investigated the effects of altered gravity on the mRNA expression of NOS isoforms, sGC, GC-A/GC-B and multidrug resistance-associated proteins 4/5 (MRP4/MRP5) as selective cGMP exporters in human melanoma cells with different metastatic potential and pigmentation. A specific centrifuge (DLR, Cologne Germany) was used to generate hypergravity (5 g for 24 h) and a fast-rotating 2-D clinostat (60 rpm) to simulate microgravity values ≤ 0.012 g for 24 h. The results demonstrate that hypergravity up-regulates the endothelial NOS-sGC-MRP4/MRP5 pathway in non-metastatic melanoma cells, but down-regulates it in simulated microgravity when compared to 1 g. Additionally, the suppression of sGC expression and activity has been suggested to correlate inversely to tumor aggressiveness. Finally, hypergravity is ineffective in highly metastatic melanoma cells, whereas simulated microgravity down-regulates predominantly the expression of the cancer-related genes iNOS and GC-A/GC-B (shown additionally on protein levels) as well as motility in comparison to 1 g. The results suggest that future studies in real microgravity can benefit from considering GC-cGMP signaling as possible factor for melanocyte transformation.

Cellular signaling with nitric oxide and cyclic GMP

Directory of Open Access Journals (Sweden)

F. Murad

1999-11-01

Full Text Available During the past two decades, nitric oxide signaling has been one of the most rapidly growing areas in biology. This simple free radical gas can regulate an ever growing list of biological processes. In most instances nitric oxide mediates its biological effects by activating guanylyl cyclase and increasing cyclic GMP synthesis. However, the identification of effects of nitric oxide that are independent of cyclic GMP is also growing at a rapid rate. The effects of nitric oxide can mediate important physiological regulatory events in cell regulation, cell-cell communication and signaling. Nitric oxide can function as an intracellular messenger, neurotransmitter and hormone. However, as with any messenger molecule, there can be too much or too little of the substance and pathological events ensue. Methods to regulate either nitric oxide formation, metabolism or function have been used therapeutically for more than a century as with nitroglycerin therapy. Current and future research should permit the development of an expanded therapeutic armamentarium for the physician to manage effectively a number of important disorders. These expectations have undoubtedly fueled the vast research interests in this simple molecule.

Biophysical Techniques for Detection of cAMP and cGMP in Living Cells

Directory of Open Access Journals (Sweden)

Viacheslav O. Nikolaev

2013-04-01

Full Text Available Cyclic nucleotides cAMP and cGMP are ubiquitous second messengers which regulate myriads of functions in virtually all eukaryotic cells. Their intracellular effects are often mediated via discrete subcellular signaling microdomains. In this review, we will discuss state-of-the-art techniques to measure cAMP and cGMP in biological samples with a particular focus on live cell imaging approaches, which allow their detection with high temporal and spatial resolution in living cells and tissues. Finally, we will describe how these techniques can be applied to the analysis of second messenger dynamics in subcellular signaling microdomains.

The Role of Aquaporin 1 Activated by cGMP in Myocardial Edema Caused by Cardiopulmonary Bypass in Sheep

Directory of Open Access Journals (Sweden)

Fang-bao Ding

2013-11-01

Full Text Available Background/Aims: Most cardiac procedures involve the use of cardiopulmonary bypass (CPB, which pumps oxygenated blood to the body while the heart and lungs are isolated. CPB can cause profound alterations V in the homeostasis of physiological fluids, which often results in myocardial edema. In our study, we used sheep CPB model of in vivo and in vitro to assess the relationship between cGMP and AQP1 during CPB. Methods: ODQ, a specific inhibitor of soluble guanylate cyclase (sGC, was used to treat the CPB animals or cardiomyocytes. Left ventricular function of each group was determined by pressure-volume system. Water content of myocardial tissue was assessed by dry-wet weight, and cardiomyocytes water permeability was also calculated. The concentration of cGMP was determined by Radioimmunoassay (RIA. mRNA and protein expression of AQP1 were detected by real-time PCR and western blot, respectively. Results: The relative expression level of AQP1 mRNA and protein at each time point (0, 6, 12, 24 or 48 h after CPB was significantly increased (1.18-fold at 12 h, 1.77-fold at 24 h and 2.18-fold at 48h compared with each sham group, the protein expression of AQP1 also showed a rising trend after CPB. The degree of myocardial edema (75.1% at 12 h, 79.3% at 24 h and 81.0% at 48h increased following the CPB surgery. The mRNA expression level of AQP1 was significantly decreased by 39.7% (pin vitro experiments showed the same changing trends as in vivo. Conclusion: cGMP pathway controls water channels and then affects water intake during CPB through an AQP1-mediated pathway.

An environmental assessment system for environmental technologies

DEFF Research Database (Denmark)

Clavreul, Julie; Baumeister, Hubert; Christensen, Thomas Højlund

2014-01-01

A new model for the environmental assessment of environmental technologies, EASETECH, has been developed. The primary aim of EASETECH is to perform life-cycle assessment (LCA) of complex systems handling heterogeneous material flows. The objectives of this paper are to describe the EASETECH...

Nitric oxide-soluble guanylyl cyclase-cyclic GMP signaling in the striatum: New targets for the treatment of Parkinson's disease?

Directory of Open Access Journals (Sweden)

Anthony R West

2011-06-01

Full Text Available Striatal nitric oxide (NO-producing interneurons play an important role in the regulation of corticostriatal synaptic transmission and motor behavior. Striatal NO synthesis is driven by concurrent activation of NMDA and dopamine (DA D1 receptors. NO diffuses into the dendrites of medium-sized spiny neurons (MSNs which contain high levels of NO receptors called soluble guanylyl cyclases (sGC. NO-mediated activation of sGC leads to the synthesis of the second messenger cGMP. In the intact striatum, transient elevations in intracellular cGMP primarily act to increase neuronal excitability and to facilitate glutamatergic corticostriatal transmission. NO-cGMP signaling also functionally opposes the inhibitory effects of DA D2 receptor activation on corticostriatal transmission. Not surprisingly, abnormal striatal NO-sGC-cGMP signaling becomes apparent following striatal DA depletion, an alteration thought to contribute to pathophysiological changes observed in basal ganglia circuits in Parkinson’s disease (PD. Here, we discuss recent developments in the field which have shed light on the role of NO-sGC-cGMP signaling pathways in basal ganglia dysfunction and motor symptoms associated with PD and L-DOPA-induced dyskinesias.

Optogenetic manipulation of cGMP in cells and animals by the tightly light-regulated guanylyl-cyclase opsin CyclOp.

Science.gov (United States)

Gao, Shiqiang; Nagpal, Jatin; Schneider, Martin W; Kozjak-Pavlovic, Vera; Nagel, Georg; Gottschalk, Alexander

2015-09-08

Cyclic GMP (cGMP) signalling regulates multiple biological functions through activation of protein kinase G and cyclic nucleotide-gated (CNG) channels. In sensory neurons, cGMP permits signal modulation, amplification and encoding, before depolarization. Here we implement a guanylyl cyclase rhodopsin from Blastocladiella emersonii as a new optogenetic tool (BeCyclOp), enabling rapid light-triggered cGMP increase in heterologous cells (Xenopus oocytes, HEK293T cells) and in Caenorhabditis elegans. Among five different fungal CyclOps, exhibiting unusual eight transmembrane topologies and cytosolic N-termini, BeCyclOp is the superior optogenetic tool (light/dark activity ratio: 5,000; no cAMP production; turnover (20 °C) ∼17 cGMP s(-1)). Via co-expressed CNG channels (OLF in oocytes, TAX-2/4 in C. elegans muscle), BeCyclOp photoactivation induces a rapid conductance increase and depolarization at very low light intensities. In O2/CO2 sensory neurons of C. elegans, BeCyclOp activation evokes behavioural responses consistent with their normal sensory function. BeCyclOp therefore enables precise and rapid optogenetic manipulation of cGMP levels in cells and animals.

Energy and environmental assessment

DEFF Research Database (Denmark)

Lund, Henrik; Sukkumnoed, Decharut

2004-01-01

The paper introduce and discuss strategic environmental assessment (SEA) and economic assessment for energy innovation and suggests approach to influence support for sustainable energy development in Thailand.......The paper introduce and discuss strategic environmental assessment (SEA) and economic assessment for energy innovation and suggests approach to influence support for sustainable energy development in Thailand....

Integrating environmental and socioeconomic assessment

International Nuclear Information System (INIS)

Branch, K.M.; Cluett, C.; Page, T.L.

1987-01-01

Since the passage of the National Environmental Policy Act (NEPA) in 1969, considerable scientific and regulatory attention has been given to the preparation of environmental impact assessments. Part of this attention has been directed to definition of the proper scope of an environmental assessment and to debate about how the ''human environment'' should be addressed. This debate continues, and is reflected in the ongoing evolution of the definition of and relationship between the ''environmental'' and ''socioeconomic'' components of an integrated environmental impact assessment. This paper discusses the need for close integration between the environmental and socioeconomic assessment efforts and examines some of the benefits and difficulties of achieving this integration

Analysis of Pseudomonas aeruginosa diguanylate cyclases and phosphodiesterases reveals a role for bis-(3′-5′)-cyclic-GMP in virulence

Science.gov (United States)

Kulesekara, Hemantha; Lee, Vincent; Brencic, Anja; Liberati, Nicole; Urbach, Jonathan; Miyata, Sachiko; Lee, Daniel G.; Neely, Alice N.; Hyodo, Mamoru; Hayakawa, Yoshihiro; Ausubel, Frederick M.; Lory, Stephen

2006-01-01

The opportunistic pathogen Pseudomonas aeruginosa is responsible for systemic infections in immunocompromised individuals and chronic respiratory disease in patients with cystic fibrosis. Cyclic nucleotides are known to play a variety of roles in the regulation of virulence-related factors in pathogenic bacteria. A set of P. aeruginosa genes, encoding proteins that contain putative domains characteristic of diguanylate cyclases (DGCs) and phosphodiesterases (PDEs) that are responsible for the maintenance of cellular levels of the second messenger bis-(3′-5′)-cyclic dimeric GMP (c-di-GMP) was identified in the annotated genomes of P. aeruginosa strains PAO1 and PA14. Although the majority of these genes are components of the P. aeruginosa core genome, several are located on presumptive horizontally acquired genomic islands. A comprehensive analysis of P. aeruginosa genes encoding the enzymes of c-di-GMP metabolism (DGC- and PDE-encoding genes) was carried out to analyze the function of c-di-GMP in two disease-related phenomena, cytotoxicity and biofilm formation. Analysis of the phenotypes of DGC and PDE mutants and overexpressing clones revealed that certain virulence-associated traits are controlled by multiple DGCs and PDEs through alterations in c-di-GMP levels. A set of mutants in selected DGC- and PDE-encoding genes exhibited attenuated virulence in a mouse infection model. Given that insertions in different DGC and PDE genes result in distinct phenotypes, it seems likely that the formation or degradation of c-di-GMP by these enzymes is in highly localized and intimately linked to particular targets of c-di-GMP action. PMID:16477007

Exercise training improves blood flow to contracting skeletal muscle of older men via enhanced cGMP signaling

DEFF Research Database (Denmark)

Piil, Peter Bergmann; Smith Jørgensen, Tue; Egelund, Jon

2018-01-01

Physical activity has the potential to offset age-related impairments in the regulation of blood flow and O2 delivery to the exercising muscles; however, the mechanisms underlying this effect of physical activity remain poorly understood. The present study examined the role of cGMP in training...... a period of aerobic high-intensity exercise training. To determine the role of cGMP signaling, pharmacological inhibition of phosphodiesterase 5 (PDE5) was performed. Before training, inhibition of PDE5 increased (P... group; however, these effects of PDE5 inhibition were not detected after training. These findings suggest a role for enhanced cGMP signaling in the training-induced improvement of regulation of blood flow in contracting skeletal muscle of older men....

Cyclic GMP-AMP Containing Mixed Phosphodiester Linkages Is An Endogenous High Affinity Ligand for STING

Science.gov (United States)

Zhang, Xu; Shi, Heping; Wu, Jiaxi; Zhang, Xuewu; Sun, Lijun; Chen, Chuo; Chen, Zhijian J.

2013-01-01

The presence of microbial or self DNA in the cytoplasm of mammalian cells is a danger signal detected by the DNA sensor cyclic-GMP-AMP (cGAMP) synthase (cGAS), which catalyzes the production of cGAMP that in turn serves as a second messenger to activate innate immune responses. Here we show that endogenous cGAMP in mammalian cells contains two distinct phosphodiester linkages, one between 2′-OH of GMP and 5′-phosphate of AMP, and the other between 3′-OH of AMP and 5′-phosphate of GMP. This molecule, termed 2′3′-cGAMP, is unique in that it binds to the adaptor protein STING with a much greater affinity than cGAMP molecules containing other combinations of phosphodiester linkages. The crystal structure of STING bound to 2′3′-cGAMP revealed the structural basis of this high-affinity binding and a ligand-induced conformational change in STING that may underlie its activation. PMID:23747010

Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING.

Science.gov (United States)

Zhang, Xu; Shi, Heping; Wu, Jiaxi; Zhang, Xuewu; Sun, Lijun; Chen, Chuo; Chen, Zhijian J

2013-07-25

The presence of microbial or self DNA in the cytoplasm of mammalian cells is a danger signal detected by the DNA sensor cyclic-GMP-AMP (cGAMP) synthase (cGAS), which catalyzes the production of cGAMP that in turn serves as a second messenger to activate innate immune responses. Here we show that endogenous cGAMP in mammalian cells contains two distinct phosphodiester linkages, one between 2'-OH of GMP and 5'-phosphate of AMP, and the other between 3'-OH of AMP and 5'-phosphate of GMP. This molecule, termed 2'3'-cGAMP, is unique in that it binds to the adaptor protein STING with a much greater affinity than cGAMP molecules containing other combinations of phosphodiester linkages. The crystal structure of STING bound to 2'3'-cGAMP revealed the structural basis of this high-affinity binding and a ligand-induced conformational change in STING that may underlie its activation. Copyright © 2013 Elsevier Inc. All rights reserved.

The CRP/FNR family protein Bcam1349 is a c-di-GMP effector that regulates biofilm formation in the respiratory pathogen Burkholderia cenocepacia

DEFF Research Database (Denmark)

Fazli, Mustafa; O'Connell, Aileen; Nilsson, Martin

2011-01-01

Burkholderia cenocepacia is an opportunistic respiratory pathogen that can cause severe infections in immune-compromised individuals and is associated with poor prognosis for patients suffering from cystic fibrosis. The second messenger cyclic diguanosine monophosphate (c-di-GMP) has been shown...... to control a wide range of functions in bacteria, but little is known about these regulatory mechanisms in B. cenocepacia. Here we investigated the role that c-di-GMP plays in the regulation of biofilm formation and virulence in B. cenocepacia. Elevated intracellular levels of c-di-GMP promoted wrinkly...... colony, pellicle and biofilm formation in B. cenocepacia. A screen for transposon mutants unable to respond to elevated levels of c-di-GMP led to the identification of the mutant bcam1349 that did not display increased biofilm and pellicle formation with excessive c-di-GMP levels, and displayed a biofilm...

Environmental Impact Assessment: A Procedure.

Science.gov (United States)

Stover, Lloyd V.

Prepared by a firm of consulting engineers, this booklet outlines the procedural "whys and hows" of assessing environmental impact, particularly for the construction industry. Section I explores the need for environmental assessment and evaluation to determine environmental impact. It utilizes a review of the National Environmental Policy Act and…

Angiotensin II increases phosphodiesterase 5A expression in vascular smooth muscle cells: A mechanism by which angiotensin II antagonizes cGMP signaling

Science.gov (United States)

Kim, Dongsoo; Aizawa, Toru; Wei, Heng; Pi, Xinchun; Rybalkin, Sergei D.; Berk, Bradford C.; Yan, Chen

2014-01-01

Angiotensin II (Ang II) and nitric oxide (NO)/natriuretic peptide (NP) signaling pathways mutually regulate each other. Imbalance of Ang II and NO/NP has been implicated in the pathophysiology of many vascular diseases. cGMP functions as a key mediator in the interaction between Ang II and NO/NP. Cyclic nucleotide phosphodiesterase 5A (PDE5A) is important in modulating cGMP signaling by hydrolyzing cGMP in vascular smooth muscle cells (VSMC). Therefore, we examined whether Ang II negatively modulates intracellular cGMP signaling in VSMC by regulating PDE5A. Ang II rapidly and transiently increased PDE5A mRNA levels in rat aortic VSMC. Upregulation of PDE5A mRNA was associated with a time-dependent increase of both PDE5 protein expression and activity. Increased PDE5A mRNA level was transcription-dependent and mediated by the Ang II type 1 receptor. Ang II-mediated activation of extracellular signal-regulated kinases 1/2 (ERK1/2) was essential for Ang II-induced PDE5A upregulation. Pretreatment of VSMC with Ang II inhibited C-type NP (CNP) stimulated cGMP signaling, such as cGMP dependent protein kinase (PKG)-mediated phosphorylation of vasodilator-stimulated-phosphoprotein (VASP). Ang II-mediated inhibition of PKG was blocked when PDE5 activity was decreased by selective PDE5 inhibitors, suggesting that upregulation of PDE5A expression is an important mechanism for Ang II to attenuate cGMP signaling. PDE5A may also play a critical role in the growth promoting effects of Ang II because inhibition of PDE5A activity significantly decreased Ang II-stimulated VSMC growth. These observations establish a new mechanism by which Ang II antagonizes cGMP signaling and stimulates VSMC growth. PMID:15623434

Similar expression patterns of bestrophin-4 and cGMP dependent Ca2+-activated chloride channel activity in the vasculature

DEFF Research Database (Denmark)

Bouzinova, Elena V.; Larsen, Per; Matchkov, Vladimir

2008-01-01

(abstract by Matchkov et. al) that siRNA mediated downregulation of bestrophin-4 is associated with the disappearance of a recently demonstrated2 cGMP-dependent Ca2+-activated Cl- current in vascular smooth muscle cells (SMCs). Here we study the distribution of bestrophin-4-and cGMP dependent Cl- channel...... expressed epitope) Western blot detected a ~65 kDa band in cell lysates from rat mesenteric small arteries and aorta, which was not seen in pulmonary arteries and when preincubated with the immunizing peptide. The distribution of bestrophin-4 mRNA and protein has a pattern similar to the cGMP-dependent Cl......- current in SMCs of different origins. Immunohistochemistry identified bestrophin-4 both in endothelial and SMCs of the vascular tree in the brain, heart, kidney and mesentery, but not in the lungs. We suggest that bestrophin-4 is important for the cGMP dependent, Ca2+ activated Cl- conductance in many...

Nitric oxide increases cyclic GMP levels, AMP-activated protein kinase (AMPK)alpha1-specific activity and glucose transport in human skeletal muscle

DEFF Research Database (Denmark)

Deshmukh, A S; Long, Y C; de Castro Barbosa, T

2010-01-01

-nitrosohydrazino)-1,2-ethylenediamine (spermine NONOate) would increase intracellular cyclic GMP (cGMP) levels and promote glucose transport. METHODS: Skeletal muscle strips were prepared from vastus lateralis muscle biopsies obtained from seven healthy men. Muscle strips were incubated in the absence or presence...... of 5 mmol/l spermine NONOate or 120 nmol/l insulin. The L6 muscle cells were treated with spermine NONOate (20 micromol/l) and incubated in the absence or presence of insulin (120 nmol/l). The direct effect of spermine NONOate and insulin on glucose transport, cGMP levels and signal transduction...... was determined. RESULTS: In human skeletal muscle, spermine NONOate increased glucose transport 2.4-fold (p GMP levels (80-fold, p

cGMP inhibition of type 3 phosphodiesterase is the major mechanism by which C-type natriuretic peptide activates CFTR in the shark rectal gland

Science.gov (United States)

De Jonge, Hugo R.; Tilly, Ben C.; Hogema, Boris M.; Pfau, Daniel J.; Kelley, Catherine A.; Kelley, Megan H.; Melita, August M.; Morris, Montana T.; Viola, Ryan M.

2013-01-01

The in vitro perfused rectal gland of the dogfish shark (Squalus acanthias) and filter-grown monolayers of primary cultures of shark rectal gland (SRG) epithelial cells were used to analyze the signal transduction pathway by which C-type natriuretic peptide (CNP) stimulates chloride secretion. CNP binds to natriuretic receptors in the basolateral membrane, elevates cellular cGMP, and opens cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels in the apical membrane. CNP-provoked chloride secretion was completely inhibitable by the nonspecific protein kinase inhibitor staurosporine and the PKA inhibitor H89 but insensitive to H8, an inhibitor of type I and II isoforms of cGMP-dependent protein kinase (cGKI and cGKII). CNP-induced secretion could not be mimicked by nonhydrolyzable cGMP analogs added alone or in combination with the protein kinase C activator phorbolester, arguing against a role for cGK or for cGMP-induced PKC signaling. We failed to detect a dogfish ortholog of cGKII by molecular cloning and affinity chromatography. However, inhibitors of the cGMP-inhibitable isoform of phosphodiesterase (PDE3) including milrinone, amrinone, and cilostamide but not inhibitors of other PDE isoenzymes mimicked the effect of CNP on chloride secretion in perfused glands and monolayers. CNP raised cGMP and cAMP levels in the SRG epithelial cells. This rise in cAMP as well as the CNP and amrinone-provoked chloride secretion, but not the rise in cGMP, was almost completely blocked by the Gαi-coupled adenylyl cyclase inhibitor somatostatin, arguing against a role for cGMP cross-activation of PKA in CNP action. These data provide molecular, functional, and pharmacological evidence for a CNP/cGMP/PDE3/cAMP/PKA signaling cascade coupled to CFTR in the SRG. PMID:24259420

A concise discussion of the regulatory role of cGMP kinase I in cardiac physiology and pathology.

Science.gov (United States)

Hofmann, Franz

2018-06-22

The underlying cause of cardiac hypertrophy, fibrosis, and heart failure has been investigated in great detail using different mouse models. These studies indicated that cGMP and cGMP-dependent protein kinase type I (cGKI) may ameliorate these negative phenotypes in the adult heart. Recently, evidence has been published that cardiac mitochondrial BKCa channels are a target for cGKI and that activation of mitoBKCa channels may cause some of the positive effects of conditioning in ischemia/reperfusion injury. It will be pointed out that most studies could not present convincing evidence that it is the cGMP level and the activity cGKI in specific cardiac cells that reduces hypertrophy or heart failure. However, anti-fibrotic compounds stimulating nitric oxide-sensitive guanylyl cyclase may be an upcoming therapy for abnormal cardiac remodeling.

Involvement of NO-cGMP pathway in anti-hyperalgesic effect of PDE5 inhibitor tadalafil in experimental hyperalgesia.

Science.gov (United States)

Otari, K V; Upasani, C D

2015-08-01

The association of elevated level of cyclic guanosine monophosphate (cGMP) with inhibition of hyperalgesia and involvement of nitric oxide (NO)-cGMP pathway in the modulation of pain perception was previously reported. Phosphodiesterases 5 (PDE5) inhibitors, sildenafil and tadalafil (TAD) used in erectile dysfunction, are known to act via the NO-cGMP pathway. TAD exerts its action by increasing the levels of intracellular cGMP. Hence, the present study investigated the effect of TAD 5, 10, or 20 mg/kg, per os (p.o.) or L-NAME 20 mg/kg, intraperitoneally (i.p.) and TAD (20 mg/kg, p.o.) in carrageenan- and diabetes-induced hyperalgesia in rats using hot plate test at 55 ± 2 °C. In carrageenan- and diabetes-induced hyperalgesia, TAD (10 and 20 mg/kg, p.o.) significantly increased paw withdrawal latencies (PWLs) as compared to the control group. L-NAME significantly decreased PWLs as compared to the normal group and aggravated the hyperalgesia. Moreover, significant difference in PWLs of L-NAME and TAD 20 was evident. Co-administration of L-NAME (20 mg/kg) with TAD (20 mg/kg) showed significant difference in PWLs as compared to the TAD (20 mg/kg), indicating L-NAME reversed and antagonized TAD-induced anti-hyperalgesia. This suggested an important role of NO-cGMP pathway in TAD-induced anti-hyperalgesic effect.

Fuels and Materials Examination Facility: Environmental assessment, Hanford site, Richland, Washington: Environmental assessment

International Nuclear Information System (INIS)

1980-07-01

The Fuels and Materials Examination Facility (FMEF) and the High Performance Fuel Laboratory (HPFL) were originally proposed to be constructed as separate facilities in the 400 Area of the Hanford Site near Richland, Washington. The environmental effects of these two facilities were described and evaluated in the FMEF Environmental Assessment and the HPFL Final Environmental Impact Statement, ERDA-1550. For economic reasons, the two facilities will no longer be built as separate facilities. The FMEF facility plans have been modified to incorporate some of the features of the proposed HPFL facility while retaining essentially all of the capabilities of the original FMEF proposal. The purpose of this document is to update the FMEF Environmental Assessment to appropriately reflect addition of certain HPFL features into the FMEF facility and to assess the environmental affects of the facility which resulted from inclusion of HPFL features into the FMEF facility

Environmental Management Assessment of the Fernald Environmental Management Project (FEMP)

Energy Technology Data Exchange (ETDEWEB)

1993-04-01

This report documents the results of the Environmental Management Assessment performed at the Fernald Environmental Management Project (FEMP) in Fernald, Ohio. During this assessment, the activities conducted by the assessment team included review of internal documents and reports from previous audits and assessments; interviews with US Department of Energy (DOE) and FEMP contractor personnel; and inspection and observation of selected facilities and operations. The onsite portion of the assessment was conducted from March 15 through April 1, 1993, by DOE`s Office of Environmental Audit (EH-24) located within the Office of the Assistant Secretary for Environment, Safety, and Health (EH-1). EH-24 carries out independent assessments of DOE facilities and activities as part of the EH-1 Environment, Safety, and Health (ES&H) Oversight Audit Program. The EH-24 program is designed to evaluate the status of DOE facilities and activities with respect to compliance with Federal, state, and local environmental laws and regulations; compliance with DOE Orders, Guidance and Directives; conformance with accepted industry practices and standards of performance; and the status and adequacy of management systems developed to address environmental requirements. The Environmental Management Assessment of FEMP focused on the adequacy of environmental management systems. Further, in response to requests by the Office of Environmental Restoration and Waste Management (EM) and Fernald Field Office (FN), Quality Assurance and Environmental Radiation activities at FEMP were evaluated from a programmatic standpoint. The results of the evaluation of these areas are contained in the Environmental Protection Programs section in this report.

Environmental Management Assessment of the Fernald Environmental Management Project (FEMP)

International Nuclear Information System (INIS)

1993-04-01

This report documents the results of the Environmental Management Assessment performed at the Fernald Environmental Management Project (FEMP) in Fernald, Ohio. During this assessment, the activities conducted by the assessment team included review of internal documents and reports from previous audits and assessments; interviews with US Department of Energy (DOE) and FEMP contractor personnel; and inspection and observation of selected facilities and operations. The onsite portion of the assessment was conducted from March 15 through April 1, 1993, by DOE's Office of Environmental Audit (EH-24) located within the Office of the Assistant Secretary for Environment, Safety, and Health (EH-1). EH-24 carries out independent assessments of DOE facilities and activities as part of the EH-1 Environment, Safety, and Health (ES ampersand H) Oversight Audit Program. The EH-24 program is designed to evaluate the status of DOE facilities and activities with respect to compliance with Federal, state, and local environmental laws and regulations; compliance with DOE Orders, Guidance and Directives; conformance with accepted industry practices and standards of performance; and the status and adequacy of management systems developed to address environmental requirements. The Environmental Management Assessment of FEMP focused on the adequacy of environmental management systems. Further, in response to requests by the Office of Environmental Restoration and Waste Management (EM) and Fernald Field Office (FN), Quality Assurance and Environmental Radiation activities at FEMP were evaluated from a programmatic standpoint. The results of the evaluation of these areas are contained in the Environmental Protection Programs section in this report

The methodology of environmental impacts assessment of environmentally hazardous facilities

OpenAIRE

Adamenko, Yaroslav

2017-01-01

The article deals with the methodology of environmental impacts assessment of environmentally hazardous facilities and activities. The stages of evaluation of environmental impacts are proved. The algorithm and technology of decision-making in the system of environmental impact assessments based on a multi-criteria utility theory are proposed.

Beneficial effects of combined benazepril-amlodipine on cardiac nitric oxide, cGMP, and TNF-alpha production after cardiac ischemia.

Science.gov (United States)

Siragy, Helmy M; Xue, Chun; Webb, Randy L

2006-05-01

The aim of this study was to determine if myocardial inflammation is increased after myocardial ischemia and whether angiotensin-converting enzyme inhibitors, calcium channel blockers, or diuretics decrease mediators of inflammation in rats with induced myocardial ischemia. Changes in cardiac interstitial fluid (CIF) levels of nitric oxide metabolites (NOX), cyclic guanosine 3',5'-monophosphate (cGMP), angiotensin II (Ang II), and tumor necrosis factor-alpha (TNF-alpha) were monitored with/without oral administration of benazepril, amlodipine, combined benazepril-amlodipine, or hydrochlorothiazide. Using a microdialysis technique, levels of several mediators of inflammation were measured after sham operation or 30-minute occlusion of the left anterior descending coronary artery. Compared with sham animals, levels of CIF NOX and cGMP were decreased in animals with ischemia (P Benazepril or amlodipine significantly increased NOX levels (P benazepril significantly increased cGMP (P benazepril-amlodipine further increased CIF NOX and cGMP (P benazepril alone, or combined benazepril-amlodipine significantly reduced TNF-alpha (P benazepril-amlodipine may be beneficial for managing cardiac ischemia.

CSF concentrations of cAMP and cGMP are lower in patients with Creutzfeldt-Jakob disease but not Parkinson's disease and amyotrophic lateral sclerosis.

Directory of Open Access Journals (Sweden)

Patrick Oeckl

Full Text Available BACKGROUND: The cyclic nucleotides cyclic adenosine-3',5'-monophosphate (cAMP and cyclic guanosine-3',5'-monophosphate (cGMP are important second messengers and are potential biomarkers for Parkinson's disease (PD, amyotrophic lateral sclerosis (ALS and Creutzfeldt-Jakob disease (CJD. METHODOLOGY/PRINCIPAL FINDINGS: Here, we investigated by liquid chromatography/tandem mass spectrometry (LC-MS/MS the cerebrospinal fluid (CSF concentrations of cAMP and cGMP of 82 patients and evaluated their diagnostic potency as biomarkers. For comparison with a well-accepted biomarker, we measured tau concentrations in CSF of CJD and control patients. CJD patients (n = 15 had lower cAMP (-70% and cGMP (-55% concentrations in CSF compared with controls (n = 11. There was no difference in PD, PD dementia (PDD and ALS cases. Receiver operating characteristic (ROC curve analyses confirmed cAMP and cGMP as valuable diagnostic markers for CJD indicated by the area under the curve (AUC of 0.86 (cAMP and 0.85 (cGMP. We calculated a sensitivity of 100% and specificity of 64% for cAMP and a sensitivity of 67% and specificity of 100% for cGMP. The combination of both nucleotides increased the sensitivity to 80% and specificity to 91% for the term cAMPxcGMP (AUC 0.92 and to 93% and 100% for the ratio tau/cAMP (AUC 0.99. CONCLUSIONS/SIGNIFICANCE: We conclude that the CSF determination of cAMP and cGMP may easily be included in the diagnosis of CJD and could be helpful in monitoring disease progression as well as in therapy control.

Critical Role of Nitric Oxide-cGMP Cascade in the Formation of cAMP-Dependent Long-Term Memory

Science.gov (United States)

Aonuma, Hitoshi; Mizunami, Makoto; Matsumoto, Yukihisa; Unoki, Sae

2006-01-01

Cyclic AMP pathway plays an essential role in formation of long-term memory (LTM). In some species, the nitric oxide (NO)-cyclic GMP pathway has been found to act in parallel and complementary to the cAMP pathway for LTM formation. Here we describe a new role of the NO-cGMP pathway, namely, stimulation of the cAMP pathway to induce LTM. We have…

Cost benefit of investment on quality in pharmaceutical manufacturing: WHO GMP pre- and post-certification of a Nigerian pharmaceutical manufacturer.

Science.gov (United States)

Anyakora, Chimezie; Ekwunife, Obinna; Alozie, Faith; Esuga, Mopa; Ukwuru, Jonathan; Onya, Steve; Nwokike, Jude

2017-09-18

Pharmaceutical companies in Africa need to invest in both facilities and quality management systems to achieve good manufacturing practice (GMP) compliance. Compliance to international GMP standards is important to the attainment of World Health Organization (WHO) prequalification. However, most of the local pharmaceutical manufacturing companies may be deterred from investing in quality because of many reasons, ranging from financial constraints to technical capacity. This paper primarily evaluates benefits against the cost of investing in GMP, using a Nigerian pharmaceutical company, Chi Pharmaceuticals Limited, as a case study. This paper also discusses how to drive more local manufacturers to invest in quality to attain GMP compliance; and proffers practical recommendations for local manufacturers who would want to invest in quality to meet ethical and regulatory obligations. The cost benefit of improving the quality of Chi Pharmaceuticals Limited's facilities and system to attain WHO GMP certification for the production of zinc sulfate 20-mg dispersible tablets was calculated by dividing the annual benefits derived from quality improvement interventions by the annual costs of implementing quality improvement interventions, referred to as a benefit-cost ratio (BCR). Cost benefit of obtaining WHO GMP certification for the production of zinc sulfate 20-mg dispersible tablets was 5.3 (95% confidence interval of 5.0-5.5). Investment in quality improvement intervention is cost-beneficial for local manufacturing companies. Governments and regulators in African countries should support pharmaceutical companies striving to invest in quality. Collaboration of local manufacturing companies with global companies will further improve quality. Local pharmaceutical companies should be encouraged to key into development opportunities available for pharmaceutical companies in Africa.

Improvements in the automated radioimmunoassay for cAMP or cGMP

International Nuclear Information System (INIS)

Brooker, G.

1988-01-01

The work others in developing antibodies and the original radioimmunoassay for cyclic nucleotides provides the basis for these sensitive assays. The acetylation radioimmunoassay for cyclic nucleotides has enabled the measurement of cyclic AMP and cyclic GMP in very small biological samples. This is because accurate determinations can be made in samples containing less than 1 fmol of cyclic AMP or cyclic GMP. The Gamma-Flo automated radioimmunoassay system has been adapted to these assays such that cyclic nucleotides can be automatically measured at a rate of about 60 samples/hr. The Gamma-Flo instrument provides high-precision assays and eliminates human intervention in all steps of the radioimmunoassay. The automated assay has been in continuous operation in our laboratory over the last 10 years and this chapter summarizes the methodology and delineates improvements which have occurred over that time frame. Details for the preparation of the radioligands apply also to the manual acetylated radioimmunoassay for cyclic nucleotides

Environmental impacts assessment: Instruments for environmental policy making and resource management

International Nuclear Information System (INIS)

Cavelli, C.M.; Sartori, S.

1993-06-01

This review of evaluation criteria for environmental impacts assessments in Italy covers the following aspects: the efficacy of current Italian normatives governing assessment methods, the current approach of regional public administrations, the necessity for the creation of a national regulating board, environmental impacts assessment for complex environmental systems, the application of impacts assessment recommendations to resource development modelling in the planning of integrated environmental-economic systems, the involvement of the general public in decision making, techniques to determine the monetary worth of environmental resources, the use of multi-criteria analysis techniques

IL-4 induces cAMP and cGMP in human monocytic cells

Directory of Open Access Journals (Sweden)

B. Dugas

1995-01-01

Full Text Available Human monocytes, preincubated with IFN-γ respond to IL-4 by a cGMP increase through activation of an inducible NO synthase. Here, IL-4 was found to induce an accumulation of cGMP (1 – 3 min and cAMP (20 – 25 min in unstimulated monocytes. This was impaired with NOS inhibitors, but also with EGTA and calcium/calmodulin inhibitors. These results suggest that: (1 IL-4 may stimulate different NOS isoforms in resting and IFN-γ activated monocytes, and (2 cAMP accumulation may be partially dependent on the NO pathway. By RT-PCR, a type III constitutive NOS mRNA was detected in U937 monocytic cells. IL-4 also increased the [Ca2+]i in these cells. Different NOS may thus be expressed in monocytic cells depending on their differentiation and the signals they receive.

Environmental assessment of lightweight electric vehicles

CERN Document Server

Egede, Patricia

2017-01-01

This monograph adresses the challenge of the environmental assessment of leightweight electric vehicles. It poses the question whether the use of lightweight materials in electric vehicles can reduce the vehicles’ environmental impact and compares the environmental performance of a lightweight electric vehicle (LEV) to other types of vehicles. The topical approach focuses on methods from life cycle assessment (LCA), and the book concludes with a comprehensive concept on the environmental assessment of LEVs. The target audience primarily comprises LCA practitioners from research institutes and industry, but it may also be beneficial for graduate students specializing in the field of environmental assessment.

7 CFR 1955.136 - Environmental Assessment (EA) and Environmental Impact Statement (EIS).

Science.gov (United States)

2010-01-01

... 7 Agriculture 14 2010-01-01 2009-01-01 true Environmental Assessment (EA) and Environmental Impact... Disposal of Inventory Property General § 1955.136 Environmental Assessment (EA) and Environmental Impact Statement (EIS). (a) Prior to a final decision on some disposal actions, an environmental assessment must be...

cGMP-dependent protein kinase Iα associates with the antidepressant-sensitive serotonin transporter and dictates rapid modulation of serotonin uptake

Directory of Open Access Journals (Sweden)

Steiner Jennifer A

2009-08-01

Full Text Available Abstract Background The Na+/Cl--dependent serotonin (5-hydroxytryptamine, 5-HT transporter (SERT is a critical element in neuronal 5-HT signaling, being responsible for the efficient elimination of 5-HT after release. SERTs are not only targets for exogenous addictive and therapeutic agents but also can be modulated by endogenous, receptor-linked signaling pathways. We have shown that neuronal A3 adenosine receptor activation leads to enhanced presynaptic 5-HT transport in vitro and an increased rate of SERT-mediated 5-HT clearance in vivo. SERT stimulation by A3 adenosine receptors derives from an elevation of cGMP and subsequent activation of both cGMP-dependent protein kinase (PKG and p38 mitogen-activated protein kinase. PKG activators such as 8-Br-cGMP are known to lead to transporter phosphorylation, though how this modification supports SERT regulation is unclear. Results In this report, we explore the kinase isoform specificity underlying the rapid stimulation of SERT activity by PKG activators. Using immortalized, rat serotonergic raphe neurons (RN46A previously shown to support 8-Br-cGMP stimulation of SERT surface trafficking, we document expression of PKGI, and to a lower extent, PKGII. Quantitative analysis of staining profiles using permeabilized or nonpermeabilized conditions reveals that SERT colocalizes with PKGI in both intracellular and cell surface domains of RN46A cell bodies, and exhibits a more restricted, intracellular pattern of colocalization in neuritic processes. In the same cells, SERT demonstrates a lack of colocalization with PKGII in either intracellular or surface membranes. In keeping with the ability of the membrane permeant kinase inhibitor DT-2 to block 8-Br-cGMP stimulation of SERT, we found that DT-2 treatment eliminated cGMP-dependent kinase activity in PKGI-immunoreactive extracts resolved by liquid chromatography. Similarly, treatment of SERT-transfected HeLa cells with small interfering RNAs targeting

ENVIRONMENTAL IMPACT ASSESSMENT AND MONITORING ...

African Journals Online (AJOL)

protect the environment, it is imperative to conduct environmental impact assessment ... Ethiopia enacted the Environmental Impact Assessment Proclamation in 2002 ... flora, fauna, soil, air, water, climate, natural or cultural heritage, other.

CRP-Cyclic AMP Regulates the Expression of Type 3 Fimbriae via Cyclic di-GMP in Klebsiella pneumoniae.

Directory of Open Access Journals (Sweden)

Ching-Ting Lin

Full Text Available Klebsiella pneumoniae is the predominant pathogen isolated from liver abscesses of diabetic patients in Asian countries. However, the effects of elevated blood glucose levels on the virulence of this pathogen remain largely unknown. Type 3 fimbriae, encoded by the mrkABCDF genes, are important virulence factors in K. pneumoniae pathogenesis. In this study, the effects of exogenous glucose and the intracellular cyclic AMP (cAMP signaling pathway on type 3 fimbriae expression regulation were investigated. The production of MrkA, the major subunit of type 3 fimbriae, was increased in glucose-rich medium, whereas cAMP supplementation reversed the effect. MrkA production was markedly increased by cyaA or crp deletion, but slightly decreased by cpdA deletion. In addition, the mRNA levels of mrkABCDF genes and the activity of PmrkA were increased in Δcrp strain, as well as the mRNA levels of mrkHIJ genes that encode cyclic di-GMP (c-di-GMP-related regulatory proteins that influence type 3 fimbriae expression. Moreover, the activities of PmrkHI and PmrkJ were decreased in ΔlacZΔcrp strain. These results indicate that CRP-cAMP down-regulates mrkABCDF and mrkHIJ at the transcriptional level. Further deletion of mrkH or mrkI in Δcrp strain diminished the production of MrkA, indicating that MrkH and MrkI are required for the CRP regulation of type 3 fimbriae expression. Furthermore, the high activity of PmrkHI in the ΔlacZΔcrp strain was diminished in ΔlacZΔcrpΔmrkHI, but increased in the ΔlacZΔcrpΔmrkJ strain. Deletion of crp increased the intracellular c-di-GMP concentration and reduced the phosphodiesterase activity. Moreover, we found that the mRNA levels of multiple genes related to c-di-GMP metabolism were altered in Δcrp strain. These indicate that CRP regulates type 3 fimbriae expression indirectly via the c-di-GMP signaling pathway. In conclusion, we found evidence of a coordinated regulation of type 3 fimbriae expression by the CRP

Bestrophin-3 (vitelliform macular dystrophy 2-like 3 protein) is essential for the cGMP-dependent calcium-activated chloride conductance in vascular smooth muscle cells

DEFF Research Database (Denmark)

Matchkov, Vladimir; Larsen, Per; Bouzinova, Elena V.

2008-01-01

have recently characterized a cGMP-dependent Ca(2+)-activated Cl(-) current with unique characteristics in smooth muscle cells. This novel current has been shown to coexist with a "classic" (cGMP-independent) Ca(2+)-activated Cl(-) current and to have characteristics distinct from those previously...... known for Ca(2+)-activated Cl(-) currents. Here, we suggest that a bestrophin, a product of the Best gene family, is responsible for the cGMP-dependent Ca(2+)-activated Cl(-) current based on similarities between the membrane currents produced by heterologous expressions of bestrophins and the cGMP......-dependent Ca(2+)-activated Cl(-) current. This is supported by similarities in the distribution pattern of the cGMP-dependent Ca(2+)-activated Cl(-) current and bestrophin-3 (the product of Best-3 gene) expression in different smooth muscle. Furthermore, downregulation of Best-3 gene expression with small...

Environmental contaminants: assessment and control

National Research Council Canada - National Science Library

Vallero, Daniel A

2004-01-01

... Understanding Policy by Understanding Science Connections and Interrelationships of Environmental Science Environmental Assessment and Intervention Engineering Technical Note: Cleaning up a Hazardous Waste Site Social Aspects of Environmental Science Introduction to Environmental Policy The National Environmental Policy Act Issues in Environmental Science: Co...

Environmental assessment in the uranium industry

International Nuclear Information System (INIS)

Frost, S.E.

2002-01-01

The paper examines the subject matter to be dealt with in environmental impact assessments for uranium production facilities, the development of environmental impact statements and the processes used for assessing projects. Different types of regulatory process used to assess projects are described, using Canadian and Australian examples. Some of the techniques used in developing environmental assessments are described. Public participation, including that of special interest groups, is discussed. Some examples of assessments are examined, particularly looking at recent assessments for uranium mining projects in Canada. Trends in environmental assessment are described, using examples from a number of different projects over the past 25 years. Some recommendations for the future are offered. (author)

Environmental assessment in the uranium industry

International Nuclear Information System (INIS)

Frost, S.E.

2000-01-01

The paper examines the subject matter to be dealt with in environmental impact assessments for uranium production facilities, the development of environmental impact statements and the processes used for assessing projects. Different types of regulatory process used to assess projects are described, using Canadian and Australian examples. Some of the techniques used in developing environmental assessments are described. Public participation, including that of special interest groups, is discussed. Some examples of assessments are examined, particularly looking at recent assessments for uranium mining projects in Canada. Trends in environmental assessment are described, using examples from a number of different projects over the past 25 years. Some recommendations for the future are offered. (author)

Expansion of Human Tregs from Cryopreserved Umbilical Cord Blood for GMP-Compliant Autologous Adoptive Cell Transfer Therapy

Directory of Open Access Journals (Sweden)

Howard R. Seay

2017-03-01

Full Text Available Umbilical cord blood is a traditional and convenient source of cells for hematopoietic stem cell transplantation. Thymic regulatory T cells (Tregs are also present in cord blood, and there is growing interest in the use of autologous Tregs to provide a low-risk, fully human leukocyte antigen (HLA-matched cell product for treating autoimmune diseases, such as type 1 diabetes. Here, we describe a good manufacturing practice (GMP-compatible Treg expansion protocol using fluorescence-activated cell sorting, resulting in a mean 2,092-fold expansion of Tregs over a 16-day culture for a median yield of 1.26 × 109 Tregs from single-donor cryopreserved units. The resulting Tregs passed prior clinical trial release criteria for Treg purity and sterility, including additional rigorous assessments of FOXP3 and Helios expression and epigenetic analysis of the FOXP3 Treg-specific demethylated region (TSDR. Compared with expanded adult peripheral blood Tregs, expanded cord blood Tregs remained more naive, as assessed by continued expression of CD45RA, produced reduced IFN-γ following activation, and effectively inhibited responder T cell proliferation. Immunosequencing of the T cell receptor revealed a remarkably diverse receptor repertoire within cord blood Tregs that was maintained following in vitro expansion. These data support the feasibility of generating GMP-compliant Tregs from cord blood for adoptive cell transfer therapies and highlight potential advantages in terms of safety, phenotypic stability, autoantigen specificity, and tissue distribution.

Hypercapnic vasodilatation in isolated rat basilar arteries is exerted via low pH and does not involve nitric oxide synthase stimulation or cyclic GMP production

DEFF Research Database (Denmark)

You, J P; Wang, Qian; Zhang, W

1994-01-01

this relaxation by 54% and 70%, respectively. The effect of L-NOARG was completely reversed by L-arginine. Blockade of nerve excitation with tetrodotoxin (TTX) had no affect on the 15% CO2 elicited vasodilatation. Measurements of cGMP in vessel segments showed no significant increase in cGMP content in response...... to hypercapnia. L-NOARG and MB, but not TTX, significantly reduced the basal cGMP content in cerebral vessels. Adding 1.5% halothane to the incubation medium did not result in a significant increase in cGMP content. Lowering the pH by cumulative application of 0.12 M HCl resulted in relaxation identical...... elicits vasodilatation of isolated rat basilar arteries by a mechanism independent of nitric oxide synthase (NOS) activity. The markedly reduced basal cGMP levels in cerebral vessels by L-NOARG and MB suggest that there exists a basal NO formation in the cerebral vessel wall....

Potential repair of free radical adducts of dGMP and dG by a series of reductants. A pulse radiolytic study

International Nuclear Information System (INIS)

O'Neill, P.; Chapman, P.W.

1985-01-01

Using the technique of pulse radiolysis, it has been demonstrated that the interaction of hydroxyl-radical adducts of dG and dGMP with a series of reductants with different oxidation potentials at pH 7.0-7.4 proceeds via an electron transfer process (k approx. 1.4-34 x 10 8 dm 3 mol -1 s -1 ). The one-electron oxidation of dGMP (dG) by Br2-anion radicals was shown to result in the formation of a species, the properties of which are similar to those of the OH-radical adduct of dGMP with oxidizing properties based upon both spectral and kinetic information. The nature of the dGMP species produced on interaction with Br2-anion radicals to produce specific base damage. The implications of these findings are presented in terms of potential free radical repair of hydroxyl radical damage and of synergistic effects whereby one reductant may be regenerated at the expense of another reductant. (author)

Potentiation of cGMP signaling increases oxygen delivery and oxidative metabolism in contracting skeletal muscle of older but not young humans

DEFF Research Database (Denmark)

Nyberg, Michael Permin; Piil, Peter Bergmann; Egelund, Jon

2015-01-01

regulation remain unresolved. Cyclic guanosine monophosphate (cGMP) is one of the main second messengers that mediate smooth muscle vasodilation and alterations in cGMP signaling could, therefore, be one mechanism by which skeletal muscle perfusion is impaired with advancing age. The current study aimed...... to evaluate the effect of inhibiting the main enzyme involved in cGMP degradation, phosphodiesterase 5 (PDE5), on blood flow and O2 delivery in contracting skeletal muscle of young and older humans. A group of young (23 ± 1 years) and a group of older (72 ± 2 years) male human subjects performed submaximal...... in the older subjects correlated with the increase in leg O2 uptake (r (2) = 0.843). These findings suggest an insufficient O2 delivery to the contracting skeletal muscle of aged individuals and that reduced cGMP availability is a novel mechanism underlying impaired skeletal muscle perfusion with advancing age....

MrkH, a novel c-di-GMP-dependent transcriptional activator, controls Klebsiella pneumoniae biofilm formation by regulating type 3 fimbriae expression.

Directory of Open Access Journals (Sweden)

Jonathan J Wilksch

2011-08-01

Full Text Available Klebsiella pneumoniae causes significant morbidity and mortality worldwide, particularly amongst hospitalized individuals. The principle mechanism for pathogenesis in hospital environments involves the formation of biofilms, primarily on implanted medical devices. In this study, we constructed a transposon mutant library in a clinical isolate, K. pneumoniae AJ218, to identify the genes and pathways implicated in biofilm formation. Three mutants severely defective in biofilm formation contained insertions within the mrkABCDF genes encoding the main structural subunit and assembly machinery for type 3 fimbriae. Two other mutants carried insertions within the yfiN and mrkJ genes, which encode GGDEF domain- and EAL domain-containing c-di-GMP turnover enzymes, respectively. The remaining two isolates contained insertions that inactivated the mrkH and mrkI genes, which encode for novel proteins with a c-di-GMP-binding PilZ domain and a LuxR-type transcriptional regulator, respectively. Biochemical and functional assays indicated that the effects of these factors on biofilm formation accompany concomitant changes in type 3 fimbriae expression. We mapped the transcriptional start site of mrkA, demonstrated that MrkH directly activates transcription of the mrkA promoter and showed that MrkH binds strongly to the mrkA regulatory region only in the presence of c-di-GMP. Furthermore, a point mutation in the putative c-di-GMP-binding domain of MrkH completely abolished its function as a transcriptional activator. In vivo analysis of the yfiN and mrkJ genes strongly indicated their c-di-GMP-specific function as diguanylate cyclase and phosphodiesterase, respectively. In addition, in vitro assays showed that purified MrkJ protein has strong c-di-GMP phosphodiesterase activity. These results demonstrate for the first time that c-di-GMP can function as an effector to stimulate the activity of a transcriptional activator, and explain how type 3 fimbriae

Environmental impact assessment screening tool

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-05-01

An environmental assessment and impact planning software, SCREENER, was tested at a pilot project at the Cameco site (Port Hope). SCREENER was used to screen the impacts of a new construction project in accordance with the process and reporting requirements laid out in the Canadian Environmental Assessment Act. The software test concentrated on the activities that are directly involved with the structure construction and site preparation activities. In addition, a two and one half day training course was given to three AECB staff using the test case as a hands on example. The conclusion of this project is that an automated tool such as SCREENER (or Calyx, the new generation of environmental assessment tools from ESSA Software Ltd.), will help the AECB to standardize the approach to environmental assessment, assist in project planning, and save resources in the screening process. The new approach could allow to allocate AECB limited resources to the detailed assessments required for maximum impact activities. 2 figs. 7 refs.

Environmental impact assessment screening tool

International Nuclear Information System (INIS)

1995-05-01

An environmental assessment and impact planning software, SCREENER, was tested at a pilot project at the Cameco site (Port Hope). SCREENER was used to screen the impacts of a new construction project in accordance with the process and reporting requirements laid out in the Canadian Environmental Assessment Act. The software test concentrated on the activities that are directly involved with the structure construction and site preparation activities. In addition, a two and one half day training course was given to three AECB staff using the test case as a hands on example. The conclusion of this project is that an automated tool such as SCREENER (or Calyx, the new generation of environmental assessment tools from ESSA Software Ltd.), will help the AECB to standardize the approach to environmental assessment, assist in project planning, and save resources in the screening process. The new approach could allow to allocate AECB limited resources to the detailed assessments required for maximum impact activities

Criticism on Environmental Assessment Tools

NARCIS (Netherlands)

Abdalla, G.; Maas, G.J.; Huyghe, J.; Oostra, M.; Saji Baby, xx; Bogdan Zygmunt, xx

2011-01-01

Using environmental assessment tools to assess the sustainability of buildings, homes and mixed- use area is increasing. Environmental tools assign scores to projects using some sustainability (sub) aspects according to design and realization documents and evidences. Six European sustainable urban

Scope and profoundness of environmental assessments. A study in the frame of environmental impact assessments. Strategic environmental assessment and FFH (fauna-flora-habitat) impact assessment under specific consideration of the conflict wind energy - bird protection

International Nuclear Information System (INIS)

Erb, Mareen

2013-01-01

The legal background of environmental impact assessments and the principle regulations and guidelines for this assessment are shortly summarized. The following Issues are discussed in detail: fundamentals of environmental assessments, profoundness and scope in environmental assessments; the conflict wind energy parks and birds.

Direct interaction of the inhibitory gamma-subunit of Rod cGMP phosphodiesterase (PDE6) with the PDE6 GAFa domains.

Science.gov (United States)

Muradov, Khakim G; Granovsky, Alexey E; Schey, Kevin L; Artemyev, Nikolai O

2002-03-26

Retinal rod and cone cGMP phosphodiesterases (PDE6 family) function as the effector enzyme in the vertebrate visual transduction cascade. The activity of PDE6 catalytic subunits is controlled by the Pgamma-subunits. In addition to the inhibition of cGMP hydrolysis at the catalytic sites, Pgamma is known to stimulate a noncatalytic binding of cGMP to the regulatory GAFa-GAFb domains of PDE6. The latter role of Pgamma has been attributed to its polycationic region. To elucidate the structural basis for the regulation of cGMP binding to the GAF domains of PDE6, a photoexcitable peptide probe corresponding to the polycationic region of Pgamma, Pgamma-21-45, was specifically cross-linked to rod PDE6alphabeta. The site of Pgamma-21-45 cross-linking was localized to Met138Gly139 within the PDE6alpha GAFa domain using mass spectrometric analysis. Chimeras between PDE5 and cone PDE6alpha', containing GAFa and/or GAFb domains of PDE6alpha' have been generated to probe a potential role of the GAFb domains in binding to Pgamma. Analysis of the inhibition of the PDE5/PDE6alpha' chimeras by Pgamma supported the role of PDE6 GAFa but not GAFb domains in the interaction with Pgamma. Our results suggest that a direct binding of the polycationic region of Pgamma to the GAFa domains of PDE6 may lead to a stabilization of the noncatalytic cGMP-binding sites.

Environmental Workplace Assessment.

Science.gov (United States)

Bernier, Jacques; And Others

1994-01-01

Describes environmental workplace assessments as tools in developing customized training, highlighting the group process and individual interview techniques. Suggests that, by assessing the cultural climate of an organization, education providers can gather essential baseline information on an organization and thereby provide a guide for further…

High levels of cyclic-di-GMP in plant-associated Pseudomonas correlate with evasion of plant immunity.

Science.gov (United States)

Pfeilmeier, Sebastian; Saur, Isabel Marie-Luise; Rathjen, John Paul; Zipfel, Cyril; Malone, Jacob George

2016-05-01

The plant innate immune system employs plasma membrane-localized receptors that specifically perceive pathogen/microbe-associated molecular patterns (PAMPs/MAMPs). This induces a defence response called pattern-triggered immunity (PTI) to fend off pathogen attack. Commensal bacteria are also exposed to potential immune recognition and must employ strategies to evade and/or suppress PTI to successfully colonize the plant. During plant infection, the flagellum has an ambiguous role, acting as both a virulence factor and also as a potent immunogen as a result of the recognition of its main building block, flagellin, by the plant pattern recognition receptors (PRRs), including FLAGELLIN SENSING2 (FLS2). Therefore, strict control of flagella synthesis is especially important for plant-associated bacteria. Here, we show that cyclic-di-GMP [bis-(3'-5')-cyclic di-guanosine monophosphate], a central regulator of bacterial lifestyle, is involved in the evasion of PTI. Elevated cyclic-di-GMP levels in the pathogen Pseudomonas syringae pv. tomato (Pto) DC3000, the opportunist P. aeruginosa PAO1 and the commensal P. protegens Pf-5 inhibit flagellin synthesis and help the bacteria to evade FLS2-mediated signalling in Nicotiana benthamiana and Arabidopsis thaliana. Despite this, high cellular cyclic-di-GMP concentrations were shown to drastically reduce the virulence of Pto DC3000 during plant infection. We propose that this is a result of reduced flagellar motility and/or additional pleiotropic effects of cyclic-di-GMP signalling on bacterial behaviour. © 2015 THE AUTHORS MOLECULAR PLANT PATHOLOGY PUBLISHED BY BRITISH SOCIETY FOR PLANT PATHOLOGY AND JOHN WILEY & SONS LTD.

78 FR 67187 - Notice of Availability of the Draft General Management Plan/Wilderness Study/Environmental Impact...

Science.gov (United States)

2013-11-08

... focus on protecting natural resources and systems. Under this alternative, most of the Big Spring... Availability of the Draft General Management Plan/ Wilderness Study/Environmental Impact Statement for the... Management Plan/Wilderness Study/Environmental Impact Statement (GMP/WS/EIS) for the Ozark National Scenic...

cGMP and nitric oxide modulate thrombin-induced endothelial permeability : Regulation via different pathways in human aortic and umbilical vein endothelial cells

NARCIS (Netherlands)

Draijer, R.; Atsma, D.E.; Laarse, A. van der; Hinsbergh, V.W.M. van

1995-01-01

Previous studies have demonstrated that cGMP and cAMP reduce the endothelial permeability for fluids and macromolecules when the endothelial permeability is increased by thrombin. In this study, we have investigated the mechanism by which cGMP improves the endothelial barrier function and examined

Strategic environmental assessment

DEFF Research Database (Denmark)

Kørnøv, Lone

1997-01-01

The integration of environmental considerations into strategic decision making is recognized as a key to achieving sustainability. In the European Union a draft directive on Strategic Environmental Assessment (SEA) is currently being reviewed by the member states. The nature of the proposed SEA...... that the SEA directive will influence the decision-making process positively and will help to promote improved environmental decisions. However, the guidelines for public participation are not sufficient and the democratic element is strongly limited. On the basis of these findings, recommendations relating...

Transboundary Environmental Impact Assessment : An Introduction

NARCIS (Netherlands)

Bastmeijer, C.J.; Koivurova, T.; Bastmeijer, K.; Koivurova, T.

2008-01-01

Environmental Impact Assessment (EIA) is a well-established instrument of environmental law and policy that aims to ensure that potential adverse environmental effects of human activities are assessed before decisions on such activities are made. The instrument is increasingly being applied in

Salvinorin A preserves cerebral pial artery autoregulation after forebrain ischemia via the PI3K/AKT/cGMP pathway

Directory of Open Access Journals (Sweden)

H.P. Dong

2018-03-01

Full Text Available This study aimed to investigate the protective effect of salvinorin A on the cerebral pial artery after forebrain ischemia and explore related mechanisms. Thirty Sprague-Dawley rats received forebrain ischemia for 10 min. The dilation responses of the cerebral pial artery to hypercapnia and hypotension were assessed in rats before and 1 h after ischemia. The ischemia reperfusion (IR control group received DMSO (1 µL/kg immediately after ischemia. Two different doses of salvinorin A (10 and 20 µg/kg were administered following the onset of reperfusion. The 5th, 6th, and 7th groups received salvinorin A (20 µg/kg and LY294002 (10 µM, L-NAME (10 μM, or norbinaltorphimine (norBIN, 1 μM after ischemia. The levels of cGMP in the cerebrospinal fluid (CSF were also measured. The phosphorylation of AKT (p-AKT was measured in the cerebral cortex by western blot at 24 h post-ischemia. Cell necrosis and apoptosis were examined by hematoxylin-eosin staining (HE and TUNEL staining, respectively. The motor function of the rats was evaluated at 1, 2, and 5 days post-ischemia. The dilation responses of the cerebral pial artery were significantly impaired after ischemia and were preserved by salvinorin A treatment. In addition, salvinorin A significantly increased the levels of cGMP and p-AKT, suppressed cell necrosis and apoptosis of the cerebral cortex and improved the motor function of the rats. These effects were abolished by LY294002, L-NAME, and norBIN. Salvinorin A preserved cerebral pial artery autoregulation in response to hypercapnia and hypotension via the PI3K/AKT/cGMP pathway.

Methodology of environmental risk assessment management

Directory of Open Access Journals (Sweden)

Saša T. Bakrač

2012-04-01

Full Text Available Successful protection of environment is mostly based on high-quality assessment of potential and present risks. Environmental risk management is a complex process which includes: identification, assessment and control of risk, namely taking measures in order to minimize the risk to an acceptable level. Environmental risk management methodology: In addition to these phases in the management of environmental risk, appropriate measures that affect the reduction of risk occurrence should be implemented: - normative and legal regulations (laws and regulations, - appropriate organizational structures in society, and - establishing quality monitoring of environment. The emphasis is placed on the application of assessment methodologies (three-model concept, as the most important aspect of successful management of environmental risk. Risk assessment methodology - European concept: The first concept of ecological risk assessment methodology is based on the so-called European model-concept. In order to better understand this ecological risk assessment methodology, two concepts - hazard and risk - are introduced. The European concept of environmental risk assessment has the following phases in its implementation: identification of hazard (danger, identification of consequences (if there is hazard, estimate of the scale of consequences, estimate of consequence probability and risk assessment (also called risk characterization. The European concept is often used to assess risk in the environment as a model for addressing the distribution of stressors along the source - path - receptor line. Risk assessment methodology - Canadian concept: The second concept of the methodology of environmental risk assessment is based on the so-called Canadian model-concept. The assessment of ecological risk includes risk arising from natural events (floods, extreme weather conditions, etc., technological processes and products, agents (chemical, biological, radiological, etc

The plant natriuretic peptide receptor is a guanylyl cyclase and enables cGMP-dependent signaling

KAUST Repository

Turek, Ilona

2016-03-05

The functional homologues of vertebrate natriuretic peptides (NPs), the plant natriuretic peptides (PNPs), are a novel class of peptidic hormones that signal via guanosine 3′,5′-cyclic monophosphate (cGMP) and systemically affect plant salt and water balance and responses to biotrophic plant pathogens. Although there is increasing understanding of the complex roles of PNPs in plant responses at the systems level, little is known about the underlying signaling mechanisms. Here we report isolation and identification of a novel Leucine-Rich Repeat (LRR) protein that directly interacts with A. thaliana PNP, AtPNP-A. In vitro binding studies revealed that the Arabidopsis AtPNP-A binds specifically to the LRR protein, termed AtPNP-R1, and the active region of AtPNP-A is sufficient for the interaction to occur. Importantly, the cytosolic part of the AtPNP-R1, much like in some vertebrate NP receptors, harbors a catalytic center diagnostic for guanylyl cyclases and the recombinant AtPNP-R1 is capable of catalyzing the conversion of guanosine triphosphate to cGMP. In addition, we show that AtPNP-A causes rapid increases of cGMP levels in wild type (WT) leaf tissue while this response is significantly reduced in the atpnp-r1 mutants. AtPNP-A also causes cGMP-dependent net water uptake into WT protoplasts, and hence volume increases, whereas responses of the protoplasts from the receptor mutant are impaired. Taken together, our results suggest that the identified LRR protein is an AtPNP-A receptor essential for the PNP-dependent regulation of ion and water homeostasis in plants and that PNP- and vertebrate NP-receptors and their signaling mechanisms share surprising similarities. © 2016 Springer Science+Business Media Dordrecht

GMP production of [18F]FDOPA and issues concerning its quality analyses as in USP 'Fluorodopa F 18 Injection'

International Nuclear Information System (INIS)

Kao, C.K.; Hsu Wenlin; Xie Hengli; Lin Mingchi; Lan Wenchun; Chao Haoyu

2011-01-01

Lately, 6-[ 18 F]fluoro-L-DOPA (FDOPA) has found increase in its clinical demand for whole-body positron emission tomography (PET) scans, and two key issues in fulfilling this demand are the difficulties in producing FDOPA under the recently imposed PET drug good manufacturing practice (GMP) regulations and in providing it in the quality meeting the terms of major compendia. This paper describes the approaches for the GMP production of FDOPA and for the product testing to meet the standard of United States Pharmacopeia (USP) 'Fluorodopa F 18 Injection.' FDOPA was produced by the carrier-added electrophilic aromatic substitution reaction in the facility complying Pharmaceutical Inspection Cooperation Scheme clean room standard. The special aseptic handling technique was applied to minimize the bioburden. The product quality control followed all testing items and procedures, including three different settings of high performance liquid chromatography (HPLC). The process yielded FDOPA average 2.60±0.26 GBq (N=22) in every batch. All qualities of the product were within the specifications described in the USP 'Fluorodopa F 18 Injection.' The entire production was audited by the government authority and certified to comply with the latest PET drug GMP regulation. Our efforts in producing FDOPA following all aspects of GMP requirements have resulted in a product with the USP quality and certified as GMP complied. The routine production yields enough doses for three to four whole-body scans in each batch. The issues discussed in the report provide good reference for producers planning in routine production for PET drugs that are not commonly produced or with complicated compendial quality control tests. (author)

The added value of Good Manufacturing Practices (GMP) in the production of radiopharmaceuticals

NARCIS (Netherlands)

Gerrits, Edwin; Woerdenbag, Herman; Luurtsema, Geert; de Hooge, Marjolijn; Boersma, Hendrikus

2017-01-01

Manufacturers of medicinal products including radiopharmaceuticals have to follow regulations from their governmental organizations as well as professional societies to ensure built-in quality combined with patient safety issues. This chapter is a concise review of Good Manufacturing Practices (GMP)

Decreased levels of guanosine 3', 5'-monophosphate (cGMP) in cerebrospinal fluid (CSF) are associated with cognitive decline and amyloid pathology in Alzheimer's disease.

Science.gov (United States)

Ugarte, Ana; Gil-Bea, Francisco; García-Barroso, Carolina; Cedazo-Minguez, Ángel; Ramírez, M Javier; Franco, Rafael; García-Osta, Ana; Oyarzabal, Julen; Cuadrado-Tejedor, Mar

2015-06-01

Levels of the cyclic nucleotides guanosine 3', 5'-monophosphate (cGMP) or adenosine 3', 5'-monophosphate (cAMP) that play important roles in memory processes are not characterized in Alzheimer's disease (AD). The aim of this study was to analyse the levels of these nucleotides in cerebrospinal fluid (CSF) samples from patients diagnosed with clinical and prodromal stages of AD and study the expression level of the enzymes that hydrolyzed them [phosphodiesterases (PDEs)] in the brain of AD patients vs. For cGMP and cAMP CSF analysis, the cohort (n = 79) included cognitively normal participants (subjective cognitive impairment), individuals with stable mild cognitive impairment or AD converters (sMCI and cMCI), and mild AD patients. A high throughput liquid chromatography-tandem mass spectrometry method was used. Interactions between CSF cGMP or cAMP with mini-mental state examination (MMSE) score, CSF Aβ(1-42) and CSF p-tau were analysed. For PDE4, 5, 9 and 10 expression analysis, brains of AD patients vs. controls (n = 7 and n = 8) were used. cGMP, and not cAMP levels, were significantly lower in the CSF of patients diagnosed with mild AD when compared with nondemented controls. CSF levels of cGMP showed a significant association with MMSE-diagnosed clinical dementia and with CSF biomarker Aβ42 in AD patients. Significant increase in PDE5 expression was detected in temporal cortex of AD patients compared with that of age-matched healthy control subjects. No changes in the expression of others PDEs were detected. These results support the potential involvement of cGMP in the pathological and clinical development of AD. The cGMP reduction in early stages of AD might participate in the aggravation of amyloid pathology and cognitive decline. © 2014 British Neuropathological Society.

The effects of nitric oxide-cGMP pathway stimulation on dopamine in the medial preoptic area and copulation in DHT-treated castrated male rats.

Science.gov (United States)

Sato, Satoru M; Wersinger, Scott R; Hull, Elaine M

2007-08-01

Dopamine (DA) in the medial preoptic area (MPOA) provides important facilitative influence on male rat copulation. We have shown that the nitric oxide-cGMP (NO-cGMP) pathway modulates MPOA DA levels and copulation. We have also shown that systemic estradiol (E(2)) maintains neuronal NO synthase (nNOS) immunoreactivity in the MPOA of castrates, as well as relatively normal DA levels. This effect of E(2) on nNOS probably accounts for at least some of the previously demonstrated behavioral facilitation by intra-MPOA E(2) administration in castrates. Therefore, we hypothesized that stimulation of the MPOA NO-cGMP pathway in dihydrotestosterone (DHT)-treated castrates should restore DA levels and copulatory behaviors. Reverse-dialysis of a NO donor, sodium nitroprusside (SNP), increased extracellular DA in the MPOA of DHT-treated castrates and restored the ability to copulate to ejaculation in half of the animals. A cGMP analog, 8-Br-cGMP, also increased extracellular DA, though not as robustly, but did not restore copulatory ability. The effectiveness of the NO donor in restoring copulation and MPOA DA levels is consistent with our hypothesis. However, the lack of behavioral effects of 8-Br-cGMP, despite its increase in MPOA DA, suggests that NO may have additional mediators in the MPOA in the regulation of copulation. Furthermore, the suboptimal copulation seen in the NO donor-treated animals suggests the importance of extra-MPOA systems in the regulation of copulation.

Phosphodiesterase 9A regulates central cGMP and modulates responses to cholinergic and monoaminergic perturbation in vivo.

Science.gov (United States)

Kleiman, Robin J; Chapin, Douglas S; Christoffersen, Curt; Freeman, Jody; Fonseca, Kari R; Geoghegan, Kieran F; Grimwood, Sarah; Guanowsky, Victor; Hajós, Mihály; Harms, John F; Helal, Christopher J; Hoffmann, William E; Kocan, Geralyn P; Majchrzak, Mark J; McGinnis, Dina; McLean, Stafford; Menniti, Frank S; Nelson, Fredrick; Roof, Robin; Schmidt, Anne W; Seymour, Patricia A; Stephenson, Diane T; Tingley, Francis David; Vanase-Frawley, Michelle; Verhoest, Patrick R; Schmidt, Christopher J

2012-05-01

Cyclic nucleotides are critical regulators of synaptic plasticity and participate in requisite signaling cascades implicated across multiple neurotransmitter systems. Phosphodiesterase 9A (PDE9A) is a high-affinity, cGMP-specific enzyme widely expressed in the rodent central nervous system. In the current study, we observed neuronal staining with antibodies raised against PDE9A protein in human cortex, cerebellum, and subiculum. We have also developed several potent, selective, and brain-penetrant PDE9A inhibitors and used them to probe the function of PDE9A in vivo. Administration of these compounds to animals led to dose-dependent accumulation of cGMP in brain tissue and cerebrospinal fluid, producing a range of biological effects that implied functional significance for PDE9A-regulated cGMP in dopaminergic, cholinergic, and serotonergic neurotransmission and were consistent with the widespread distribution of PDE9A. In vivo effects of PDE9A inhibition included reversal of the respective disruptions of working memory by ketamine, episodic and spatial memory by scopolamine, and auditory gating by amphetamine, as well as potentiation of risperidone-induced improvements in sensorimotor gating and reversal of the stereotypic scratching response to the hallucinogenic 5-hydroxytryptamine 2A agonist mescaline. The results suggested a role for PDE9A in the regulation of monoaminergic circuitry associated with sensory processing and memory. Thus, PDE9A activity regulates neuronal cGMP signaling downstream of multiple neurotransmitter systems, and inhibition of PDE9A may provide therapeutic benefits in psychiatric and neurodegenerative diseases promoted by the dysfunction of these diverse neurotransmitter systems.

Environmental assessment: challenges and opportunities

International Nuclear Information System (INIS)

Hilbig, J.; Moffett, D.; Beri, K.

2007-01-01

As part of a $4.5 billion investment,Bruce Power is refurbishing Bruce A Units 1 and 2, having successfully completed an environmental assessment to return these units to service after a lay-up of almost 10 years. The project includes implementing a series of refurbishments and upgrades which will enhance safety, increase electricity generation capacity and improve reliability for the 30-year extended life of the units. This paper describes four challenges that were successfully managed during the extensive environmental assessment: (i) defining the scope of the Project; (ii) understanding the EA trigger under the Canadian Environmental Assessment Act; (iii) maintaining an effective relationship with the regulatory agencies; and (iv) managing stakeholder communications. (author)

Environmental assessment: challenges and opportunities

International Nuclear Information System (INIS)

Hilbig, J.; Moffett, D.; Beri, K.

2007-01-01

As part of a $4.5 billion investment, Bruce Power is refurbishing Bruce A Units 1 and 2, having successfully completed an environmental assessment to return these units to service after a lay-up of almost 10 years. The project includes implementing a series of refurbishments and upgrades which will enhance safety, increase electricity generation capacity and improve reliability for the 30-year extended life of the units. This paper describes four challenges that were successfully managed during the extensive environmental assessment: (i) defining the scope of the Project; (ii) understanding the EA trigger under the Canadian Environmental Assessment Act; (iii) maintaining an effective relationship with the regulatory agencies; and (iv) managing stakeholder communications. (author)

Nuclear cGMP-dependent kinase regulates gene expression via activity-dependent recruitment of a conserved histone deacetylase complex.

Directory of Open Access Journals (Sweden)

Yan Hao

2011-05-01

Full Text Available Elevation of the second messenger cGMP by nitric oxide (NO activates the cGMP-dependent protein kinase PKG, which is key in regulating cardiovascular, intestinal, and neuronal functions in mammals. The NO-cGMP-PKG signaling pathway is also a major therapeutic target for cardiovascular and male reproductive diseases. Despite widespread effects of PKG activation, few molecular targets of PKG are known. We study how EGL-4, the Caenorhabditis elegans PKG ortholog, modulates foraging behavior and egg-laying and seeks the downstream effectors of EGL-4 activity. Using a combination of unbiased forward genetic screen and proteomic analysis, we have identified a conserved SAEG-1/SAEG-2/HDA-2 histone deacetylase complex that is specifically recruited by activated nuclear EGL-4. Gene expression profiling by microarrays revealed >40 genes that are sensitive to EGL-4 activity in a SAEG-1-dependent manner. We present evidence that EGL-4 controls egg laying via one of these genes, Y45F10C.2, which encodes a novel protein that is expressed exclusively in the uterine epithelium. Our results indicate that, in addition to cytoplasmic functions, active EGL-4/PKG acts in the nucleus via a conserved Class I histone deacetylase complex to regulate gene expression pertinent to behavioral and physiological responses to cGMP. We also identify transcriptional targets of EGL-4 that carry out discrete components of the physiological response.

Analysis of proton wires in the enzyme active site suggests a mechanism of c-di-GMP hydrolysis by the EAL domain phosphodiesterases.

Science.gov (United States)

Grigorenko, Bella L; Knyazeva, Marina A; Nemukhin, Alexander V

2016-11-01

We report for the first time a hydrolysis mechanism of the cyclic dimeric guanosine monophosphate (c-di-GMP) by the EAL domain phosphodiesterases as revealed by molecular simulations. A model system for the enzyme-substrate complex was prepared on the base of the crystal structure of the EAL domain from the BlrP1 protein complexed with c-di-GMP. The nucleophilic hydroxide generated from the bridging water molecule appeared in a favorable position for attack on the phosphorus atom of c-di-GMP. The most difficult task was to find a pathway for a proton transfer to the O3' atom of c-di-GMP to promote the O3'P bond cleavage. We show that the hydrogen bond network extended over the chain of water molecules in the enzyme active site and the Glu359 and Asp303 side chains provides the relevant proton wires. The suggested mechanism is consistent with the structural, mutagenesis, and kinetic experimental studies on the EAL domain phosphodiesterases. Proteins 2016; 84:1670-1680. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

How strategic environmental assessment can inform lenders about potential environmental risks

DEFF Research Database (Denmark)

Banhalmi-Zakar, Zsuzsa; Larsen, Sanne Vammen

2015-01-01

at a time when it can be used as an input to bank lending decisions, which can assist banks in making lending decisions with better environmental outcomes. For these reasons, we argue that in some circumstances, and particularly for project finance transactions, SEA may be a more useful environmental......In this paper, we explore the potential for strategic environmental assessment (SEA) to be a useful tool for banks to manage environmental risks and inform lending decisions. SEA is an environmental assessment tool that was developed to assist strategic-level decision-makers, such as policy...

Evidence for a Messenger Function of Cyclic GMP During Phosphodiesterase Induction in Dictyostelium discoideum

NARCIS (Netherlands)

Haastert, Peter J.M. van; Pasveer, Frank J.; Meer, Rob C. van der; Heijden, Paul R. van der; Walsum, Hans van; Konijn, Theo M.

1982-01-01

Chemotactic stimulation of vegetative or aggregative Dictyostelium discoideum cells induced a transient elevation of cyclic GMP levels. The addition of chemoattractants to postvegetative cells by pulsing induced phosphodiesterase activity. The following lines of evidence suggest a messenger function

Genetic Dissection of the Regulatory Network Associated with High C-di-GMP Levels in Pseudomonas putida KT2440

Directory of Open Access Journals (Sweden)

María Isabel Ramos-González

2016-07-01

Full Text Available Most bacteria grow in nature forming multicellular structures named biofilms. The bacterial second messenger cyclic diguanosine monophosphate (c-di-GMP is a key player in the regulation of the transition from planktonic to sessile lifestyles and this regulation is crucial in the development of biofilms. In Pseudomonas putida KT2440, Rup4959, a multidomain response regulator with diguanylate cyclase activity, when overexpressed causes an increment in the intracellular levels of c-di-GMP that gives rise to a pleiotropic phenotype consisting of increased biofilm formation and crinkly colony morphology. In a broad genomic screen we have isolated mutant derivatives that lose the crinkly morphology, designed as cfc (crinkle free colony. A total of nineteen different genes have been identified as being related with the emergence of the cfc phenotype either because the expression or functionality of Rup4959 is compromised, or due to a lack of transduction of the c-di-GMP signal to downstream elements involved in the acquisition of the phenotype. Discernment between these possibilities was investigated by using a c-di-GMP biosensor and by HPLC-MS quantification of the second messenger. Interestingly five of the identified genes encode proteins with AAA+ ATPase domain. Among the bacterial determinants found in this screen are the global transcriptional regulators GacA, AlgU and FleQ and two enzymes involved in the arginine biosynthesis pathway. We present evidences that this pathway seems to be an important element to both the availability of the free pool of the second messenger c-di-GMP and to its further transduction as a signal for biosynthesis of biopolimers. In addition we have identified an uncharacterized hybrid sensor histidine kinase whose phosphoaceptor conserved histidine residue has been shown in this work to be required for in vivo activation of the orphan response regulator Rup4959, which suggests these two elements constitute a two

Environmental impact assessment: Process and implementation

International Nuclear Information System (INIS)

Chen, S.Y.; Tsai, S.Y.

1989-01-01

In this paper, the procedures and issues regarding the preparation of an environmental impact assessment in accordance with the National Environmental Policy Act (NEPA) as promulgated by the US Congress in 1969 are discussed. NEPA procedures and requirements are covered in general, while particular attention is given to the preparation of the environmental impact assessment. Also included is a discussion of the social impact assessment. The aim of the social impact assessment is to address the social issues involved in enhancing public understanding of the hazardous risks, thereby mitigating any conflicts that may arise in the NEPA process. 3 refs., 1 fig., 1 tab

Structural and functional characteristics of cGMP-dependent methionine oxidation in Arabidopsis thaliana proteins

KAUST Repository

Marondedze, Claudius; Turek, Ilona; Parrott, Brian Jonathan; Thomas, Ludivine; Jankovic, Boris R.; Lilley, Kathryn S; Gehring, Christoph A

2013-01-01

molecule, the cell-permeant second messenger analogue, 8-bromo-3,5-cyclic guanosine monophosphate (8-Br-cGMP), results in a time-dependent increase in the content of oxidised methionine residues. Interestingly, the group of proteins affected by c

cGMP and NHR signaling co-regulate expression of insulin-like peptides and developmental activation of infective larvae in Strongyloides stercoralis.

Directory of Open Access Journals (Sweden)

Jonathan D Stoltzfus

2014-07-01

Full Text Available The infectious form of the parasitic nematode Strongyloides stercoralis is a developmentally arrested third-stage larva (L3i, which is morphologically similar to the developmentally arrested dauer larva in the free-living nematode Caenorhabditis elegans. We hypothesize that the molecular pathways regulating C. elegans dauer development also control L3i arrest and activation in S. stercoralis. This study aimed to determine the factors that regulate L3i activation, with a focus on G protein-coupled receptor-mediated regulation of cyclic guanosine monophosphate (cGMP pathway signaling, including its modulation of the insulin/IGF-1-like signaling (IIS pathway. We found that application of the membrane-permeable cGMP analog 8-bromo-cGMP potently activated development of S. stercoralis L3i, as measured by resumption of feeding, with 85.1 ± 2.2% of L3i feeding in 200 µM 8-bromo-cGMP in comparison to 0.6 ± 0.3% in the buffer diluent. Utilizing RNAseq, we examined L3i stimulated with DMEM, 8-bromo-cGMP, or the DAF-12 nuclear hormone receptor (NHR ligand Δ7-dafachronic acid (DA--a signaling pathway downstream of IIS in C. elegans. L3i stimulated with 8-bromo-cGMP up-regulated transcripts of the putative agonistic insulin-like peptide (ILP -encoding genes Ss-ilp-1 (20-fold and Ss-ilp-6 (11-fold in comparison to controls without stimulation. Surprisingly, we found that Δ7-DA similarly modulated transcript levels of ILP-encoding genes. Using the phosphatidylinositol-4,5-bisphosphate 3-kinase inhibitor LY294002, we demonstrated that 400 nM Δ7-DA-mediated activation (93.3 ± 1.1% L3i feeding can be blocked using this IIS inhibitor at 100 µM (7.6 ± 1.6% L3i feeding. To determine the tissues where promoters of ILP-encoding genes are active, we expressed promoter::egfp reporter constructs in transgenic S. stercoralis post-free-living larvae. Ss-ilp-1 and Ss-ilp-6 promoters are active in the hypodermis and neurons and the Ss-ilp-7 promoter is active in the

Strategic environmental assessment can help solve environmental impact assessment failures in developing countries

International Nuclear Information System (INIS)

Alshuwaikhat, Habib M.

2005-01-01

The current trend of industrialization and urbanization in developing nations has a huge impact on anthropogenic and natural ecosystems. Pollution sources increase with the expansion of cities and cause contamination of water, air and soil. The absence of urban environmental planning and management strategies has resulted in greater concern for future urban development. This paper advocates the adoption of strategic environmental assessment (SEA) as a means to achieve sustainable development in developing countries. It investigates project-level environmental impact assessment (EIA) and its limitations. The exploration of SEA and its features are addressed. The effective implementation of SEA can create a roadmap for sustainable development. In many developing countries, the lack of transparency and accountability and ineffective public participation in the development of the policy, plan and program (PPP) would be mitigated by the SEA process. Moreover, the proactive and broadly based characteristics of SEA would benefit the institutional development of the PPP process, which is rarely experienced in many developing countries. The paper also explores the prospects for SEA and its guiding principles in developing countries. Finally, the paper calls for a coordinated effort between all government, nongovernment and international organizations involved with PPPs to enable developing countries to pursue a path of sustainable development through the development and application of strategic environmental assessment

GMP-compliant automated synthesis of [{sup 18}F]AV-45 (Florbetapir F 18) for imaging {beta}-amyloid plaques in human brain

Energy Technology Data Exchange (ETDEWEB)

Yao, C.-H. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Lin, K.-J. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Department of Medical Imaging and Radiological Sciences, Chang Gung University, 259 Wen-Hua 1st Road, Kweishan, Taoyuan 333, Taiwan (China); Weng, C.-C. [Department of Medical Imaging and Radiological Sciences, Chang Gung University, 259 Wen-Hua 1st Road, Kweishan, Taoyuan 333, Taiwan (China); Hsiao, I.-T. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Department of Medical Imaging and Radiological Sciences, Chang Gung University, 259 Wen-Hua 1st Road, Kweishan, Taoyuan 333, Taiwan (China); Ting, Y.-S. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Yen, T.-C. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Department of Medical Imaging and Radiological Sciences, Chang Gung University, 259 Wen-Hua 1st Road, Kweishan, Taoyuan 333, Taiwan (China); Jan, T.-R. [Department and Graduate Institute of Veterinary Medicine, National Taiwan University, Taipei, Taiwan (China); Skovronsky, Daniel [Avid Radiopharmaceuticals, Inc., Philadelphia, PA 19104 (United States); Kung, M.-P. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Wey, S.-P., E-mail: spwey@mail.cgu.edu.t [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Department of Medical Imaging and Radiological Sciences, Chang Gung University, 259 Wen-Hua 1st Road, Kweishan, Taoyuan 333, Taiwan (China)

2010-12-15

We report herein the Good Manufacturing Practice (GMP)-compliant automated synthesis of {sup 18}F-labeled styrylpyridine, AV-45 (Florbetapir), a novel tracer for positron emission tomography (PET) imaging of {beta}-amyloid (A{beta}) plaques in the brain of Alzheimer's disease patients. [{sup 18}F]AV-45 was prepared in 105 min using a tosylate precursor with Sumitomo modules for radiosynthesis under GMP-compliant conditions. The overall yield was 25.4{+-}7.7% with a final radiochemical purity of 95.3{+-}2.2% (n=19). The specific activity of [{sup 18}F]AV-45 reached as high as 470{+-}135 TBq/mmol (n=19). The present studies show that [{sup 18}F]AV-45 can be manufactured under GMP-compliant conditions and could be widely available for routine clinical use.

Environmental Assessment

OpenAIRE

The Inspection Panel

2017-01-01

The Inspection Panel, the World Bank’s independent accountability mechanism, has released the third report in its Emerging Lessons Series. The latest report identifies lessons from Panel cases related to environmental assessment (EA) issues. The Panel is an impartial fact-finding body, independent from the World Bank management and staff, reporting directly to the Board. In response to com...

The search for mutations in the gene for the beta subunit of the cGMP phosphodiesterase (PDEB) in patients with autosomal recessive retinitis pigmentosa

DEFF Research Database (Denmark)

Riess, O; Noerremoelle, A; Weber, B

1992-01-01

The finding of a mutation in the beta subunit of the cyclic GMP (cGMP) phosphodiesterase gene causing retinal degeneration in mice (the Pdeb gene) prompted a search for disease-causing mutations in the human phosphodiesterase gene (PDEB gene) in patients with retinitis pigmentosa. All 22 exons...

Captive solvent [11C]acetate synthesis in GMP conditions

International Nuclear Information System (INIS)

Soloviev, Dmitri; Tamburella, Claire

2006-01-01

Reliable procedure for the production of 1-[ 11 C]acetate in GMP conditions was developed based on a combination of the captive-solvent Grignard reaction conducted in the sterile catheter followed by the convenient solid-phase extraction purification on a series of ion-exchange cartridges. The described procedure proved to be reliable in more than 30 patient productions. The process provides stable radiochemical yields (65% EOB) of sodium acetate (1-[ 11 C]) of the Ph.Eur. quality (radiochemical purity better than 95%) in a short time (5 min)

Environmental impact assessment of fish farm hatcheries ...

African Journals Online (AJOL)

Environmental impact assessment of fish farm hatcheries management in lower ... Environmental impact assessments were taken to determine the causes of ... Of significance of impact assessment were activities like air, traffic, noise, had ...

Specificity of Good Manufacturing Practice (GMP) for Biomedical Cell Products.

Science.gov (United States)

Tulina, M A; Pyatigorskaya, N V

2018-03-01

The article describes special aspects of Good Manufacturing Practice (GMP) for biomedical cell products (BMCP) that imply high standards of aseptics throughout the entire productio process, strict requirements to donors and to the procedure of biomaterial isolation, guaranty of tracing BMCP products, defining processing procedures which allow to identify BMCP as minimally manipulated; continuous quality control and automation of the control process at all stages of manufacturing, which will ensure product release simultaneously with completion of technological operations.

Radiation environmental impact assessment of copper exploitation

International Nuclear Information System (INIS)

Fan Guang; Wen Zhijian

2010-01-01

The radiation environmental impact of mineral exploitation on the surrounding environment has become a public concern. This paper presents the radiation environmental impact assessment of copper exploitation. Based on the project description and detailed investigations of surrounding environment, systematic radiation environmental impacts have been identified. The environmental impacts are assessed during both construction and operation phase. The environmental protection measures have also been proposed. The related conclusion and measures can play an active role in copper exploitation and environmental protection. (authors)

The GDP-switched GAF domain of DcpA modulates the concerted synthesis/hydrolysis of c-di-GMP in Mycobacterium smegmatis.

Science.gov (United States)

Chen, Hui-Jie; Li, Na; Luo, Ye; Jiang, Yong-Liang; Zhou, Cong-Zhao; Chen, Yuxing; Li, Qiong

2018-04-09

The second messenger c-di-GMP [bis-(3'-5')-cyclic dimeric guanosine monophosphate] plays a key role in bacterial growth, survival and pathogenesis, and thus its intracellular homeostasis should be finely maintained. Mycobacterium smegmatis encodes a GAF (mammalian c G MP-regulated phosphodiesterases, Anabaena a denylyl cyclases and Escherichia coli transcription activator F hlA) domain containing bifunctional enzyme DcpA ( d iguanylate c yclase and p hosphodiesterase A ) that catalyzes the synthesis and hydrolysis of c-di-GMP . Here, we found that M. smegmatis DcpA catalyzes the hydrolysis of c-di-GMP at a higher velocity, compared with synthetic activity, resulting in a sum reaction from the ultimate substrate GTP to the final product pGpG [5'-phosphoguanylyl-(3'-5')-guanosine]. Fusion with the N-terminal GAF domain enables the GGDEF (Gly-Gly-Asp-Glu-Phe) domain of DcpA to dimerize and accordingly gain synthetic activity. Screening of putative metabolites revealed that GDP is the ligand of the GAF domain. Binding of GDP to the GAF domain down-regulates synthetic activity, but up-regulates hydrolytic activity, which, in consequence, might enable a timely response to the transient accumulation of c-di-GMP at the stationary phase or under stresses. Combined with the crystal structure of the EAL (Glu-Ala-Leu) domain and the small-angle X-ray scattering data, we propose a putative regulatory model of the GAF domain finely tuned by the intracellular GTP/GDP ratio. These findings help us to better understand the concerted control of the synthesis and hydrolysis of c-di-GMP in M. smegmatis in various microenvironments. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

A Scientific Calculator for Exact Real Number Computation Based on LRT, GMP and FC++

Directory of Open Access Journals (Sweden)

J. A. Hernández

2012-03-01

Full Text Available Language for Redundant Test (LRT is a programming language for exact real number computation. Its lazy evaluation mechanism (also called call-by-need and its infinite list requirement, make the language appropriate to be implemented in a functional programming language such as Haskell. However, a direction translation of the operational semantics of LRT into Haskell as well as the algorithms to implement basic operations (addition subtraction, multiplication, division and trigonometric functions (sin, cosine, tangent, etc. makes the resulting scientific calculator time consuming and so inefficient. In this paper, we present an alternative implementation of the scientific calculator using FC++ and GMP. FC++ is a functional C++ library while GMP is a GNU multiple presicion library. We show that a direct translation of LRT in FC++ results in a faster scientific calculator than the one presented in Haskell.El lenguaje de verificación redundante (LRT, por sus siglas en inglés es un lenguaje de programación para el cómputo con números reales exactos. Su método de evaluación lazy (o mejor conocido como llamada por necesidad y el manejo de listas infinitas requerido, hace que el lenguaje sea apropiado para su implementación en un lenguaje funcional como Haskell. Sin embargo, la implementación directa de la semántica operacional de LRT en Haskell así como los algoritmos para funciones básicas (suma, resta, multiplicación y división y funciones trigonométricas (seno, coseno, tangente, etc hace que la calculadora científica resultante sea ineficiente. En este artículo, presentamos una implementación alternativa de la calculadora científica usando FC++ y GMP. FC++ es una librería que utiliza el paradigma Funcional en C++ mientras que GMP es una librería GNU de múltiple precisión. En el artículo mostramos que la implementación directa de LRT en FC++ resulta en una librería más eficiente que la implementada en Haskell.

Methodologies of environmental impact assessment

International Nuclear Information System (INIS)

Schroll, H.

1994-01-01

This article gives a brief introduction covering the objectives of environmental impact assessment (EIA) and sustainable development, before going on to describe the screening procedure to define the environmental and socio-economic impacts of projects. The EIA procedure outlined encompasses a description of the project, examination of all environmental effects (scoping), identification of existing and predicted environmental conditions and impacts, alternative measures and mitigating measures, co-ordination, with environmental regulations, public participation, and monitoring and approval of the EIA. (UK)

16 CFR 260.8 - Environmental assessment.

Science.gov (United States)

2010-01-01

....8 Commercial Practices FEDERAL TRADE COMMISSION GUIDES AND TRADE PRACTICE RULES GUIDES FOR THE USE OF ENVIRONMENTAL MARKETING CLAIMS § 260.8 Environmental assessment. (a) National Environmental Policy... and analysis to determine whether issuing the Guides for the Use of Environmental Marketing Claims...

Ethanol extract of seeds of Oenothera odorata induces vasorelaxation via endothelium-dependent NO-cGMP signaling through activation of Akt-eNOS-sGC pathway.

Science.gov (United States)

Kim, Hye Yoom; Oh, Hyuncheol; Li, Xiang; Cho, Kyung Woo; Kang, Dae Gill; Lee, Ho Sub

2011-01-27

The vasorelaxant effect of ethanol extract of seeds of Oenothera odorata (Onagraceae) (one species of evening primroses) (ESOO) and its mechanisms involved were defined. Changes in vascular tension, guanosine 3',5'-cyclic monophosphate (cGMP) levels, and Akt expression were measured in carotid arterial rings from rats. Seeds of Oenothera odorata were extracted with ethanol (94%) and the extract was filtered, concentrated and stored at -70°C. ESOO relaxed endothelium-intact, but not endothelium-denuded, carotid arterial rings in a concentration-dependent manner. Similarly, ESOO increased cGMP levels of the carotid arterial rings. Pretreatment of endothelium-intact arterial rings with L-NAME, an inhibitor of nitric oxide synthase (NOS), or ODQ, an inhibitor of soluble guanylyl cyclase (sGC), blocked the ESOO-induced vasorelaxation and increase in cGMP levels. Nominally Ca(2+)-free but not L-typed Ca(2+) channel inhibition attenuated the ESOO-induced vasorelaxation. Thapsigargin, Gd(3+), and 2-aminoethyl diphenylborinate, modulators of store-operated Ca(2+) entry (SOCE), significantly attenuated the ESOO-induced vasorelaxation and increase in cGMP levels. Further, wortmannin, an inhibitor of Akt, attenuated the ESOO-induced vasorelaxation and increases in cGMP levels and phosphorylated Akt2 expression. K(+) channel blockade with TEA, 4-aminopyridine, and glibenclamide attenuated the ESOO-induced vascular relaxation. Taken together, the present study demonstrates that ESOO relaxes vascular smooth muscle via endothelium-dependent NO-cGMP signaling through activation of the Akt-eNOS-sGC pathway. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

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

Framework for conducting environmental assessments of trade negotiations

International Nuclear Information System (INIS)

2001-02-01

This document described the complex task of assessing the environmental impacts of trade negotiations with particular emphasis on the framework of the Strategic Environmental Assessment which the Government of Canada will conduct through a systematic process which can identify and evaluate possible and significant environmental impacts of an initiative. The objective of the assessment is to integrate environmental considerations into decision-making processes at the earliest possible stage. The first part of the framework identifies the importance of recognizing environmental considerations of trade and explains how the framework will contribute to environmental policy. The second part of the framework outlines the process and analytical requirements for conducting an environmental assessment of a trade negotiation. Environmental Assessment Committees will be formed by the Department of Foreign Affairs and International Trade, and will include representatives from federal government departments and agencies. All analyses will be conducted in four stages which will include identifying the economic effect of the negotiation, identifying the likely environmental impact of such changes, assessing the significance of the likely environmental impacts, and identifying enhancement/mitigation options to inform the negotiations. The framework is designed to be flexible enough to be used at current and future trade negotiations in the World Trade Organization, the Free Trade Area of the Americas and in bilateral Free Trade Agreements. An environmental assessment of trade negotiations is considered to be an important decision-making tool for promoting sustainable development. 16 refs., 1 tab

cGMP signaling as a target for the prevention and treatment of breast cancer.

Science.gov (United States)

Windham, Perrin F; Tinsley, Heather N

2015-04-01

One in eight women in the United States will be diagnosed with invasive breast cancer in her lifetime. Advances in therapeutic strategies, diagnosis, and improved awareness have resulted in a significant reduction in breast cancer related mortality. However, there is a continued need for more effective and less toxic drugs for both the prevention and the treatment of breast cancer in order to see a continued decline in the morbidity and mortality associated with this disease. Recent studies suggest that the cGMP signaling pathway may be aberrantly regulated in breast cancer. As such, this pathway may serve as a source of novel targets for future breast cancer drug discovery efforts. This review provides an overview of cGMP signaling in normal physiology and in breast cancer as well as current strategies being investigated for targeting this pathway in breast cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Nitric oxide participates in cold-inhibited Camellia sinensis pollen germination and tube growth partly via cGMP in vitro.

Directory of Open Access Journals (Sweden)

Yu-Hua Wang

Full Text Available Nitric oxide (NO plays essential roles in many biotic and abiotic stresses in plant development procedures, including pollen tube growth. Here, effects of NO on cold stress inhibited pollen germination and tube growth in Camellia sinensis were investigated in vitro. The NO production, NO synthase (NOS-like activity, cGMP content and proline (Pro accumulation upon treatment with NO scavenger cPTIO, NOS inhibitor L-NNA, NO donor DEA NONOate, guanylate cyclase (GC inhibitor ODQ or phosphodiesterase (PDE inhibitor Viagra at 25°C (control or 4°C were analyzed. Exposure to 4°C for 2 h reduced pollen germination and tube growth along with increase of NOS-like activity, NO production and cGMP content in pollen tubes. DEA NONOate treatment inhibited pollen germination and tube growth in a dose-dependent manner under control and reinforced the inhibition under cold stress, during which NO production and cGMP content promoted in pollen tubes. L-NNA and cPTIO markedly reduced the generation of NO induced by cold or NO donor along with partly reverse of cold- or NO donor-inhibited pollen germination and tube growth. Furthermore, ODQ reduced the cGMP content under cold stress and NO donor treatment in pollen tubes. Meanwhile, ODQ disrupted the reinforcement of NO donor on the inhibition of pollen germination and tube growth under cold condition. Additionally, Pro accumulation of pollen tubes was reduced by ODQ compared with that receiving NO donor under cold or control condition. Effects of cPTIO and L-NNA in improving cold-treated pollen germination and pollen tube growth could be lowered by Viagra. Moreover, the inhibitory effects of cPTIO and L-NNA on Pro accumulation were partly reversed by Viagra. These data suggest that NO production from NOS-like enzyme reaction decreased the cold-responsive pollen germination, inhibited tube growth and reduced Pro accumulation, partly via cGMP signaling pathway in C. sinensis.

76 FR 75557 - Draft Environmental Impact Statement for General Management Plan/Wilderness Study, Hawaii...

Science.gov (United States)

2011-12-02

... Environmental Impact Statement for General Management Plan/ Wilderness Study, Hawaii Volcanoes National Park, Hawaii AGENCY: National Park Service, Interior. ACTION: Notice of intent. SUMMARY: The National Park... updating the General Management Plan (GMP) for Hawaii Volcanoes National Park. As part of this conservation...

Regional Environmental Monitoring and Assessment Program Data (REMAP)

Data.gov (United States)

U.S. Environmental Protection Agency — The Regional Environmental Monitoring and Assessment Program (REMAP) was initiated to test the applicability of the Environmental Monitoring and Assessment Program...

Planning Environmental Impact Assessment Orienting Sustainable Development:Opportunities and Challenges

Institute of Scientific and Technical Information of China (English)

Sun Yanjun; Chen Xingeng; Bao Yun; Peng Xiaochun; Gao Changbo

2005-01-01

Strategic Environmental Assessment is a frontier subject in the field of Environmental Impact Assessment. In the past two decades, especially in recent years, much more importance has been attached to Strategic Environmental Assessment. The Environmental Impact Assessment Law of the P.R.China which was promulgated provides a great opportunity for the development of Planning Environmental Impact Assessment and brings great challenges for the development of traditional Project Environmental Impact Assessment and Planning Environmental Impact Assessment at the same time.In order to promote the implementation of"The EIA Law", the inherent limitations of Project Environmental Impact Assessment must be identified sufficiendy and the theory research and practice of Planning Environmental Impact Assessment should be strengthened as well. Measures should be taken currendy to enforce the operation system. The authors wish to offer a few references to the progress and implementation of Planning Environmental Impact Assessment in China.

Environmental flow assessments for transformed estuaries

Science.gov (United States)

Sun, Tao; Zhang, Heyue; Yang, Zhifeng; Yang, Wei

2015-01-01

Here, we propose an approach to environmental flow assessment that considers spatial pattern variations in potential habitats affected by river discharges and tidal currents in estuaries. The approach comprises four steps: identifying and simulating the distributions of critical environmental factors for habitats of typical species in an estuary; mapping of suitable habitats based on spatial distributions of the Habitat Suitability Index (HSI) and adopting the habitat aggregation index to understand fragmentation of potential suitable habitats; defining variations in water requirements for a certain species using trade-off analysis for different protection objectives; and recommending environmental flows in the estuary considering the compatibility and conflict of freshwater requirements for different species. This approach was tested using a case study in the Yellow River Estuary. Recommended environmental flows were determined by incorporating the requirements of four types of species into the assessments. Greater variability in freshwater inflows could be incorporated into the recommended environmental flows considering the adaptation of potential suitable habitats with variations in the flow regime. Environmental flow allocations should be conducted in conjunction with land use conflict management in estuaries. Based on the results presented here, the proposed approach offers flexible assessment of environmental flow for aquatic ecosystems that may be subject to future change.

Investigation of the role of the NO-cGMP pathway on YC-1 and DEA/NO effects on thoracic aorta smooth muscle responses in a rat preeclampsia model.

Science.gov (United States)

Turgut, Nergiz Hacer; Temiz, Tijen Kaya; Turgut, Bülent; Karadas, Baris; Parlak, Mesut; Bagcivan, Ihsan

2013-10-01

The present study was designed to investigate the effects of YC-1, a nitric oxide (NO)-independent soluble guanylate cyclase (sGC) activator, and DEA/NO, a NO donor, on smooth muscle responses in the preeclampsia model with suramin-treated rats and on the levels of cyclic guanosine monophosphate (cGMP) of thoracic aorta rings isolated from term-pregnant rats. Rats of 2 groups, control group and suramin group, were given intraperitoneal injection of saline or suramin, respectively. Suramin injection caused increased blood pressure, protein in urine, and fetal growth retardation. Thoracic aorta rings were exposed to contractile and relaxant agents. KCl contraction and papaverine relaxation responses were similar. Relaxation responses of YC-1 and DEA/NO decreased in suramin group. In both groups in the presence of ODQ, a sGC inhibitor, the relaxation responses of YC-1 and DEA/NO decreased. The cGMP content was determined by radioimmunoassay technique. The content of cGMP in the suramin group decreased. In the presence of YC-1 and DEA/NO in both groups, cGMP content increased, but in ODQ-added groups, there was a significant decrease. We conclude that in preeclampsia, the decrease of relaxation responses and the decrease of cGMP content could be due to the reduction in stimulation of sGC and the decrease in cGMP levels.

Environmental impact assessment - a selected bibliography

International Nuclear Information System (INIS)

Lawson, W.J.

1989-01-01

This bibliography of literature relevant to the environmental impact assessment process is essentially a list of material dealing with the environmental impact assessment process held by Griffith University Library. The list is however well supplemented with citations of material not held in the Griffith University Library. Some economic and social impact assessment citations have been included in the bibliography, as the the environmental impact assessment concept has been interpreted very broadly. The citations are arranged according to broad subject areas, such as methodology, critical reviews, social impacts etc. Citations in each of these subject areas, which are listed in the table of contents, are identified by prefixes which are given in parentheses before the subjects headings. Within each subject area the citations are arragend in alphabetic author sequence

Environmental Assessment of R&D Programmes

DEFF Research Database (Denmark)

Lyhne, Ivar; Byriel, Inger Pihl

2013-01-01

cause severe negative environmental impacts. This paper presents an innovative environmental assessment practice on R&D programmes in Denmark. It reports on the challenges and experiences of assessing the Danish R&D programme ForskEL, which promotes R&D projects within the electricity sector......Despite their important role in shaping the technologies of the future, public research and development (R&D) programmes are rarely based on systematic assessments of the environmental effects. R&D programmes thus allocate a huge amount of financial resources to projects, which potentially may....... The programme is characterised by uncertainty about impacts and incomparable project types and technologies. A methodology for dealing with these challenges is presented, and experiences from a testing of the methodology on the 2012 programme are reflected upon. Finally the assessment is discussed in terms...

HMW-GS affect the properties of glutenin particles in GMP and thus flour quality

NARCIS (Netherlands)

Don, C.; Mann, G.; Bekes, F.; Hamer, R.J.

2006-01-01

Using a unique set of deletion lines, (Olympic×Gabo, varying in high molecular weight glutenin subunit (HMW-GS) composition, but with the same genetic background) it was shown that the presence of glutenin particles in glutenin macropolymer (GMP) is directly related to the presence of certain

Crystallization and preliminary X-ray analysis of the flagellar motor `brake' molecule YcgR with c-di-GMP from Escherichia coli.

Science.gov (United States)

Hou, Yanjie; Li, De Feng; Wang, Da Cheng

2013-06-01

In Escherichia coli and Salmonella enterica, bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP), a ubiquitous bacterial second-messenger molecule that participates in many cellular processes, can regulate flagellar motor speed and reduce cell swimming velocity by binding to the PilZ-containing protein YcgR. Here, the crystallization and preliminary X-ray crystallographic analysis of YcgR with c-di-GMP are reported. The crystals diffracted to 2.3 Å resolution and belonged to space group R3:H, with unit-cell parameters a = b = 93.96, c = 109.61 Å. The asymmetric unit appeared to contain one subunit with a Matthews coefficient of 3.21 Å(3) Da(-1). The results reported here provide a sound basis for solving the crystal structure of YcgR with c-di-GMP and revealing its structure-function relationship based on the three-dimensional structure.

Role of cyclic GMP in cells with the properties of smooth muscle cultured from the rat myometrium

International Nuclear Information System (INIS)

Krall, J.F.; Morin, A.

1986-01-01

Cells growing in culture with previously described properties of rat uterine smooth muscle accumulated 45 Ca 2+ from the medium. Ca 2+ uptake by these cells was stimulated by the addition to the medium of 8-bromo-cGMP but not by 8-bromo-cAMP. Ca 2+ uptake was also stimulated by carbachol and by the nitro-vasodilator nitroprusside. Although cholinergic agonists have been shown previously to stimulate contraction but not cGMP synthesis in the rat myometrium, both carbachol and nitroprusside stimulated cGMP production by the cultured cells. These results suggested the cells had cholinergic receptor-medicated functions that reflected some neurotransmitter-sensitive properties of uterine smooth muscle in situ. When determined by a specific radioligand binding assay, subcellular fractions of the cultured cells bound muscarinic cholinergic agonists and antagonists with affinities expected of the muscarinic receptor. The cells were also sensitive to the β-adrenergic catecholamine agonist isoproterenol, which stimulated cAMP production but not Ca 2+ uptake. Carbachol failed to inhibit isoproterenol-dependent cAMP production, which is an important property of the cholinergic receptor in uterine smooth muscle in situ. These results suggest some but not all acetylcholine-sensitive properties of uterine smooth muscle may be retained in cell culture

Heat shock factor-1 intertwines insulin/IGF-1, TGF-β and cGMP signaling to control development and aging

Directory of Open Access Journals (Sweden)

Barna János

2012-11-01

Full Text Available Abstract Background Temperature affects virtually all cellular processes. A quick increase in temperature challenges the cells to undergo a heat shock response to maintain cellular homeostasis. Heat shock factor-1 (HSF-1 functions as a major player in this response as it activates the transcription of genes coding for molecular chaperones (also called heat shock proteins that maintain structural integrity of proteins. However, the mechanisms by which HSF-1 adjusts fundamental cellular processes such as growth, proliferation, differentiation and aging to the ambient temperature remain largely unknown. Results We demonstrate here that in Caenorhabditis elegans HSF-1 represses the expression of daf-7 encoding a TGF-β (transforming growth factor-beta ligand, to induce young larvae to enter the dauer stage, a developmentally arrested, non-feeding, highly stress-resistant, long-lived larval form triggered by crowding and starvation. Under favorable conditions, HSF-1 is inhibited by crowding pheromone-sensitive guanylate cyclase/cGMP (cyclic guanosine monophosphate and systemic nutrient-sensing insulin/IGF-1 (insulin-like growth factor-1 signaling; loss of HSF-1 activity allows DAF-7 to promote reproductive growth. Thus, HSF-1 interconnects the insulin/IGF-1, TGF-β and cGMP neuroendocrine systems to control development and longevity in response to diverse environmental stimuli. Furthermore, HSF-1 upregulates another TGF-β pathway-interacting gene, daf-9/cytochrome P450, thereby fine-tuning the decision between normal growth and dauer formation. Conclusion Together, these results provide mechanistic insight into how temperature, nutrient availability and population density coordinately influence development, lifespan, behavior and stress response through HSF-1.

Public participation in Malawi's environmental impact assessment ...

African Journals Online (AJOL)

Since the adoption of the Environmental Management Act of 1996, Malawi has been using environmental impact assessment (EIA) as a tool for predicting and assessing the impact of development projects on the environment. This study assessed the extent of public participation in Malawi's EIA process. Desktop study of ...

Expression of Cyclic GMP-AMP Synthase in Patients With Systemic Lupus Erythematosus.

Science.gov (United States)

An, Jie; Durcan, Laura; Karr, Reynold M; Briggs, Tracy A; Rice, Gillian I; Teal, Thomas H; Woodward, Joshua J; Elkon, Keith B

2017-04-01

Type I interferon (IFN) is implicated in the pathogenesis of systemic lupus erythematosus (SLE) and interferonopathies such as Aicardi-Goutières syndrome. A recently discovered DNA-activated type I IFN pathway, cyclic GMP-AMP synthase (cGAS), has been linked to Aicardi-Goutières syndrome and mouse models of lupus. The aim of this study was to determine whether the cGAS pathway contributes to type I IFN production in patients with SLE. SLE disease activity was measured by the Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index. Expression of messenger RNA for cGAS and IFN-stimulated genes (ISGs) was determined by quantitative polymerase chain reaction analysis. Cyclic GMP-AMP (cGAMP) levels were examined by multiple reaction monitoring with ultra-performance liquid chromatography tandem mass spectrometry. Expression of cGAS in peripheral blood mononuclear cells (PBMCs) was significantly higher in SLE patients than in normal controls (n = 51 and n = 20 respectively; P < 0.01). There was a positive correlation between cGAS expression and the IFN score (P < 0.001). The expression of cGAS in PBMCs showed a dose response to type I IFN stimulation in vitro, consistent with it being an ISG. Targeted measurement of cGAMP by tandem mass spectrometry detected cGAMP in 15% of the SLE patients (7 of 48) but none of the normal (0 of 19) or rheumatoid arthritis (0 of 22) controls. Disease activity was higher in SLE patients with cGAMP versus those without cGAMP. Increased cGAS expression and cGAMP in a proportion of SLE patients indicates that the cGAS pathway should be considered as a contributor to type I IFN production. Whereas higher cGAS expression may be a consequence of exposure to type I IFN, detection of cGAMP in patients with increased disease activity indicates potential involvement of this pathway in disease expression. © 2016, American College of Rheumatology.

31 CFR 26.3 - Availability of Environmental Impact Assessment Summaries (EIA Summaries) and Environmental...

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Availability of Environmental Impact Assessment Summaries (EIA Summaries) and Environmental Impact Assessments (EIAs). 26.3 Section 26.3 Money and... DEVELOPMENT BANDS (MDBs) § 26.3 Availability of Environmental Impact Assessment Summaries (EIA Summaries) and...

[Effect of twirling-reinforcing-reducing needling manipulations on contents of serum acetylcholine and arterial NOS and cGMP in stress-induced hypertension rats].

Science.gov (United States)

Liu, Wei; Zhu, Ling-Qun; Chen, Si-Si; Lu, Shu-Chao; Tang, Jie; Liu, Qing-Guo

2015-04-01

To observe the effect of twirling-reinforcing or reducing needling manipulations on plasma acetylcholine (Ach) content and expression of nitric oxide synthetase (NOS) and cyclic guanosine monophosphate (cGMP) in thoracic artery tissue in stress-induced hypertension rats. A total of 60 male rats were randomly divided into blank control, model, acupuncture (no-needle-manipulation) , twirling-reinforcing needling and twirling-reducing needling groups (n = 12 in each group). The stress hypertension model was established by giving the animals with noise and electric shock stimulation (paw), twice a day for 15 days. Acupuncture stimulation was applied to bilateral "Taichong" (LR 3) for 1 min, followed by retaining the needles for 20 min. The treatment was conducted once daily for 7 days. Systolic blood pressure of the rat's tail was detected with non-invasive method and plasma Ach, and NOS and cGMP contents in the thoracic artery tissue were measured using ELISA method. Compared with the control group, the systolic blood pressure was significantly higher in the model group after 15 days' stress stimulation (P arterial NOS and cGMP were markedly down-regulated (P arterial cGMP content was found in the no-needle-manipulation group (P > 0.05). The effect of the twirling-reducing needling was superior to that of no-needle-manipulation and twirling-reinforcing needling in lowering blood pressure and raising plasma Ach content (P hypertensive effect in stress hypertension rats, which may be associated with its effects in raising blood Ach, and arterial NOS and cGMP levels.

Environmental Impact Assessment in Antarctica

NARCIS (Netherlands)

Bastmeijer, C.J.; Roura, R.; Bastmeijer, K.; Koivurova, T.

2008-01-01

This publication focuses on the instrument of Environmental Impact Assessment (EIA) that has been developed within the Antarctic Treaty System (ATS) as one of the tools to promote environmental protection. The states involved in the ATS already recognized the importance of this instrument in 1975

Setting boundaries of participation in environmental impact assessment

Energy Technology Data Exchange (ETDEWEB)

Salomons, Geoffrey H., E-mail: gsalomon@ualberta.ca [University of Alberta, Department of Political Science, 10-16 Henry Marshall Tory Building, University of Alberta, Edmonton, AB T6G 2H4 (Canada); Hoberg, George, E-mail: george.hoberg@ubc.ca [University of British Columbia, Faculty of Forestry, Forest Sciences Centre 2045, 2424 Main Mall, Vancouver, British Columbia V6T 1Z4 (Canada)

2014-02-15

Public participation processes are touted as an effective way to increase the capacity and legitimacy of environmental assessment and the regulatory process that rely on them. Recent changes to the Canadian environmental assessment process narrowed the criteria for who can participate in environmental assessments from any who were interested to those who were most directly affected. This article examines the potential consequences of this change by exploring other areas of Canadian regulatory law where a similar directed affected test has been applied. This new standard risks institutionalizing the long-understood representational bias confronted by more diffuse interest like environmental protection. Restricting participation to the “directly affected” is far too narrow a test for processes like environmental assessment that are designed to determine the public interest. -- Highlights: • Public participation can improve the legitimacy of environmental assessments. • New Canadian rules narrow the range of eligible participants. • Similar rules in Alberta have excluded environmental representation. • The new rules may institutionalize bias against more diffuse interests. • Restricting participation to the “directly affected” is far too narrow.

Setting boundaries of participation in environmental impact assessment

International Nuclear Information System (INIS)

Salomons, Geoffrey H.; Hoberg, George

2014-01-01

Public participation processes are touted as an effective way to increase the capacity and legitimacy of environmental assessment and the regulatory process that rely on them. Recent changes to the Canadian environmental assessment process narrowed the criteria for who can participate in environmental assessments from any who were interested to those who were most directly affected. This article examines the potential consequences of this change by exploring other areas of Canadian regulatory law where a similar directed affected test has been applied. This new standard risks institutionalizing the long-understood representational bias confronted by more diffuse interest like environmental protection. Restricting participation to the “directly affected” is far too narrow a test for processes like environmental assessment that are designed to determine the public interest. -- Highlights: • Public participation can improve the legitimacy of environmental assessments. • New Canadian rules narrow the range of eligible participants. • Similar rules in Alberta have excluded environmental representation. • The new rules may institutionalize bias against more diffuse interests. • Restricting participation to the “directly affected” is far too narrow

Institutional Assessment of Environmentally Oriented Subsoil Use

Directory of Open Access Journals (Sweden)

Irina Gennadyevna Polyanskaya

2017-06-01

Full Text Available The article solves two relevant problems related to the implementation of the institutional assessment of environmentally oriented subsoil use: 1 the definition of the ‘environmental security’ and 2 the determination of the development level of institutional bases of environmentally oriented subsoil use including the institutional capacity of subsoil use and institutional capacity of environmental security. The article shows an analysis of the existing definitions of “environmental security” and offers the own one. Despite the significant national and foreign experience in the institutional capacity assessment of various processes, there are still some difficulties in defining and measuring the institutional capacity. We eliminate these difficulties by employing 1 original factors, previously identified, and the content of the “institutional capacity” term; 2 quality characteristics for the institutional capacity assessment of the process regulated at the macroeconomic level, and 3 a consistent methodological tool for the institutional assessment of environmentally oriented subsoil use. The study is based on the hypothesis of the necessity of legal and discreet state intervention in the process of subsoil use. Therefore, we identify the evaluation indicator of state regulation in the environmentally oriented subsoil use as the institutional capacity level calculated by using the fuzzy-set theory. As a result, the institutional capacity levels of the environmentally oriented subsoil use have been defined for both the transport corridor «Arctic-Central Asia» and for the countries composing it. The obtained values of the assessment of institutional capacity levels of the environmentally oriented subsoil use can serve as a basis for identifying the vector of its increase

cGMP-dependent protein kinase type II knockout mice exhibit working memory impairments, decreased repetitive behavior, and increased anxiety-like traits.

Science.gov (United States)

Wincott, Charlotte M; Abera, Sinedu; Vunck, Sarah A; Tirko, Natasha; Choi, Yoon; Titcombe, Roseann F; Antoine, Shannon O; Tukey, David S; DeVito, Loren M; Hofmann, Franz; Hoeffer, Charles A; Ziff, Edward B

2014-10-01

Neuronal activity regulates AMPA receptor trafficking, a process that mediates changes in synaptic strength, a key component of learning and memory. This form of plasticity may be induced by stimulation of the NMDA receptor which, among its activities, increases cyclic guanosine monophosphate (cGMP) through the nitric oxide synthase pathway. cGMP-dependent protein kinase type II (cGKII) is ultimately activated via this mechanism and AMPA receptor subunit GluA1 is phosphorylated at serine 845. This phosphorylation contributes to the delivery of GluA1 to the synapse, a step that increases synaptic strength. Previous studies have shown that cGKII-deficient mice display striking spatial learning deficits in the Morris Water Maze compared to wild-type littermates as well as lowered GluA1 phosphorylation in the postsynaptic density of the prefrontal cortex (Serulle et al., 2007; Wincott et al., 2013). In the current study, we show that cGKII knockout mice exhibit impaired working memory as determined using the prefrontal cortex-dependent Radial Arm Maze (RAM). Additionally, we report reduced repetitive behavior in the Marble Burying task (MB), and heightened anxiety-like traits in the Novelty Suppressed Feeding Test (NSFT). These data suggest that cGKII may play a role in the integration of information that conveys both anxiety-provoking stimuli as well as the spatial and environmental cues that facilitate functional memory processes and appropriate behavioral response. Published by Elsevier Inc.

A Study on improvement of environmental assessment system in social, economic, and environmental sectors

Energy Technology Data Exchange (ETDEWEB)

Nam, Young Sook; Koo, Doh Wan; Keum, Kee Yong [Korea Environment Institute, Seoul (Korea)

1998-12-01

The environmental assessment system is assessed as a mechanism that can achieve the goal for environmental policy in 21st century. As it can evaluate social and economic feasibility of large-scale development program, this system can achieve a sustainable society by mitigating social conflicts arising from environmental problems. For making the environmental assessment system substantial, this study was implemented by the need of improvement of the system, by analyzing problems of social, economic, and environmental evaluation, which is implemented under the present system. 44 refs., 1 fig., 25 tabs.

Preliminary environmental site assessments in New York City

International Nuclear Information System (INIS)

Lundy, P.; Gasson, D.R.; Longendyke, S.T.

1991-01-01

Preliminary Environmental Site Assessments are often performed prior to real estate transactions or refinancing. These assessments are typically performed for real estate buyers, sellers and lending institutions. Undertaking a Preliminary Environmental Site Assessment in New York City can often be quite complex and time-consuming. This is due, in part, to the age and density of buildings in the city as well as the myriad of regulatory agencies with jurisdiction over environmental issues. This paper will discuss how environmental assessments are performed with a special emphasis on building in New York City. In includes hazardous wastes management for Radon, PCB's and asbestos

The exopolysaccharide gene cluster Bcam1330-Bcam1341 is involved in Burkholderia cenocepacia biofilm formation, and its expression is regulated by c-di-GMP and Bcam1349

DEFF Research Database (Denmark)

Fazli, Mustafa; McCarthy, Yvonne; Givskov, Michael

2013-01-01

In Burkholderia cenocepacia, the second messenger cyclic diguanosine monophosphate (c-di-GMP) has previously been shown to positively regulate biofilm formation and the expression of cellulose and type-I fimbriae genes through binding to the transcriptional regulator Bcam1349. Here, we provide...... evidence that cellulose and type-I fimbriae are not involved in B. cenocepacia biofilm formation in flow chambers, and we identify a novel Bcam1349/c-di-GMP-regulated exopolysaccharide gene cluster which is essential for B. cenocepacia biofilm formation. Overproduction of Bcam1349 in trans promotes wrinkly...... matrix exopolysaccharide and to be essential for flow-chamber biofilm formation. We demonstrate that Bcam1349 binds to the promoter region of genes in the Bcam1330-Bcam1341 cluster and that this binding is enhanced by the presence of c-di-GMP. Furthermore, we demonstrate that overproduction of both c-di-GMP...

About ATMPs, SOPs and GMP: The Hurdles to Produce Novel Skin Grafts for Clinical Use.

Science.gov (United States)

Hartmann-Fritsch, Fabienne; Marino, Daniela; Reichmann, Ernst

2016-09-01

The treatment of severe full-thickness skin defects represents a significant and common clinical problem worldwide. A bio-engineered autologous skin substitute would significantly reduce the problems observed with today's gold standard. Within 15 years of research, the Tissue Biology Research Unit of the University Children's Hospital Zurich has developed autologous tissue-engineered skin grafts based on collagen type I hydrogels. Those products are considered as advanced therapy medicinal products (ATMPs) and are routinely produced for clinical trials in a clean room facility following the guidelines for good manufacturing practice (GMP). This article focuses on hurdles observed for the translation of ATMPs from research into the GMP environment and clinical application. Personalized medicine in the field of rare diseases has great potential. However, ATMPs are mainly developed and promoted by academia, hospitals, and small companies, which face many obstacles such as high financial burdens.

Environmental Impact Assessment and Space Activities

Science.gov (United States)

Viikari, L.

Environmental Impact Assessment (EIA) is a common tool for environment a l protection and management on Earth today, as prior assessment of the environmental consequences of planned activities. It is meant to provide the decision-makers with as comprehensive as possible information about the different environmental effects the proposed activity would entail, including alternative courses of action and the zero-alternative (i.e. the no action alternative). Additionally, plans for mitigation in respect of each alternative are to be outlined. The assessments take account of i.a. environmental impacts on ecosystems, diminution of aesthetic and scientific values, long-term or cumulative effects, as well as transfrontier implications. They also consider issues such as pollution control, environmental protection measures, reporting, post-project analysis, rehabilitation and so on. Also uncertainties in the assessment process are to be expressly presented. Most importantly, a common requirement also is that the results of the impact studies are presented in a way comprehensible to the g neral public,e too. Although the central aspect of the EIA is to provide the decision-makers with scientific information, the process also has other important implications. One of the most relevant of them is the involvement of those people potentially affected in some way by the proposed activity: most EIA systems require in some way the participation of the public, alongside with the relevant governmental authorities and other stake-holders. Such public involvement has various aims and goals: it may serve as a testimony to good governance in general, or be considered in more practical terms as improved planning, due to the concrete contribution of the public to the decision-making process. Obviously, it also is a tool for reducing conflict and developing wider support for the eventual decisions. In short, it enables the public to gain information about planned activities and influence

Development and validation of an LC-MS/MS method for quantification of cyclic guanosine 3',5'-monophosphate (cGMP) in clinical applications: a comparison with a EIA method.

Science.gov (United States)

Zhang, Yanhua; Dufield, Dawn; Klover, Jon; Li, Wenlin; Szekely-Klepser, Gabriella; Lepsy, Christopher; Sadagopan, Nalini

2009-02-15

An LC-MS/MS method was developed and validated to quantify endogenous cyclic guanosine 3',5'-monophosphate (cGMP) in human plasma. The LC-MS/MS and competitive enzyme immunoassay (EIA) assays were compared. cGMP concentrations of 20 human plasma samples were measured by both methods. For the MS-based assay, plasma samples were subjected to a simple protein precipitation procedure by acetonitrile prior to analysis by electrospray ionization LC-MS/MS. De-protonated analytes generated in negative ionization mode were monitored through multiple reaction monitoring (MRM). A stable isotope-labeled internal standard, (13)C(10),(15)N(5)-cGMP, which was biosynthesized in-house, was used in the LC-MS/MS method. The competitive EIA was validated using a commercially available cGMP fluorescence assay kit. The intra-assay accuracy and precision for MS-based assay for cGMP were 6-10.1% CV and -3.6% to 7.3% relative error (RE), respectively, while inter-assay precision and accuracy were 5.6-8.1% CV and -2.1% to 6.3% RE, respectively. The intra-assay accuracy and precision for EIA were 17.9-27.1% CV and -4.9% to 24.5% RE, respectively, while inter-assay precision and accuracy were 15.1-39.5% CV and -30.8% to 4.37% RE, respectively. Near the lower limits of detection, there was little correlation between the cGMP concentration values in human plasma generated by these two methods (R(2)=0.197, P=0.05). Overall, the MS-based assay offered better selectivity, recovery, precision and accuracy over a linear range of 0.5-20ng/mL. The LC-MS/MS method provides an effective tool for the quantitation of cGMP to support clinical mechanistic studies of curative pharmaceuticals.

Activation of a cGMP-sensitive calcium-dependent chloride channel may cause transition from calcium waves to whole-cell oscillations in smooth muscle cells

DEFF Research Database (Denmark)

Jacobsen, Jens Christian; Aalkjær, Christian; Nilsson, Holger

2007-01-01

waves sweeping through the cytoplasm when the SR is stimulated to release calcium. A rise in cyclic guanosine monophosphate (cGMP) leads to the experimentally observed transition from waves to whole-cell calcium oscillations. At the same time membrane potential starts to oscillate and the frequency...... approximately doubles. In this transition, the simulated results point to a key role for a recently discovered cGMP-sensitive calcium-dependent chloride channel. This channel depolarizes the membrane in response to calcium released from the SR. In turn, depolarization causes uniform opening of L-type calcium...... onset of oscillations in membrane potential within the individual cell may underlie sudden intercellular synchronization and the appearance of vasomotion. Key words: Vasomotion, Chloride channel, cGMP, Mathematical model, Calcium waves....

Isosorbide 5 mononitrate administration increases nitric oxide blood levels and reduces proteinuria in IgA glomerulonephritis patients with abnormal urinary endothelin/cyclic GMP ratio.

Science.gov (United States)

Roccatello, D; Mengozzi, G; Ferro, M; Cesano, G; Polloni, R; Mosso, R; Bonetti, G; Inconis, T; Paradisi, L; Sena, L M

1995-09-01

An endothelin urinary hyperexcretion, which is not counterbalanced by an adequate increase in cGMP biosynthesis, was previously detected in some patients with IgA Nephropathy (IgAN). Since this imbalance might potentiate local ET1-mediated hemodynamics effects, 9 IgAN patients with an increased (> or = 0.1) urinary ET1/cGMP ratio (group 1) and 5 IgAN patients with comparable renal function and reduced ET1/cGMP ratio (group 2) were given standard doses of isosorbide 5 mononitrate (as a nitric oxide source). Blood nitric oxide (NO) levels, as detected by electron paramagnetic resonance, significantly increased after isosorbide administration (p effective renal plasma flow (p counterbalancing effects of nitric oxide on endothelin-mediated mesangial contraction.

Predictions of models for environmental radiological assessment

International Nuclear Information System (INIS)

Peres, Sueli da Silva; Lauria, Dejanira da Costa; Mahler, Claudio Fernando

2011-01-01

In the field of environmental impact assessment, models are used for estimating source term, environmental dispersion and transfer of radionuclides, exposure pathway, radiation dose and the risk for human beings Although it is recognized that the specific information of local data are important to improve the quality of the dose assessment results, in fact obtaining it can be very difficult and expensive. Sources of uncertainties are numerous, among which we can cite: the subjectivity of modelers, exposure scenarios and pathways, used codes and general parameters. The various models available utilize different mathematical approaches with different complexities that can result in different predictions. Thus, for the same inputs different models can produce very different outputs. This paper presents briefly the main advances in the field of environmental radiological assessment that aim to improve the reliability of the models used in the assessment of environmental radiological impact. The intercomparison exercise of model supplied incompatible results for 137 Cs and 60 Co, enhancing the need for developing reference methodologies for environmental radiological assessment that allow to confront dose estimations in a common comparison base. The results of the intercomparison exercise are present briefly. (author)

36 CFR 220.7 - Environmental assessment and decision notice.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Environmental assessment and decision notice. 220.7 Section 220.7 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE NATIONAL ENVIRONMENTAL POLICY ACT (NEPA) COMPLIANCE § 220.7 Environmental assessment and decision notice. (a) Environmental assessment...

Islet isolation and GMP, ISO 9001:2000: what do we need--a 3-year experience.

Science.gov (United States)

Hengster, P; Hermann, M; Pirkebner, D; Draxl, A; Margreiter, R

2005-10-01

Pancreatic islet cell isolation and transplantation has been performed for many years at several institutions. Although all institutions aim to produce high-quality islets, applied standards widely deviate from standards in the pharmaceutical industry. The legal situation within the European Union has changed requirements for setting up and running such a laboratory. The process is now clearly defined as a production of a pharmaceutical and therefore must be licensed by federal authorities. Analysis of workload for establishing an islet isolation program that fulfil GMP and ISO 9001 criteria including an estimation of costs and the impact of such a system on the isolation process. The definition of quality parameters and documentation is a central issue of all islet isolation laboratories. Therefore, GMP and ISO 9001:2000 do not add additional work per se. On the other hand, clear guidelines, a clear policy, working place descriptions, forms, checklists, and, particularly standard operating procedures, are instrumental for smooth functioning within the department. Collection of data such as errors, improvement measures, and preventive measures reduces subsequent costs. A clear definition of responsibilities minimizes organizational problems. Steering of inspection devices prevents bias errors and validating the processes clearly points out incorrect assumptions. Documentation helps to prove the correctness of the production at any time and is of use also for scientific evaluations. We strongly feel that GMP criteria are mandatory and together with an ISO 9001:2000 quality management system offers significant advantages for the process of islet isolation and a continuous improvement process.

Integrated Environmental Assessment Part III: ExposureAssessment

Energy Technology Data Exchange (ETDEWEB)

McKone, Thomas E.; Small, Mitchell J.

2006-06-01

Human exposure assessment is a key step in estimating the environmental and public health burdens that result chemical emissions in the life cycle of an industrial product or service. This column presents the third in a series of overviews of the state of the art in integrated environmental assessment - earlier columns described emissions estimation (Frey and Small, 2003) and fate and transport modeling (Ramaswami, et al., 2004). When combined, these first two assessment elements provide estimates of ambient concentrations in the environment. Here we discuss how both models and measurements are used to translate ambient concentrations into metrics of human and ecological exposure, the necessary precursors to impact assessment. Exposure assessment is the process of measuring and/or modeling the magnitude, frequency and duration of contact between a potentially harmful agent and a target population, including the size and characteristics of that population (IPCS, 2001; Zartarian, et al., 2005). Ideally the exposure assessment process should characterize the sources, routes, pathways, and uncertainties in the assessment. Route of exposure refers to the way that an agent enters the receptor during an exposure event. Humans contact pollutants through three routes--inhalation, ingestion, and dermal uptake. Inhalation occurs in both outdoor environments and indoor environments where most people spend the majority of their time. Ingestion includes both water and food, as well as soil and dust uptake due to hand-to-mouth activity. Dermal uptake occurs through contacts with consumer products; indoor and outdoor surfaces; the water supply during washing or bathing; ambient surface waters during swimming or boating; soil during activities such as work, gardening, and play; and, to a lesser extent, from the air that surrounds us. An exposure pathway is the course that a pollutant takes from an ambient environmental medium (air, soil, water, biota, etc), to an exposure medium

76 FR 44891 - Monsanto Co.; Availability of Petition, Plant Pest Risk Assessment, and Environmental Assessment...

Science.gov (United States)

2011-07-27

...] Monsanto Co.; Availability of Petition, Plant Pest Risk Assessment, and Environmental Assessment for... Monsanto petition, our plant pest risk assessment, and our draft environmental assessment for the proposed...-2817 before coming. The petition, draft environmental assessment, and plant pest risk assessment are...

Theory and Practice of Transboundary Environmental Impact Assessment

NARCIS (Netherlands)

Bastmeijer, C.J.; Koivurova, T.

2008-01-01

Environmental Impact Assessment (EIA) is a well-established instrument of environmental law and policy that aims to ensure that potential adverse environmental effects of human activities are assessed before decisions on such activities are made. The instrument is increasingly being applied in

GMP and AMP as methyl radical traps in the reaction with pentaamminemethylcobalt(III)

DEFF Research Database (Denmark)

Kofod, Pauli

2004-01-01

as the PBN/13??H3 adduct (PBN = phenyl-N-tert-butylnitrone). When the purine nucleotide was used in large excess, the efficiency of the trapping by the C8 atom was determined by integration of the 13C NMR signals to be 20-25% for GMP and 15-20% for AMP, respectively, at 37??C. ?? 2004 Elsevier Inc. All...

Comparative study for environmental assessment by program characters

Energy Technology Data Exchange (ETDEWEB)

Kim, Suk Chul; Lee, Young Soo; Park, Young Min; Park, Suk Soon; Chung, Kyung Tae; Cho, Hong Yun; Chae, Jang Won; Lee, Sang Don; Lee, Chan Ho; Choi, Joon Kyu; Kim, Kang Joo; Chung, Won Moo; Jin, Jae Yool [Korea Environment Institute, Seoul (Korea)

1998-12-01

The level of environmental assessment in Korea was diagnosed by examining the situation of its model for the entire environmental assessment implemented. Also, it proposed an improvement scheme for its problems to be able to advance. It is expected to be utilized as developing optimum model for Korea and establishing a systematic and concrete guideline for environmental assessment modeling. 244 refs., 65 figs., 28 tabs.

The EAL domain protein YciR acts as a trigger enzyme in a c-di-GMP signalling cascade in E. coli biofilm control

Science.gov (United States)

Lindenberg, Sandra; Klauck, Gisela; Pesavento, Christina; Klauck, Eberhard; Hengge, Regine

2013-01-01

C-di-GMP—which is produced by diguanylate cyclases (DGC) and degraded by specific phosphodiesterases (PDEs)—is a ubiquitous second messenger in bacterial biofilm formation. In Escherichia coli, several DGCs (YegE, YdaM) and PDEs (YhjH, YciR) and the MerR-like transcription factor MlrA regulate the transcription of csgD, which encodes a biofilm regulator essential for producing amyloid curli fibres of the biofilm matrix. Here, we demonstrate that this system operates as a signalling cascade, in which c-di-GMP controlled by the DGC/PDE pair YegE/YhjH (module I) regulates the activity of the YdaM/YciR pair (module II). Via multiple direct interactions, the two module II proteins form a signalling complex with MlrA. YciR acts as a connector between modules I and II and functions as a trigger enzyme: its direct inhibition of the DGC YdaM is relieved when it binds and degrades c-di-GMP generated by module I. As a consequence, YdaM then generates c-di-GMP and—by direct and specific interaction—activates MlrA to stimulate csgD transcription. Trigger enzymes may represent a general principle in local c-di-GMP signalling. PMID:23708798

Procedures development and methodology of control for application of good manufacture practices (GMP) on human blood irradiation

International Nuclear Information System (INIS)

Boghi, Claudio

2008-01-01

The irradiation of human blood is used to avoid the TA-GVHD (transfusion-associated graft-versus-host-disease), a rare but devastating adverse effect of leukocytes present in blood components for a immunocompetent transfusion recipients. Usually this irradiation practice is performed to a physical elimination of leukocytes. The implementation of the procedures will assure that the properly dose in a range of 25 Gy to 50 Gy will be delivered to the blood in the bag collected in a blood tissue bank. The studies of the procedures in order to establish a GMP (Good Manufacturing Practices) were developed under the guidelines of the standard ISO 11137 - Sterilization of health care products - Requirements for validation and routine control - Radiation sterilization. In this work, two dosimetric systems were used for dose mapping during the studies of irradiator qualification, loading pattern, irradiation process validation and auditing. The CaS0 4 :Dy dosimeter presented difficulties concerning to uncertainty on dose measurement, stability, traceability and calibration. The PMMA and Gafchromic dosimetric systems have shown a better performance and were adopted on studies of irradiators qualification that are necessary to implementation of GMP. The irradiation tests have been done in a Gammacell 220 irradiator. The developed procedures can be adapted for different kinds of gamma irradiators, allowing implanting a quality assurance program and a GMP for blood irradiation. (author)

Environmental Tools and Radiological Assessment

Science.gov (United States)

This presentation details two tools (SADA and FRAMES) available for use in environmental assessments of chemicals that can also be used for radiological assessments of the environment. Spatial Analysis and Decision Assistance (SADA) is a Windows freeware program that incorporate...

cGMP-dependent protein kinase I, the circadian clock, sleep and learning.

Science.gov (United States)

Feil, Robert; Hölter, Sabine M; Weindl, Karin; Wurst, Wolfgang; Langmesser, Sonja; Gerling, Andrea; Feil, Susanne; Albrecht, Urs

2009-07-01

The second messenger cGMP controls cardiovascular and gastrointestinal homeostasis in mammals. However, its physiological relevance in the nervous system is poorly understood.1 Now, we have reported that the cGMP-dependent protein kinase type I (PRKG1) is implicated in the regulation of the timing and quality of sleep and wakefulness.2Prkg1 mutant mice showed altered distribution of sleep and wakefulness as well as reduction in rapid-eye-movement sleep (REMS) duration and in non-REMS consolidation. Furthermore, the ability to sustain waking episodes was compromised. These observations were also reflected in wheel-running and drinking activity. A decrease in electroencephalogram power in the delta frequency range (1-4 Hz) under baseline conditions was observed, which was normalized after sleep deprivation. Together with the finding that circadian clock amplitude is reduced in Prkg1 mutants these results indicate a decrease of the wake-promoting output of the circadian system affecting sleep. Because quality of sleep might affect learning we tested Prkg1 mutants in several learning tasks and find normal spatial learning but impaired object recognition memory in these animals. Our findings indicate that Prkg1 impinges on circadian rhythms, sleep and distinct aspects of learning.

Relation of Environmental Impact Assessment (EIA and Strategic Environmental Assessment (SEA and the Importance of Strategic Environmental Assessment in Landscape Planning Process

Directory of Open Access Journals (Sweden)

Gizem CENGİZ GÖKÇE

2015-07-01

Full Text Available The main goal in the countries which have not completed their development progress is industrialization and development just as soon as possible. Therefore, negative effects of industrialization and development on envi ronment and/or nature cannot be mostly discussed adequately. One of the planning approach instruments that targets sustainability, Environmental Impact Assessment (EIA is used in many countries effectively. But in recent years, that has understood; EIA is an impact assessment instrument that contains defensive preventions only on the basis of projects and this situation has caused some concerns against EIA. In this direction, Strategical Environmental Assessment (SEA exists as the final point of the instruments which are formed to provide sustainable development . In this study; the importance and the requirement of effectively taking a role of landscape architectures that have ecological based job, in the SEA workings which isn’t have got a legal status in Turkey yet, are emphasized by reviewing the relations between EIA and SEA concepts.

Immunohistochemical distribution of cAMP- and cGMP-phosphodiesterase (PDE) isoenzymes in the human prostate

NARCIS (Netherlands)

Uckert, Stefan; Oelke, Matthias; Stief, Christian G.; Andersson, K.-E.; Jonas, Udo; Hedlund, Petter

2006-01-01

With the introduction of sildenafil citrate (Viagra), the concept of phosphodiesterase (PDE) inhibition has gained tremendous interest in the field of urology. Cyclic nucleotide second messengers cGMP and cAMP have been assumed to be involved in the control of the normal function of the prostate.

A novel crosstalk between Alk7 and cGMP signaling differentially regulates brown adipocyte function

Directory of Open Access Journals (Sweden)

Aileen Balkow

2015-08-01

Conclusions: We found a so far unknown crosstalk between cGMP and Alk7 signaling pathways. Tight regulation of Alk7 is required for efficient differentiation of brown adipocytes. Alk7 has differential effects on adipogenic differentiation and the development of the thermogenic program in brown adipocytes.

Integrated environmental and economic assessment of waste management systems

DEFF Research Database (Denmark)

Martinez Sanchez, Veronica

in the “Optimization approach” the scenarios are the results of an optimization process. • The cost approach describes cost principles and level of LCA integration. Conventional and Environmental LCCs are financial assessments, i.e. include marketed goods/services, but while Environmental LCCs include environmental...... assessment of SWM systems alongside environmental impacts assessment to take budget constrains into account. In light of the need for combined environmental and economic assessment of SWM, this PhD thesis developed a consistent and comprehensive method for integrated environmental and economic assessment...... of SWM technologies and systems. The method resulted from developing further the generic Life Cycle Costing (LCC) framework suggested by Hunkeler et al. (2008) and Swarr et al. (2011) to apply it on the field of SWM. The method developed includes: two modelling approaches (Accounting and Optimization...

Building better environmental risk assessments

Directory of Open Access Journals (Sweden)

Raymond eLayton

2015-08-01

Full Text Available Risk assessment is a reasoned, structured approach to address uncertainty based on scientific and technical evidence. It forms the foundation for regulatory decision making, which is bound by legislative and policy requirements, as well as the need for making timely decisions using available resources. In order to be most useful, environmental risk assessments (ERA for genetically modified (GM crops should provide consistent, reliable, and transparent results across all types of GM crops, traits, and environments. The assessments must also separate essential information from scientific or agronomic data of marginal relevance or value for evaluating risk and complete the assessment in a timely fashion. Challenges in conducting ERAs differ across regulatory systems – examples are presented from Canada, Malaysia, and Argentina. One challenge faced across the globe is the conduct of risk assessments with limited resources. This challenge can be overcome by clarifying risk concepts, placing greater emphasis on data critical to assess environmental risk (for example, phenotypic and plant performance data rather than molecular data, and adapting advances in risk analysis from other relevant disciplines.

Building Better Environmental Risk Assessments

Science.gov (United States)

Layton, Raymond; Smith, Joe; Macdonald, Phil; Letchumanan, Ramatha; Keese, Paul; Lema, Martin

2015-01-01

Risk assessment is a reasoned, structured approach to address uncertainty based on scientific and technical evidence. It forms the foundation for regulatory decision-making, which is bound by legislative and policy requirements, as well as the need for making timely decisions using available resources. In order to be most useful, environmental risk assessments (ERAs) for genetically modified (GM) crops should provide consistent, reliable, and transparent results across all types of GM crops, traits, and environments. The assessments must also separate essential information from scientific or agronomic data of marginal relevance or value for evaluating risk and complete the assessment in a timely fashion. Challenges in conducting ERAs differ across regulatory systems – examples are presented from Canada, Malaysia, and Argentina. One challenge faced across the globe is the conduct of risk assessments with limited resources. This challenge can be overcome by clarifying risk concepts, placing greater emphasis on data critical to assess environmental risk (for example, phenotypic and plant performance data rather than molecular data), and adapting advances in risk analysis from other relevant disciplines. PMID:26301217

Building Better Environmental Risk Assessments.

Science.gov (United States)

Layton, Raymond; Smith, Joe; Macdonald, Phil; Letchumanan, Ramatha; Keese, Paul; Lema, Martin

2015-01-01

Risk assessment is a reasoned, structured approach to address uncertainty based on scientific and technical evidence. It forms the foundation for regulatory decision-making, which is bound by legislative and policy requirements, as well as the need for making timely decisions using available resources. In order to be most useful, environmental risk assessments (ERAs) for genetically modified (GM) crops should provide consistent, reliable, and transparent results across all types of GM crops, traits, and environments. The assessments must also separate essential information from scientific or agronomic data of marginal relevance or value for evaluating risk and complete the assessment in a timely fashion. Challenges in conducting ERAs differ across regulatory systems - examples are presented from Canada, Malaysia, and Argentina. One challenge faced across the globe is the conduct of risk assessments with limited resources. This challenge can be overcome by clarifying risk concepts, placing greater emphasis on data critical to assess environmental risk (for example, phenotypic and plant performance data rather than molecular data), and adapting advances in risk analysis from other relevant disciplines.

Discussion of some issues in assessing nuclear and radiation environmental impacts and in related assessment

International Nuclear Information System (INIS)

Pan Ziqiang

1998-01-01

The author discusses some noticeable issues in drafting assessment report of nuclear and radiation environmental impacts and relevant aspects needed to be considered from the point of view of comprehensive environmental assessment. The considerable issue are principles of radioactive waste management, optimization of radiation protection and collective dose, and uncertainty of the assessment. Implementing reporting system on assessment of nuclear and radiation environmental impacts would improve environmental protection for nuclear and radiation facilities. However, trade's, regional , country and global assessment of environmental impacts has to be enhanced. For this purpose, it is necessary to develop methodology of qualitative and quantitative comprehensive assessment

Environmental assessment of wood domestic heating. Synthetic report

International Nuclear Information System (INIS)

2005-12-01

This report proposes a synthesis of the results of an environmental assessment of wood domestic heating. This study is based on a life cycle analysis which quantifies the impacts on the environment of all the related activities: fuel extraction, retailing, final use, and so on. Environmental impacts are assessed by means of different indicators: energetic assessment, greenhouse effect assessment, air pollution (acidification), water pollution (eutrophication), toxic material emissions in air and into the soils. Wood is compared to other heating sources (gas, fuel, electricity). Ways to improve this environmental assessment are discussed for the different types of wood (logs, pellets)

Environmental risk assessment system for phosphogypsum tailing dams.

Science.gov (United States)

Sun, Xin; Ning, Ping; Tang, Xiaolong; Yi, Honghong; Li, Kai; Zhou, Lianbi; Xu, Xianmang

2013-01-01

This paper may be of particular interest to the readers as it provides a new environmental risk assessment system for phosphogypsum tailing dams. In this paper, we studied the phosphogypsum tailing dams which include characteristics of the pollution source, environmental risk characteristics and evaluation requirements to identify the applicable environmental risk assessment methods. Two analytical methods, that is, the analytic hierarchy process (AHP) and fuzzy logic, were used to handle the complexity of the environmental and nonquantitative data. Using our assessment method, different risk factors can be ranked according to their contributions to the environmental risk, thereby allowing the calculation of their relative priorities during decision making. Thus, environmental decision-makers can use this approach to develop alternative management strategies for proposed, ongoing, and completed PG tailing dams.

Ecological risk assessment as a framework for environmental impact assessments

CSIR Research Space (South Africa)

Claassen, Marius

1999-01-01

Full Text Available Environmental impact assessments in South Africa are usually conducted according to the integrated environmental management (IEM) procedure. The preliminary investigation reported here, indicated that most of the ecological requirements specified...

A potent series targeting the malarial cGMP-dependent protein kinase clears infection and blocks transmission

NARCIS (Netherlands)

Baker, D.A.; Stewart, L.B.; Large, J.M.; Bowyer, P.W.; Ansell, K.H.; Jimenez-Diaz, M.B.; Bakkouri, M. El; Birchall, K.; Dechering, K.J.; Bouloc, N.S.; Coombs, P.J.; Whalley, D.; Harding, D.J.; Smiljanic-Hurley, E.; Wheldon, M.C.; Walker, E.M.; Dessens, J.T.; Lafuente, M.J.; Sanz, L.M.; Gamo, F.J.; Ferrer, S.B.; Hui, R.; Bousema, T.; Angulo-Barturen, I.; Merritt, A.T.; Croft, S.L.; Gutteridge, W.E.; Kettleborough, C.A.; Osborne, S.A.

2017-01-01

To combat drug resistance, new chemical entities are urgently required for use in next generation anti-malarial combinations. We report here the results of a medicinal chemistry programme focused on an imidazopyridine series targeting the Plasmodium falciparum cyclic GMP-dependent protein kinase

Ca 2+ signaling by plant Arabidopsis thaliana Pep peptides depends on AtPepR1, a receptor with guanylyl cyclase activity, and cGMP-activated Ca 2+ channels

KAUST Repository

Qia, Zhi; Verma, Rajeev K.; Gehring, Christoph A; Yamaguchi, Yube; Zhao, Yichen; Ryan, Clarence A.; Berkowitz, Gerald A.

2010-01-01

receptor- like kinase receptor AtPepR1 has guanylyl cyclase activity, generating cGMP from GTP, and that cGMP can activate CNGC2- dependent cytosolic Ca 2+ elevation. AtPep-dependent expression of pathogen-defense genes (PDF1.2, MPK3, and WRKY33

75 FR 78994 - Notice of Intent To Prepare an Environmental Assessment, Request for Comments on Environmental...

Science.gov (United States)

2010-12-17

... Prepare an Environmental Assessment, Request for Comments on Environmental Issues, and Notice of Public...: Notice of intent to prepare an Environmental Assessment, request for comments on Environmental Issues... and/or special expertise with respect to environmental issues to formally cooperate with GSA in the...

Environmental impact assessment in the Nordic Countries

International Nuclear Information System (INIS)

Broden, K.; Palsson, S.E.; Poroddsson, P.

2000-12-01

A meeting on Environmental Impact Assessment has been held in Iceland, September 2-6, 2000. It was held within the framework of the project NKS/SOS-3 (Radioactive waste), subproject NKS/SOS-3.1 (Environmental Impact Assessment). The meeting included presentations, discussions and a study trip to the Egilsstadir and Myvatn districts. (au)

Road ecology in environmental impact assessment

International Nuclear Information System (INIS)

Karlson, Mårten; Mörtberg, Ulla; Balfors, Berit

2014-01-01

Transport infrastructure has a wide array of effects on terrestrial and aquatic ecosystems, and road and railway networks are increasingly being associated with a loss of biodiversity worldwide. Environmental Impact Assessment (EIA) and Strategic Environmental Assessment (SEA) are two legal frameworks that concern physical planning, with the potential to identify, predict, mitigate and/or compensate transport infrastructure effects with negative impacts on biodiversity. The aim of this study was to review the treatment of ecological impacts in environmental assessment of transport infrastructure plans and projects. A literature review on the topic of EIA, SEA, biodiversity and transport infrastructure was conducted, and 17 problem categories on the treatment of biodiversity were formulated by means of a content analysis. A review of environmental impact statements and environmental reports (EIS/ER) produced between 2005 and 2013 in Sweden and the UK was then conducted using the list of problems as a checklist. The results show that the treatment of ecological impacts has improved substantially over the years, but that some impacts remain problematic; the treatment of fragmentation, the absence of quantitative analysis and that the impact assessment study area was in general delimited without consideration for the scales of ecological processes. Actions to improve the treatment of ecological impacts could include improved guidelines for spatial and temporal delimitation, and the establishment of a quantitative framework including tools, methods and threshold values. Additionally, capacity building and further method development of EIA and SEA friendly spatial ecological models can aid in clarifying the costs as well as the benefits in development/biodiversity tradeoffs. - Highlights: • The treatment of ecological impacts in EIA and SEA has improved. • Quantitative methods for ecological impact assessment were rarely used • Fragmentation effects were recognized

Road ecology in environmental impact assessment

Energy Technology Data Exchange (ETDEWEB)

Karlson, Mårten, E-mail: mkarlso@kth.se; Mörtberg, Ulla, E-mail: mortberg@kth.se; Balfors, Berit, E-mail: balfors@kth.se

2014-09-15

Transport infrastructure has a wide array of effects on terrestrial and aquatic ecosystems, and road and railway networks are increasingly being associated with a loss of biodiversity worldwide. Environmental Impact Assessment (EIA) and Strategic Environmental Assessment (SEA) are two legal frameworks that concern physical planning, with the potential to identify, predict, mitigate and/or compensate transport infrastructure effects with negative impacts on biodiversity. The aim of this study was to review the treatment of ecological impacts in environmental assessment of transport infrastructure plans and projects. A literature review on the topic of EIA, SEA, biodiversity and transport infrastructure was conducted, and 17 problem categories on the treatment of biodiversity were formulated by means of a content analysis. A review of environmental impact statements and environmental reports (EIS/ER) produced between 2005 and 2013 in Sweden and the UK was then conducted using the list of problems as a checklist. The results show that the treatment of ecological impacts has improved substantially over the years, but that some impacts remain problematic; the treatment of fragmentation, the absence of quantitative analysis and that the impact assessment study area was in general delimited without consideration for the scales of ecological processes. Actions to improve the treatment of ecological impacts could include improved guidelines for spatial and temporal delimitation, and the establishment of a quantitative framework including tools, methods and threshold values. Additionally, capacity building and further method development of EIA and SEA friendly spatial ecological models can aid in clarifying the costs as well as the benefits in development/biodiversity tradeoffs. - Highlights: • The treatment of ecological impacts in EIA and SEA has improved. • Quantitative methods for ecological impact assessment were rarely used • Fragmentation effects were recognized

Activation and polar sequestration of PopA, a c-di-GMP effector protein involved in Caulobacter crescentus cell cycle control

DEFF Research Database (Denmark)

Ozaki, Shogo; Schalch-Moser, Annina; Zumthor, Ludwig

2014-01-01

that PopA originated through gene duplication from its paralogue response regulator PleD and subsequent co-option as c-di-GMP effector protein. While the C-terminal catalytic domain (GGDEF) of PleD is activated by phosphorylation of the N-terminal receiver domain, functional adaptation has reversed signal......A to the cell pole in response to c-di-GMP binding. In agreement with the divergent activation and targeting mechanisms, distinct markers sequester PleD and PopA to the old cell pole upon S-phase entry. Together these data indicate that PopA adopted a novel role as topology specificity factor to help recruit...

Technology needs assessment for DOE environmental restoration programs

International Nuclear Information System (INIS)

Duray, J.R.; Carlson, T.J.; Carpenter, C.E.; Cummins, L.E.; Daub, G.J.

1992-01-01

The 'Technology Needs Assessment Final Report' describes current and planned environmental restoration activity, identifies technologies intended to be used or under consideration, and ranks technology deficiencies in the U.S. Department of Energy's environmental restoration program. Included in the ranking are treatment technologies, characterization technologies, and non-technology issues that affect environmental restoration. Data used for the assessment was gathered during interviews in the spring of 1991 with DOE site personnel responsible for the environmental restoration work. (author)

Environmental assessment of incinerator residue utilisation

OpenAIRE

Toller, Susanna; Kärrman, Erik; Gustafsson, Jon Petter; Magnusson, Y.

2009-01-01

Incineration ashes may be treated either as a waste to be dumped in landfill, or as a resource that is suit able for re-use. In order to choose the best management scenario, knowledge is needed on the potential environmental impact that may be expected, including not only local, but also regional and global impact. In this study. A life cycle assessment (LCA) based approach Was Outlined for environmental assessment of incinerator residue utilisation, in which leaching of trace elements as wel...

Environmental Safety and Health Analytical Laboratory, Pantex Plant, Amarillo, Texas. Final Environmental Assessment

International Nuclear Information System (INIS)

1995-06-01

The US Department of Energy (DOE) has prepared an Environmental Assessment (EA) of the construction and operation of an Environmental Safety and Health (ES ampersand H) Analytical Laboratory and subsequent demolition of the existing Analytical Chemistry Laboratory building at Pantex Plant near Amarillo, Texas. In accordance with the Council on Environmental Quality requirements contained in 40 CFR 1500--1508.9, the Environmental Assessment examined the environmental impacts of the Proposed Action and discussed potential alternatives. Based on the analysis of impacts in the EA, conducting the proposed action, construction of an analytical laboratory and demolition of the existing facility, would not significantly effect the quality of the human environment within the meaning of the National Environmental Policy Act of 1969 (NEPA) and the Council on Environmental Quality regulations in 40 CFR 1508.18 and 1508.27

Radiological assessments, environmental monitoring, and study design

International Nuclear Information System (INIS)

Hansen, W.R.; Elle, D.R.

1980-01-01

Studies of the behavior of transuranic elements in the environment form the basic data for applied programs in radiological assessment, environmental monitoring, derivation of radiation-protection standards, and environmental impact statements. This chapter introduces some of the major information requirements of these applications of transuranic research data. Characteristics of the source terms from nuclear activities usually are needed for an analysis of environmental pathways or deployment of monitoring systems. Major inhalation and ingestion pathways are considered in assessments of hazards from transuranics and are discussed from the viewpoint of research needed

Environmental Management Assessment of the Stanford Linear Accelerator Center

International Nuclear Information System (INIS)

1994-01-01

This report documents the results of the Environmental Management Assessment of the Stanford Linear Accelerator Center (SLAC), Menlo Park, California. During this assessment, the activities conducted by the assessment team included reviews of internal documents and reports from previous assessments; interviews with the US Department of Energy (DOE), US Environmental Protection Agency, State Water Resources Board, California Regional Water Quality Control Board, and SLAC contractor personnel; and inspections and observations of selected facilities and operations. Onsite portion of the assessment was conducted from January 18 through January 31, 1994, by the DOE Office of Environmental Audit (EH-24), located within the Office of Environment, Safety and Health (EH), and the Environment and Safety Support Division (ESS), located within the Oakland Operations Office (OAK). The EH-24 environmental management assessment and the OAK functional appraisal were combined to minimize disruptions to the site. The management disciplines and three technical areas (air quality, groundwater, and inactive waste sites) were evaluated by EH-24, and four other technical areas (surface water, waste management, toxic and chemical materials, and environmental radiation) were assessed by ESS

Environmental economic impact assessment in China: Problems and prospects

International Nuclear Information System (INIS)

Lindhjem, Henrik; Hu Tao; Ma Zhong; Skjelvik, John Magne; Song Guojun; Vennemo, Haakon; Wu Jian; Zhang Shiqiu

2007-01-01

The use of economic valuation methods to assess environmental impacts of projects and policies has grown considerably in recent years. However, environmental valuation appears to have developed independently of regulations and practice of environmental impact assessment (EIA), despite its potential benefits to the EIA process. Environmental valuation may be useful in judging significance of impacts, determining mitigation level, comparing alternatives and generally enabling a more objective analysis of tradeoffs. In China, laws and regulations require the use of environmental valuation in EIA, but current practice lags far behind. This paper assesses the problems and prospects of introducing environmental valuation into the EIA process in China. We conduct four case studies of environmental economic impact assessment (EEIA), three of which are based on environmental impact statements of construction projects (a power plant, a wastewater treatment plant and a road construction project) and one for a regional pollution problem (wastewater irrigation). The paper demonstrates the potential usefulness of environmental valuation but also discusses several challenges to the introduction and wider use of EEIA, many of which are likely to be of relevance far beyond the Chinese context. The paper closes with suggesting some initial core elements of an EEIA guideline

Federal environmental assessment panel process

International Nuclear Information System (INIS)

Edwards, R.A.; King, J.M.

1996-01-01

The Government of Canada inaugurated an environmental assessment process in 1973. Since that time, the Department of Natural Resources, or its predecessor, the Department of Energy Mines and Resources, and industrial clients of the Department, have been major participants in the process. In 1995, the authors interviewed representatives of a number of client industries and selected individuals, to ask their opinion of the public hearing part of the environmental assessment process, with the objective of identifying shortcomings and proposing improvements. Respondents criticized the hearings as costly, time-wasting, bureaucratic, and uncertain in cost, time, and outcome. A number of observations on noted areas of shortcoming are presented in this paper, with suggestions for improvement

Federal environmental assessment panel process

Energy Technology Data Exchange (ETDEWEB)

Edwards, R A; King, J M [Natural Resources Canada, Ottawa, ON (Canada)

1997-12-31

The Government of Canada inaugurated an environmental assessment process in 1973. Since that time, the Department of Natural Resources, or its predecessor, the Department of Energy Mines and Resources, and industrial clients of the Department, have been major participants in the process. In 1995, the authors interviewed representatives of a number of client industries and selected individuals, to ask their opinion of the public hearing part of the environmental assessment process, with the objective of identifying shortcomings and proposing improvements. Respondents criticized the hearings as costly, time-wasting, bureaucratic, and uncertain in cost, time, and outcome. A number of observations on noted areas of shortcoming are presented in this paper, with suggestions for improvement.

Power and environmental assessment

DEFF Research Database (Denmark)

Cashmore, Matthew Asa; Richardson, Tim

2013-01-01

The significance of politics and power dynamics has long been recognised in environmental assessment (EA) research, but there has not been sustained attention to power, either theoretically or empirically. The aim of this special issue is to encourage the EA community to engage more consistently...

Environmental assessment of incinerator residue utilisation

OpenAIRE

Toller, Susanna

2008-01-01

 In Sweden, utilisation of incinerator residues outside disposal areas is restricted by environmental concerns, as such residues commonly contain greater amounts of potentially toxic trace elements than the natural materials they replace. On the other hand, utilisation can also provide environmental benefits by decreasing the need for landfill and reducing raw material extraction. This thesis provides increased knowledge and proposes better approaches for environmental assessment of incinerat...

Role of cyclic di-GMP in Xylella fastidiosa biofilm formation, plant virulence, and insect transmission.

Science.gov (United States)

Chatterjee, Subhadeep; Killiny, Nabil; Almeida, Rodrigo P P; Lindow, Steven E

2010-10-01

Xylella fastidiosa must coordinately regulate a variety of traits contributing to biofilm formation, host plant and vector colonization, and transmission between plants. Traits such as production of extracellular polysaccharides (EPS), adhesins, extracellular enzymes, and pili are expressed in a cell-density-dependent fashion mediated by a cell-to-cell signaling system involving a fatty acid diffusible signaling factor (DSF). The expression of gene PD0279 (which has a GGDEF domain) is downregulated in the presence of DSF and may be involved in intracellular signaling by modulating the levels of cyclic di-GMP. PD0279, designated cyclic di-GMP synthase A (cgsA), is required for biofilm formation, plant virulence, and vector transmission. cgsA mutants exhibited a hyperadhesive phenotype in vitro and overexpressed gumJ, hxfA, hxfB, xadA, and fimA, which promote attachment of cells to surfaces and, hence, biofilm formation. The mutants were greatly reduced in virulence to grape albeit still transmissible by insect vectors, although at a reduced level compared with transmission rates of the wild-type strain, despite the fact that similar numbers of cells of the cgsA mutant were acquired by the insects from infected plants. High levels of EPS were measured in cgsA mutants compared with wild-type strains, and scanning electron microscopy analysis also revealed a thicker amorphous layer surrounding the mutants. Overexpression of cgsA in a cgsA-complemented mutant conferred the opposite phenotypes in vitro. These results suggest that decreases of cyclic di-GMP result from the accumulation of DSF as cell density increases, leading to a phenotypic transition from a planktonic state capable of colonizing host plants to an adhesive state that is insect transmissible.

Applicable international environmental impact assessment laws for ...

African Journals Online (AJOL)

Lawrence Hart

1971-05-28

May 28, 1971 ... appraise selected International Environmental laws and the Nigerian Environmental Impact Assessment methodology ... maze of pipelines, delivery lines, flow lines, canals and .... Toxic Materials and international waterways.

Environmental Risk Assessment System for Phosphogypsum Tailing Dams

OpenAIRE

Xin Sun; Ping Ning; Xiaolong Tang; Honghong Yi; Kai Li; Lianbi Zhou; Xianmang Xu

2013-01-01

This paper may be of particular interest to the readers as it provides a new environmental risk assessment system for phosphogypsum tailing dams. In this paper, we studied the phosphogypsum tailing dams which include characteristics of the pollution source, environmental risk characteristics and evaluation requirements to identify the applicable environmental risk assessment methods. Two analytical methods, that is, the analytic hierarchy process (AHP) and fuzzy logic, were used to handle the...

PPARα autocrine regulation of Ca²⁺-regulated exocytosis in guinea pig antral mucous cells: NO and cGMP accumulation.

Science.gov (United States)

Tanaka, Saori; Sugiyama, Nanae; Takahashi, Yuko; Mantoku, Daiki; Sawabe, Yukinori; Kuwabara, Hiroko; Nakano, Takashi; Shimamoto, Chikao; Matsumura, Hitoshi; Marunaka, Yoshinori; Nakahari, Takashi

2014-12-15

In antral mucous cells, acetylcholine (ACh, 1 μM) activates Ca(2+)-regulated exocytosis, consisting of a peak in exocytotic events that declines rapidly (initial phase) followed by a second slower decline (late phase) lasting during ACh stimulation. GW7647 [a peroxisome proliferation activation receptor α (PPARα) agonist] enhanced the ACh-stimulated initial phase, and GW6471 (a PPARα antagonist) abolished the GW7647-induced enhancement. However, GW6471 produced the delayed, but transient, increase in the ACh-stimulated late phase, and it also decreased the initial phase and produced the delayed increase in the late phase during stimulation with ACh alone. A similar delayed increase in the ACh-stimulated late phase is induced by an inhibitor of the PKG, Rp8BrPETcGMPS, suggesting that GW6471 inhibits cGMP accumulation. An inhibitor of nitric oxide synthase 1 (NOS1), N(5)-[imino(propylamino)methyl]-L-ornithine hydrochloride (N-PLA), also abolished the GW7647-induced-enhancement of ACh-stimulated initial phase but produced the delayed increase in the late phase. However, in the presence of N-PLA, an NO donor or 8BrcGMP enhanced the ACh-stimulated initial phase and abolished the delayed increase in the late phase. Moreover, GW7647 and ACh stimulated NO production and cGMP accumulation in antral mucosae, which was inhibited by GW6471 or N-PLA. Western blotting and immunohistochemistry revealed that NOS1 and PPARα colocalize in antral mucous cells. In conclusion, during ACh stimulation, a PPARα autocrine mechanism, which accumulates NO via NOS1 leading to cGMP accumulation, modulates the Ca(2+)-regulated exocytosis in antral mucous cells. Copyright © 2014 the American Physiological Society.

Assessment of the implementation of environmental management ...

African Journals Online (AJOL)

Assessment of the implementation of environmental management system in the construction ... Journal of Fundamental and Applied Sciences ... The Environmental Management System (EMS) illustrates a possible solution to reduce the ...

43 CFR 46.310 - Contents of an environmental assessment.

Science.gov (United States)

2010-10-01

... implementation without the need for further analysis. Adaptive management includes a monitoring component... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Contents of an environmental assessment... OF THE NATIONAL ENVIRONMENTAL POLICY ACT OF 1969 Environmental Assessments § 46.310 Contents of an...

Environmental assessment, proposed generating station for Darlington

International Nuclear Information System (INIS)

1975-04-01

This document indicates the intention of Ontario Hydro to seek approval from the Provincial Government for its plan to construct and operate a 3400 MWe nuclear generating station at the Darlington site, west of Bowmanville. This preliminary proposal also contains the environmental assessment. The environmental section of this proposal describes and assesses the existing environment and the environmental influences which would occur due to the construction and operation of a nuclear generating station, consisting of four 850 MW units, at the Darlington site. This proposed station is similar to the Bruce GS A station presently under construction. (author)

Selecting environmental indicator for use in strategic environmental assessment

International Nuclear Information System (INIS)

Donnelly, Alison; Jones, Mike; O'Mahony, Tadhg; Byrne, Gerry

2007-01-01

The primary aim of carrying out Strategic Environmental Assessment (SEA) is to provide for a high level of environmental protection and to integrate environmental considerations into the planning process. The SEA Directive (2001/42/EC) recommends monitoring to determine the environmental impact of the implementation of plans and programmes. Environmental indicators are a useful tool by which this impact may be measured. However, careful consideration must be given to developing a set of indicators in order to isolate, plan or programme specific impacts. Here, we demonstrate the effectiveness of a workshop-based approach to develop appropriate criteria for selecting environmental indicator for use in SEA. A multi-disciplinary team was used in the approach which consisted of representatives from each of four environmental fields i.e. biodiversity, water, air and climatic factors, together with SEA experts, planning experts, academics and consultants. The team reviewed various sets of criteria, already in existence, for environmental indicator development but not specifically for SEA indicators. The results of this review together with original criteria were applied to the final list agreed upon. Some of the criteria recommended includes, relevance to plan, ability to prioritise, and ability to identify conflict with other plan or SEA objectives

The value of environmental impact assessments

International Nuclear Information System (INIS)

Sohocki, D.D.

1996-01-01

The environment and the economy are inextricably linked. Today the environmental, economic, and social associated with project and program decisions are at times of such a magnitude and duration that they exceed our ability to understand, let alone mitigate them. Energy production, distribution, pricing, policies, end uses, and externalities demonstrate the need for wise planning and informed decision making. International cooperation, based upon mutually shared respect, responsibility, and innovative solutions is an essential component of addressing contemporary issues, impacts, and opportunities. Both egypt and the united states have laws requiring environmental impact assessments. Just as egypt can learn from our successes and failures in the environmental impact assessment field over the past 36 years, the united states and other nations can learn as egypt develops and innovates its own approaches and solutions

GIS based procedure of cumulative environmental impact assessment.

Science.gov (United States)

Balakrishna Reddy, M; Blah, Baiantimon

2009-07-01

Scale and spatial limits of impact assessment study in a GIS platform are two very important factors that could have a bearing on the genuineness and quality of impact assessment. While effect of scale has been documented and well understood, no significant study has been carried out on spatial considerations in an impact assessment study employing GIS technique. A novel technique of impact assessment demonstrable through GIS approach termed hereby as 'spatial data integrated GIS impact assessment method (SGIAM)' is narrated in this paper. The technique makes a fundamental presumption that the importance of environmental impacts is dependent, among other things, on spatial distribution of the effects of the proposed action and of the affected receptors in a study area. For each environmental component considered (e.g., air quality), impact indices are calculated through aggregation of impact indicators which are measures of the severity of the impact. The presence and spread of environmental descriptors are suitably quantified through modeling techniques and depicted. The environmental impact index is calculated from data exported from ArcINFO, thus giving significant importance to spatial data in the impact assessment exercise.

The cyclic-di-GMP diguanylate cyclase CdgA has a role in biofilm formation and exopolysaccharide production in Azospirillum brasilense.

Science.gov (United States)

Ramírez-Mata, Alberto; López-Lara, Lilia I; Xiqui-Vázquez, Ma Luisa; Jijón-Moreno, Saúl; Romero-Osorio, Angelica; Baca, Beatriz E

2016-04-01

In bacteria, proteins containing GGDEF domains are involved in production of the second messenger c-di-GMP. Here we report that the cdgA gene encoding diguanylate cyclase A (CdgA) is involved in biofilm formation and exopolysaccharide (EPS) production in Azospirillum brasilense Sp7. Biofilm quantification using crystal violet staining revealed that inactivation of cdgA decreased biofilm formation. In addition, confocal laser scanning microscopy analysis of green-fluorescent protein-labeled bacteria showed that, during static growth, the biofilms had differential levels of development: bacteria harboring a cdgA mutation exhibited biofilms with considerably reduced thickness compared with those of the wild-type Sp7 strain. Moreover, DNA-specific staining and treatment with DNase I, and epifluorescence studies demonstrated that extracellular DNA and EPS are components of the biofilm matrix in Azospirillum. After expression and purification of the CdgA protein, diguanylate cyclase activity was detected. The enzymatic activity of CdgA-producing cyclic c-di-GMP was determined using GTP as a substrate and flavin adenine dinucleotide (FAD(+)) and Mg(2)(+) as cofactors. Together, our results revealed that A. brasilense possesses a functional c-di-GMP biosynthesis pathway. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

PRINCIPLES OF ENVIRONMENTAL ASSESSMENT IN THE LIFECYCLE OF PRODUCTS

Directory of Open Access Journals (Sweden)

Joanna Kulczycka

2017-02-01

Full Text Available One of the aims of the European Commission (EC activities is to introduce uniform rules for the environmental performance assessment based on the life cycle assessment method (LCA, which can be widely used e.g. in eco-labeling, assessment of goods, services, technology, etc. Therefore, from 1 November 2013 the European Commission implemented a pilot phase of the project on developing common methods for measuring the environmental performance of the product and organisation, aims to develop guidance documents in this field. The pilot phase includes development of the Category Rules relating to the calculation, verification and communication for environmental footprint of the 25 categories of products and two organizations. Therefore, the article presents the principle of environmental performance based on life cycle assessment in relation to the objectives of the proposed methodology of environmental footprint.

Role of the nitric oxide/cyclic GMP/Ca2+ signaling pathway in the pyrogenic effect of interleukin-1beta.

Science.gov (United States)

Palmi, Mitri; Meini, Antonella

2002-04-01

Interleukin-1beta (IL-1beta) has a wide spectrum of inflammatory, metabolic, haemopoietic, and immunological properties. Because it produces fever when injected into animals and humans, it is considered an endogenous pyrogen. There is evidence to suggest that Ca2+ plays a critical role in the central mechanisms of thermoregulation, and in the intracellular signaling pathways controlling fever induced by IL-1beta and other pyrogens. Data from different labs indicate that Ca2+ and Na+ determine the temperature set point in the posterior hypothalamus (PH) of various mammals and that changes in Ca2+ and PGE2 concentrations in the cerebrospinal fluid (CSF) of these animals are associated with IL-1beta-induced fever. Antipyretic drugs such as acetylsalicylic acid, dexamethasone, and lipocortin 5-(204-212) peptide counteract IL-1beta-induced fever and abolish changes in Ca2+ and PGE2 concentrations in CSF. In vitro studies have established that activation of the nitric oxide (NO)/cyclic GMP (cGMP) pathway is part of the signaling cascade transducing Ca2+ mobilization in response to IL-1beta and that the ryanodine (RY)- and inositol-(1,4,5)-trisphosphate (IP3)-sensitive pools are the main source of the mobilized Ca2+. It is concluded that the NO/cGMP/Ca2+ pathway is part of the signaling cascade subserving some of the multiple functions of IL-1beta.

Environmental assessment for the Processing and Environmental Technology Laboratory (PETL)

International Nuclear Information System (INIS)

1995-09-01

The U.S. Department of Energy (DOE) has prepared an environmental assessment (EA) on the proposed Processing and Environmental Technology Laboratory (PETC) at Sandia National Laboratories/New Mexico (SNL/NM). This facility is needed to integrate, consolidate, and enhance the materials science and materials process research and development (R ampersand D) currently in progress at SNL/NM. Based on the analyses in the EA, DOE has determined that the proposed action is not a major Federal action significantly affecting the quality of the human environment within the meaning of the National Environmental Policy Act (NEPA) of 1969. Therefore, an environmental impact statement is not required, and DOE is issuing this Finding of No Significant Impact (FONSI)

Environmental assessment for the Processing and Environmental Technology Laboratory (PETL)

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-09-01

The U.S. Department of Energy (DOE) has prepared an environmental assessment (EA) on the proposed Processing and Environmental Technology Laboratory (PETC) at Sandia National Laboratories/New Mexico (SNL/NM). This facility is needed to integrate, consolidate, and enhance the materials science and materials process research and development (R&D) currently in progress at SNL/NM. Based on the analyses in the EA, DOE has determined that the proposed action is not a major Federal action significantly affecting the quality of the human environment within the meaning of the National Environmental Policy Act (NEPA) of 1969. Therefore, an environmental impact statement is not required, and DOE is issuing this Finding of No Significant Impact (FONSI).

Graphical Methodology of Global Pollution Index for the Environmental Impact Assessment Using Two Environmental Components

OpenAIRE

Corneliu Cojocaru; Diana Mariana Cocârţă; Irina Aura Istrate; Igor Creţescu

2017-01-01

One of the applied methods for environmental impact assessment is the index of global pollution (IGP) proposed by Rojanschi in 1991. This methodology enables the global estimation for the ecosystem state affected more or less by human activities. Unfortunately, Rojanschi’s method has a limitation; it can be applied only if at least three environmental components are considered. Frequently, many environmental impact assessment applications rely on analysis of only two environmental components....

Comparison of phosphorylation of ribosomal proteins from HeLa and Krebs II ascites-tumour cells by cyclic AMP-dependent and cyclic GMP-dependent protein kinases

DEFF Research Database (Denmark)

Issinger, O G; Beier, H; Speichermann, N

1980-01-01

Phosphorylation of eukaryotic ribosomal proteins in vitro by essentially homogeneous preparations of cyclic AMP-dependent protein kinase catalytic subunit and cyclic GMP-dependent protein kinase was compared. Each protein kinase was added at a concentration of 30nM. Ribosomal proteins were...... by the cyclic AMP-dependent enzyme. Between 0.1 and 0.2 mol of phosphate was incorporated/mol of these phosphorylated proteins. With the exception of protein S7, the same proteins were also major substrates for the cyclic GMP-dependent protein kinase. Time courses of the phosphorylation of individual proteins...... from the small and large ribosomal subunits in the presence of either protein kinase suggested four types of phosphorylation reactions: (1) proteins S2, S10 and L5 were preferably phosphorylated by the cyclic GMP-dependent protein kinase; (2) proteins S3 and L6 were phosphorylated at very similar rates...

Environmental Assessments and Stakeholder Involvement

International Nuclear Information System (INIS)

Wesolowski, Cassandra

2006-01-01

Directives and legislation on EIA and SEA need to provide more guidance on how and when public participation should be used. There are now several examples of how well public participation can be performed and the methods are becoming more proactive and innovative. By increasing the role of public participation within the Environmental Assessment process, plans, programmes and projects will become more publicly acceptable. There does need to be a balance as to where public participation is performed in the system, as too much can be a stress on resources and time, as well as producing ineffective results. Key stages such as scoping, preparing the environmental statement or report and decision-making need to be highlighted for the benefits public participation can have. The Aarhus Convention is certainly making a difference in the UK; however it is difficult to judge exactly how much difference yet. It was only fully implemented in the UK in 2005 although some Authorities were applying the three pillars prior to implementation. It is not clear how aware the general public are of the Convention and their rights. Empowering communities in the UK. will communities for decision-making in Environmental Assessments? Providing the public with resources to enable them to fully engage in the process will improve the participation and increase their confidence, but how will this increase their influence within the decision-making process? Ultimately, should the stakeholders and public just influence the incremental decisions made in Environmental Assessments or have more responsibility within the major decisions taken? It will be interesting to see how these issues are addressed over the coming years

Environmental Assessments and Stakeholder Involvement

Energy Technology Data Exchange (ETDEWEB)

Wesolowski, Cassandra [Univ. of Manchester, School of Environment and Development (United Kingdom). Planning and Landscape

2006-09-15

Directives and legislation on EIA and SEA need to provide more guidance on how and when public participation should be used. There are now several examples of how well public participation can be performed and the methods are becoming more proactive and innovative. By increasing the role of public participation within the Environmental Assessment process, plans, programmes and projects will become more publicly acceptable. There does need to be a balance as to where public participation is performed in the system, as too much can be a stress on resources and time, as well as producing ineffective results. Key stages such as scoping, preparing the environmental statement or report and decision-making need to be highlighted for the benefits public participation can have. The Aarhus Convention is certainly making a difference in the UK; however it is difficult to judge exactly how much difference yet. It was only fully implemented in the UK in 2005 although some Authorities were applying the three pillars prior to implementation. It is not clear how aware the general public are of the Convention and their rights. Empowering communities in the UK. will communities for decision-making in Environmental Assessments? Providing the public with resources to enable them to fully engage in the process will improve the participation and increase their confidence, but how will this increase their influence within the decision-making process? Ultimately, should the stakeholders and public just influence the incremental decisions made in Environmental Assessments or have more responsibility within the major decisions taken? It will be interesting to see how these issues are addressed over the coming years.

Environmental risk assessment: an Australian perspective. Supervising Scientist Report 102

International Nuclear Information System (INIS)

Beer, T.; Ziolkowski, F.

1995-01-01

Environmental risk assessment can be used as a strategic tool to set environmental priorities and as a tactical tool to set environmental standards. This report is designed to inform Australian environmental managers about the techniques and applications of environmental risk assessment and to familiarize risk analysts with some of the issues that are of concern to environmental managers. The use of risk assessment is illustrated by applying its techniques to five case studies which include: risk from chemicals and from contaminated sites; risk to people and to the natural environment from development, such as uranium mining; climate change; and risk associated with political decision-making. Then, by considering Australian and overseas practice, a generic framework is presented within which environmental risk assessment in Australia can be undertaken, and possible methods of implementation are discussed. refs., 38 figs

Environmental assessment of incinerator residue utilisation

Energy Technology Data Exchange (ETDEWEB)

Toller, Susanna

2008-10-15

In Sweden, utilisation of incinerator residues outside disposal areas is restricted by environmental concerns, as such residues commonly contain greater amounts of potentially toxic trace elements than the natural materials they replace. On the other hand, utilisation can also provide environmental benefits by decreasing the need for landfill and reducing raw material extraction. This thesis provides increased knowledge and proposes better approaches for environmental assessment of incinerator residue utilisation, particularly bottom ash from municipal solid waste incineration (MSWI). A life cycle assessment (LCA) based approach was outlined for environmental assessment of incinerator residue utilisation, in which leaching of trace elements as well as other emissions to air and water and the use of resources were regarded as constituting the potential environmental impact from the system studied. Case studies were performed for i) road construction with or without MSWI bottom ash, ii) three management scenarios for MSWI bottom ash and iii) three management scenarios for wood ash. Different types of potential environmental impact predominated in the activities of the system and the scenarios differed in use of resources and energy. Utilising MSWI bottom ash in road construction and recycling of wood ash on forest land saved more natural resources and energy than when these materials were managed according to the other scenarios investigated, including dumping in landfill. There is a potential for trace element leaching regardless of how the ash is managed. Trace element leaching, particularly of copper (Cu), was identified as being relatively important for environmental assessment of MSWI bottom ash utilisation. CuO is suggested as the most important type of Cu-containing mineral in weathered MSWI bottom ash, whereas in the leachate Cu is mainly present in complexes with dissolved organic matter (DOM). The hydrophilic components of the DOM were more important for Cu

Environmental impact assessment in the Fijian state sector

International Nuclear Information System (INIS)

Turnbull, Jane

2003-01-01

For over 20 years, the South Pacific state of Fiji has required developers to conduct more than 70 environmental impact assessments (EIA), without specifying the environmental quality or impacts it considers (in)appropriate. It has ignored aspects of EIA to which agencies funding development have paid little attention--assessing alternatives, monitoring outcomes and enforcing consent conditions. This infers the Fijian state is not serious about using EIA to control environmental quality. Factors other than technical shortcomings are shaping the way the state constrains EIA practice. Unless these factors change, the comprehensive EIA system proposed in Sustainable Development legislation will not prevent environmental degradation

Methods of Environmental Impact Assessment in Colombia

Directory of Open Access Journals (Sweden)

Javier Toro Calderón

2013-10-01

Full Text Available The Environmental Impact Assessment (EIA in Colombia constitutes the primary tool for making decisions with respect to projects, works and activities (PWA with potential for significant environmental impacts. In the case of the infrastructure of the PWA, the EIA is mandatory and determines the environmental license (EL for construction and operation. This paper analyzes the methods used to assess the environmental impact of the PWA that have applied for licenses with the Ministry of Environment and Sustainable Development. It was found that the method most frequently used is the qualitative proposal by Conesa, with modifications that reduce the effectiveness of the EIA and favor the subjectivity and bias of the evaluator. Finally a series of recom­mendations to improve the process in the country are proposed.

Environmental assessment of nanomaterial use in Denmark

DEFF Research Database (Denmark)

Kjølholt, Jesper; Gottschalk, Fadri; Brinch, Anna

This is the concluding report of the project "Nanomaterials – occurrence and effects in the Danish environment" (abbreviated NanoDEN), which part the Danish Government's initiative "Better Control of Nanomaterials" (“Bedre styr på nanomaterialer”) which is administered by the Danish Environmental...... Protection Agency. The projects in NanoDEN have aimed to investigate and generate new environmentally relevant knowledge on of nanomaterials on the Danish market and to assess the possible associated risks to the environment. The results from the sub-projects are summarized in the current report...... and it is assessed whether and how nanomaterials may pose a risk for the environment in Denmark. The assessment is based on investigations of nine selected nanomaterials, which are expected to be environmentally relevant based on knowledge of consumption quantities or how they are used. These data contribute...

3,7-Bis(2-hydroxyethyl)icaritin, a potent inhibitor of phosphodiesterase-5, prevents monocrotaline-induced pulmonary arterial hypertension via NO/cGMP activation in rats.

Science.gov (United States)

Lan, Tao-Hua; Chen, Xiao-Ling; Wu, Yun-Shan; Qiu, Hui-Liang; Li, Jun-Zhe; Ruan, Xin-Min; Xu, Dan-Ping; Lin, Dong-Qun

2018-06-15

Pulmonary arterial hypertension (PAH) is a chronic progressive disease which leads to elevated pulmonary arterial pressure and right heart failure. 3,7-Bis(2-hydroxyethyl)icaritin (ICT), an icariin derivatives, was reported to have potent inhibitory activity on phosphodiesterase type 5 (PDE5) which plays a crucial role in the pathogenesis of PAH. The present study was designed to investigate the effects of ICT on monocrotaline (MCT)-induced PAH rat model and reveal the underlying mechanism. MCT-induced PAH rat models were established with intragastric administration of ICT (10, 20, 40 mg/kg/d), Icariin (ICA) (40 mg/kg/d) and Sildenafil (25 mg/kg/d). The mean pulmonary arterial pressure (mPAP) and right ventricle hypertrophy index (RVHI) were measured. Pulmonary artery remodeling was assessed by H&E staining. Blood and lung tissue were collected to evaluate the level of endothelin 1 (ET-1), nitric oxide (NO), and cyclic guanosine monophosphate (cGMP). The expressions endothelial nitric oxide synthase (eNOS) and PDE5A in lung tissues were determined by Western blot analysis. The results showed that ICT reduced RVHI and mPAP, and reversed lung vascular remodeling in rats with MCT-induced PAH. ICT also reversed MCT-induced ET-1 elevation, NO and cGMP reduction in serum or lung tissue. Moreover, ICT administration significantly induced eNOS activation and PDE5A inhibition. ICT with lower dose had better effects than ICA. In summary, ICT is more effective in preventing MCT-induced PAH in rats via NO/cGMP activation compared with ICA. These findings demonstrate a novel mechanism of the action of ICT that may have value in prevention of PAH. Copyright © 2018 Elsevier B.V. All rights reserved.

Multi-indicator assessment of water environment in government environmental auditing

Institute of Scientific and Technical Information of China (English)

HE Gui-zhen; LU Yong-long; MA Hua; WANG Xiao-long

2007-01-01

This study focuses on a multi-indicator assessment methodology for governmental environmental auditing of water protection programs. The environmental status of Wuli Lake in China was assessed using the global indicators (driver-status-response) developed by the CSD, and four additional indicators proposed by the author- water quality, pollution load, aquatic ecosystem status and lake sediment deposition. Various hydrological, chemical, biological and environmental parameters were used to estimate the values of the indicators for assessment of environmental status of the lake based on time series data sets for twenty years. The indicators proposed can be customized to meeting the needs for particular assessment of water protection programs. This method can be used to evaluate the performance of national environmental protection programs and provide technical support for environmental auditors.

Managing Air Quality - Human Health, Environmental and Economic Assessments

Science.gov (United States)

Human health and environmental assessments characterize health and environmental risks associated with exposure to pollution. Economic assessments evaluate the cost and economic impact of a policy or regulation & can estimate economic benefits.

cGMP-dependent protein kinase type I is implicated in the regulation of the timing and quality of sleep and wakefulness.

Directory of Open Access Journals (Sweden)

Sonja Langmesser

Full Text Available Many effects of nitric oxide (NO are mediated by the activation of guanylyl cyclases and subsequent production of the second messenger cyclic guanosine-3',5'-monophosphate (cGMP. cGMP activates cGMP-dependent protein kinases (PRKGs, which can therefore be considered downstream effectors of NO signaling. Since NO is thought to be involved in the regulation of both sleep and circadian rhythms, we analyzed these two processes in mice deficient for cGMP-dependent protein kinase type I (PRKG1 in the brain. Prkg1 mutant mice showed a strikingly altered distribution of sleep and wakefulness over the 24 hours of a day as well as reductions in rapid-eye-movement sleep (REMS duration and in non-REM sleep (NREMS consolidation, and their ability to sustain waking episodes was compromised. Furthermore, they displayed a drastic decrease in electroencephalogram (EEG power in the delta frequency range (1-4 Hz under baseline conditions, which could be normalized after sleep deprivation. In line with the re-distribution of sleep and wakefulness, the analysis of wheel-running and drinking activity revealed more rest bouts during the activity phase and a higher percentage of daytime activity in mutant animals. No changes were observed in internal period length and phase-shifting properties of the circadian clock while chi-squared periodogram amplitude was significantly reduced, hinting at a less robust oscillator. These results indicate that PRKG1 might be involved in the stabilization and output strength of the circadian oscillator in mice. Moreover, PRKG1 deficiency results in an aberrant pattern, and consequently a reduced quality, of sleep and wakefulness, possibly due to a decreased wake-promoting output of the circadian system impinging upon sleep.

Cyclic GMP-AMP Synthase is Activated by Double-stranded DNA-Induced Oligomerization

OpenAIRE

Li, Xin; Shu, Chang; Yi, Guanghui; Chaton, Catherine T.; Shelton, Catherine L.; Diao, Jiasheng; Zuo, Xiaobing; Kao, C Cheng; Herr, Andrew B.; Li, Pingwei

2013-01-01

Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor mediating innate antimicrobial immunity. It catalyzes the synthesis of a noncanonical cyclic dinucleotide 2′,5′ cGAMP that binds to STING and mediates the activation of TBK1 and IRF-3. Activated IRF-3 translocates to the nucleus and initiates the transcription of the IFN-β gene. The structure of mouse cGAS bound to an 18 bp dsDNA revealed that cGAS interacts with dsDNA through two binding sites, forming a 2:2 complex. Enzyme assays and ...

76 FR 48119 - Oral Rabies Vaccine Trial; Availability of a Risk Assessment and an Environmental Assessment

Science.gov (United States)

2011-08-08

...] Oral Rabies Vaccine Trial; Availability of a Risk Assessment and an Environmental Assessment AGENCY... environmental assessment relative to an oral rabies vaccination field trial in West Virginia. The environmental... rabies vaccine, analyzes the use of that vaccine in field safety and efficacy trials in West Virginia...

Spatiotemporal and functional characterisation of the Plasmodium falciparum cGMP-dependent protein kinase.

Directory of Open Access Journals (Sweden)

Christine S Hopp

Full Text Available Signalling by 3'-5'-cyclic guanosine monophosphate (cGMP exists in virtually all eukaryotes. In the apicomplexan parasite Plasmodium, the cGMP-dependent protein kinase (PKG has previously been reported to play a critical role in four key stages of the life cycle. The Plasmodium falciparum isoform (PfPKG is essential for the initiation of gametogenesis and for blood stage schizont rupture and work on the orthologue from the rodent malaria parasite P. berghei (PbPKG has shown additional roles in ookinete differentiation and motility as well as liver stage schizont development. In the present study, PfPKG expression and subcellular location in asexual blood stages was investigated using transgenic epitope-tagged PfPKG-expressing P. falciparum parasites. In Western blotting experiments and immunofluorescence analysis (IFA, maximal PfPKG expression was detected at the late schizont stage. While IFA suggested a cytosolic location, a degree of overlap with markers of the endoplasmic reticulum (ER was found and subcellular fractionation showed some association with the peripheral membrane fraction. This broad localisation is consistent with the notion that PfPKG, as with the mammalian orthologue, has numerous cellular substrates. This idea is further supported by the global protein phosphorylation pattern of schizonts which was substantially changed following PfPKG inhibition, suggesting a complex role for PfPKG during schizogony.

Experiences of using the GMP audit preparation tool in pharmaceutical contract manufacturer audits.

Science.gov (United States)

Linna, Anu; Korhonen, Mirka; Airaksinen, Marja; Juppo, Anne Mari

2010-06-01

Use of external contractors is nowadays inevitable in the pharmaceutical industry. Therefore the amount of current good manufacturing practice audits has been increasing. During the audit, a large amount of items should be covered in a limited amount of time. Consequently, pharmaceutical companies should have systematic and effective ways to manage and prepare for the audits. This study is a continuation to the earlier study, where a tool for the preparation of cGMP audit was developed and its content was validated. The objective of this study was to evaluate the usefulness of the developed tool in audit preparation and during the actual cGMP audit. Three qualitative research methods were used in this study (observation, interviews, and opinion survey). First, the validity of the information given through the tool was examined by comparing the responses to the actual conditions observed during the contract manufacturer audits (n = 15). Additionally the opinions of the contract manufacturers of the tool were gathered (n = 10) and the auditors were interviewed (n = 2). The developed tool was proven to be useful in audit preparation phase from both the auditor's and the contract manufacturers' point of view. Furthermore, using the tool can also save some time when performing the audit. The results show that using the tool can give significant support in audit preparation phase and also during the actual audit.

34 CFR 75.601 - Applicant's assessment of environmental impact.

Science.gov (United States)

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Applicant's assessment of environmental impact. 75.601... Conditions Must Be Met by a Grantee? Construction § 75.601 Applicant's assessment of environmental impact. An applicant shall include with its application its assessment of the impact of the proposed construction on...

Discussion on the post-project assessment of environmental impact for nuclear facilities

International Nuclear Information System (INIS)

Shang Zhaorong

2013-01-01

The paper introduces the background of post-project assessment of environmental impact in the world and focuses on the characteristic of environmental impact assessment for Chinese nuclear facilities construction projects, analyzes the necessity, principle and contents of post-project assessment of environmental impact on current Chinese nuclear facilities operation. It is considered that to start the post-project assessment of environmental impact, perfect the post-project assessment mechanism, introduce the post-project assessment into environmental impact assessment system are just at the night time. (author)

Derivation of xeno-free and GMP-grade human embryonic stem cells--platforms for future clinical applications.

Directory of Open Access Journals (Sweden)

Shelly E Tannenbaum

Full Text Available Clinically compliant human embryonic stem cells (hESCs should be developed in adherence to ethical standards, without risk of contamination by adventitious agents. Here we developed for the first time animal-component free and good manufacturing practice (GMP-compliant hESCs. After vendor and raw material qualification, we derived xeno-free, GMP-grade feeders from umbilical cord tissue, and utilized them within a novel, xeno-free hESC culture system. We derived and characterized three hESC lines in adherence to regulations for embryo procurement, and good tissue, manufacturing and laboratory practices. To minimize freezing and thawing, we continuously expanded the lines from initial outgrowths and samples were cryopreserved as early stocks and banks. Batch release criteria included DNA-fingerprinting and HLA-typing for identity, characterization of pluripotency-associated marker expression, proliferation, karyotyping and differentiation in-vitro and in-vivo. These hESCs may be valuable for regenerative therapy. The ethical, scientific and regulatory methodology presented here may serve for development of additional clinical-grade hESCs.

Reactive oxygen species drive evolution of pro-biofilm variants in pathogens by modulating cyclic-di-GMP levels

DEFF Research Database (Denmark)

Chua, Song Lin; Ding, Yichen; Liu, Yang

2016-01-01

. Comparative genomic analysis of the RSCVs revealed that mutations in the wspF gene, which encodes for a repressor of WspR diguanylate cyclase (DGC), were responsible for increased intracellular cyclic-di-GMP content and production of Psl exopolysaccharide. Psl provides the first line of defence against ROS...

cGMP may have trophic effects on beta cell function comparable to those of cAMP, implying a role for high-dose biotin in prevention/treatment of diabetes.

Science.gov (United States)

McCarty, Mark F

2006-01-01

Incretin hormones have trophic effects on beta cell function that can aid prevention and treatment of diabetes. cAMP is the primary mediator of these effects, and has been shown to potentiate glucose-stimulated insulin secretion, promote proper beta cells differentiation by increasing expression of the crucial transcription factor PDX-1, and prevent beta cell apoptosis. cGMP's role in beta cell function has received far less scrutiny, but there is emerging evidence that it may have a trophic impact on beta cell function analogous to that of cAMP. An increase in plasma glucose boosts beta cell production of cGMP, which acts as a feed-forward mediator to enhance glucose-stimulated insulin secretion. cGMP also has an anti-apoptotic effect in beta cells, and there is now indirect evidence that it promotes expression of PDX-1. Supraphysiological concentrations of biotin can directly activate guanylate cyclase, and there is limited evidence that high intakes of this vitamin can be therapeutically beneficial in diabetics and in rodent models of diabetes. Beneficial effects of cGMP on muscle insulin sensitivity and on control of hepatic glucose output may contribute to biotin's utility in diabetes. The fact that nitric oxide/cGMP exert a range of favorable effects on vascular health should further encourage exploration of biotin's preventive and therapeutic potential. If an appropriate high-dose biotin regimen could achieve a modest systemic increase in guanylate cyclase activity, without entailing unacceptable side effects or risks, such a regimen might have considerable potential for promoting vascular health and preventing or managing diabetes.

Biodiversity in environmental assessment-current practice and tools for prediction

International Nuclear Information System (INIS)

Gontier, Mikael; Balfors, Berit; Moertberg, Ulla

2006-01-01

Habitat loss and fragmentation are major threats to biodiversity. Environmental impact assessment and strategic environmental assessment are essential instruments used in physical planning to address such problems. Yet there are no well-developed methods for quantifying and predicting impacts of fragmentation on biodiversity. In this study, a literature review was conducted on GIS-based ecological models that have potential as prediction tools for biodiversity assessment. Further, a review of environmental impact statements for road and railway projects from four European countries was performed, to study how impact prediction concerning biodiversity issues was addressed. The results of the study showed the existing gap between research in GIS-based ecological modelling and current practice in biodiversity assessment within environmental assessment

Cyclic GMP-AMP as an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA.

Science.gov (United States)

Kato, Kazuki; Omura, Hiroki; Ishitani, Ryuichiro; Nureki, Osamu

2017-06-20

The innate immune system functions as the first line of defense against invading bacteria and viruses. In this context, the cGAS/STING [cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase/STING] signaling axis perceives the nonself DNA associated with bacterial and viral infections, as well as the leakage of self DNA by cellular dysfunction and stresses, to elicit the host's immune responses. In this pathway, the noncanonical cyclic dinucleotide 2',3'-cyclic GMP-AMP (2',3'-cGAMP) functions as a second messenger for signal transduction: 2',3'-cGAMP is produced by the enzyme cGAS upon its recognition of double-stranded DNA, and then the 2',3'-cGAMP is recognized by the receptor STING to induce the phosphorylation of downstream factors, including TBK1 (TANK binding kinase 1) and IRF3 (interferon regulatory factor 3). Numerous crystal structures of the components of this cGAS/STING signaling axis have been reported and these clarify the structural basis for their signal transduction mechanisms. In this review, we summarize recent progress made in the structural dissection of this signaling pathway and indicate possible directions of forthcoming research.

Phenotypic stability and plasticity in GMP-derived cells as determined by their underlying regulatory network.

Science.gov (United States)

Ramírez, Carlos; Mendoza, Luis

2018-04-01

Blood cell formation has been recognized as a suitable system to study celular differentiation mainly because of its experimental accessibility, and because it shows characteristics such as hierarchical and gradual bifurcated patterns of commitment, which are present in several developmental processes. Although hematopoiesis has been extensively studied and there is a wealth of molecular and cellular data about it, it is not clear how the underlying molecular regulatory networks define or restrict cellular differentiation processes. Here, we infer the molecular regulatory network that controls the differentiation of a blood cell subpopulation derived from the granulocyte-monocyte precursor (GMP), comprising monocytes, neutrophils, eosinophils, basophils and mast cells. We integrate published qualitative experimental data into a model to describe temporal expression patterns observed in GMP-derived cells. The model is implemented as a Boolean network, and its dynamical behavior is studied. Steady states of the network can be clearly identified with the expression profiles of monocytes, mast cells, neutrophils, basophils, and eosinophils, under wild-type and mutant backgrounds. All scripts are publicly available at https://github.com/caramirezal/RegulatoryNetworkGMPModel. lmendoza@biomedicas.unam.mx. Supplementary data are available at Bioinformatics online.

Strategic environmental assessment for UK LLW management - 16392

International Nuclear Information System (INIS)

Craze, Andrew; Clark, Matthew; Davis, Pete

2009-01-01

NDA is delivering a Strategic Environmental Assessment (SEA) to underpin the UK Nuclear Industry Low Level Waste Strategy. The purpose of this assessment is embed sustainability issues into our decision making and to fulfill our requirements under the European Union's Strategic Environmental Assessment (SEA) Directive (2004/42/EU) and transposing UK Regulations, and to underpin the development of the strategy. The outputs of the SEA have provided input into particular aspects of the strategy, leading to a more robust and better informed result. Development of options to be assessed under the SEA has looked at a number of factors, including: - what the strategy is aiming to achieve - expectation from stakeholders as to what should be addressed - consideration of tactical approaches to implementation of the strategy in addition to high level strategic issues - links to other projects and programmes (for example the Environmental Safety Case for the Low Level Waste Repository. The SEA aims to provide a robust assessment of the environmental and sustainability impacts of alternative strategies for providing continued capability and capacity for the management and disposal of LLW in the UK. The assessment also considers other, more tactical, issues around implementation of the strategy, for example: issues around the location of LLW management facilities; the environmental impacts of alternative waste treatment options (metal recycling etc); considerations of alternative approaches to the classification of radioactive waste and opportunities that would result. Critical to the development of the SEA has been the involvement of statutory and non-statutory stakeholders, who have informed both the output and the approach taken. (authors)

Environmental radiation exposure: Regulation, monitoring, and assessment

International Nuclear Information System (INIS)

Chen, S.Y.; Yu, C.; Hong, K.J.

1991-01-01

Radioactive releases to the environment from nuclear facilities constitute a public health concern. Protecting the public from such releases can be achieved through the establishment and enforcement of regulatory standards. In the United States, numerous standards have been promulgated to regulate release control at nuclear facilities. Most recent standards are more restrictive than those in the past and require that radioactivity levels be as low as reasonably achievable (ALARA). Environmental monitoring programs and radiological dose assessment are means of ensuring compliance with regulations. Environmental monitoring programs provide empirical information on releases, such as the concentrations of released radioactivity in environmental media, while radiological dose assessment provides the analytical means of quantifying dose exposures for demonstrating compliance

Environmental assessment of the Carlsbad Environmental Monitoring and Research Center Facility

International Nuclear Information System (INIS)

1995-10-01

This Environmental Assessment has been prepared to determine if the Carlsbad Environmental Monitoring and Research Center (the Center), or its alternatives would have significant environmental impacts that must be analyzed in an Environmental Impact Statement. DOE's proposed action is to continue funding the Center. While DOE is not funding construction of the planned Center facility, operation of that facility is dependent upon continued funding. To implement the proposed action, the Center would initially construct a facility of approximately 2,300 square meters (25,000 square feet). The Phase 1 laboratory facilities and parking lot will occupy approximately 1.2 hectares (3 acres) of approximately 8.9 hectares (22 acres) of land which were donated to New Mexico State University (NMSU) for this purpose. The facility would contain laboratories to analyze chemical and radioactive materials typical of potential contaminants that could occur in the environment in the vicinity of the DOE Waste Isolation Pilot Plant (WIPP) site or other locations. The facility also would have bioassay facilities to measure radionuclide levels in the general population and in employees of the WIPP. Operation of the Center would meet the DOE requirement for independent monitoring and assessment of environmental impacts associated with the planned disposal of transuranic waste at the WIPP

Environmental assessment of the Carlsbad Environmental Monitoring and Research Center Facility

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-10-01

This Environmental Assessment has been prepared to determine if the Carlsbad Environmental Monitoring and Research Center (the Center), or its alternatives would have significant environmental impacts that must be analyzed in an Environmental Impact Statement. DOE`s proposed action is to continue funding the Center. While DOE is not funding construction of the planned Center facility, operation of that facility is dependent upon continued funding. To implement the proposed action, the Center would initially construct a facility of approximately 2,300 square meters (25,000 square feet). The Phase 1 laboratory facilities and parking lot will occupy approximately 1.2 hectares (3 acres) of approximately 8.9 hectares (22 acres) of land which were donated to New Mexico State University (NMSU) for this purpose. The facility would contain laboratories to analyze chemical and radioactive materials typical of potential contaminants that could occur in the environment in the vicinity of the DOE Waste Isolation Pilot Plant (WIPP) site or other locations. The facility also would have bioassay facilities to measure radionuclide levels in the general population and in employees of the WIPP. Operation of the Center would meet the DOE requirement for independent monitoring and assessment of environmental impacts associated with the planned disposal of transuranic waste at the WIPP.

40 CFR 8.9 - Measures to assess and verify environmental impacts.

Science.gov (United States)

2010-07-01

... environmental impacts. 8.9 Section 8.9 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL ENVIRONMENTAL IMPACT ASSESSMENT OF NONGOVERNMENTAL ACTIVITIES IN ANTARCTICA § 8.9 Measures to assess and verify environmental impacts. (a) The operator shall conduct appropriate monitoring of key environmental indicators as...

Improving environmental impact and cost assessment for supplier evaluation

Science.gov (United States)

Beucker, Severin; Lang, Claus

2004-02-01

Improving a company"s environmental and financial performance necessitates the evaluation of environmental impacts deriving from the production and cost effects of corporate actions. These effects have to be made transparent and concrete targets have to be developed. Such an evaluation has to be done on a regular basis but with limited expenses. To achieve this, different instruments of environmental controlling such as LCA and environmental performance indicators have to be combined with methods from cost accounting. Within the research project CARE (Computer Aided Resource Efficiency Accounting for Medium-Sized Enterprises), the method Resource Efficiency Accounting (REA) is used to give the participating companies new insights into hidden costs and environmental effects of their production and products. The method combines process based cost accounting with environmental impact assessment methodology and offers results that can be integrated into a company"s environmental controlling system and business processes like cost accounting, supplier assessment, etc. Much of the data necessary for the combined assessment can be available within a company"s IT system and therefore can be efficiently used for the assessment process. The project CARE puts a strong focus on the use of company data and information systems for the described assessment process and offers a methodological background for the evaluation and the structuring of such data. Besides the general approach of the project CARE the paper will present results from a case study in which the described approach is used for the evaluation of suppliers.

Cyclic Di-GMP Binding by an Assembly ATPase (PilB2) and Control of Type IV Pilin Polymerization in the Gram-Positive Pathogen Clostridium perfringens.

Science.gov (United States)

Hendrick, William A; Orr, Mona W; Murray, Samantha R; Lee, Vincent T; Melville, Stephen B

2017-05-15

The Gram-positive pathogen Clostridium perfringens possesses type IV pili (TFP), which are extracellular fibers that are polymerized from a pool of pilin monomers in the cytoplasmic membrane. Two proteins that are essential for pilus functions are an assembly ATPase (PilB) and an inner membrane core protein (PilC). Two homologues each of PilB and PilC are present in C. perfringens , called PilB1/PilB2 and PilC1/PilC2, respectively, along with four pilin proteins, PilA1 to PilA4. The gene encoding PilA2, which is considered the major pilin based on previous studies, is immediately downstream of the pilB2 and pilC2 genes. Purified PilB2 had ATPase activity, bound zinc, formed hexamers even in the absence of ATP, and bound the second messenger molecule cyclic di-GMP (c-di-GMP). Circular dichroism spectroscopy of purified PilC2 indicated that it retained its predicted degree of alpha-helical secondary structure. Even though no direct interactions between PilB2 and PilC2 could be detected in vivo or in vitro even in the presence of c-di-GMP, high levels of expression of a diguanylate cyclase from C. perfringens (CPE1788) stimulated polymerization of PilA2 in a PilB2- and PilC2-dependent manner. These results suggest that PilB2 activity is controlled by c-di-GMP levels in vivo but that PilB2-PilC2 interactions are either transitory or of low affinity, in contrast to results reported previously from in vivo studies of the PilB1/PilC1 pair in which PilC1 was needed for polar localization of PilB1. This is the first biochemical characterization of a c-di-GMP-dependent assembly ATPase from a Gram-positive bacterium. IMPORTANCE Type IV pili (TFP) are protein fibers involved in important bacterial functions, including motility, adherence to surfaces and host cells, and natural transformation. All clostridia whose genomes have been sequenced show evidence of the presence of TFP. The genetically tractable species Clostridium perfringens was used to study proteins involved in

Environmental assessment [of nuclear installations

International Nuclear Information System (INIS)

Townsley, M.

1989-01-01

The European Community has introduced a directive which instructs that for all projects likely to have a significant effect on the environment consent should only be given after a rigorous assessment of such effects has been carried out and presented as an environmental statement. Projects requiring environmental assessment include nuclear power stations, any thermal power station over 300MW, any radioactive waste storage or disposal facility, any installation which produces electricity, power lines, installations for fuel production, fuel reprocessing, radioactive waste processing and fuel enrichment. The statement must include a description of the likely effects, direct and indirect, on the environment of the development, with reference to human beings, flora, fauna, soil, water, air, climate, landscape, interactions of two or more of these, material assets and cultural heritage. Measures to avoid or remedy the impact must be included. (U.K.)

Assessing the Environmental Risks of Nanomaterials

DEFF Research Database (Denmark)

Grieger, Khara Deanne; Hansen, Steffen Foss; Baun, Anders

to a wide range of technical limitations. For instance, serious knowledge gaps remain within e.g. the detection of NM in the environment, developing adequate testing equipment and protocols, and toxicity endpoints (Grieger et al., 2009). In the past few years, many scientists and organizations have...... considered. Furthermore, we recommend the use of biomonitoring in some environmental ‘hot spots’ to serve as early warning detectors while the field of NM environmental risk assessment matures, as recommended in our previous work. Ultimately, this analysis may aid the advancement of environmental risk...

A statistical proposal for environmental impact assessment of development projects

International Nuclear Information System (INIS)

Plazas C, Julian A; De J Lema T, Alvaro; Leon P, Juan Diego

2009-01-01

Environmental impact assessment of development projects is a fundamental process, which main goal is to avoid that their construction and functioning, lead to serious and negative consequences on the environment. Some of the most important limitations of the models employed to assess environmental impacts, are the subjectivity of its parameters and weights, and the multicolineality among the variables, which represent high quantities of similar information. This work presents a multivariate statistical-based method that tries to diminish such limitations. For this purpose, environmental impact assessment, is valuated through different environmental impact attributes and environmental elements, synthesized in an environmental quality index (ICA in Spanish). ICA can be applied at different levels, such as at a project level, or applied only at a partial level on one or some environmental components.

Is Environmental Impact Assessment fulfilling its potential?

DEFF Research Database (Denmark)

Larsen, Sanne Vammen

2014-01-01

fuel with CO2-neutral energy sources. A variety of these projects are subject to environmental impact assessment (EIA), which raises the following questions: What role does an impact assessment play? When is the project environmentally friendly? How are climate change-related impacts assessed......One of the topics receiving much attention in recent years is climate change and the potential of its integration in impact assessment, both in terms of achieving mitigation and adaptation. Renewable energy projects are part of the efforts to mitigate climate change, replacing the use of fossil...... adaptation is absent. Also, the results show an emphasis on positive impacts in the reports, and in a few cases discussions of enhancements. Identification and assessment of negative climate change impacts are less apparent. This leads to a discussion of the results in the light of the purpose of EIA....

Risk analysis within environmental impact assessment of proposed construction activity

Energy Technology Data Exchange (ETDEWEB)

Zeleňáková, Martina; Zvijáková, Lenka

2017-01-15

Environmental impact assessment is an important process, prior to approval of the investment plan, providing a detailed examination of the likely and foreseeable impacts of proposed construction activity on the environment. The objective of this paper is to develop a specific methodology for the analysis and evaluation of environmental impacts of selected constructions – flood protection structures using risk analysis methods. The application of methodology designed for the process of environmental impact assessment will develop assumptions for further improvements or more effective implementation and performance of this process. The main objective of the paper is to improve the implementation of the environmental impact assessment process. Through the use of risk analysis methods in environmental impact assessment process, the set objective has been achieved. - Highlights: This paper is informed by an effort to develop research with the aim of: • Improving existing qualitative and quantitative methods for assessing the impacts • A better understanding of relations between probabilities and consequences • Methodology for the EIA of flood protection constructions based on risk analysis • Creative approaches in the search for environmentally friendly proposed activities.

Risk analysis within environmental impact assessment of proposed construction activity

International Nuclear Information System (INIS)

Zeleňáková, Martina; Zvijáková, Lenka

2017-01-01

Environmental impact assessment is an important process, prior to approval of the investment plan, providing a detailed examination of the likely and foreseeable impacts of proposed construction activity on the environment. The objective of this paper is to develop a specific methodology for the analysis and evaluation of environmental impacts of selected constructions – flood protection structures using risk analysis methods. The application of methodology designed for the process of environmental impact assessment will develop assumptions for further improvements or more effective implementation and performance of this process. The main objective of the paper is to improve the implementation of the environmental impact assessment process. Through the use of risk analysis methods in environmental impact assessment process, the set objective has been achieved. - Highlights: This paper is informed by an effort to develop research with the aim of: • Improving existing qualitative and quantitative methods for assessing the impacts • A better understanding of relations between probabilities and consequences • Methodology for the EIA of flood protection constructions based on risk analysis • Creative approaches in the search for environmentally friendly proposed activities.

Environmental Impact Assessment (EIA, Strategic Environmental Assessment (SEA and Sustainability in Minas Gerais

Directory of Open Access Journals (Sweden)

Evandro Sanguinetto

2011-07-01

Full Text Available This paper was aimed at conducting a bibliographical research on Environmental Impact Assessment (EIA, Strategic Environmental Assessment (SEA and their relation to the Ecological Economic Zoning (EEZ in the state of Minas Gerais. It is believed that the EIA is subject to failures as it does not take into account larger impacts upon space, time, cumulative and synergistic effects, whereas reflecting a reductionist point of view of the undertaking to the detriment of a broader, systemic, holistic perspective. With a view to compensate for such failure, the SEA is seen as an appropriate tool for the evaluation of political impacts, plans and programs which, conversely, guides the implementation of projects in an more integrated manner. Therefore, two EIAs can be used as reference; one refers to a rural electrification program in the state of Minas Gerais and the other approaches the integration planning of water sources in the metropolitan area of the state of São Paulo. While planning the Ecological Economic Zoning of the state, Minas Gerais takes a decisive step forward the reduction of conflicts related with multiple interests of economic development, providing and forming the basis for the essential balance among profit, preservation and environmental conservation, social justice, respect and cultural diversity, political and institutional maturation, ethic and plurality, which splash the sustainability colors on the canvas of the future.

Health Impact Assessment Practice and Potential for Integration within Environmental Impact and Strategic Environmental Assessments in Italy

Science.gov (United States)

Linzalone, Nunzia; Assennato, Giorgio; Ballarini, Adele; Cadum, Ennio; Cirillo, Mario; Cori, Liliana; De Maio, Francesca; Musmeci, Loredana; Natali, Marinella; Rieti, Sabrina; Soggiu, Maria Eleonora; Bianchi, Fabrizio

2014-01-01

Avoiding or minimizing potential environmental impact is the driving idea behind protecting a population’s health via Environmental Impact Assessments (EIAs) and Strategic Environmental Assessments (SEAs). However, both are often carried out without any systematic approach. This paper describes the findings of a review of HIA, EIA and SEA experiences carried out by the authors, who act as institutional competent subjects at the national and regional levels in Italy. The analysis of how health is tackled in EIA and SEA procedures could support the definition of a protocol for the integration of HIA with EIA and SEA. Although EIA and SEA approaches include the aim of protecting health, significant technical and methodological gaps are present when assessing health systematically, and their basic principles regarding assessment are unsatisfactory for promoting and addressing healthcare concepts stated by the WHO. HIA is still poorly integrated into the decision-making process, screening and monitoring phases are only occasionally implemented, and operational details are not well-defined. The collaborative approach of institutions involved in environment and health is a core element in a systematic advancement toward supporting effective decisions and effective protection of the environment and health. At the Italian national level, the definition of guidelines and tools for HIA, also in relation with EIA and SEA, is of great interest. PMID:25493391

Strategic environmental assessment in post-modern times

International Nuclear Information System (INIS)

Fischer, Thomas B.

2003-01-01

The increasing awareness of the findings of policy and decision making theory in the environmental assessment community has recently led to an intensifying debate on the theoretical foundations and the appropriate practical use of strategic environmental assessment (SEA). In this context, most of the recent suggestions on how to improve practice have been influenced--consciously or sub-consciously--by the post-modernist paradigm, focusing particularly on a better integration of SEA into 'real' decision making and procedural flexibility. There have also been suggestions that traditional project environmental impact assessment (EIA)-based SEA approaches are generally inadequate. Reacting to the latter criticism, this paper aims at defending 'traditional' systematically structured and normative approaches to SEA. While it is acknowledged that a purely professional and technological paradigm to SEA is something of the past, it is proposed that leaving the design of 'flexible' SEA to the will of proponents and stakeholders might ultimately render it incapable of protecting the environment

Wind turbine environmental assessment -- Vol 1: Screening document

International Nuclear Information System (INIS)

2000-04-01

The environmental effects of the proposed construction and operation of up to three wind turbines on the Toronto waterfront are evaluated in accordance with the requirements of the Canadian Environmental Assessment Act (CEAA) and Regulations. The nine sections of the report provide background on the environmental assessment and the wind turbine project; provide justification for the project and describes alternative sites and wind turbine technologies; outlines the scope of the project; sketches the biophysical and socio-economic environment; presents an evaluation of the environmental impacts and proposed mitigating measures; describes the public consultation program that was carried out; summarizes the comments received from interested parties; presents the conclusion of the environmental impact assessment; and responds to the public comments received on the draft screening document. Most of the concerns raised involved avoidance reactions by birds, disruption or fragmentation of wildlife, the potential for high kill rate of small nocturnal migrants and young birds, and the effect of noise on breeding birds. The overall recommendation of the consultants is that the project is not likely to cause significant adverse environmental effects and its construction and operations should be authorized. 115 refs., 8 tabs., 2 figs. (14 appendices are in volume 2)

Assessing Environmental Impact on Aquatic Macrophyte Species ...

African Journals Online (AJOL)

Impact of environmental variables on distribution and composition of aquatic macrophyte community in a tropical river was assessed for one year (March 2009 to February 2010). Hypothesis tested was that the spatial variation in environmental variables on the river's longitudinal gradient affects macrophyte species ...

Dealing with uncertainties in environmental burden of disease assessment

Directory of Open Access Journals (Sweden)

van der Sluijs Jeroen P

2009-04-01

Full Text Available Abstract Disability Adjusted Life Years (DALYs combine the number of people affected by disease or mortality in a population and the duration and severity of their condition into one number. The environmental burden of disease is the number of DALYs that can be attributed to environmental factors. Environmental burden of disease estimates enable policy makers to evaluate, compare and prioritize dissimilar environmental health problems or interventions. These estimates often have various uncertainties and assumptions which are not always made explicit. Besides statistical uncertainty in input data and parameters – which is commonly addressed – a variety of other types of uncertainties may substantially influence the results of the assessment. We have reviewed how different types of uncertainties affect environmental burden of disease assessments, and we give suggestions as to how researchers could address these uncertainties. We propose the use of an uncertainty typology to identify and characterize uncertainties. Finally, we argue that uncertainties need to be identified, assessed, reported and interpreted in order for assessment results to adequately support decision making.

Environmental Warning System Based on the DPSIR Model: A Practical and Concise Method for Environmental Assessment

Directory of Open Access Journals (Sweden)

Wenqi Wang

2018-05-01

Full Text Available Though we are in urgent need of environmental warnings to slow environmental deterioration, currently, there is no internationally concise method for environmental warnings. In addition, the existing approaches do not combine the three aspects of ecology, resources, and environment. At the same time, the three elements of the environment (air, water, and soil are separated in most environmental warning systems. Thus, the method this paper gives is an innovative attempt and aims to make environmental assessment more practical. This paper establishes the index system of an environmental early warning based on the Driving–Pressure–State–Influence–Response (DPSIR model. The Analytic Hierarchy Process (AHP method was used to determine the weights. Next, single and integrated index methods further assess the environmental warning state, in which the weighted summation method is used to summarize the data and results. The case of Tianjin is used to confirm the applicability of this method. In conclusion, the method in this paper is more well-behaved and, therefore, more suitable to assist cities in their environmental assessment.

The environmental impact assessment of uranium mining in Australia

International Nuclear Information System (INIS)

Morvell, G.

2002-01-01

Federal environmental impact assessment legislation has existed in Australia since 1974. A number of uranium mines have been developed in this time, utilizing a range of mining techniques, including opencut, underground and in-situ leach. Projects have also been undertaken in a variety of geographical areas requiring consideration of diverse biodiversity, cultural heritage and social impact issues. Assessment of uranium mining proposals in Australia is also conducted in a climate of political opposition from a cross section of the Australian community. This paper outlines some of the key issues that arose during recent assessments and which provide a lead to the role of environmental impact assessment in environmental policy development. Issues are also relevant to recent assessments on a replacement nuclear reactor, shipments of waste for reprocessing and proposed assessments on proposals for low and intermediate level nuclear waste facilities. (author)

Guidance on the environmental risk assessment of plant pests

DEFF Research Database (Denmark)

Baker, R.; Candresse, T.; Dormannsne Simon, E.

2011-01-01

The European Food Safety Authority (EFSA) requested the Panel on Plant Health to develop a methodology for assessing the environmental risks posed by harmful organisms that may enter, establish and spread in the European Union. To do so, the Panel first reviewed the methods for assessing...... the environmental risks of plant pests that have previously been used in pest risk assessment. The limitations identified by the review led the Panel to define the new methodology for environmental risk assessment which is described in this guidance document. The guidance is primarily addressed to the EFSA PLH...... (biodiversity) and the functional (ecosystem services) aspects of the environment, this new approach includes methods for assessing both aspects for the first time in a pest risk assessment scheme. A list of questions has been developed for the assessor to evaluate the consequences for structural biodiversity...

Spatial information in public consultation within environmental impact assessments

NARCIS (Netherlands)

Mwenda, A.N.

2015-01-01

Thesis Summary

Spatial information in public consultation within Environmental Impact Assessments

Angela N. Mwenda

Established in the United States of America in 1970, Environmental Impact Assessment (EIA) is an interdisciplinary approach that

Collaborative environmental assessment in the Northwest Territories, Canada

International Nuclear Information System (INIS)

Armitage, Derek R.

2005-01-01

Recent trends in environmental assessment theory and practice indicate a growing concern with collaboration and learning. Although there are few examples of the institutional, organizational, and socio-political forms and processes required to foster this collaboration and learning, the establishment of an environmental planning, management, and assessment regime in Canada's Northwest Territories offers useful insights. Consequently, this paper identifies and examines the institutional, organizational, and socio-political conditions that have encouraged more collaborative forms of environmental assessment practice in the Northwest Territories. Key issues highlighted include: (1) the development of decentralized regulatory organizations more responsive to changing circumstances; (2) strategies for more effective communication and participation of community interests; (3) efforts to build a collaborative vision of economic and social development through region-specific land use plans; (4) the integration of knowledge frameworks; and (5) a concern with the capacity required to encourage effective intervention in the assessment process

Production of GMP certified herbal products in Malaysian Nuclear Agency

International Nuclear Information System (INIS)

Daryl Jesus Arapoc; Bohari Yaacob; Zainah Adam

2015-01-01

This paper will discuss on up scaling production of herbal product. A pilot scale production plant were developed in Block 37 and equipped with automated and semi-automated production machines which have the capacity to produce 100 thousand pieces of tablet per hour. In order to ensure the quality of the products, raw material inspections, IPQC and FPQC will be done on each batch. Besides that, certification of GMP will be done concurrently. One of the products that will be launch soon is the Mas Cotek tablet. This product is the result of numerous years of researches that had been done in BTP. This includes formulation and production of the product itself. It is hope that more herbal products can be produce in near future. (author)

GMP reverses the facilitatory effect of glutamate on inhibitory avoidance task in rats.

Science.gov (United States)

Rubin, M A; Jurach, A; da Costa Júnior, E M; Lima, T T; Jiménez-Bernal, R E; Begnini, J; Souza, D O; de Mello, C F

1996-09-02

Previous studies have demonstrated that post-training intrahippocampal glutamate administration improves inhibitory avoidance task performance in rats. Antagonism of the agonist actions of glutamate by guanine nucleotides has been shown at the molecular and behavioural level. In the present investigation we demonstrate that intrahippocampal co-administration of GMP (guanosine 5'-monophosphate) reverses the facilitatory effect of glutamate on the inhibitory avoidance learning paradigm and inhibits [3H]glutamate binding in hippocampal synaptic plasma membranes. These results suggest that guanine nucleotides may modulate glutamate actions.

Environmental compliance assessment review

International Nuclear Information System (INIS)

Hilliday, G.H.

1991-01-01

During the period 1972-1991, The United States Congress passed stringent environmental statues which the Environment Protection Agency implemented via regulations. The statues and regulations contain severe civil and criminal penalties. Civil violations resulted in fines, typically payable by the company. The act of willfully and knowingly violating the permit conditions or regulations can result in criminal charges being imposed upon the responsible part, i.e., either the company or individual. Criminal charges can include fines, lawyer fees, court costs and incarceration. This paper describes steps necessary to form an effective Environmental Compliance Assessment Review [CAR] program, train field and engineering personnel and perform a CAR audit. Additionally, the paper discusses the findings of a number of Exploration and Production [E and P] field audits

The Gyc76C Receptor Guanylyl Cyclase and the Foraging cGMP-Dependent Kinase Regulate Extracellular Matrix Organization and BMP Signaling in the Developing Wing of Drosophila melanogaster.

Science.gov (United States)

Schleede, Justin; Blair, Seth S

2015-10-01

The developing crossveins of the wing of Drosophila melanogaster are specified by long-range BMP signaling and are especially sensitive to loss of extracellular modulators of BMP signaling such as the Chordin homolog Short gastrulation (Sog). However, the role of the extracellular matrix in BMP signaling and Sog activity in the crossveins has been poorly explored. Using a genetic mosaic screen for mutations that disrupt BMP signaling and posterior crossvein development, we identify Gyc76C, a member of the receptor guanylyl cyclase family that includes mammalian natriuretic peptide receptors. We show that Gyc76C and the soluble cGMP-dependent kinase Foraging, likely linked by cGMP, are necessary for normal refinement and maintenance of long-range BMP signaling in the posterior crossvein. This does not occur through cell-autonomous crosstalk between cGMP and BMP signal transduction, but likely through altered extracellular activity of Sog. We identify a novel pathway leading from Gyc76C to the organization of the wing extracellular matrix by matrix metalloproteinases, and show that both the extracellular matrix and BMP signaling effects are largely mediated by changes in the activity of matrix metalloproteinases. We discuss parallels and differences between this pathway and other examples of cGMP activity in both Drosophila melanogaster and mammalian cells and tissues.

Cyclic GMP-AMP Synthase is an Innate Immune Sensor of HIV and Other Retroviruses

OpenAIRE

Gao, Daxing; Wu, Jiaxi; Wu, You-Tong; Du, Fenghe; Aroh, Chukwuemika; Yan, Nan; Sun, Lijun; Chen, Zhijian J.

2013-01-01

Retroviruses, including HIV, can activate innate immune responses, but the host sensors for retroviruses are largely unknown. Here we show that HIV infection activates cyclic-GMP-AMP (cGAMP) synthase (cGAS) to produce cGAMP, which binds to and activates the adaptor protein STING to induce type-I interferons and other cytokines. Inhibitors of HIV reverse transcriptase, but not integrase, abrogated interferon-β induction by the virus, suggesting that the reverse transcribed HIV DNA triggers the...

Environmental impact assessment Geopressure Subprogram

Energy Technology Data Exchange (ETDEWEB)

None

1977-07-01

This environmental impact assessment (EIA) addresses the expected programmatic activities of the Geopressure Subprogram of the Division of Geothermal Energy. The goal of the Geopressure Subprogram is to stimulate development of geopressured resources as an economic, reliable, operationally safe, and environmentally acceptable energy source. The subprogram includes activities in the areas of engineering research and development; resource exploration, assessment, and development; resource utilization including pilot and demonstration facilities; and environmental research and control technology development. It should be recognized that most of the subprogram activities extend over several years and are in their early stages of implementation at this time. The zones of potential geopressure development are in the region located along the Texas and Louisiana Gulf Coasts extending up to 200 miles (300 km) inland. Geopressured zones are sedimentary basins where water is trapped at high pressures within or below thick, nearly impermeable shale sequences. The confined water supports most or all of the weight of the overburden. This inhibits sediment compaction and causes formation pore pressure to exceed hydrostatic pressure. in sedimentary basins that are underlain by thin oceanic crust, upward thermal conduction from the mantle heats geopressured fluids and sediments to abnormally high temperatures, often in excess of 260 C (500 F).

ENVIRONMENTAL IMPACT ASSESSMENT OF A HEALTH TECHNOLOGY: A SCOPING REVIEW.

Science.gov (United States)

Polisena, Julie; De Angelis, Gino; Kaunelis, David; Gutierrez-Ibarluzea, Iñaki

2018-06-13

The Health Technology Expert Review Panel is an advisory body to Canadian Agency for Drugs and Technologies in Health (CADTH) that develops recommendations on health technology assessments (HTAs) for nondrug health technologies using a deliberative framework. The framework spans several domains, including the environmental impact of the health technology(ies). Our research objective was to identify articles on frameworks, methods or case studies on the environmental impact assessment of health technologies. A literature search in major databases and a focused gray literature search were conducted. The main search concepts were HTA and environmental impact/sustainability. Eligible articles were those that described a conceptual framework or methods used to conduct an environmental assessment of health technologies, and case studies on the application of an environmental assessment. From the 1,710 citations identified, thirteen publications were included. Two articles presented a framework to incorporate environmental assessment in HTAs. Other approaches described weight of evidence practices and comprehensive and integrated environmental impact assessments. Central themes derived include transparency and repeatability, integration of components in a framework or of evidence into a single outcome, data availability to ensure the accuracy of findings, and familiarity with the approach used. Each framework and methods presented have different foci related to the ecosystem, health economics, or engineering practices. Their descriptions suggested transparency, repeatability, and the integration of components or of evidence into a single outcome as their main strengths. Our review is an initial step of a larger initiative by CADTH to develop the methods and processes to address the environmental impact question in an HTA.

Short-term dehydroepiandrosterone treatment increases platelet cGMP production in elderly male subjects.

Science.gov (United States)

Martina, Valentino; Benso, Andrea; Gigliardi, Valentina Ramella; Masha, Andi; Origlia, Carla; Granata, Riccarda; Ghigo, Ezio

2006-03-01

Several clinical and population-based studies suggest that dehydroepiandrosterone (DHEA) and its sulphate (DHEA-S) play a protective role against atherosclerosis and coronary artery disease in human. However, the mechanisms underlying this action are still unknown. It has recently been suggested that DHEA-S could delay atheroma formation through an increase in nitric oxide (NO) production. Twenty-four aged male subjects [age (mean +/- SEM): 65.4 +/- 0.7 year; range: 58.2-67.6 years] underwent a blinded placebo controlled study receiving DHEA (50 mg p.o. daily at bedtime) or placebo for 2 months. Platelet cyclic guanosine-monophosphate (cGMP) concentration (as marker of NO production) and serum levels of DHEA-S, DHEA, IGF-I, insulin, glucose, oestradiol (E(2)), testosterone, plasminogen activator inhibitor (PAI)-1 antigen (PAI-1 Ag), homocysteine and lipid profile were evaluated before and after the 2-month treatment with DHEA or placebo. At the baseline, all variables in the two groups were overlapping. All parameters were unchanged after treatment with placebo. Conversely, treatment with DHEA (a) increased (P < 0.001 vs. baseline) platelet cGMP (111.9 +/- 7.1 vs. 50.1 +/- 4.1 fmol/10(6) plts), DHEA-S (13.6 +/- 0.8 vs. 3.0 +/- 0.3 micromol/l), DHEA (23.6 +/- 1.7 vs. 15.3 +/- 1.4 nmol/l), testosterone (23.6 +/- 1.0 vs. 17.7 +/- 1.0 nmol/l) and E(2) (72.0 +/- 5.0 vs. 60.0 +/- 4.0 pmol/l); and (b) decreased (P < 0.05 vs. baseline) PAI-1 Ag (27.4 +/- 3.8 vs. 21.5 +/- 2.5 ng/ml) and low-density lipoprotein (LDL) cholesterol (3.4 +/- 0.2 vs. 3.0 +/- 0.2 mmol/l). IGF-I, insulin, glucose, triglycerides, total cholesterol, HDL cholesterol, HDL2 cholesterol, HDL3 cholesterol, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and homocysteine levels were not modified by DHEA treatment. This study shows that short-term treatment with DHEA increased platelet cGMP production, a marker of NO production, in healthy elderly subjects. This effect is coupled with a decrease in PAI-1

Environmental Assessment. Moanalua Shopping Center Redevelopment Oahu, Hawaii

National Research Council Canada - National Science Library

Pingree, Ryan; Halperin, William

2004-01-01

The Department of the Navy has prepared an Environmental Assessment (EA) and determined that an Environmental Impact Statement is not required for the redevelopment of the Moanalua Shopping Center (MSC) Oahu Hawaii...

Environmental Assessment for decontamination and dismantlement, Pinellas Plant

International Nuclear Information System (INIS)

1995-06-01

The US Department of Energy (DOE) has prepared an Environmental Assessment (EA) (DOE/EA-1092) of the proposed decontamination and dismantlement of the Pinellas Plant in Largo, Florida. Under the Decontamination and Dismantlement EA, the DOE proposes to clean up facilities, structures, and utilities; dismantle specific structures; and mitigate or eliminate any environmental impacts associated with the cleanup, dismantlement, and related activities. Related activities include utilization of specific areas by new tenants prior to full-scale cleanup. Based on the analyses in the EA, the DOE has determined that the proposed action is not a major Federal action significantly affecting the quality of the human environment, within the meaning of the National Environmental Policy Act of 1969. Therefore, the preparation of an environmental impact statement is not required. This report contains the Environmental Assessment, as well as the Finding of No Significant Impact (FONSI)

Participatory Risk Assessment for Environmental Decision-Making

International Nuclear Information System (INIS)

Homan, Jacqueline; Petts, Judith

2001-01-01

Recent research, discussion and practice in the role environmental decision-making as an integral part of a democratic society have resulted in legislation, policy and guidance that encourage, and indeed may require, greater participation. The focus of this research paper is to explore these participatory ideas in the context of environmental risk assessment. Participation methods have generic application. However, the importance of fitting method to purpose requires that different contexts and issues relative to the objectives be addressed. In relation to environmental risk assessment these issues include: the complexity of risk issues per se; the inherent uncertainty that dominates any risk assessment; the quantitative nature of many risk assessments and the difficulty of dealing with low probability-high consequence outconies; the possibility of controversy in relation to decisions involving risk and thus the careful attention needed to the process and identification of participants; the traditional role and culture of experts in risk decisions and the challenge of reconciling this with the role of lay knowledge and the potential for the public to act as quality assurers in the risk decision process; the tendency for people to need reassurance when confronted with risk, even during a participation process; the need to acknowledge the public's ability to deal with complex technical issues and the need for information and data to respond to their questions, and the fact that 'risk' per se will often not be the only issue of public concern. The contributions to the risk debate from the social sciences are having considerable influence on the practice of environmental decision-making. Calls for increased stakeholder involvement in risk decisions are requiring greater access to and engagement with environmental risk assessments. Mechanisms for this level of involvement, however, are not well defined. For these aspirational calls to be realised in practice, decision

Participatory Risk Assessment for Environmental Decision-Making

Energy Technology Data Exchange (ETDEWEB)

Homan, Jacqueline; Petts, Judith [Univ. of Birmingham (United Kingdom). Centre for Environmental Research and Training; Pollard, Simon; Twigger-Ross, Clare [National Centre for Risk Analysis and Options Appraisal, London (United Kingdom)

2001-07-01

Recent research, discussion and practice in the role environmental decision-making as an integral part of a democratic society have resulted in legislation, policy and guidance that encourage, and indeed may require, greater participation. The focus of this research paper is to explore these participatory ideas in the context of environmental risk assessment. Participation methods have generic application. However, the importance of fitting method to purpose requires that different contexts and issues relative to the objectives be addressed. In relation to environmental risk assessment these issues include: the complexity of risk issues per se; the inherent uncertainty that dominates any risk assessment; the quantitative nature of many risk assessments and the difficulty of dealing with low probability-high consequence outconies; the possibility of controversy in relation to decisions involving risk and thus the careful attention needed to the process and identification of participants; the traditional role and culture of experts in risk decisions and the challenge of reconciling this with the role of lay knowledge and the potential for the public to act as quality assurers in the risk decision process; the tendency for people to need reassurance when confronted with risk, even during a participation process; the need to acknowledge the public's ability to deal with complex technical issues and the need for information and data to respond to their questions, and the fact that 'risk' per se will often not be the only issue of public concern. The contributions to the risk debate from the social sciences are having considerable influence on the practice of environmental decision-making. Calls for increased stakeholder involvement in risk decisions are requiring greater access to and engagement with environmental risk assessments. Mechanisms for this level of involvement, however, are not well defined. For these aspirational calls to be realised in

An integrated risk assessment approach: Risk assessment in the programmatic environmental impact statement

International Nuclear Information System (INIS)

Morris, J.M.

1994-01-01

The following paper is an informal summary of salient points made in the presentation entitled open-quotes An Integrated Risk Assessment Approach: Risk Assessment in the Programmatic Environmental Impact Statement (PEIS).close quotes. This presentation was given at the U.S. DOE Integrated Planning Workshop in Denver, Colorado on June 2, 1994. Integrated decision analysis is very important in environmental restoration and waste management in the evaluation of such things as land use planning, waste load forecasting, cost analyses, and technology development activities. Integrated risk assessment is an approach that addresses multiple components of risk, including: risks from surplus facilities as well as typical environmental restoration sites, risks to the public, risks to workers, ecological risk, risks before, during and after remediation activities, and others

Environmental justice, impact assessment and the politics of knowledge: The implications of assessing the social distribution of environmental outcomes

International Nuclear Information System (INIS)

Walker, Gordon

2010-01-01

Claims of environmental injustice have increasingly become part of environmental conflicts, both explicitly through the work of environmental justice campaigning groups and implicitly through the arguments deployed about the rights and wrongs of a given situation. Such claims can centre on different notions of justice, including those concerned with questions of distribution and procedure. This paper focuses on distributional or outcome justice and explores what implications follow when the distributional concerns of environmental justice are included in the practice of impact assessment processes, including through social impact assessment (SIA). The current use of impact assessment methods in the UK is reviewed showing that although practices are evolving there is a little routine assessment of distributional inequalities. It is argued that whilst this should become part of established practice to ensure that inequalities are revealed and matters of justice are given a higher profile, the implications for conflict within decision making processes are not straightforward. On the one hand, there could be scope for conflict to be ameliorated by analysis of inequalities informing the debate between stakeholders, and facilitating the implementation of mitigation and compensation measures for disadvantaged groups. On the other hand, contestation over how evidence is produced and therefore what it shows, and disagreement as to the basis on which justice and injustice are to be determined, means that conflict may also be generated and sustained within what are essentially political and strategic settings.

The Environmental Assessment Technique: An Empirical Study.

Science.gov (United States)

Overall, Jesse U., IV

The purpose of the study was to investigate the effectiveness of Alexander Astin's Environmental Assessment Technique (EAT) in describing the environmental press at a large public university, California State University at Los Angeles. Results indicate that EAT is a very economical method for broadly describing aspects of a university's…

An Assessment of Environmental Impacts Assessment (EIA in Malaysia

Directory of Open Access Journals (Sweden)

Abdul Hamid Masdiah

2017-01-01

Full Text Available The effectiveness of Environmental Impact Assessment (EIA in evaluating the planning project is a debatable issue among academics and practitioners, since EIA has been claimed to be unable to eliminate the environmental issues. Focusing only on technical improvements is not sufficient for rectifying the problems of EIA; the process of EIA should be clearly identified instead to maximise the effective use of EIA. It is important to note that the effective use of EIA, particularly on process-related issues could significantly minimise bad environmental effects. In summary, this study aims to explore and identify the effectiveness of EIA in the planning process and barriers to evaluate the environmental performance in Malaysia. The findings of this study could be a baseline for organisation to minimize emission, avoid the risk of prosecution and fines arising from potential environment breaches and cost reduction within the organisation.

A new paradigm for Environmental Assessment (EA) in Korea

International Nuclear Information System (INIS)

Song, Young-Il; Glasson, John

2010-01-01

Over the last 30 years, Environmental Impact Assessment (EIA) in Korea has played an important role in decision-making processes particularly for environmentally sensitive projects. However, the EIA system alone has sometimes not been effective enough to ensure the successful resolution of environmental concerns. In order to compensate for the limitations of the EIA system, a new assessment system called Prior Environmental Review System (PERS), which is relevant to Strategic Environmental Assessment (SEA) in some aspects, was introduced in 1993. PERS aims to balance development and preservation by identifying possible environmental impacts of some administrative plans mainly related to development projects in the early stages of planning. However, PERS still appeared to have some weak points such as a limited range of subjects to be assessed, and weakness of tiering (or vertical integration) from PERS to EIA. Therefore, the necessity for reform of the Korean Environmental Assessment (EA) system, including PERS, was raised. In response, the Korean government sought to establish its policy direction for implementing SEA by enhancing the objectivity and expertise of PERS. The policy was approved by the National Assembly in May 2005, and went into effect in June 2006. The introduction of SEA, by enhancing PERS, provides a framework for a system of EA from the strategic level, including PPPs, to the project level. Yet, despite such improvements, some managerial and technical problems associated with subsequent EA implementation remain. This paper critically reviews the evolution of the EA system in Korea and suggests essential improvements for the current EA system based on experiences of implementation of both EIA and SEA since June 2006, in the context of international good practice.

Environmental income improves household-level poverty assessments and dynamics

DEFF Research Database (Denmark)

Walelign, Solomon Zena; Charlery, Lindy Callen; Smith-Hall, Carsten

2016-01-01

Household-level poverty assessments and analyses of poverty dynamics in developing countries typically do not include environmental income. Using household (n = 427 in 2006, 2009 and 2012) total income panel data sets, with and without environmental income, from Nepal, we analysed the importance...... of environmental income in household-level poverty assessments (Foster-Greer-Thorbecke indices) and dynamics (movements in the Poverty Transition Matrix). Random effects logit and ordered logit models were applied to estimate variables covarying with poverty categories and compared for annual household incomes...... with and without environmental income. Using the without environmental income data set significantly changed the number of households classified as poor, as well as rates of movements in and out of poverty. Excluding household-level environmental income also distorted estimation of covariates of poverty incidence...

Environmental assessment of solid waste systems and technologies: EASEWASTE

DEFF Research Database (Denmark)

Kirkeby, Janus Torsten; Birgisdottir, Harpa; Hansen, Trine Lund

2006-01-01

A new model has been developed for evaluating the overall resource consumption and environmental impacts of municipal solid waste management systems by the use of life cycle assessment. The model is named EASEWASTE (Environmental Assessment of Solid Waste Systems and Technologies) and is able...... may not always be the most environmentally friendly. The EASEWASTE model can identify the most environmentally sustainable solution, which may differ among waste materials and regions and can add valuable information about environmental achievements from each process in a solid waste management system....... to compare different waste management strategies, waste treatment methods and waste process technologies. The potential environmental impacts can be traced back to the most important processes and waste fractions that contribute to the relevant impacts. A model like EASEWASTE can be used by waste planners...

A mathematical model for environmental risk assessment in manufacturing industry

Institute of Scientific and Technical Information of China (English)

何莉萍; 徐盛明; 陈大川; 党创寅

2002-01-01

Environmental conscious manufacturing has become an important issue in industry because of market pressure and environmental regulations. An environmental risk assessment model was developed based on the network analytic method and fuzzy set theory. The "interval analysis method" was applied to deal with the on-site monitoring data as basic information for assessment. In addition, the fuzzy set theory was employed to allow uncertain, interactive and dynamic information to be effectively incorporated into the environmental risk assessment. This model is a simple, practical and effective tool for evaluating the environmental risk of manufacturing industry and for analyzing the relative impacts of emission wastes, which are hazardous to both human and ecosystem health. Furthermore, the model is considered useful for design engineers and decision-maker to design and select processes when the costs, environmental impacts and performances of a product are taken into consideration.

A Concept for Multi-Criteria Environmental Assessment of Aircraft Trajectories

Directory of Open Access Journals (Sweden)

Sigrun Matthes

2017-08-01

Full Text Available Comprehensive assessment of the environmental aspects of flight movements is of increasing interest to the aviation sector as a potential input for developing sustainable aviation strategies that consider climate impact, air quality and noise issues simultaneously. However, comprehensive assessments of all three environmental aspects do not yet exist and are in particular not yet operational practice in flight planning. The purpose of this study is to present a methodology which allows to establish a multi-criteria environmental impact assessment directly in the flight planning process. The method expands a concept developed for climate optimisation of aircraft trajectories, by representing additionally air quality and noise impacts as additional criteria or dimensions, together with climate impact of aircraft trajectory. We present the mathematical framework for environmental assessment and optimisation of aircraft trajectories. In that context we present ideas on future implementation of such advanced meteorological services into air traffic management and trajectory planning by relying on environmental change functions (ECFs. These ECFs represent environmental impact due to changes in air quality, noise and climate impact. In a case study for Europe prototype ECFs are implemented and a performance assessment of aircraft trajectories is performed for a one-day traffic sample. For a single flight fuel-optimal versus climate-optimized trajectory solution is evaluated using prototypic ECFs and identifying mitigation potential. The ultimate goal of such a concept is to make available a comprehensive assessment framework for environmental performance of aircraft operations, by providing key performance indicators on climate impact, air quality and noise, as well as a tool for environmental optimisation of aircraft trajectories. This framework would allow studying and characterising changes in traffic flows due to environmental optimisation, as well

ENVIRONMENTAL AUDITING: AN INTEGRATED ENVIRONMENTAL ASSESSMENT OF THE U.S. MID-ATLANTIC REGION

Science.gov (United States)

Many of today's environmental problems are regional in scope and their effects overlap and interact. We developed a simple method to provide an integrated assessment of environmental conditions and estimate cumulative impacts across a large region, by combining data on land-cove...

Integrated manure management to reduce environmental impact: II. Environmental impact assessment of strategies

NARCIS (Netherlands)

Vries, de J.W.; Groenestein, C.M.; Schroder, J.J.; Hoogmoed, W.B.; Sukkel, W.; Groot Koerkamp, P.W.G.; Boer, de I.J.M.

2015-01-01

Manure management contributes to adverse environmental impacts through losses of nitrogen (N), phosphorus, and carbon (C). In this study, we aimed to assess the potential of newly designed strategies for integrated manure management (IS) to reduce environmental impact. An important aspect of the

Strategic Environmental Assessment and Sustainable Development

Science.gov (United States)

Tian, Mingjing; Gao, Qingjun; Wang, Nan; Yang, Xigen; Xu, Xin; Zhang, Lu

2018-04-01

The development of social science and technology economy, the international community more and more attention to environmental and development issues. So the main goal pursued by people is not only to meet the needs of social and natural resources, while at the same time being able to protect the needs of future generations. This is the path of sustainable development. Therefore, this paper is a detailed study of strategic environmental assessment and sustainable development.

Technological progress and challenges towards cGMP manufacturing of human pluripotent stem cells based therapeutic products for allogeneic and autologous cell therapies.

Science.gov (United States)

Abbasalizadeh, Saeed; Baharvand, Hossein

2013-12-01

Recent technological advances in the generation, characterization, and bioprocessing of human pluripotent stem cells (hPSCs) have created new hope for their use as a source for production of cell-based therapeutic products. To date, a few clinical trials that have used therapeutic cells derived from hESCs have been approved by the Food and Drug Administration (FDA), but numerous new hPSC-based cell therapy products are under various stages of development in cell therapy-specialized companies and their future market is estimated to be very promising. However, the multitude of critical challenges regarding different aspects of hPSC-based therapeutic product manufacturing and their therapies have made progress for the introduction of new products and clinical applications very slow. These challenges include scientific, technological, clinical, policy, and financial aspects. The technological aspects of manufacturing hPSC-based therapeutic products for allogeneic and autologous cell therapies according to good manufacturing practice (cGMP) quality requirements is one of the most important challenging and emerging topics in the development of new hPSCs for clinical use. In this review, we describe main critical challenges and highlight a series of technological advances in all aspects of hPSC-based therapeutic product manufacturing including clinical grade cell line development, large-scale banking, upstream processing, downstream processing, and quality assessment of final cell therapeutic products that have brought hPSCs closer to clinical application and commercial cGMP manufacturing. © 2013.

Recovery in environmental risk assessment at EFSA

NARCIS (Netherlands)

Brock, T.C.M.

2016-01-01

EFSA performs environmental risk assessments (ERAs) for single potential stressors such as plant protection products, genetically modified organisms and feed additives and for invasive alien species that are harmful for plant health. In this risk assessment domain, the EFSA Scientific Committee

Construction and expression of a functional monoclonal antibody SZ-51 specific for GMP-140 chimeric fab fragment in Escherichia coli

International Nuclear Information System (INIS)

Gu Jianming; Zhang Xiaomin; Xia Lijun; Wan Haiying; Liu Yue; Li Peixia; Ruan Changgeng

1996-04-01

The variable region cDNAs of a monoclonal antibody SZ-51 specific for α-granule membrane protein (GMP-140) on the surface of activated human platelets were spliced with the constant region cDNA of the heavy chain CH1 and light chain k of human Ig G by means of the gene recombination techniques. The above recombinant gene was amplified by the polymerase chain reaction (PCR). The expression vector of phage plasmid pHEN1 SZ-51 Fab/Hu was constructed. The pHEN1-51 Fab/Hu was introduced into non-suppressor E. coli HB2151. The amount of expression of SZ-51 chimeric Fab/Hu measured by quantitative ELISA was about 500 μg/L. Western blot demonstrated that the SZ-51 chimeric Fab fragment could specifically bind to GMP-140. (2 figs.)

Geomorphological hazards and environmental impact: Assessment and mapping

Science.gov (United States)

Panizza, Mario

In five sections the author develops the methods for the integration of geomorphological concepts into Environmental Impact and Mapping. The first section introduces the concepts of Impact and Risk through the relationships between Geomorphological Environment and Anthropical Element. The second section proposes a methodology for the determination of Geomorphological Hazard and the identification of Geomorphological Risk. The third section synthesizes the procedure for the compilation of a Geomorphological Hazards Map. The fourth section outlines the concepts of Geomorphological Resource Assessment for the analysis of the Environmental Impact. The fifth section considers the contribution of geomorphological studies and mapping in the procedure for Environmental Impact Assessment.

Human exposure assessment to environmental chemicals using biomonitoring.

Science.gov (United States)

Calafat, Antonia M; Ye, Xiaoyun; Silva, Manori J; Kuklenyik, Zsuzsanna; Needham, Larry L

2006-02-01

In modern societies, humans may be exposed to a wide spectrum of environmental chemicals. Although the health significance of this exposure for many chemicals is unknown, studies to investigate the prevalence of exposure are warranted because of the chemicals' potential harmful health effects, as often indicated in animal studies. Three tools have been used to assess exposure: exposure history/questionnaire information, environmental monitoring, and biomonitoring (i.e. measuring concentrations of the chemicals, their metabolites, or their adducts in human specimens). We present an overview on the use of biomonitoring in exposure assessment using phthalates, bisphenol A and other environmental phenols, and perfluorinated chemicals as examples. We discuss some factors relevant for interpreting and understanding biomonitoring data, including selection of both biomarkers of exposure and human matrices, and toxicokinetic information. The use of biomonitoring in human risk assessment is not discussed.

Assessment of Environmental Sustainability in Health Care Organizations

Directory of Open Access Journals (Sweden)

María Carmen Carnero

2015-06-01

Full Text Available Healthcare organizations should set a standard in corporate social responsibility and encourage environmental sustainability, since protection of the environment implies the development of preventive measures in healthcare. Environmental concern has traditionally focused on manufacturing plants. However, a Health Care Organization (HCO is the only type of company which generates all existing classes of waste, and 20% is dangerous, being infectious, toxic or radioactive in nature. Despite the extensive literature analysing environmental matters, there is no objective model for assessing the environmental sustainability of HCOs in such a way that the results may be compared over time for an organization, and between different organizations, to give a comparison or benchmarking tool for HCOs. This paper presents a Multi-Criteria Decision Analysis model integrating a Fuzzy Analytic Hierarchy Process and utility theory, to evaluate environmental sustainability in HCOs. The model uses criteria assessed as a function of the number of annual treatments undertaken. The model has been tested in two HCOs of very different sizes.

Three Antagonistic Cyclic di-GMP-Catabolizing Enzymes Promote Differential Dot/Icm Effector Delivery and Intracellular Survival at the Early Steps of Legionella pneumophila Infection

Science.gov (United States)

Allombert, Julie; Lazzaroni, Jean-Claude; Baïlo, Nathalie; Gilbert, Christophe; Charpentier, Xavier; Doublet, Patricia

2014-01-01

Legionella pneumophila is an intracellular pathogen which replicates within protozoan cells and can accidently infect alveolar macrophages, causing an acute pneumonia in humans. The second messenger cyclic di-GMP (c-di-GMP) has been shown to play key roles in the regulation of various bacterial processes, including virulence. While investigating the function of the 22 potential c-di-GMP-metabolizing enzymes of the L. pneumophila Lens strain, we found three that directly contribute to its ability to infect both protozoan and mammalian cells. These three enzymes display diguanylate cyclase (Lpl0780), phosphodiesterase (Lpl1118), and bifunctional diguanylate cyclase/phosphodiesterase (Lpl0922) activities, which are all required for the survival and intracellular replication of L. pneumophila. Mutants with deletions of the corresponding genes are efficiently taken up by phagocytic cells but are partially defective for the escape of the Legionella-containing vacuole (LCV) from the host degradative endocytic pathway and result in lower survival. In addition, Lpl1118 is required for efficient endoplasmic reticulum recruitment to the LCV. Trafficking and biogenesis of the LCV are dependent upon the orchestrated actions of several type 4 secretion system Dot/Icm effectors proteins, which exhibit differentially altered translocation in the three mutants. While translocation of some effectors remained unchanged, others appeared over- and undertranslocated. A general translocation offset of the large repertoire of Dot/Icm effectors may be responsible for the observed defects in the trafficking and biogenesis of the LCV. Our results suggest that L. pneumophila uses cyclic di-GMP signaling to fine-tune effector delivery and ensure effective evasion of the host degradative pathways and establishment of a replicative vacuole. PMID:24379287

Ecological geology environmental assessment of open-pit mines

International Nuclear Information System (INIS)

Dong Shuangfa; Jiang Xue

2010-01-01

In this paper, there is a detail description of ecological geology environmental assessment of open-pit mines, including method, process and results. We took ecological geology environmental assessment work on the base of the results of some open-pit mines such as extremely low content magnetite in Hebei Province, inducted and summarized the ecological geology environment quality. The results are reasonable. It provides basic data for the second mines programming in Hebei Province. (authors)

Environmental Risk Assessment Strategy for Nanomaterials

Directory of Open Access Journals (Sweden)

Janeck J. Scott‐Fordsmand

2017-10-01

Full Text Available An Environmental Risk Assessment (ERA for nanomaterials (NMs is outlined in this paper. Contrary to other recent papers on the subject, the main data requirements, models and advancement within each of the four risk assessment domains are described, i.e., in the: (i materials, (ii release, fate and exposure, (iii hazard and (iv risk characterisation domains. The material, which is obviously the foundation for any risk assessment, should be described according to the legislatively required characterisation data. Characterisation data will also be used at various levels within the ERA, e.g., exposure modelling. The release, fate and exposure data and models cover the input for environmental distribution models in order to identify the potential (PES and relevant exposure scenarios (RES and, subsequently, the possible release routes, both with regard to which compartment(s NMs are distributed in line with the factors determining the fate within environmental compartment. The initial outcome in the risk characterisation will be a generic Predicted Environmental Concentration (PEC, but a refined PEC can be obtained by applying specific exposure models for relevant media. The hazard information covers a variety of representative, relevant and reliable organisms and/or functions, relevant for the RES and enabling a hazard characterisation. The initial outcome will be hazard characterisation in test systems allowing estimating a Predicted No-Effect concentration (PNEC, either based on uncertainty factors or on a NM adapted version of the Species Sensitivity Distributions approach. The risk characterisation will either be based on a deterministic risk ratio approach (i.e., PEC/PNEC or an overlay of probability distributions, i.e., exposure and hazard distributions, using the nano relevant models.

Environmental Risk Assessment Strategy for Nanomaterials.

Science.gov (United States)

Scott-Fordsmand, Janeck J; Peijnenburg, Willie J G M; Semenzin, Elena; Nowack, Bernd; Hunt, Neil; Hristozov, Danail; Marcomini, Antonio; Irfan, Muhammad-Adeel; Jiménez, Araceli Sánchez; Landsiedel, Robert; Tran, Lang; Oomen, Agnes G; Bos, Peter M J; Hund-Rinke, Kerstin

2017-10-19

An Environmental Risk Assessment (ERA) for nanomaterials (NMs) is outlined in this paper. Contrary to other recent papers on the subject, the main data requirements, models and advancement within each of the four risk assessment domains are described, i.e., in the: (i) materials, (ii) release, fate and exposure, (iii) hazard and (iv) risk characterisation domains. The material, which is obviously the foundation for any risk assessment, should be described according to the legislatively required characterisation data. Characterisation data will also be used at various levels within the ERA, e.g., exposure modelling. The release, fate and exposure data and models cover the input for environmental distribution models in order to identify the potential (PES) and relevant exposure scenarios (RES) and, subsequently, the possible release routes, both with regard to which compartment(s) NMs are distributed in line with the factors determining the fate within environmental compartment. The initial outcome in the risk characterisation will be a generic Predicted Environmental Concentration (PEC), but a refined PEC can be obtained by applying specific exposure models for relevant media. The hazard information covers a variety of representative, relevant and reliable organisms and/or functions, relevant for the RES and enabling a hazard characterisation. The initial outcome will be hazard characterisation in test systems allowing estimating a Predicted No-Effect concentration (PNEC), either based on uncertainty factors or on a NM adapted version of the Species Sensitivity Distributions approach. The risk characterisation will either be based on a deterministic risk ratio approach (i.e., PEC/PNEC) or an overlay of probability distributions, i.e., exposure and hazard distributions, using the nano relevant models.

Environmental assessment of energy production from waste and biomass

DEFF Research Database (Denmark)

Tonini, Davide

. To evaluate the environmental and energy performance of bioenergy and wasteto-energy systems life cycle assessment was used in this thesis. This was supported by other tools such as material, substance, energy flow analysis and energy system analysis. The primary objective of this research was to provide...... a consistent framework for the environmental assessment of innovative bioenergy and waste-to-energy systems including the integration of LCA with other tools (mentioned earlier). The focus was on the following aspects: - Evaluation of potential future energy scenarios for Denmark. This was doneby integrating...... assessing the environmental performance of the waste refinery, a detailed knowledge of the waste composition is recommendable as this determines the energy outputs and thereby the assessment results. The benefits offered by the waste refinery compared with incinerators and MBT plants are primarily related...

Environmental assessment, Pinellas Plant site, Petersburg, Florida

International Nuclear Information System (INIS)

1983-07-01

The purpose of this environmental assessment is to describe the operations at the Pinellas Plant, discuss the locale in which the plant is situated and assess the actual and possible impacts of plant operation on the surrounding environment. The facility and the local environment are described; impacts on the economy, local community and the environment discussed, and alternatives presented. A comparison of the environmental impact of operating the Pinellas Plant versus the benefits gained by its operation suggests that the plant should continue its function of supplying nuclear weapons components for the US Department of Energy

Characteristics of environmental gamma-rays and dose assessment

International Nuclear Information System (INIS)

Saito, Kimiaki; Moriuchi, Shigeru

1986-01-01

Environmental radioactivity has attracted much attention in terms of exposure to the population, although its exposure doses are minimal. This paper presents problems encountered in the assessment of exposure doses using model and monitoring systems, focusing on the characteristics, such as energy distribution, direction distribution, and site, of environmental gamma-rays. The assessment of outdoor and indoor exposure doses of natural gamma-rays is discussed in relation to the shielding effect of the human body. In the assessment of artificial gamma-rays, calculation of exposure doses using build-up factor, the shielding effect of the human body, and energy dependency of the measuring instrument are covered. A continuing elucidation about uncertainties in dose assessment is emphasized. (Namekawa, K.)

YfiBNR mediates cyclic di-GMP dependent small colony variant formation and persistence in Pseudomonas aeruginosa.

Directory of Open Access Journals (Sweden)

Jacob G Malone

2010-03-01

Full Text Available During long-term cystic fibrosis lung infections, Pseudomonas aeruginosa undergoes genetic adaptation resulting in progressively increased persistence and the generation of adaptive colony morphotypes. This includes small colony variants (SCVs, auto-aggregative, hyper-adherent cells whose appearance correlates with poor lung function and persistence of infection. The SCV morphotype is strongly linked to elevated levels of cyclic-di-GMP, a ubiquitous bacterial second messenger that regulates the transition between motile and sessile, cooperative lifestyles. A genetic screen in PA01 for SCV-related loci identified the yfiBNR operon, encoding a tripartite signaling module that regulates c-di-GMP levels in P. aeruginosa. Subsequent analysis determined that YfiN is a membrane-integral diguanylate cyclase whose activity is tightly controlled by YfiR, a small periplasmic protein, and the OmpA/Pal-like outer-membrane lipoprotein YfiB. Exopolysaccharide synthesis was identified as the principal downstream target for YfiBNR, with increased production of Pel and Psl exopolysaccharides responsible for many characteristic SCV behaviors. An yfi-dependent SCV was isolated from the sputum of a CF patient. Consequently, the effect of the SCV morphology on persistence of infection was analyzed in vitro and in vivo using the YfiN-mediated SCV as a representative strain. The SCV strain exhibited strong, exopolysaccharide-dependent resistance to nematode scavenging and macrophage phagocytosis. Furthermore, the SCV strain effectively persisted over many weeks in mouse infection models, despite exhibiting a marked fitness disadvantage in vitro. Exposure to sub-inhibitory concentrations of antibiotics significantly decreased both the number of suppressors arising, and the relative fitness disadvantage of the SCV mutant in vitro, suggesting that the SCV persistence phenotype may play a more important role during antimicrobial chemotherapy. This study establishes Yfi

Environmental impact assessment of nuclear desalination

International Nuclear Information System (INIS)

2010-03-01

Nuclear desalination is gaining interest among the IAEA Member States, as indicated by the planned projects, and it is expected that the number of nuclear desalination plants will increase in the near future. The IAEA has already provided its Member States with reports and documents that disseminate information regarding the technical and economic feasibility of nuclear desalination. With the rising environmental awareness, in the scope of IAEA's activities on seawater desalination using nuclear power, a need was identified for a report that would provide a generic assessment of the environmental issues in nuclear desalination. In order to offer an overview of specific environmental impacts which are to be expected, their probable magnitude, and recommended mitigation measures, this publication encompasses information provided by the IAEA Member States as well as other specialized sources. It is intended for decision makers and experts dealing with environmental, desalination and water management issues, offering insight into the environmental aspects that are essential in planning and developing nuclear desalination

[Ecological environmental quality assessment of Hangzhou urban area based on RS and GIS].

Science.gov (United States)

Xu, Pengwei; Zhao, Duo

2006-06-01

In allusion to the shortage of traditional ecological environmental quality assessment, this paper studied the spatial distribution of assessing factors at a mid-small scale, and the conversion of integer character to girding assessing cells. The main assessing factors including natural environmental condition, environmental quality, natural landscape and urbanization pressure, which were classified into four types with about eleven assessing factors, were selected from RS images and GIS-spatial analyzing environmental quality vector graph. Based on GIS, a comprehensive assessment model for the ecological environmental quality in Hangzhou urban area was established. In comparison with observed urban heat island effects, the assessment results were in good agreement with the ecological environmental quality in the urban area of Hangzhou.

Environmental Methods Review: Retooling Impact Assessment for the New Century

Science.gov (United States)

1998-03-01

Environmental Assessment Research Council. Netherlands, Commission for Environmental Impact Assessment. 1993. Year book of the Commission for Environmental...professional standards. Currently. the main avenues to obtain information in order to maintain or improve competence include: • journals. books ...World Wide Web • professional associations and networks such as IAIA. All of these. however. rely on using the expertise of others secondhand . Who

Environmental assessment: Industry perspective

International Nuclear Information System (INIS)

Meadley, T.

1994-01-01

The Canadian mining industry supports the concept of environmental assessment, but the current process at the time of the conference had a number of problems that the industry felt should be addressed. The author makes the following suggestions: that the process for individual projects should be separated from policy issues; that panel members should be drawn from a full-time staff; that there should be better referral criteria to determine which projects require full scale assessment including public hearings; that either the government or project opponents should participate but not both; that the financial burden on proponents should be reduced; that funding of intervenors should be controlled; that there should be a definite time frame

An investigation of environmental and sustainability discourses associated with the substantive purposes of environmental assessment

Energy Technology Data Exchange (ETDEWEB)

Rozema, Jaap G., E-mail: j.rozema@uea.ac.uk [Science, Society and Sustainability Research Group, School of Environmental Sciences, University of East Anglia (UEA), Norwich, NR4 7TJ (United Kingdom); Bond, Alan J., E-mail: alan.bond@uea.ac.uk [Science, Society and Sustainability Research Group, School of Environmental Sciences, University of East Anglia (UEA), Norwich, NR4 7TJ (United Kingdom); Cashmore, Matthew, E-mail: cashmore@plan.aau.dk [Danish Centre for Environmental Assessment, Department of Development and Planning, Aalborg University, Fibigerstraede 13, 9220 Aalborg O (Denmark); Chilvers, Jason, E-mail: jason.chilvers@uea.ac.uk [Science, Society and Sustainability Research Group, School of Environmental Sciences, University of East Anglia (UEA), Norwich, NR4 7TJ (United Kingdom)

2012-02-15

This paper investigates the discursive construction of the substantive purposes of environmental assessment (EA). It addresses these purposes by exploring the complex and often multifaceted linkages between political factors and plural views of democracy, public participation, and the role of science that are embedded in environmental and sustainability discourses. The interaction between policy-making and public actors leads to the formulation of divergent and potentially competing rationales for public participation, and for social appraisal more generally. Participatory approaches have also given impetus to the development of several interpretations on the role of science in assessment procedures. Science is important in mediating public participation and the two are therefore reciprocally linked. This leads to discourses that become manifest in the construction of substantive purposes. Discourse analysis in EA is a relevant method for examining trends and patterns in sustainable development. It is argued that public participation is an important, if not decisive, variable in the articulation and civil legitimacy of certain purposes. A general proposition that results from this paper is that EA, although typically presented as an objective scientific tool, is an intrinsically normative process. Enhanced knowledge on the construction, and reconstruction over time, of substantive purposes is required if environmental and sustainability discourses are to be used and understood as meaningful analytical instruments to assess the socio-political implications of EA. - Highlights: Black-Right-Pointing-Pointer Substantive purposes related to environmental assessment may be best analyzed through discourse analysis. Black-Right-Pointing-Pointer Environmental and sustainability discourses are contingent on the level of participatory democracy and civic science. Black-Right-Pointing-Pointer Public participation is a decisive variable in the construction of the substantive

An investigation of environmental and sustainability discourses associated with the substantive purposes of environmental assessment

International Nuclear Information System (INIS)

Rozema, Jaap G.; Bond, Alan J.; Cashmore, Matthew; Chilvers, Jason

2012-01-01

This paper investigates the discursive construction of the substantive purposes of environmental assessment (EA). It addresses these purposes by exploring the complex and often multifaceted linkages between political factors and plural views of democracy, public participation, and the role of science that are embedded in environmental and sustainability discourses. The interaction between policy-making and public actors leads to the formulation of divergent and potentially competing rationales for public participation, and for social appraisal more generally. Participatory approaches have also given impetus to the development of several interpretations on the role of science in assessment procedures. Science is important in mediating public participation and the two are therefore reciprocally linked. This leads to discourses that become manifest in the construction of substantive purposes. Discourse analysis in EA is a relevant method for examining trends and patterns in sustainable development. It is argued that public participation is an important, if not decisive, variable in the articulation and civil legitimacy of certain purposes. A general proposition that results from this paper is that EA, although typically presented as an objective scientific tool, is an intrinsically normative process. Enhanced knowledge on the construction, and reconstruction over time, of substantive purposes is required if environmental and sustainability discourses are to be used and understood as meaningful analytical instruments to assess the socio-political implications of EA. - Highlights: ► Substantive purposes related to environmental assessment may be best analyzed through discourse analysis. ► Environmental and sustainability discourses are contingent on the level of participatory democracy and civic science. ► Public participation is a decisive variable in the construction of the substantive purpose of environmental assessment.

Graphical Methodology of Global Pollution Index for the Environmental Impact Assessment Using Two Environmental Components

Directory of Open Access Journals (Sweden)

Corneliu Cojocaru

2017-04-01

Full Text Available One of the applied methods for environmental impact assessment is the index of global pollution (IGP proposed by Rojanschi in 1991. This methodology enables the global estimation for the ecosystem state affected more or less by human activities. Unfortunately, Rojanschi’s method has a limitation; it can be applied only if at least three environmental components are considered. Frequently, many environmental impact assessment applications rely on analysis of only two environmental components. Therefore, this work aimed to develop a new graphical method to extend Rojanschi’s approach for the case of two environmental components. The proposed method avoids the average value of evaluation grades and uses only the graphical correspondence for calculation of the index of global pollution. A right-angle triangle graph methodology was proposed, where bases represented the values of evaluation grades. Thus, for the case of two environmental components, the index of global pollution was calculated as the relation between the ideal and real ecosystem states represented by the ratio between areas of external and enclosed right triangles. The developed graphical method was tested and validated for real case studies: the environmental impact assessment from a refinery located on the Romanian Black Sea Coast considering Air and Water environmental components and from a coal-fired thermoelectric power plant from Eastern Romania regarding Air and Soil environmental components. In this way, it was provided a reliable and faster tool to be used for the pollution characterization of human-derived chemicals for better decisions in risk management.

The Gyc76C Receptor Guanylyl Cyclase and the Foraging cGMP-Dependent Kinase Regulate Extracellular Matrix Organization and BMP Signaling in the Developing Wing of Drosophila melanogaster.

Directory of Open Access Journals (Sweden)

Justin Schleede

2015-10-01

Full Text Available The developing crossveins of the wing of Drosophila melanogaster are specified by long-range BMP signaling and are especially sensitive to loss of extracellular modulators of BMP signaling such as the Chordin homolog Short gastrulation (Sog. However, the role of the extracellular matrix in BMP signaling and Sog activity in the crossveins has been poorly explored. Using a genetic mosaic screen for mutations that disrupt BMP signaling and posterior crossvein development, we identify Gyc76C, a member of the receptor guanylyl cyclase family that includes mammalian natriuretic peptide receptors. We show that Gyc76C and the soluble cGMP-dependent kinase Foraging, likely linked by cGMP, are necessary for normal refinement and maintenance of long-range BMP signaling in the posterior crossvein. This does not occur through cell-autonomous crosstalk between cGMP and BMP signal transduction, but likely through altered extracellular activity of Sog. We identify a novel pathway leading from Gyc76C to the organization of the wing extracellular matrix by matrix metalloproteinases, and show that both the extracellular matrix and BMP signaling effects are largely mediated by changes in the activity of matrix metalloproteinases. We discuss parallels and differences between this pathway and other examples of cGMP activity in both Drosophila melanogaster and mammalian cells and tissues.

Model of environmental life cycle assessment for coal mining operations.

Science.gov (United States)

Burchart-Korol, Dorota; Fugiel, Agata; Czaplicka-Kolarz, Krystyna; Turek, Marian

2016-08-15

This paper presents a novel approach to environmental assessment of coal mining operations, which enables assessment of the factors that are both directly and indirectly affecting the environment and are associated with the production of raw materials and energy used in processes. The primary novelty of the paper is the development of a computational environmental life cycle assessment (LCA) model for coal mining operations and the application of the model for coal mining operations in Poland. The LCA model enables the assessment of environmental indicators for all identified unit processes in hard coal mines with the life cycle approach. The proposed model enables the assessment of greenhouse gas emissions (GHGs) based on the IPCC method and the assessment of damage categories, such as human health, ecosystems and resources based on the ReCiPe method. The model enables the assessment of GHGs for hard coal mining operations in three time frames: 20, 100 and 500years. The model was used to evaluate the coal mines in Poland. It was demonstrated that the largest environmental impacts in damage categories were associated with the use of fossil fuels, methane emissions and the use of electricity, processing of wastes, heat, and steel supports. It was concluded that an environmental assessment of coal mining operations, apart from direct influence from processing waste, methane emissions and drainage water, should include the use of electricity, heat and steel, particularly for steel supports. Because the model allows the comparison of environmental impact assessment for various unit processes, it can be used for all hard coal mines, not only in Poland but also in the world. This development is an important step forward in the study of the impacts of fossil fuels on the environment with the potential to mitigate the impact of the coal industry on the environment. Copyright © 2016 Elsevier B.V. All rights reserved.

Determining Vulnerability Importance in Environmental Impact Assessment

International Nuclear Information System (INIS)

Toro, Javier; Duarte, Oscar; Requena, Ignacio; Zamorano, Montserrat

2012-01-01

The concept of vulnerability has been used to describe the susceptibility of physical, biotic, and social systems to harm or hazard. In this sense, it is a tool that reduces the uncertainties of Environmental Impact Assessment (EIA) since it does not depend exclusively on the value assessments of the evaluator, but rather is based on the environmental state indicators of the site where the projects or activities are being carried out. The concept of vulnerability thus reduces the possibility that evaluators will subjectively interpret results, and be influenced by outside interests and pressures during projects. However, up until now, EIA has been hindered by a lack of effective methods. This research study analyzes the concept of vulnerability, defines Vulnerability Importance and proposes its inclusion in qualitative EIA methodology. The method used to quantify Vulnerability Importance is based on a set of environmental factors and indicators that provide a comprehensive overview of the environmental state. The results obtained in Colombia highlight the usefulness and objectivity of this method since there is a direct relation between this value and the environmental state of the departments analyzed. - Research Highlights: ► The concept of vulnerability could be considered defining Vulnerability Importance included in qualitative EIA methodology. ► The use of the concept of environmental vulnerability could reduce the subjectivity of qualitative methods of EIA. ► A method to quantify the Vulnerability Importance proposed provides a comprehensive overview of the environmental state. ► Results in Colombia highlight the usefulness and objectivity of this method.

Assessing the wider environmental value of remediating land contamination

NARCIS (Netherlands)

Bardos, R.P.; Kearney, T.E.; Nathanail, C.P.; Weenk, A.; Martin, I.D.

2000-01-01

The aim of this paper is to consider qualitative and quantitative approaches for assessing the wider environmental value of remediating land contamination. In terms of the environmental element of sustainable development, a remediation project's overall environmental performance is the sum of the

Proposing an Environmental Excellence Self-Assessment Model

DEFF Research Database (Denmark)

Meulengracht Jensen, Peter; Johansen, John; Wæhrens, Brian Vejrum

2013-01-01

that the EEA model can be used in global organizations to differentiate environmental efforts depending on the maturity stage of the individual sites. Furthermore, the model can be used to support the decision-making process regarding when organizations should embark on more complex environmental efforts......This paper presents an Environmental Excellence Self-Assessment (EEA) model based on the structure of the European Foundation of Quality Management Business Excellence Framework. Four theoretical scenarios for deploying the model are presented as well as managerial implications, suggesting...

Risk and environmental impact assessment: nuclear and environmental licensing interface

International Nuclear Information System (INIS)

Costa, Eduardo M.; Monteiro, Iara A.

1997-01-01

The main aims of this paper are the identification and discussion of interfaces and application of common concepts in the existing nuclear and environmental licensing procedures. Risk and impact assessment of nuclear electricity generation are two of these concepts which are discussed detail. The risk concept, which had initially focused on engineering projects, has been extended to many other areas of human activity. Risk resulting from the use of ionization radiation has been associated to the dose for the critical members of the public. Therefore, radiation protection applies basic dose limits which are established in national and international recommendations. These recommendations are increasing the emphasis to keep all the exposures to ionizing radiation as low as reasonable achievable, economical and social factors being taken into account. On the other hand, environmental impact assessment has been used as a tool in planning and decision-making processes, thus including environmental concern in the discussion of social and economical development strategies. This paper aims to discuss the association of these two concepts by presenting the procedures of control of radiological impact during normal operation of a nuclear power plant and the various forms of risk communication to the public in the case of events occurrence. (author). 13 refs

Citizen involvement in sustainability-centred environmental assessment follow-up

International Nuclear Information System (INIS)

Hunsberger, Carol A.; Gibson, Robert B.; Wismer, Susan K.

2005-01-01

In Canada, many project proponents and planners in the public and private sectors are required to forecast and minimize the adverse environmental effects of their undertakings. However, environmental assessments have traditionally been weak in the areas of planning and conducting effective monitoring, encouraging public participation, integrating social and ecological considerations, encouraging environmental rehabilitation and enhancement, and examining cumulative effects of multiple projects. This paper attempts to address these deficiencies together by drawing from theory and practice in citizen-based monitoring, in the interests of sustainable livelihoods, using local knowledge. Informed by case study research in several regions of Canada, the discussion focuses on opportunities for using citizen-based approaches to broad and continuing regional monitoring as a foundation for the project-centred work that is the usual concern of environmental assessment follow-up. Such approaches have advantages beyond the usual expectations of project-centred monitoring and beyond the conventional arguments for increasing local involvement in environmental assessments. However, there are also challenges including those of integrating local and conventional (or scientific) knowledge systems, addressing concerns about the credibility and biases of citizens and project proponents, ensuring attention to broader sustainability goals such as increased stewardship and civility, and developing practical ways of coordinating and funding integrated and participatory monitoring programs. The concluding recommendations call for a dramatically different approach to follow-up activities on the part of private and public project proponents, as well as novel thinking for environmental assessment practitioners

Phenotype overlap in Xylella fastidiosa is controlled by the cyclic di-GMP phosphodiesterase Eal in response to antibiotic exposure and diffusible signal factor-mediated cell-cell signaling.

Science.gov (United States)

de Souza, Alessandra A; Ionescu, Michael; Baccari, Clelia; da Silva, Aline M; Lindow, Steven E

2013-06-01

Eal is an EAL domain protein in Xylella fastidiosa homologous to one involved in resistance to tobramycin in Pseudomonas aeruginosa. EAL and HD-GYP domain proteins are implicated in the hydrolysis of the secondary messenger bis-(3'-5')-cyclic dimeric GMP (cyclic di-GMP). Cell density-dependent communication mediated by a Diffusible Signal Factor (DSF) also modulates cyclic di-GMP levels in X. fastidiosa, thereby controlling the expression of virulence genes and genes involved in insect transmission. The possible linkage of Eal to both extrinsic factors such as antibiotics and intrinsic factors such as quorum sensing, and whether both affect virulence, was thus addressed. Expression of eal was induced by subinhibitory concentrations of tobramycin, and an eal deletion mutant was more susceptible to this antibiotic than the wild-type strain and exhibited phenotypes similar to those of an rpfF deletion mutant blocked in DSF production, such as hypermotility, reduced biofilm formation, and hypervirulence to grape. Consistent with that, the rpfF mutant was more susceptible than the wild-type strain to tobramycin. Therefore, we propose that cell-cell communication and antibiotic stress can apparently lead to similar modulations of cyclic di-GMP in X. fastidiosa, resulting in similar phenotypes. However, the effect of cell density is dominant compared to that of antibiotic stress, since eal is suppressed by RpfF, which may prevent inappropriate behavioral changes in response to antibiotic stress when DSF accumulates.

Environmental sustainability assessment of palm biodiesel production in Thailand

International Nuclear Information System (INIS)

Silalertruksa, Thapat; Gheewala, Shabbir H.

2012-01-01

The study assesses the environmental sustainability of palm biodiesel production systems in Thailand by focusing on their energy efficiency and environmental impact potentials. The Net Energy Balance (NEB) and Renewability indicate energy gain for palm biodiesel and its co-products as compared to fossil energy inputs. In addition, life cycle assessment also reveals lower values of environmental impact potentials of biodiesel as compared to conventional diesel. For example, palm biodiesel can provide greenhouse gas (GHG) reduction of around 46–73% as compared to diesel. Nitrogen-fertilizer production and application in the plantation and the air emissions from the ponds treating palm oil mill effluent (POME) are found to be the major environmental aspects. However, the energy and environmental performances depend on various factors such as the management efficiency of empty fruit bunches (EFB) and POME and the possible land-use change in the future. Recommendations are made for improving environmental performance of palm biodiesel and for securing the long-term availability of crude palm oil supply with a view towards sustainable palm biodiesel production. -- Highlights: ► Environmental sustainability of palm biodiesel production in Thailand is assessed. ► Palm biodiesel can provide GHG reduction of around 46–73% as compared to diesel. ► Net energy ratio and renewability of palm biodiesel both range between 2 and 4. ► Efficient use of by-products in the value chain enhances environmental benefits.

Draft environmental assessment: Ocean Thermal Energy Conversion (OTEC) Pilot Plants

Energy Technology Data Exchange (ETDEWEB)

Sullivan, S.M.; Sands, M.D.; Donat, J.R.; Jepsen, P.; Smookler, M.; Villa, J.F.

1981-02-01

This Environmental Assessment (EA) has been prepared, in accordance with the National Environmental Policy Act of 1969, for the deployment and operation of a commercial 40-Megawatt (MW) Ocean Thermal Energy Conversion (OTEC) Pilot Plant (hereafter called the Pilot Plant). A description of the proposed action is presented, and a generic environment typical of the candidate Pilot Plant siting regions is described. An assessment of the potential environmental impacts associated with the proposed action is given, and the risk of credible accidents and mitigating measures to reduce these risks are considered. The Federal and State plans and policies the proposed action will encompass are described. Alternatives to the proposed action are presented. Appendix A presents the navigation and environmental information contained in the US Coast Pilot for each of the candidate sites; Appendix B provides a brief description of the methods and calculations used in the EA. It is concluded that environmental disturbances associated with Pilot Plant activities could potentially cause significant environmental impacts; however, the magnitude of these potential impacts cannot presently be assessed, due to insufficient engineering and environmental information. A site- and design-specific OTEC Pilot Plant Environmental Impact Statement (EIS) is required to resolve the potentially significant environmental effects associated with Pilot Plant deployment and operation. (WHK)

The DNA sensor, cyclic GMP-AMP synthase, is essential for induction of IFN-β during Chlamydia trachomatis infection.

Science.gov (United States)

Zhang, Yugen; Yeruva, Laxmi; Marinov, Anthony; Prantner, Daniel; Wyrick, Priscilla B; Lupashin, Vladimir; Nagarajan, Uma M

2014-09-01

IFN-β has been implicated as an effector of oviduct pathology resulting from genital chlamydial infection in the mouse model. In this study, we investigated the role of cytosolic DNA and engagement of DNA sensors in IFN-β expression during chlamydial infection. We determined that three-prime repair exonuclease-1, a host 3' to 5' exonuclease, reduced IFN-β expression significantly during chlamydial infection using small interfering RNA and gene knockout fibroblasts, implicating cytosolic DNA as a ligand for this response. The DNA sensor cyclic GMP-AMP synthase (cGAS) has been shown to bind cytosolic DNA to generate cyclic GMP-AMP, which binds to the signaling adaptor stimulator of IFN genes (STING) to induce IFN-β expression. We determined that cGAS is required for IFN-β expression during chlamydial infection in multiple cell types. Interestingly, although infected cells deficient for STING or cGAS alone failed to induce IFN-β, coculture of cells depleted for either STING or cGAS rescued IFN-β expression. These data demonstrate that cyclic GMP-AMP produced in infected cGAS(+)STING(-) cells can migrate into adjacent cells via gap junctions to function in trans in cGAS(-)STING(+) cells. Furthermore, we observed cGAS localized in punctate regions on the cytosolic side of the chlamydial inclusion membrane in association with STING, indicating that chlamydial DNA is most likely recognized outside the inclusion as infection progresses. These novel findings provide evidence that cGAS-mediated DNA sensing directs IFN-β expression during Chlamydia trachomatis infection and suggest that effectors from infected cells can directly upregulate IFN-β expression in adjacent uninfected cells during in vivo infection, contributing to pathogenesis. Copyright © 2014 by The American Association of Immunologists, Inc.

Human platelet lysate in mesenchymal stromal cell expansion according to a GMP grade protocol: a cell factory experience.

Science.gov (United States)

Becherucci, Valentina; Piccini, Luisa; Casamassima, Serena; Bisin, Silvia; Gori, Valentina; Gentile, Francesca; Ceccantini, Riccardo; De Rienzo, Elena; Bindi, Barbara; Pavan, Paola; Cunial, Vanessa; Allegro, Elisa; Ermini, Stefano; Brugnolo, Francesca; Astori, Giuseppe; Bambi, Franco

2018-05-02

The use of platelet lysate (PL) for the ex-vivo expansion of mesenchymal stromal/stem cells (MSCs) was initially proposed by Doucet et al. in 2005, as an alternative to animal serum. Moreover, regulatory authorities discourage the use of fetal bovine serum (FBS) or other animal derivatives, to avoid risk of zoonoses and xenogeneic immune reactions. Even if many studies investigated PL composition, there still are some open issues related to its use in ex-vivo MSC expansion, especially according to good manufacturing practice (GMP) grade protocols. As an authorized cell factory, we report our experience using standardized PL produced by Azienda Ospedaliero Universitaria Meyer Transfusion Service for MSC expansion according to a GMP grade clinical protocol. As suggested by other authors, we performed an in-vitro test on MSCs versus MSCs cultured with FBS that still represents the best way to test PL batches. We compared 12 MSC batches cultured with DMEM 5% PL with similar batches cultured with DMEM 10% FBS, focusing on the MSC proliferation rate, MSC surface marker expression, MSC immunomodulatory and differentiation potential, and finally MSC relative telomere length. Results confirmed the literature data as PL increases cell proliferation without affecting the MSC immunophenotype, immunomodulatory potential, differentiation potential and relative telomere length. PL can be considered a safe alternative to FBS for ex-vivo expansion of MSC according to a GMP grade protocol. Our experience confirms the literature data: a large number of MSCs for clinical applications can be obtained by expansion with PL, without affecting the MSC main features. Our experience underlines the benefits of a close collaboration between the PL producers (transfusion service) and the end users (cell factory) in a synergy of skills and experiences that can lead to standardized PL production.

Brain Region-Specific Effects of cGMP-Dependent Kinase II Knockout on AMPA Receptor Trafficking and Animal Behavior

Science.gov (United States)

Kim, Seonil; Pick, Joseph E.; Abera, Sinedu; Khatri, Latika; Ferreira, Danielle D. P.; Sathler, Matheus F.; Morison, Sage L.; Hofmann, Franz; Ziff, Edward B.

2016-01-01

Phosphorylation of GluA1, a subunit of AMPA receptors (AMPARs), is critical for AMPAR synaptic trafficking and control of synaptic transmission. cGMP-dependent protein kinase II (cGKII) mediates this phosphorylation, and cGKII knockout (KO) affects GluA1 phosphorylation and alters animal behavior. Notably, GluA1 phosphorylation in the KO…

Modern biogeochemistry environmental risk assessment

CERN Document Server

Bashkin, Vladimir N

2006-01-01

Most books deal mainly with various technical aspects of ERA description and calculationsAims at generalizing the modern ideas of both biogeochemical and environmental risk assessment during recent yearsAims at supplementing the existing books by providing a modern understanding of mechanisms that are responsible for the ecological risk for human beings and ecosystem

Environmental impact assessment around TRIGA research reactor

International Nuclear Information System (INIS)

Lee, Jeong Ho; Lee, Hyun Duk; Lee, Young Bok; Cheong, Kyu Hoi; Ahn, Jong Sung; Kim, Kug Chan; You, Byung Sun; Kim, Byung Woo; Kim, Sang Bok; Han Moon Hee

1985-01-01

Population distribution, atmospheric change, X/Q, characteristics of terrestrial ecosystem around Seoul site were surveyed. Environmental radiation and radioactivities such as grossα, grossβ, Cs-137, Sr-90 and H-3 of various environmental samples were analyzed. The values of environmental radiation dose tended to increase gradually in the light of the recent five years' results of environmental radiation monitoring around the nuclear power plants from 1980 to 1984, however, the changes were not significant. In addition, continuous assessment of environmental radiation monitoring on the roofs of main building and life science building at KAERI showed that the environmental radiation dose tended to increase a little during the night time. Judging from the above results, it is concluded that environmental contamination level by radioactive materials could be ignored in the case of radioisotope production or experiment using radioisotopes except the release of gaseous radioactive materials such as Ar-41 of short half life by the operation of nuclear reactor. (Author)

Assessing environmental impacts in a life cycle perspective

DEFF Research Database (Denmark)

Hauschild, Michael Zwicky

2005-01-01

is focused on the product system which comprises all the processes which the product and its components meet throughout their lives- from the extraction of raw materials via manufacture, use and waste management to final disposal, or in short from the cradle to the grave (see Figure 1). The focus......What are the environmental impacts from an armchairor a cellular phone or a steak, if you take into account all the activities needed to produce, maintain, use or consume and eventually dispose of it? Life cycle impact assessment is the part of life cycle assessment (LCA) where the inventory...... of material flows in the life cycle of a product are translated into environmental impacts and consumption of resources, and questions like these are given an answer. The environmental impacts may range from very local (e.g. land use) to global (like climate change). As an environmental analysis tool, LCA...

Environmental site assessments should include radon gas testing

International Nuclear Information System (INIS)

Nardi, M.A.

1991-01-01

There are two emerging influences that will require radon gas testing as part of many property transfers and most site assessments. These requirements come from lending regulators and state legislatures. Fannie Mae and others have developed environmental investigation guidelines for the purchase of environmentally contaminated real estate. These guidelines include radon gas testing for many properties. Several states have enacted laws that require environmental disclosure forms be prepared to ensure that the parties involved in certain real estate transactions are aware of the environmental liabilities that may come with the transfer of property. Indiana has recently enacted legislation that would require the disclosure of the presence of radon gas on many commercial real estate transactions. With more lenders and state governments likely to follow this trend, radon gas testing should be performed during all property transfers and site assessment to protect the parties involved from any legal liabilities

Andrographolide inhibits hypoxia-induced hypoxia-inducible factor 1α and endothelin 1 expression through the heme oxygenase 1/CO/cGMP/MKP-5 pathways in EA.hy926 cells.

Science.gov (United States)

Lin, Hung-Chih; Su, Shih-Li; Lin, Wan-Chun; Lin, Ai-Hsuan; Yang, Ya-Chen; Lii, Chong-Kuei; Chen, Haw-Wen

2018-03-01

Andrographolide is a potent anti-inflammatory agent found in Andrographis paniculata. Endothelin 1 (ET-1) is an endothelium-derived vasoconstrictor with pro-inflammatory properties secreted in response to hypoxia. Mitogen-activated protein kinase phosphatase 5 (MKP-5) is a dual-specificity phosphatase that dephosphorylates threonine and tyrosine residues of MAPKs. We showed previously that hypoxia-induced HIF-1α expression and ET-1 secretion are dependent on p38 MAPK in EA.hy926 cells. Here, we investigate what role MKP-5 plays in andrographolide's inhibition of hypoxia-induced expression of HIF-1α and ET-1. Hypoxic conditions were created using the hypoxia-mimetic agent CoCl 2 . Andrographolide enhanced HO-1 and MKP-5 expression and cellular cGMP content in addition to inhibiting hypoxia-induced ROS generation. Concomitantly, the HO-1 byproduct CO and the cGMP analogue 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) increased MKP-5 expression, and pretreatment with CO and 8-Br-cGMP inhibited hypoxia-induced HIF-1α and ET-1 expression. Transfection of HO-1 siRNA or pretreatment with the HO-1 inhibitor ZnPP-9 or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a specific inhibitor of soluble guanylate cyclase, reduced andrographolide-induced MKP-5 expression. Moreover, silencing MKP-5 or treatment with the phosphatase inhibitor vanadate abrogated andrographolide's suppressing hypoxia-induced p38 MAPK activation and HIF-1α expression. The inhibition of hypoxia-induced HIF-1α and ET-1 expression by andrographolide is likely associated with HO-1/CO/cGMP/MKP-5 pathways, which is involved in inhibiting hypoxia-induced p38 MAPK activation. © 2017 Wiley Periodicals, Inc.

Radiation environmental impact assessment of the radioisotope's application on nuclear medical science

International Nuclear Information System (INIS)

Liu Hongshi

2004-01-01

The radiation environmental impact assessment of the radioisotope's application on nuclear medical science is introduced, including the assessment criteria, the assessment methods and the environmental impact assessment of three wastes emission. (authors)

The screening and scoping of Environmental Impact Assessment and Strategic Environmental Assessment of Carbon Capture and Storage in the Netherlands

International Nuclear Information System (INIS)

Koornneef, Joris; Faaij, Andre; Turkenburg, Wim

2008-01-01

The Environmental Impact Assessment (EIA) and Strategic Environmental Assessment (SEA) are procedural tools which have as goal to assess and evaluate possible environmental effects of, respectively, a proposed project or policy plan. The goal of this article is to explore possible bottlenecks in applying both the EIA and SEA procedures on Carbon Capture and Storage (CCS) activities in the Netherlands, as experience is currently minimal or lacking. In this study we focus mainly on the institutional and procedural aspects of the screening and scoping phases of both procedures. This is achieved by reviewing EIA and SEA procedures for analogue projects for the three distinctive process steps of a CCS project, namely the power plant with capture, the transport and finally the underground storage of the CO 2 . Additionally, EIA and SEA or similar procedures on CCS in other countries are reviewed and the legal framework for the Dutch EIA and SEA is studied. This article shows a concise overview of the EIA and SEA procedure in the Netherlands and the relation between both procedures. Based on our findings we have constructed a conceptual taxonomy for the scope of both procedures for CCS in the Netherlands. This taxonomy conceptualizes the possible integration of assessing the environmental impacts for tiered levels of decision making. This integration might be needed for first CCS projects as decisions on the strategic (spatial planning) level are currently absent for CCS in the Netherlands. Perpendicular to such integration is the integration of linked activities in the CCS chain and their alternatives, into one procedure. We argue that it would be beneficial to combine the separate EIA procedures for CCS activities into one procedure or at least provide close linkage between them. This issue should be carefully considered by regulators, competent authorities and project initiators in an early stage to avoid delaying legal procedures in the future. For the same reason

Using Art to Assess Environmental Education Outcomes

Science.gov (United States)

Flowers, Ami A.; Carroll, John P.; Green, Gary T.; Larson, Lincoln R.

2015-01-01

Construction of developmentally appropriate tools for assessing the environmental attitudes and awareness of young learners has proven to be challenging. Art-based assessments that encourage creativity and accommodate different modes of expression may be a particularly useful complement to conventional tools (e.g. surveys), but their efficacy and…

New technologies - How to assess environmental effects

Science.gov (United States)

Sullivan, P. J.; Lavin, M. L.

1981-01-01

A method is provided for assessing the environmental effects of a room-and-pillar mining system (RP) and a new hydraulic borehole mining system (HBM). Before environmental assessment can begin, each technology is defined in terms of its engineering characteristics at both the conceptual and preliminary design stages. The mining sites are also described in order to identify the significant advantages and constraints for each system. This can be a basic physical and biological survey of the region at the conceptual stage, but a more specific representation of site characteristics is required at the preliminary stage. Assessment of potential environmental effects of each system at the conceptual design is critical to its hardware development and application. A checklist can be used to compare and identify the negative impacts of each method, outlining the resource affected, the type of impact involved, and the exact activity causing that impact. At the preliminary design stage, these impacts should be evaluated as a result of either utilization or alteration. Underground coal mining systems have three major utilization impacts - the total area disturbed, the total water resources withdrawn from other uses, and the overall energy efficiency of the process - and one major alteration impact - the degradation of water quality by sedimentation and acid contamination. A comparison of the RP and HBM systems shows the HBM to be an environmentally less desirable system for the Central Appalachia region.

Critical factors in environmental impact assessment

International Nuclear Information System (INIS)

Creasey, R.

1999-01-01

Environmental impact assessment (EIA) has shown that it is of proven benefit to the overall planning and environmental management of resource development projects, but certain elements within the application and practice of EIA remain problematic for proponents and regulatory decision makers alike. The use of the word 'critical' in the title of this paper suggests that if the components identified are not considered or implemented properly through the process of EIA, the product will be of less value to both the proponent and decision maker. In the context of EIA, the regulatory, financial, legal and social benefits that accrue make the need for good EIA practice even more imperative. A discussion is included that highlights a number of issues that need to be addressed to improve the effectiveness of EIA, a tool necessary to attaining provincial and federal regulatory approvals. To a large extent, the discussion reflects items of contemporary public concern, and those emerging issues of the scientific and regulatory community. At the same time, it needs to be realized that not all the identified items are necessarily new to the practice of impact assessment, but are nonetheless important to professional environmental impact assessment and decision making. Insight is also provided into the direction of decision making of the Energy and Utilities Board as it will affect the regulatory review and administration of resource development projects in the province of Alberta. 16 refs

The Contribution of Project Environmental Assessment to Assessing and Managing Cumulative Effects: Individually and Collectively Insignificant?

Science.gov (United States)

Noble, Bram; Liu, Jialang; Hackett, Paul

2017-04-01

This paper explores the opportunities and constraints to project-based environmental assessment as a means to support the assessment and management of cumulative environmental effects. A case study of the hydroelectric sector is used to determine whether sufficient information is available over time through project-by-project assessments to support an adequate understanding of cumulative change. Results show inconsistency from one project to the next in terms of the components and indicators assessed, limited transfer of baseline information between project assessments over time, and the same issues and concerns being raised by review panels-even though the projects reviewed are operating in the same watershed and operated by the same proponent. Project environmental assessments must be managed, and coordinated, as part of a larger system of impact assessment, if project-by-project assessments are to provide a meaningful forum for learning and understanding cumulative change. The paper concludes with recommendations for improved project-based assessment practice in support of cumulative effects assessment and management.

Formerly Utilized Sites Remedial Action Program environmental compliance assessment checklists

Energy Technology Data Exchange (ETDEWEB)

Levine, M.B.; Sigmon, C.F.

1989-09-29

The purpose of the Environmental Compliance Assessment Program is to assess the compliance of Formerly Utilized Site Remedial Action Program (FUSRAP) sites with applicable environmental regulations and Department of Energy (DOE) Orders. The mission is to identify, assess, and decontaminate sites utilized during the 1940s, 1950s, and 1960s to process and store uranium and thorium ores in support of the Manhattan Engineer District and the Atomic Energy Commission. To conduct the FUSRAP environmental compliance assessment, checklists were developed that outline audit procedures to determine the compliance status of the site. The checklists are divided in four groups to correspond to these regulatory areas: Hazardous Waste Management, PCB Management, Air Emissions, and Water Discharges.

Formerly Utilized Sites Remedial Action Program environmental compliance assessment checklists

International Nuclear Information System (INIS)

Levine, M.B.; Sigmon, C.F.

1989-01-01

The purpose of the Environmental Compliance Assessment Program is to assess the compliance of Formerly Utilized Site Remedial Action Program (FUSRAP) sites with applicable environmental regulations and Department of Energy (DOE) Orders. The mission is to identify, assess, and decontaminate sites utilized during the 1940s, 1950s, and 1960s to process and store uranium and thorium ores in support of the Manhattan Engineer District and the Atomic Energy Commission. To conduct the FUSRAP environmental compliance assessment, checklists were developed that outline audit procedures to determine the compliance status of the site. The checklists are divided in four groups to correspond to these regulatory areas: Hazardous Waste Management, PCB Management, Air Emissions, and Water Discharges