Effects of energetic restriction diet on butyrylcholinesterase in obese women from southern Brazil - A longitudinal study.

PubMed

Santos, Willian Dos; Tureck, Luciane Viater; Saliba, Louise Farah; Schenknecht, Caroline Schovanz; Scaraboto, Débora; Souza, Ricardo Lehtonen R; Furtado-Alle, Lupe

2017-01-01

Butyrylcholinesterase (BChE) activity has been associated with obesity, lipid concentrations, and CHE2 locus phenotypes. This, the aim of this study was to evaluate the effects of an energetic restriction diet intervention on anthropometrical and biochemical variables and on absolute and relative BChE activity in CHE2 C5+ and CHE2 C5- individuals. One hundred eleven premenopausal obese women from Southern Brazil participated in an energetic restriction diet intervention (deficit of 2500 kJ/day) for 8 weeks. Their anthropometric and biochemical parameters were evaluated before and after the intervention. Plasma BChE activity was measured, and BChE bands in plasma and CHE2 locus phenotypes were detected by electrophoresis. The dietetic intervention decreased anthropometric and biochemical parameters as well as absolute BChE activity and relative activity of the G4 band. The CHE2 C5+ phenotype presented a different effect when compared with the CHE2 C5- phenotype. The CHE2 C5+ phenotype showed an effect in absolute BChE activity and in the relative activity of the G4 form, maintaining higher BChE activity regardless of the metabolic changes. In our study, 8 weeks was not sufficient time to lower the body mass index to normal, but it was enough to significantly reduce the absolute BChE activity, which became similar to the levels in nonobese individuals. CHE2 C5+ individuals were resistant to the decrease in BChE activity compared to CHE2 C5- individuals. This shows that the diet did not affect the CHE2 and G4 fraction complex and that the products of the CHE2 locus in association with BChE have a role in energy metabolism, maintaining high levels of enzymatic activity even after dietary intervention.

Antibiofilm activity of coconut (Cocos nucifera Linn.) husk fibre extract.

PubMed

Viju, N; Satheesh, S; Vincent, S G P

2013-01-01

In this study, antibiofilm activity of coconut husk extract (CHE) was tested by various assays in the laboratory. The effects of CHE on extracellular polymeric substance (EPS) production, hydrophobicity and adhesion ability of Pseudomonas sp., Alteromonas sp. and Gallionella sp. and the antimicrobial activity of the extract against these bacteria were assessed. CHE was found to possess antibacterial activity against all the bacterial strains and affected the EPS production. The CHE affected the growth of the biofilm-forming bacteria in a culture medium. The hydrophobicity of the bacterial cells was also changed due to the CHE treatment. The active compound of the CHE was characterised by thin-layer chromatography (TLC), high performance liquid chromatography (HPLC) and fourier transform infrared (FT-IR) analysis. HPLC spectrum showed a single peak and the FT-IR spectrum indicated the presence of an OH-group-containing compound in the extract. In conclusion the CHE could be used as a source for the isolation of antifouling compounds.

Antibiofilm activity of coconut (Cocos nucifera Linn.) husk fibre extract

PubMed Central

Viju, N.; Satheesh, S.; Vincent, S.G.P.

2012-01-01

In this study, antibiofilm activity of coconut husk extract (CHE) was tested by various assays in the laboratory. The effects of CHE on extracellular polymeric substance (EPS) production, hydrophobicity and adhesion ability of Pseudomonas sp., Alteromonas sp. and Gallionella sp. and the antimicrobial activity of the extract against these bacteria were assessed. CHE was found to possess antibacterial activity against all the bacterial strains and affected the EPS production. The CHE affected the growth of the biofilm-forming bacteria in a culture medium. The hydrophobicity of the bacterial cells was also changed due to the CHE treatment. The active compound of the CHE was characterised by thin-layer chromatography (TLC), high performance liquid chromatography (HPLC) and fourier transform infrared (FT-IR) analysis. HPLC spectrum showed a single peak and the FT-IR spectrum indicated the presence of an OH-group-containing compound in the extract. In conclusion the CHE could be used as a source for the isolation of antifouling compounds. PMID:23961225

Characterization of plasma cholinesterase from the White stork (Ciconia ciconia) and its in vitro inhibition by anticholinesterase pesticides.

PubMed

Oropesa, Ana-Lourdes; Gravato, Carlos; Sánchez, Susana; Soler, Francisco

2013-11-01

Blood plasma cholinesterase (ChE) activity is a sensitive biomarker of exposure to organophosphorus (OP) and carbamate (CB) insecticides in vertebrates. Several studies indicate that more than one ChE form may be present in blood of birds. In this study the predominant ChE activity (acetylcholinesterase - AChE- or butyrylcholinesterase - BChE-), the range of ChE activity as well as ChE age-dependent changes in non-exposed individuals of White stork (Ciconia ciconia) have been established. The in vitro sensitivity of ChE to OP and CB insecticides such as paraoxon-methyl, carbofuran and carbaryl was also investigated. Plasma ChE was characterised using three substrates (acetylthiocholine iodide, propionylthiocholine iodide, and S-butyrylthiocholine iodide) and three ChE inhibitors (eserine sulphate, BW284C51 and iso-OMPA). The results indicated that propionylthiocholine was the preferred substrate by plasma cholinesterase followed by acetylcholine and butyrylcholine and the predominant enzymatic activity in plasma of White storks was BChE. Normal plasma BChE activity in White stork was 0.32±0.01μmol/min/ml for adults and 0.28±0.03μmol/min/ml for juveniles. So, the age had no significant effect on the range of BChE activity. The study on the in vitro inhibitory potential of tested anticholinesterase pesticides on plasma ChE activity revealed that paraoxon-methyl is the most potent inhibitor followed by carbofuran and finally by carbaryl. The percentage of in vitro plasma ChE inhibition was observed to be similar between adults and juveniles. Copyright © 2013 Elsevier Inc. All rights reserved.

Disruption of Chemoreceptor Signaling Arrays by High Levels of CheW, the Receptor-Kinase Coupling Protein

PubMed Central

Cardozo, Marcos J.; Massazza, Diego A.; Parkinson, John S.; Studdert, Claudia A.

2017-01-01

Summary During chemotactic signaling by Escherichia coli, the small cytoplasmic CheW protein couples the histidine kinase CheA to chemoreceptor control. Although essential for assembly and operation of receptor signaling complexes, CheW in stoichiometric excess disrupts chemotactic behavior. To explore the mechanism of the CheW excess effect, we measured the physiological consequences of high cellular levels of wild-type CheW and of several CheW variants with reduced or enhanced binding affinities for receptor molecules. We found that high levels of CheW interfered with trimer assembly, prevented CheA activation, blocked cluster formation, disrupted chemotactic ability, and elevated receptor methylation levels. The severity of these effects paralleled the receptor binding affinities of the CheW variants. Because trimer formation may be an obligate step in the assembly of ternary signaling complexes and higher-order receptor arrays, we suggest that all CheW excess effects stem from disruption of trimer assembly. We propose that the CheW-binding sites in receptor dimers overlap their trimer contact sites and that high levels of CheW saturate the receptor binding sites, preventing trimer assembly. The CheW-trapped receptor dimers seem to be improved substrates for methyltransferase reactions, but cannot activate CheA or assemble into clusters, processes that are essential for chemotactic signaling. PMID:20487303

Time course of cholinesterase inhibition in adult rats treated acutely with carbaryl, carbofuran, formetanate, methomyl, methiocarb, oxamyl or propoxur

DOE Office of Scientific and Technical Information (OSTI.GOV)

Padilla, S.; Marshall, R.S.; Hunter, D.L.

To compare the toxicity of seven N-methyl carbamates, time course profiles for brain and red blood cell (RBC) cholinesterase (ChE) inhibition were established for each. Adult, male, Long Evans rats (n = 4-5 dose group) were dosed orally with either carbaryl (30 mg/kg in corn oil); carbofuran (0.5 mg/kg in corn oil); formetanate HCl (10 mg/kg in water); methomyl (3 mg/kg in water); methiocarb (25 mg/kg in corn oil); oxamyl (1 mg/kg in water); or propoxur (20 mg/kg in corn oil). This level of dosing produced at least 40% brain ChE inhibition. Brain and blood were taken from 0.5 tomore » 24 h after dosing for analysis of ChE activity using two different methods: (1) a radiometric method which limits the amount of reactivation of ChE activity, and (2) a spectrophotometric method (Ellman method using traditional, unmodified conditions) which may encourage reactivation. The time of peak ChE inhibition was similar for all seven N-methyl carbamate pesticides: 0.5-1.0 h after dosing. By 24 h, brain and RBC ChE activity in all animals returned to normal. The spectrophotometric method underestimated ChE inhibition. Moreover, there was a strong, direct correlation between brain and RBC ChE activity (radiometric assay) for all seven compounds combined (r {sup 2} = 0.73, slope 1.1), while the spectrophotometric analysis of the same samples showed a poor correlation (r {sup 2} = 0.09). For formetanate, propoxur, methomyl, and methiocarb, brain and RBC ChE inhibitions were not different over time, but for carbaryl, carbofuran and oxamyl, the RBC ChE was slightly more inhibited than brain ChE. These data indicate (1) the radiometric method is superior for analyses of ChE activity in tissues from carbamate-treated animals (2) that animals treated with these N-methyl carbamate pesticides are affected rapidly, and recover rapidly, and (3) generally, assessment of RBC ChE is an accurate predictor of brain ChE inhibition for these seven pesticides.« less

The measurement of cholinesterase activities as a biomarker in chub (Leuciscus cephalus): the fish length should not be ignored.

PubMed

Flammarion, P; Noury, P; Garric, J

2002-01-01

Biomarkers are early warning systems of the exposure of aquatic organisms to pollutants. Among them, the measurement of the cholinesterase (ChE) activities in fish muscle is a biomarker of the exposure to organophosphosphates and carbamates pesticides. As such it has been used in numerous field studies both in marine and continental waters. Cyprinids (chub, Leuciscus cephalus) were sampled in river sites (France) in relatively clean and polluted areas. We performed the statistical analysis of the ChE activities and we generally observed a statistical relationship between ChE activities and fish length, the larger fish having the lower ChE activities. We concluded that the great majority of the significant differences in ChE activities between sites could be due in fact to differences in fish length between field samples. We stress the importance of taking into account the fish length whenever differences in ChE levels between field sites must be interpreted.

In vitro Cytotoxicity and Anti-herpes Simplex Virus Type 1 Activity of Hydroethanolic Extract, Fractions, and Isolated Compounds from Stem Bark of Schinus terebinthifolius Raddi.

PubMed

Nocchi, Samara Requena; de Moura-Costa, Gislaine Franco; Novello, Claudio Roberto; Rodrigues, Juliana; Longhini, Renata; de Mello, João Carlos Palazzo; Filho, Benedito Prado Dias; Nakamura, Celso Vataru; Ueda-Nakamura, Tânia

2016-01-01

Herpes simplex virus type 1 (HSV-1) is associated with orofacial infections and is transmitted by direct contact with infected secretions. Several efforts have been expended in the search for drugs to the treatment for herpes. Schinus terebinthifolius is used in several illnesses and among them, for the topical treatment of skin wounds, especially wounds of mucous membranes, whether infected or not. To evaluate the cytotoxicity and anti-HSV-1 activity of the crude hydroethanolic extract (CHE) from the stem bark of S. terebinthifolius, as well as its fractions and isolated compounds. The CHE was subjected to bioguided fractionation. The anti-HSV-1 activity and the cytotoxicity of the CHE, its fractions, and isolated compounds were evaluated in vitro by SRB method. A preliminar investigation of the action of CHE in the virus-host interaction was conducted by the same assay. CHE presented flavan-3-ols and showed anti-HSV-1 activity, better than its fractions and isolated compounds. The class of substances found in CHE can bind to proteins to form unstable complexes and enveloped viruses, as HSV-1 may be vulnerable to this action. Our results suggest that the CHE interfered with virion envelope structures, masking viral receptors that are necessary for adsorption or entry into host cells. The plant investigated exhibited potential for future development treatment against HSV-1, but further tests are necessary, especially to elucidate the mechanism of action of CHE, as well as preclinical and clinical studies to confirm its safety and efficacy. Crude hydroethanolic extract (CHE) presents promising activity against herpes simplex virus type 1 (HSV 1), with selectivity index (SI) = 22.50CHE has flavan-3-ols in its composition, such as catechin and gallocatechinThe fractions and isolated compounds obtained from CHE by bioguided fractionation are less active than the CHE against HSV-1CHE interferes with viral entry process in the host cell and acts directly on the viral particle. Abbreviations used: HSV: Herpes simplex virus, CHE: Crude hydroethanolic extract, WF: Water fraction, AF: Ethyl-acetate fraction, MPLC: Medium-performance liquid chromatography, TLC: Thin-layer chromatography, NMR: Nuclear magnetic resonance, ESI-MS: Electrospray ionization mass spectrometry, SRB: Sulforhodamine B, CPE: Cytopathic effect, CC50: 50% cytotoxic concentration, EC50: 50% effective concentration, PBS: Phosphate-buffered saline.

Recovery of cholinesterase activity in mallard ducklings administered organophosphorus pesticides

USGS Publications Warehouse

Fleming, W.J.; Bradbury, S.P.

1981-01-01

Oral doses of the organophosphorus pesticides acephate, dicrotophos, fensulfothion, fonofos, malathion, and parathion were administered to mallard ducklings (Anas platyrhynchos), and brain and plasma cholinesterase (ChE) activities were determined for up to 77 d after dosing. In vivo recovery of brain ChE activity to within 2 standard deviations of the mean activity of undosed birds occurred within 8 d, after being depressed an average of 25-58% at 24 h after dosing. In vivo recovery of plasma ChE appeared as fast as or faster than that of brain, but the pattern of recovery was more erratic and therefore statistical comparison with brain ChE recovery was not attempted. In vitro tests indicated that the potential for dephosphorylation to contribute to in vivo recovery of inhibited brain ChE differed among chemical treatments. Some ducklings died as a result of organophosphate dosing. In an experiment in which ducklings within each treatment group received the same dose (mg/kg), the brain ChE activity in birds that died was less than that in birds that survived. Brain ChE activities in ducklings that died were significantly different among pesticide treatments: fensulfothion > parathion> acephate > malathion (p < 0.05).

Identical phosphatase mechanisms achieved through distinct modes of binding phosphoprotein substrate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pazy, Y.; Motaleb, M.A.; Guarnieri, M.T.

2010-04-05

Two-component signal transduction systems are widespread in prokaryotes and control numerous cellular processes. Extensive investigation of sensor kinase and response regulator proteins from many two-component systems has established conserved sequence, structural, and mechanistic features within each family. In contrast, the phosphatases which catalyze hydrolysis of the response regulator phosphoryl group to terminate signal transduction are poorly understood. Here we present structural and functional characterization of a representative of the CheC/CheX/FliY phosphatase family. The X-ray crystal structure of Borrelia burgdorferi CheX complexed with its CheY3 substrate and the phosphoryl analogue BeF{sub 3}{sup -} reveals a binding orientation between a response regulatormore » and an auxiliary protein different from that shared by every previously characterized example. The surface of CheY3 containing the phosphoryl group interacts directly with a long helix of CheX which bears the conserved (E - X{sub 2} - N) motif. Conserved CheX residues Glu96 and Asn99, separated by a single helical turn, insert into the CheY3 active site. Structural and functional data indicate that CheX Asn99 and CheY3 Thr81 orient a water molecule for hydrolytic attack. The catalytic residues of the CheX-CheY3 complex are virtually superimposable on those of the Escherichia coli CheZ phosphatase complexed with CheY, even though the active site helices of CheX and CheZ are oriented nearly perpendicular to one other. Thus, evolution has found two structural solutions to achieve the same catalytic mechanism through different helical spacing and side chain lengths of the conserved acid/amide residues in CheX and CheZ.« less

Determining a threshold sub-acute dose leading to minimal physiological alterations following prolonged exposure to the nerve agent VX in rats.

PubMed

Bloch-Shilderman, E; Rabinovitz, I; Egoz, I; Yacov, G; Allon, N; Nili, U

2018-02-01

VX, a potent inhibitor of cholinesterase (ChE), is considered as one of the most toxic, persistent and least volatile nerve agents. VX is absorbed in various environmental surfaces and is gradually released long after its initial dispersal. Its toxicity is mainly caused by disrupting central and peripheral cholinergic nervous system activity, leading to potential long-term detrimental effects on health. The primary objective of the present study was to assess the threshold VX dose leading to minimal physiological alterations following prolonged VX exposure. Characterization of such a threshold is crucial for dealing with unresolved operative dilemmas such as when it is safe enough to resettle a population that has been evacuated from a VX-contaminated area. Rats, continuously exposed to various doses of VX (0.225-45 µg/kg/day) for 4 weeks via implanted mini-osmotic pumps, showed a dose-dependent and continuous decrease in ChE activity in whole blood, brain and muscles, ranging between 20 and 100%. Exposure to 13.5 µg/kg/day led to a stable low ChE activity level (~ 20%), accompanied by transient and negligible electrocorticogram spectral power transformations, especially in the theta and alpha brain wave frequencies, and a significant decrease in total brain M2 receptor density. These changes were neither accompanied by observable signs of intoxication nor by changes in motor function, circadian rhythm or TSPO level (a reliable marker of brain damage). Following exposure to lower doses of 2.25 and 0.225 µg/kg/day, the only change measured was a reduction in ChE activity of 60 and 20%, respectively. Based on these results, we delineate ChE inhibition as the physiological measure most susceptible to alterations following prolonged VX exposure, and determine for the first time the threshold sub-acute VX dose for minimal physiological effects (up to 20% reduction in ChE activity) in the rat as 0.225 µg/kg/day.

Recovery of cholinesterase activity in five avian species exposed to dicrotophos, an organophosphorus pesticide

USGS Publications Warehouse

Fleming, W.J.; Grue, C.E.

1981-01-01

The responses of brain and plasma cholinesterase (ChE) activities were examined in mallard ducks, bobwhite quail, barn owls, starlings, and common grackles given oral doses of dicrotophos, an organophosphorus insecticide. Up to an eightfold difference in response of brain ChE activity to dicrotophos was found among these species. Brain ChE activity recovered to within 2 SD of normal within 26 days after being depressed 55 to 64%. Recovery of brain ChE activity was similar among species and followed the model Y = a + b (log10X).

In vitro Cytotoxicity and Anti-herpes Simplex Virus Type 1 Activity of Hydroethanolic Extract, Fractions, and Isolated Compounds from Stem Bark of Schinus terebinthifolius Raddi

PubMed Central

Nocchi, Samara Requena; de Moura-Costa, Gislaine Franco; Novello, Claudio Roberto; Rodrigues, Juliana; Longhini, Renata; de Mello, João Carlos Palazzo; Filho, Benedito Prado Dias; Nakamura, Celso Vataru; Ueda-Nakamura, Tânia

2016-01-01

Background: Herpes simplex virus type 1 (HSV-1) is associated with orofacial infections and is transmitted by direct contact with infected secretions. Several efforts have been expended in the search for drugs to the treatment for herpes. Schinus terebinthifolius is used in several illnesses and among them, for the topical treatment of skin wounds, especially wounds of mucous membranes, whether infected or not. Objective: To evaluate the cytotoxicity and anti-HSV-1 activity of the crude hydroethanolic extract (CHE) from the stem bark of S. terebinthifolius, as well as its fractions and isolated compounds. Materials and Methods: The CHE was subjected to bioguided fractionation. The anti-HSV-1 activity and the cytotoxicity of the CHE, its fractions, and isolated compounds were evaluated in vitro by SRB method. A preliminar investigation of the action of CHE in the virus–host interaction was conducted by the same assay. Results: CHE presented flavan-3-ols and showed anti-HSV-1 activity, better than its fractions and isolated compounds. The class of substances found in CHE can bind to proteins to form unstable complexes and enveloped viruses, as HSV-1 may be vulnerable to this action. Our results suggest that the CHE interfered with virion envelope structures, masking viral receptors that are necessary for adsorption or entry into host cells. Conclusion: The plant investigated exhibited potential for future development treatment against HSV-1, but further tests are necessary, especially to elucidate the mechanism of action of CHE, as well as preclinical and clinical studies to confirm its safety and efficacy. SUMMARY Crude hydroethanolic extract (CHE) presents promising activity against herpes simplex virus type 1 (HSV 1), with selectivity index (SI) = 22.50CHE has flavan-3-ols in its composition, such as catechin and gallocatechinThe fractions and isolated compounds obtained from CHE by bioguided fractionation are less active than the CHE against HSV-1CHE interferes with viral entry process in the host cell and acts directly on the viral particle. Abbreviations used: HSV: Herpes simplex virus, CHE: Crude hydroethanolic extract, WF: Water fraction, AF: Ethyl-acetate fraction, MPLC: Medium-performance liquid chromatography, TLC: Thin-layer chromatography, NMR: Nuclear magnetic resonance, ESI-MS: Electrospray ionization mass spectrometry, SRB: Sulforhodamine B, CPE: Cytopathic effect, CC50: 50% cytotoxic concentration, EC50: 50% effective concentration, PBS: Phosphate-buffered saline. PMID:27076754

In vivo dose response relationship between physostigmine and cholinesterase activity in RBC and tissues of rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Somani, S.M.; Dube, S.N.

1989-01-01

Dose response of physostigmine (Phy) was studied in rat using various doses. Rats were sacrificed 15 min after Phy administration. Blood and tissues were analyzed for ChE activity by radiometric method and Phy concentration by HPLC method. A comparison of ChE values in different tissues of rats indicated that ChE activity was highest in brain and least in diaphragm. The enzyme activity was eleven times more in brain as compared to diaphragm. Phy produced a dose-dependent inhibition of ChE in RBC, brain and diaphragm from 50 to 200 {mu}g/kg, then ChE inhibition was plateaued from 200 to 500 {mu}g/kg inmore » these tissues. A dose related ChE inhibition was seen in heart and thigh muscle from 50 to 500 {mu}g/kg. Phy concentration increased linearly from 50 to 400 {mu}g/kg in plasma, brain, heart and thigh muscle. These results indicate that ChE inhibition is linear up to 200 {mu}g/kg in RBC, 150 {mu}g/kg in brain and 300 {mu}g/kg in heart. This linearity is not consistent in other tissues.« less

Brain cholinesterase activity of apparently normal wild birds

USGS Publications Warehouse

Hill, E.F.

1988-01-01

Organophosphorus and carbamate pesticides are potent anticholinesterase substances that have killed large numbers of wild birds of various species. Cause of death is diagnosed by demonstration of depressed brain cholinesterase (ChE) activity in combination with chemical detection of anticholinesterase residue in the affected specimen. ChE depression is determined by comparison of the affected specimen to normal ChE activity for a sample of control specimens of the same species, but timely procurement of controls is not always possible. Therefore, a reference file of normal whole brain ChE activity is provided for 48 species of wild birds from North America representing 11 orders and 23 families for use as emergency substitutes in diagnosis of anticholinesterase poisoning. The ChE values, based on 83 sets of wild control specimens from across the United States, are reproducible provided the described procedures are duplicated. Overall, whole brain ChE activity varied nearly three-fold among the 48 species represented, but it was usually similar for closely related species. However, some species were statistically separable in most families and some species of the same genus differed as much as 50%.

Brain cholinesterase activity of nestling great egrets, snowy egrets, and black-crowned night-herons

USGS Publications Warehouse

Custer, T.W.; Ohlendorf, H.M.

1989-01-01

Inhibition of brain cholinesterase (ChE) activity in birds is often used to diagnose exposure or death from organophosphorus or carbmate pesticides. Brain ChE activity in the young of altricial species increase with age; however, this relationship has only been demonstrated in the European starling (Sturnus vulgaris). Brain ChE activity of nestling great egrets (Casmerodius albus) collected from a colony in Texas increased significantly with age and did not differ among individuals from different nests. Brain ChE activity of nestling snowy egrets (Egretta thula) and black-crowned night -herons (Nycticorax nycticorax) collected in one colony each from Rhode Island, Texas, and California also increased significantly with age and did not differ among individuals from different nests or colonies. This study further demonstrates that age must be considered when evaluating exposure of nestling altricial birds to ChE inhibitors.

Brain cholinesterase activity of nestling great egrets snowy egrets and black-crowned night-herons

USGS Publications Warehouse

Custer, T.W.; Ohlendorf, H.M.

1989-01-01

Inhibition of brain cholinesterase (ChE) activity in birds is often used to diagnose exposure or death from organophosphorus or carbamate pesticides. Brain ChE activity in the young of altricial species increases with age; however, this relationship has only been demonstrated in the European starling (Sturnus vulgaris). Brain ChE activity of nestling great egrets (Casmerodius albus) collected from a colony in Texas (USA) increased significantly with age and did not differ among individuals from different nests. Brain ChE activity of nestling snowy egrets (Egretta thula) and black-crowned night-herons (Nycticorax nycticorax) collected in one colony each from Rhode Island, Texas and California (USA) also increased significantly with age and did not differ among individuals from different nests or colonies. This study further demonstrates that age must be considered when evaluating exposure of nestling altricial birds to ChE inhibitors.

Paradoxical enhancement of chemoreceptor detection sensitivity by a sensory adaptation enzyme

PubMed Central

Han, Xue-Sheng; Dahlquist, Frederick W.; Parkinson, John S.

2017-01-01

A sensory adaptation system that tunes chemoreceptor sensitivity enables motile Escherichia coli cells to track chemical gradients with high sensitivity over a wide dynamic range. Sensory adaptation involves feedback control of covalent receptor modifications by two enzymes: CheR, a methyltransferase, and CheB, a methylesterase. This study describes a CheR function that opposes the signaling consequences of its catalytic activity. In the presence of CheR, a variety of mutant serine chemoreceptors displayed up to 40-fold enhanced detection sensitivity to chemoeffector stimuli. This response enhancement effect did not require the known catalytic activity of CheR, but did involve a binding interaction between CheR and receptor molecules. Response enhancement was maximal at low CheR:receptor stoichiometry and quantitative analyses argued against a reversible binding interaction that simply shifts the ON–OFF equilibrium of receptor signaling complexes. Rather, a short-lived CheR binding interaction appears to promote a long-lasting change in receptor molecules, either a covalent modification or conformation that enhances their response to attractant ligands. PMID:28827352

Biomonitoring of Organophosphorus Agent Exposure by Reactivation of Cholinesterase Enzyme Based on Carbon Nanotube-Enhanced Flow-Injection Amperometric Detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Du, Dan; Wang, Jun; Smith, Jordan N.

2009-11-15

A portable, rapid, and sensitive assessment of sub-clinical organophosphorus (OPs) agent exposure based on reactivation of cholinesterase (ChE) from OP-inhibited ChE using rat saliva (in vitro) was developed using an electrochemical sensor coupled with a microflow-injection system. The sensor was based on a carbon nanotube (CNT)-modified screen printed carbon electrode (SPE), which was integrated into a flow cell. Due to the extent of inter-individual ChE activity variability, ChE biomonitoring often requires an initial base-line determination (non-inhibited) of enzyme activity which is then directly compared with activity after OP exposure. This manuscript described an alternative strategy where reactivation of the phosphorylatedmore » enzyme was exploited to enable measurement of both inhibited and baseline ChE activity (i.e. after reactivation) in the same sample. The use of CNT makes the electrochemical detection of the products from enzymatic reactions more feasible with extremely high sensitivity and at low potentials. Paraoxon was selected as a model OP compound for in vitro inhibition studies. Some experiment parameters, (e.g. inhibition and reactivation times), have been optimized such that, 92 - 95% ChE reactivation can be achieved over a broad range of ChE inhibition (5 - 94 %) with paraoxon. The extent of enzyme inhibition using this electrochemical sensor correlates well with conventional enzyme activity measurements.« less

Characterization of cholinesterases in the damselfish Sergeant major (Abudefduf saxatilis).

PubMed

Rodríguez-Fuentes, Gabriela; Soto, Mélina; Luna-Ramírez, Karen

2013-10-01

Cholinesterase (ChE) activity has been used for many years as a biomarker of exposure to organophosphate and carbamate pesticides. Recent studies have demonstrated that there could be biological factors that determine ChE type and levels; thus, juvenile Sergeant major (Abudefduf saxatilis) ChE enzymes were biochemically characterized. ChE enzymes found in the head and trunk were evaluated for their substrate preference and sensitivity to selective inhibitors. The use of the head and trunk was chosen as a strategy to reduce dissection time and to ensure sample uniformity between stations. The results indicated that there are two types of ChE enzymes in the head: acetylcholinesterase (AChE) and atypical butyrylcholinesterase (BChE) that exhibits intermediate characteristics of human AChE and BChE activities. Atypical BChE is predominantly found in the trunk. The results also indicated that the ChE activity found in A. saxatilis may be used as a biomarker in studies monitoring the Mexican Caribbean. Copyright © 2013 Elsevier Inc. All rights reserved.

Regional cholinesterase activity in white-throated sparrow brain is differentially affected by acephate (Orthene®)

USGS Publications Warehouse

Vyas, N.B.; Kuenzel, W.J.; Hill, E.F.; Romo, G.A.; Komaragiri, M.V.S.

1996-01-01

Effects of a 14-day dietary exposure to an organophosphorus pesticide, acephate (acetylphosphoramidothioic acid O,S-dimethyl ester), were determined on cholinesterase activity in three regions (basal ganglia, hippocampus, and hypothalamus) of the white-throated sparrow, Zonotrichia albicollis, brain. All three regions experienced depressed cholinesterase activity between 0.5–2 ppm acephate. The regions exhibited cholinesterase recovery at 2–16 ppm acephate; however, cholinesterase activity dropped and showed no recovery at higher dietary levels (>16 ppm acephate). Evidence indicates that the recovery is initiated by the magnitude of depression, not the duration. In general, as acephate concentration increased, differences in ChE activity among brain regions decreased. Three terms are introduced to describe ChE response to acephate exposure: 1) ChE resistance threshold, 2) ChE compensation threshold, and 3) ChE depression threshold. It is hypothesized that adverse effects to birds in the field may occur at pesticide exposure levels customarily considered negligible.

[Psychosocial factors of chronic hand eczema].

PubMed

Li, Li; Liu, Panpan; Li, Ji; Xie, Hongfu; Kuang, Yehong; Li, Jie; Su, Juan; Zhu, Wu

2017-02-28

To study the psychosocial factors in patient with chronic hand eczema (CHE).
 Methods: Personality traits, emotional state, and quality of life of 240 patients with CHE and 221 normal control (NC) subjects were assessed by General Questionnaire, Eysenck Personality Questionnaire (EPQ), Self-Rating Depression Scale (SDS), Self-Rating Anxiety (SAS), and Eczema Quality of Life Scale (EQOLS).
 Results: In comparison, EPQ scores, scores of extraversion (E) factor in patients with CHE were significantly lower than those in NC subjects (P<0.01), but scores of neuroticism (N) factor in patients with CHE were significantly higher than those in NC subjects (P<0.01), while there was no significant difference in scores of psychoticism (P) and lie (L) factors between two groups (P>0.05). Patients with CHE had significantly higher scores in SDS and SAS compared with the NC subjects (P<0.01). Patients with CHE had significantly higher scores in scale of morbid, physical, social, psychological, general quality of life, and total scores of EQOLS compared with the NC subjects (P<0.01). The level of skin lesions and the degree of itch were significantly correlated with scores in scale SDS, SAS, morbid, physical, social, psychological, general quality of life, and total scores of EQOLS compared with the NC subjects (P<0.05).
 Conclusion: Personality of patients with CHE is prone to emotional instability of introverts.Patients with CHE have a higher level of depression and anxiety, and exert a negative effect on their quality of life, which is related to severity of disease.

Characterizing biological variability in livestock blood cholinesterase activity for biomonitoring organophosphate nerve agent exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Halbrook, R.S.; Shugart, L.R.; Watson, A.P.

1992-09-01

A biomonitoring protocol, using blood cholinesterase (ChE) activity in livestock as a monitor of potential organophosphate nerve agent exposure during the planned destruction of US unitary chemical warfare agent stockpiles, is described. The experimental design included analysis of blood ChE activity in individual healthy sheep, horses, and dairy and beef cattle during a 10- to 12-month period. Castrated and sexually intact males, pregnant and lactating females, and adult and immature animals were examined through at least one reproductive cycle. The same animals were used throughout the period of observation and were not exposed to ChE-inhibiting organophosphate or carbamate compounds. Amore » framework for an effective biomonitoring protocol within a monitoring area includes establishing individual baseline blood ChE activity for a sentinel group of 6 animals on the bases of blood samples collected over a 6-month period, monthly collection of blood samples for ChE-activity determination during monitoring, and selection of adult animals as sentinels. Exposure to ChE-inhibiting compounds would be suspected when all blood ChE activity of all animals within the sentinel group are decreased greater than 20% from their own baseline value. Sentinel species selection is primarily a logistical and operational concern; however, sheep appear to be the species of choice because within-individual baseline ChE activity and among age and gender group ChE activity in sheep had the least variability, compared with data from other species. This protocol provides an effective and efficient means for detecting abnormal depressions in blood ChE activity in livestock and can serve as a valuable indicator of the extent of actual plume movement and/or deposition in the event of organophosphate nerve agent release.« less

Protective effect of chelerythrine against ethanol-induced gastric ulcer in mice.

PubMed

Li, Wei-Feng; Hao, Ding-Jun; Fan, Ting; Huang, Hui-Min; Yao, Huan; Niu, Xiao-Feng

2014-02-05

The quaternary benzo[c]phenanthridine alkaloid, chelerythrine (CHE), is of great practical and research interest because of its pronounced, widespread physiological effects, primarily antimicrobial and anti-inflammatory, arising from its ability to interact with proteins and DNA. Although CHE was originally shown to possess anti-inflammatory properties, its effects on acute gastric ulcer have not been previously explored. The aim of the present study is to evaluate the protective effect of CHE on ethanol induced gastric ulcer in mice. Administration of CHE at doses of 1, 5 and 10mg/kg bodyweight prior to ethanol ingestion dose-dependently inhibited gastric ulcer. The gastric mucosal lesion was assessed by ulcer area, gastric juice acidity, myeloperoxidase (MPO) activities, macroscopic and histopathological examinations. CHE significantly reduced the gastric ulcer index, myeloperoxidase activities, macroscopic and histological score in a dose-dependent manner. In addition, CHE also significantly inhibited nitric oxide (NO) concentration, pro-inflammatory interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) level in serum and gastric mucosal in the mice exposed to ethanol induced ulceration in a dose-dependent manner. In addition, immunohistochemical analysis revealed that CHE markedly attenuated the overexpression of nuclear factor-κB in gastric mucosa of mice. It was concluded that CHE represents a potential therapeutic option to reduce the risk of gastric ulceration. In addition, acute toxicity study revealed no abnormal sign to the mice treated with CHE (15mg/kg). These findings suggest that the gastroprotective activity of CHE might contribute in adjusting the inflammatory cytokine by regulating the NF-κB signalling pathway. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Binary mixtures of azinphos-methyl oxon and chlorpyrifos oxon produce in vitro synergistic cholinesterase inhibition in Planorbarius corneus.

PubMed

Cacciatore, Luis Claudio; Kristoff, Gisela; Verrengia Guerrero, Noemí R; Cochón, Adriana C

2012-07-01

In this study, the cholinesterase (ChE) and carboxylesterase (CES) activities present in whole organism homogenates from Planorbarius corneus and their in vitro sensitivity to organophosphorous (OP) pesticides were studied. Firstly, a characterization of ChE and CES activities using different substrates and selective inhibitors was performed. Secondly, the effects of azinphos-methyl oxon (AZM-oxon) and chlorpyrifos oxon (CPF-oxon), the active oxygen analogs of the OP insecticides AZM and CPF, on ChE and CES activities were evaluated. Finally, it was analyzed whether binary mixtures of the pesticide oxons cause additive, antagonistic or synergistic ChE inhibition in P. corneus homogenates. The results showed that the extracts of P. corneus preferentially hydrolyzed acetylthiocholine (AcSCh) over propionylthiocholine (PrSCh) and butyrylthiocholine (BuSCh). Besides, AcSCh hydrolyzing activity was inhibited by low concentrations of BW284c51, a selective inhibitor of AChE activity, and also by high concentrations of substrate. These facts suggest the presence of a typical AChE activity in this species. However, the different dose-response curves observed with BW284c51 when using PrSCh or BuSCh instead of AcSCh suggest the presence of at least another ChE activity. This would probably correspond to an atypical BuChE. Regarding CES activity, the highest specific activity was obtained when using 2-naphthyl acetate (2-NA), followed by 1-naphthyl acetate (1-NA); p-nitrophenyl acetate (p-NPA), and p-nitrophenyl butyrate (p-NPB). The comparison of the IC(50) values revealed that, regardless of the substrate used, CES activity was approximately one order of magnitude more sensitive to AZM-oxon than ChE activity. Although ChE activity was very sensitive to CPF-oxon, CES activity measured with 1-NA, 2-NA, and p-NPA was poorly inhibited by this pesticide. In contrast, CES activity measured with p-NPB was equally sensitive to CPF-oxon than ChE activity. Several specific binary combinations of AZM-oxon and CPF-oxon caused a synergistic effect on the ChE inhibition in P. corneus homogenates. The degree of synergism tended to increase as the ratio of AZM-oxon to CPF-oxon decreased. These results suggest that synergism is likely to occur in P. corneus snails exposed in vivo to binary mixtures of the OPs AZM and CPF. Copyright © 2012 Elsevier Ltd. All rights reserved.

A cheZ-Like Gene in Azorhizobium caulinodans Is a Key Gene in the Control of Chemotaxis and Colonization of the Host Plant.

PubMed

Liu, Xiaolin; Liu, Wei; Sun, Yu; Xia, Chunlei; Elmerich, Claudine; Xie, Zhihong

2018-02-01

Chemotaxis can provide bacteria with competitive advantages for survival in complex environments. The CheZ chemotaxis protein is a phosphatase, affecting the flagellar motor in Escherichia coli by dephosphorylating the response regulator phosphorylated CheY protein (CheY∼P) responsible for clockwise rotation. A cheZ gene has been found in Azorhizobium caulinodans ORS571, in contrast to other rhizobial species studied so far. The CheZ protein in strain ORS571 has a conserved motif similar to that corresponding to the phosphatase active site in E. coli The construction of a cheZ deletion mutant strain and of cheZ mutant strains carrying a mutation in residues of the putative phosphatase active site showed that strain ORS571 participates in chemotaxis and motility, causing a hyperreversal behavior. In addition, the properties of the cheZ deletion mutant revealed that ORS571 CheZ is involved in other physiological processes, since it displayed increased flocculation, biofilm formation, exopolysaccharide (EPS) production, and host root colonization. In particular, it was observed that the expression of several exp genes, involved in EPS synthesis, was upregulated in the cheZ mutant compared to that in the wild type, suggesting that CheZ negatively controls exp gene expression through an unknown mechanism. It is proposed that CheZ influences the Azorhizobium -plant association by negatively regulating early colonization via the regulation of EPS production. This report established that CheZ in A. caulinodans plays roles in chemotaxis and the symbiotic association with the host plant. IMPORTANCE Chemotaxis allows bacteria to swim toward plant roots and is beneficial to the establishment of various plant-microbe associations. The level of CheY phosphorylation (CheY∼P) is central to the chemotaxis signal transduction. The mechanism of the signal termination of CheY∼P remains poorly characterized among Alphaproteobacteria , except for Sinorhizobium meliloti , which does not contain CheZ but which controls CheY∼P dephosphorylation through a phosphate sink mechanism. Azorhizobium caulinodans ORS571, a microsymbiont of Sesbania rostrata , has an orphan cheZ gene besides two cheY genes similar to those in S. meliloti In addition to controlling the chemotaxis response, the CheZ-like protein in strain ORS571 is playing a role by decreasing bacterial adhesion to the host plant, in contrast to the general situation where chemotaxis-associated proteins promote adhesion. In this study, we identified a CheZ-like protein among Alphaproteobacteria functioning in chemotaxis and the A. caulinodans - S. rostrata symbiosis. Copyright © 2018 American Society for Microbiology.

Time course of cholinesterase activity in plasma, brain and muscle of rat pretreated with physostigmine, and then soman

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giacobini, E.; Boyer, A.; Somani, S.M.

1986-03-05

Time course of /sup 3/H-physostigmine (Phy) concentration and cholinesterase (ChE) activity in plasma and tissues was studied in rats pretreated with Phy and then soman. Rats were dosed with Phy (100 ..mu..g/kg, i.v.), 5 or 15 min prior to soman (105 ..mu..g/kg, 1.5 LD/sub 50/, s.c.) treatment and were sacrificed at various times; Phys conc. and ChE activity were determined. BuChE activity in plasma was 5% of control from 7-30 min after Phy i.v. pretreatment and soman or soman alone treatment. Plasma Phy conc. steadily declined (32.6 ng/ml at 7 min) to 15 ng/ml at 30 min. ChE activity inmore » muscle was 60-50% of control for Phy pretreated but soman alone gave 85-72% activity from 2-30 min. Brain ChE activity was about 5% of control within 2 min after soman treatment; however, with Phy pretreatment, the activity was about 52% at 7 min, 40% at 22 min, which recovered to 45% of control at 35 min, indicating that Phy protected brain ChE. Brain Phy conc. steadily declined (58.6 ng/g at 7 min) to 11.7 ng/g at 30 min. However, pretreatment of rat with a higher dose of Phy and then soman showed BuChE in plasma and ChE in brain and muscle to be about 25, 35 and 51%, in comparison to about 5% in plasma and brain with soman alone treatment, indicating higher protection of ChE enzyme with higher conc. of Phy in plasma and brain.« less

[The activity of blood cholinesterase in rats exposed to dimethypo after drug intervention].

PubMed

Wan, Weiguo; Xu, Mailing; Zou, Hejian; Lu, Ailing; Shen, Xinyu; Chen, Yuming

2002-12-01

To investigate the activity of ChE in rats poisoned by dimehypo and then treated with pralidoxime methylchloride or unithiol. Rats were divided into control group (dimehypo); intervention groups [dimehypo plus pralidoxime methylchloride or dimehypo plus unithiol (sodium dimercaptopropanesulphonate)]. Rats were dosed with 4 different doses of dimehypo: 1/16, 1/8, 1/4 and 1/2 of LD50 respectively(the LD50 of dimehypo is 342 mg/kg). After being poisoned with dimehypo orally, rats were immediately injected intramuscularly with pralidoxime methylchloride or unithiol. The activity of ChE in blood was detected before and 1/2, 1, 2, 4 and 24 h after poisoning in dimehypo and intervention groups. The ChE activity of four dose subgroups at 1 h after poisoning were (1.04 +/- 0.21), (0.84 +/- 0.12), (0.71 +/- 0.12), (0.66 +/- 0.07) U/ml respectively; the ChE activity of pralidoxime methylchloride intervention groups were (1.01 +/- 0.18), (1.17 +/- 0.11), (1.01 +/- 0.04), (1.03 +/- 0.12) U/ml respectively; and the ChE activity of unithiol intervention groups were (1.15 +/- 0.15), (1.26 +/- 0.27), (1.08 +/- 0.08), (1.04 +/- 0.12) U/ml respectively. The inhibited ChE in blood was recovered by either treatment with pyraldoxime methylchloride or unithiol. These two drugs had similar effects of recovering the activity of ChE(P > 0.05), but at higher doses(1/4 and 1/2 of LD50) the effects of both were not so good. Pralidoxime methylchloride and unithiol could partly recover the activity of ChE inhibited by dimehypo.

Variation in plasma cholinesterase activity among greenhouse workers, fruitgrowers, and slaughtermen.

PubMed Central

Lander, F; Lings, S

1991-01-01

The purpose of the study was to compare the plasma cholinesterase (ChE) activities of 100 greenhouse workers and 43 fruitgrowers engaged in spraying insecticides with those of 113 slaughtermen who served as controls. The ChE activity in the greenhouse workers and fruitgrowers was not significantly lower than in the controls. Nevertheless the ChE activity of greenhouse workers declined with increasing exposure. The wearing of protective gloves appears to be of particular value for the safety of workers. PMID:2015206

The source of high signal cooperativity in bacterial chemosensory arrays

PubMed Central

Piñas, Germán E.; Frank, Vered; Vaknin, Ady; Parkinson, John S.

2016-01-01

The Escherichia coli chemosensory system consists of large arrays of transmembrane chemoreceptors associated with a dedicated histidine kinase, CheA, and a linker protein, CheW, that couples CheA activity to receptor control. The kinase activity responses to receptor ligand occupancy changes can be highly cooperative, reflecting allosteric coupling of multiple CheA and receptor molecules. Recent structural and functional studies have led to a working model in which receptor core complexes, the minimal units of signaling, are linked into hexagonal arrays through a unique interface 2 interaction between CheW and the P5 domain of CheA. To test this array model, we constructed and characterized CheA and CheW mutants with amino acid replacements at key interface 2 residues. The mutant proteins proved defective in interface 2-specific in vivo cross-linking assays, and formed signaling complexes that were dispersed around the cell membrane rather than clustered at the cell poles as in wild type chemosensory arrays. Interface 2 mutants down-regulated CheA activity in response to attractant stimuli in vivo, but with much less cooperativity than the wild type. Moreover, mutant cells containing fluorophore-tagged receptors exhibited greater basal anisotropy that changed rapidly in response to attractant stimuli, consistent with facile changes in loosely packed receptors. We conclude that interface 2 lesions disrupt important network connections between core complexes, preventing receptors from operating in large, allosteric teams. This work confirms the critical role of interface 2 in organizing the chemosensory array, in directing the clustered array to the cell poles, and in producing its highly cooperative signaling properties. PMID:26951681

An Evaluation of Blood Cholinesterase Testing Methods for Military Health

DTIC Science & Technology

2008-05-01

activity found that only one device has been validated for ChE testing in the field: the Model 400 Test-mate™ ChE kit by EQM Research, Inc. (Cincinnati...OH). Suggested future modifications to the Model 400 Test-mate™ ChE kit include displaying/recording of acetyl-ChE activity uncorrected for...cholinesterase activity , that are routinely monitored by the Department of Defense (DoD). Within DoD, definitive cholinesterase testing is conducted by

Catastrophic Health Expenditure After the Implementation of Health Sector Evolution Plan: A Case Study in the West of Iran.

PubMed

Piroozi, Bakhtiar; Moradi, Ghobad; Nouri, Bijan; Mohamadi Bolbanabad, Amjad; Safari, Hossein

2016-03-14

One of the main objectives of health systems is the financial protection against out-of-pocket (OOP) health expenditures. OOP health expenditures can lead to catastrophic payments, impoverishment or poverty among households. In Iran, health sector evolution plan (HSEP) has been implemented since 2014 in order to achieve universal health coverage and reduce the OOP health expenditures as a percentage of total health expenditures. This study aimed to explore the percentage of households facing catastrophic health expenditures (CHE) after the implementation of HSEP and the factors that determine CHE. A total of 663 households were selected through a cluster sampling based on the census framework of Sanandaj Health Center in July 2015. Data were gathered using face-to-face interviews based on the household section of the World Health Survey questionnaire. In this study, according to the World Health Organization (WHO) definition, if household health expenditures were equal to or more than 40% of the household capacity to pay, household was considered to be facing CHE. The determinants of CHE were analyzed using logistic regression model. The rates of households facing CHE were 4.8%. The key determinants of CHE were household economic status, presence of elderly or disabled members in the household and utilization of inpatient or rehabilitation services. The comparison of our findings and those of other studies carried out using a methodology comparable with ours in different parts of Iran before the implementation of HSEP suggests that the implementation of recent reforms has reduced CHE at the household level. Utilization of inpatient and rehabilitation services, the presence of elderly or disabled members in the household and the low economic status of the household would increase the likelihood of facing CHE. These variables should be considered by health policy-makers in order to review and revise content of recent reform, thus financially protecting public against CHE. © 2016 by Kerman University of Medical Sciences

Catastrophic Health Expenditure After the Implementation of Health Sector Evolution Plan: A Case Study in the West of Iran

PubMed Central

Piroozi, Bakhtiar; Moradi, Ghobad; Nouri, Bijan; Mohamadi Bolbanabad, Amjad; Safari, Hossein

2016-01-01

Background: One of the main objectives of health systems is the financial protection against out-of-pocket (OOP) health expenditures. OOP health expenditures can lead to catastrophic payments, impoverishment or poverty among households. In Iran, health sector evolution plan (HSEP) has been implemented since 2014 in order to achieve universal health coverage and reduce the OOP health expenditures as a percentage of total health expenditures. This study aimed to explore the percentage of households facing catastrophic health expenditures (CHE) after the implementation of HSEP and the factors that determine CHE. Methods: A total of 663 households were selected through a cluster sampling based on the census framework of Sanandaj Health Center in July 2015. Data were gathered using face-to-face interviews based on the household section of the World Health Survey questionnaire. In this study, according to the World Health Organization (WHO) definition, if household health expenditures were equal to or more than 40% of the household capacity to pay, household was considered to be facing CHE. The determinants of CHE were analyzed using logistic regression model. Results: The rates of households facing CHE were 4.8%. The key determinants of CHE were household economic status, presence of elderly or disabled members in the household and utilization of inpatient or rehabilitation services. Conclusion: The comparison of our findings and those of other studies carried out using a methodology comparable with ours in different parts of Iran before the implementation of HSEP suggests that the implementation of recent reforms has reduced CHE at the household level. Utilization of inpatient and rehabilitation services, the presence of elderly or disabled members in the household and the low economic status of the household would increase the likelihood of facing CHE. These variables should be considered by health policy-makers in order to review and revise content of recent reform, thus financially protecting public against CHE. PMID:27694669

Long term exposure to low dose neurotoxic pesticides affects hatching, viability and cholinesterase activity of Artemia sp.

PubMed

Gambardella, Chiara; Nichino, Daniela; Iacometti, Camillo; Ferrando, Sara; Falugi, Carla; Faimali, Marco

2018-03-01

The brine shrimp Artemia was used as a model organism to test toxicity of several neuroactive pesticides (chlorpyrifos (CLP), chlorpyrifos oxon (CLP ox), diazinon (DZN), carbaryl (CBR)) following exposure to far below than lethal doses. Cysts were exposed to the pesticides in order to test a scenario similar to actual coastal environment contamination, by analyzing different responses. Cysts were rehydrated in water containing the pesticides at concentrations ranging from 10 -11 to 10 -5  M, for 72, 96 and 192 h, respectively. For these exposure times, morpho-functional and biochemical parameters, such as hatching speed and viability were investigated in the larvae together with cholinesterase (ChE) activity quantification and histochemical localization. Finally, ChE inhibition was also compared with conventional selective ChE inhibitors. Results showed that CLP ox and CBR caused a significant dose-dependent decrease in hatching speed, followed by high percentages of larval death, while CLP and DZN were responsible for irregular hatching patterns. In addition, the pesticides mostly caused larval death some days post-hatching, whereas this effect was negligible for the specific ChE inhibitors, suggesting that part of pesticide toxicity may be due to molecules other than the primary target. ChE activity was observed in the protocerebrum lobes, linked to the development of pair eyes. Such activity was inhibited in larvae exposed to all pesticides. When compared to conventional selective inhibitors of ChE activities, this inhibition demonstrated that the selected pesticides mainly affect acetylcholinesterase and, to a lesser extent, pseudocholinesterases. In conclusion, the brine shrimp is a good model to test the environmental toxicity of long term exposure to cholinergic pesticides, since changes in hatching speed, viability and ChE activity were observed. Copyright © 2018 Elsevier B.V. All rights reserved.

Health care expenditure of households in magway, myanmar.

PubMed

Khaing, Inn Kynn; Malik, Amonov; Oo, Myo; Hamajima, Nobuyuki

2015-02-01

Myanmar has a high proportion of out-of-pocket (OOP) health care expenditures with limited cost-sharing mechanisms. In Myanmar, there were limited data on the frequency of catastrophic health expenditure (CHE) due to OOP payments, as well as on the factors associated with CHE. This study aimed to investigate health care expenditure, the frequency of CHE, and the factors influencing CHE among households in Magway, Myanmar. A cross-sectional household survey was conducted in 2012 for 700 households (350 in urban areas and 350 in rural areas) in Magway. CHE was defined as a condition wherein the total amount of household health care expenditure was 40% or more of non-food expenditure in the past year. Multiple logistic regression analysis was applied to estimate odds ratios (ORs) and 95% confident intervals (CIs) of CHE. In the previous year, 28.3% of 350 urban households and 51.4% of 350 rural households utilized outpatient services. Households with at least one member admitted to a medical facility were 10.0% and 12.9%, respectively. Those with CHE were 25.2% in the urban areas and 22.7% in the rural areas. The adjusted OR of CHE was 7.79 (95% CI 3.73-16.26) for hospitalization and 1.08 (95% CI 0.36-3.23) for outpatient care, relative to no services used. These findings indicated that nearly one fourth of households in Magway faced CHE due to inpatient care. A safety-net mechanism to protect households from CHE in Myanmar seems essential.

Molecular Interaction and Cellular Location of RecA and CheW Proteins in Salmonella enterica during SOS Response and Their Implication in Swarming.

PubMed

Irazoki, Oihane; Aranda, Jesús; Zimmermann, Timo; Campoy, Susana; Barbé, Jordi

2016-01-01

In addition to its role in DNA damage repair and recombination, the RecA protein, through its interaction with CheW, is involved in swarming motility, a form of flagella-dependent movement across surfaces. In order to better understand how SOS response modulates swarming, in this work the location of RecA and CheW proteins within the swarming cells has been studied by using super-resolution microscopy. Further, and after in silico docking studies, the specific RecA and CheW regions associated with the RecA-CheW interaction have also been confirmed by site-directed mutagenesis and immunoprecipitation techniques. Our results point out that the CheW distribution changes, from the cell poles to foci distributed in a helical pattern along the cell axis when SOS response is activated or RecA protein is overexpressed. In this situation, the CheW presents the same subcellular location as that of RecA, pointing out that the previously described RecA storage structures may be modulators of swarming motility. Data reported herein not only confirmed that the RecA-CheW pair is essential for swarming motility but it is directly involved in the CheW distribution change associated to SOS response activation. A model explaining not only the mechanism by which DNA damage modulates swarming but also how both the lack and the excess of RecA protein impair this motility is proposed.

Purification and characterization of novel extracellular cholesterol esterase from Acinetobacter sp.

PubMed

Du, Liangjun; Huo, Ying; Ge, Fanglan; Yu, Jiajun; Li, Wei; Cheng, Guiying; Yong, Bin; Zeng, Lihuang; Huang, Min

2010-12-01

CHE4-1, a bacterial strain that belongs to the genus Acinetobacter and expresses high level of inducible extracellular cholesterol esterase (CHE), was isolated from feces of carnivore Panthera pardus var. The cholesterol esterase of the strain CHE4-1 was purified by ultrafiltration followed with DEAE-Sepharose FF chromatography and Phenyl-Sepharose CL-4B chromatography, and then by Sephadex G-50 gel filtration. Different from other known microbial cholesterol esterase, the purified CHE from CHE4-1 strain is a monomer with molecular weight of 6.5 kD and has high activity to both long-chain and short-chain cholesterol ester. Enzymatic activity was enhanced in the presence of metal ion Ca(2+), Zn(2+) and boracic acid, and was not significantly affected by several detergents including sodium cholate, Triton X100 and Tween-80. The enzyme was found to be stable during long-term aqueous storage at 4 °C, indicating its potential as a clinical diagnostic reagent. To the best of our knowledge, this is the first report regarding purification and characterization of CHE from Acinetobacter sp. The results demonstrated that this particular CHE is a novel cholesterol esterase.

A Drosophila protein family implicated in pheromone perception is related to Tay-Sachs GM2-activator protein.

PubMed

Starostina, Elena; Xu, Aiguo; Lin, Heping; Pikielny, Claudio W

2009-01-02

Low volatility, lipid-like cuticular hydrocarbon pheromones produced by Drosophila melanogaster females play an essential role in triggering and modulating mating behavior, but the chemosensory mechanisms involved remain poorly understood. Recently, we showed that the CheB42a protein, which is expressed in only 10 pheromone-sensing taste hairs on the front legs of males, modulates progression to late stages of male courtship behavior in response to female-specific cuticular hydrocarbons. Here we report that expression of all 12 genes in the CheB gene family is predominantly or exclusively gustatory-specific, and occurs in many different, often non-overlapping patterns. Only the Gr family of gustatory receptor genes displays a comparable variety of gustatory-specific expression patterns. Unlike Grs, however, expression of all but one CheB gene is sexually dimorphic. Like CheB42a, other CheBs may therefore function specifically in gustatory perception of pheromones. We also show that CheBs belong to the ML superfamily of lipid-binding proteins, and are most similar to human GM2-activator protein (GM2-AP). In particular, GM2-AP residues involved in ligand binding are conserved in CheBs but not in other ML proteins. Finally, CheB42a is specifically secreted into the inner lumen of pheromone-sensing taste hairs, where pheromones interact with membrane-bound receptors. We propose that CheB proteins interact directly with lipid-like Drosophila pheromones and modulate their detection by the gustatory signal transduction machinery. Furthermore, as loss of GM2-AP in Tay-Sachs disease prevents degradation of GM2 gangliosides and results in neurodegeneration, the function of CheBs in pheromone response may involve biochemical mechanisms critical for lipid metabolism in human neurons.

Measurement of cholinesterase enzyme activity before and after exposure to organophosphate pesticides in farmers of a suburb region of Mazandaran, a northern province of Iran.

PubMed

Pakravan, N; Shokrzadeh, M; Bari, M A Khalat; Shadboorestan, Amir

2016-03-01

Accidental toxicity by organophosphate (OP) agents may occur among farmers during spraying season due to improper use and handling. Plasma cholinesterase (ChE) activity measurement is recommended to monitor the extent of exposure to the OP agent. The aim of the current study was to measure plasma ChE activity before and after exposure with OP pesticides. This was a prospective study conducted on 36 farmers working in the farm field. The plasma ChE level was measured before spraying and 2 days and 8 weeks after spraying season and exposure to OP agent. Farmers were observed for clinical signs and symptoms of toxicity after exposure. Vertimac was the most common agent used by farmers followed by diazinon and chlorpyrifos. The plasma ChE level significantly decreased after exposure by over 50%. The level returned to preexposure level after 8 weeks. Exposure to OP pesticide is a major concern in the developing countries. More than 50% reduction in the plasma ChE activity after spraying is an alarming message for health-care system and policy makers. Furthermore, workplace evaluation, serial ChE monitoring, and appropriate training and education to exposed individuals would be initial important steps to avoid the toxicity or reduce the severity of poisoning. © The Author(s) 2015.

Organophosphate and carbamate insecticides in agricultural waters and cholinesterase (ChE) inhibition in common carp (Cyprinus carpio)

USGS Publications Warehouse

Gruber, S.J.; Munn, M.D.

1998-01-01

Cholinesterase (ChE) activity was used as a biomarker for assessing exposure of common carp (Cyprinus carpio) to organophosphate and carbamate insecticides from irrigated agricultural waters. Carp were collected from a lake (Royal Lake) that receives most of its water from irrigation return flows and from a reference lake (Billy Clapp Lake) outside of the irrigation system. Results indicated that the mean whole-brain ChE activity of carp from Royal Lake (3.47 μmol/min/g tissue) was 34.2% less than that of carp from Billy Clapp Lake (5.27 μmol/min/g tissue) (p = 0.003). The depressed ChE activity in brain tissue of Royal Lake carp was in response to ChE-inhibiting insecticides detected in water samples in the weeks prior to tissue sampling; the most frequently detected insecticides included chlorpyrifos, azinphos-methyl, carbaryl, and ethoprop. Neither sex nor size appears to be a covariable in the analysis; ChE activity was not correlated with fish length or weight in either lake and there was no significant difference in ChE activity between the two sexes within each lake. Although organophosphate and carbamate insecticides can break down rapidly in the environment, this study suggests that in agricultural regions where insecticides are applied for extended periods of the year, nontarget aquatic biota may be exposed to high levels of ChE-inhibiting insecticides for a period of several months.

HEALTH CARE EXPENDITURE OF HOUSEHOLDS IN MAGWAY, MYANMAR

PubMed Central

KHAING, INN KYNN; MALIK, AMONOV; OO, MYO; HAMAJIMA, NOBUYUKI

2015-01-01

ABSTRACT Myanmar has a high proportion of out-of-pocket (OOP) health care expenditures with limited cost-sharing mechanisms. In Myanmar, there were limited data on the frequency of catastrophic health expenditure (CHE) due to OOP payments, as well as on the factors associated with CHE. This study aimed to investigate health care expenditure, the frequency of CHE, and the factors influencing CHE among households in Magway, Myanmar. A cross-sectional household survey was conducted in 2012 for 700 households (350 in urban areas and 350 in rural areas) in Magway. CHE was defined as a condition wherein the total amount of household health care expenditure was 40% or more of non-food expenditure in the past year. Multiple logistic regression analysis was applied to estimate odds ratios (ORs) and 95% confident intervals (CIs) of CHE. In the previous year, 28.3% of 350 urban households and 51.4% of 350 rural households utilized outpatient services. Households with at least one member admitted to a medical facility were 10.0% and 12.9%, respectively. Those with CHE were 25.2% in the urban areas and 22.7% in the rural areas. The adjusted OR of CHE was 7.79 (95% CI 3.73–16.26) for hospitalization and 1.08 (95% CI 0.36–3.23) for outpatient care, relative to no services used. These findings indicated that nearly one fourth of households in Magway faced CHE due to inpatient care. A safety-net mechanism to protect households from CHE in Myanmar seems essential. PMID:25797985

Hydroalcoholic extract of Carum carvi L. in oral mucositis: a clinical trial in male golden hamsters.

PubMed

Mardani, M; Afra, S M; Tanideh, N; Tadbir, A Andisheh; Modarresi, F; Koohi-Hosseinabadi, O; Iraji, A; Sepehrimanesh, M

2016-01-01

Several studies have attempted to prevent or improve oral mucositis (OM) but have not produced a qualified treatment yet. This study evaluates the effects of Carum carvi L. (caraway) hydroalcoholic extract (CHE) as one of the traditional medicinal plants in 5-fluorouracil (5-FU)-induced OM in golden hamsters. OM was induced in 54 male golden hamsters by 5-FU and cheek pouch scratching. Starting from day 12, 500 and 1000 mg kg(-1) per day topical CHE were administered. Pouch histopathology score, malondialdehyde and reduced glutathione contents, and activity of myeloperoxidase plus microbial cultures of cheek pouch, antimicrobial properties of CHE, and essential oil constituents were evaluated. Lower histopathology score (0, 1, and 2) and malondialdehyde level, higher reduced glutathione level and activities of myeloperoxidase were detected in 1000 and 500 mg kg(-1) per day topical CHE and control groups, respectively (P < 0.001). The CHE was more potent against Staphylococcus epidermidis and Streptococcus intermedius. γ-Terpinene (37.2%) was identified as the main constituent of essential oil. The use of CHE in topical form may be associated with reduced intensity of OM. This may be due to appropriate antibacterial activity and terpinene contents. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Low Level Chlorpyrifos Exposure Increases Anandamide Accumulation in Juvenile Rat Brain in the Absence of Brain Cholinesterase Inhibition

PubMed Central

Carr, Russell L.; Graves, Casey A.; Mangum, Lee C.; Nail, Carole A.; Ross, Matthew K.

2014-01-01

The prevailing dogma is that chlorpyrifos (CPF) mediates its toxicity through inhibition of cholinesterase (ChE). However, in recent years, the toxicological effects of developmental CPF exposure have been attributed to an unknown non-cholinergic mechanism of action. We hypothesize that the endocannabinoid system may be an important target because of its vital role in nervous system development. We have previously reported that repeated exposure to CPF results in greater inhibition of fatty acid amide hydrolase (FAAH), the enzyme that metabolizes the endocannabinoid anandamide (AEA), than inhibition of either forebrain ChE or monoacylglycerol lipase (MAGL), the enzyme that metabolizes the endocannabinoid 2-arachidonylglycerol (2-AG). This exposure resulted in the accumulation of 2-AG and AEA in the forebrain of juvenile rats; however, even at the lowest dosage level used (1.0 mg/kg), forebrain ChE inhibition was still present. Thus, it is not clear if FAAH activity would be inhibited at dosage levels that do not inhibit ChE. To determine this, 10 day old rat pups were exposed daily for 7 days to either corn oil or 0.5 mg/kg CPF by oral gavage. At 4 and 12 h post-exposure on the last day of administration, the activities of serum ChE and carboxylesterase (CES) and forebrain ChE, MAGL, and FAAH were determined as well as the forebrain AEA and 2-AG levels. Significant inhibition of serum ChE and CES was present at both 4 and 12 h. There was no significant inhibition of the activities of forebrain ChE or MAGL and no significant change in the amount of 2-AG at either time point. On the other hand, while no statistically significant effects were observed at 4 h, FAAH activity was significantly inhibited at 12 h resulting in a significant accumulation of AEA. Although it is not clear if this level of accumulation impacts brain maturation, this study demonstrates that developmental CPF exposure at a level that does not inhibit brain ChE can alter components of endocannabinoid signaling. PMID:24373905

The region preceding the C-terminal NWETF pentapeptide modulates baseline activity and aspartate inhibition of Escherichia coli Tar.

PubMed

Lai, Run-Zhi; Bormans, Arjan F; Draheim, Roger R; Wright, Gus A; Manson, Michael D

2008-12-16

The Tar chemoreceptor-CheA-CheW ternary complex of Escherichia coli is a transmembrane allosteric enzyme in which binding of ligands to the periplasmic domain modulates the activity of CheA kinase. Kinase activity is also affected by reversible methylation of four glutamyl residues in the cytoplasmic domain of the receptor. E. coli Tar contains 553 residues. Residues 549-553 comprise the NWETF pentapeptide that binds the CheR methyltransferase and CheB methylesterase. The crystal structure of the similar Tsr chemoreceptor predicts that residues 263-289 and 490-515 of Tar form the most membrane-proximal portion of the extended CD1-CD2 four-helix bundle of the cytoplasmic domain. The last methylation site, Glu-491, is in the C19 heptad, and the N22-19 and C22-19 heptads are present in all classes of bacterial transmembrane chemoreceptors. Residues 516-548 probably serve as a flexible tether for the NWETF pentapeptide. Here, we present a mutational analysis of residues 505-548. The more of this region that is deleted, the less sensitive Tar is to inhibition by aspartate. Tar deleted from residue 505 through the NWETF sequence stimulates CheA in vitro but is not inhibited by aspartate. Thus, interaction of the last two heptads (C21 and C22) of CD2 with the first two heptads (N22 and N21) of CD1 must be important for transmitting an inhibitory signal from the HAMP domain to the four-helix bundle. The R514A, K523A, R529A, R540A, and R542A substitutions, singly or together, increase the level of activation of CheA in vitro, whereas the R505A substitution decreases the level of CheA stimulation by 40% and lowers the aspartate K(i) 7-fold. The R505E substitution completely abolishes stimulation of CheA in vitro. Glu-505 may interact electrostatically with Asp-273 to destabilize the "on" signaling state by loosening the four-helix bundle.

The Azospirillum brasilense Che1 chemotaxis pathway controls swimming velocity, which affects transient cell-to-cell clumping.

PubMed

Bible, Amber; Russell, Matthew H; Alexandre, Gladys

2012-07-01

The Che1 chemotaxis-like pathway of Azospirillum brasilense contributes to chemotaxis and aerotaxis, and it has also been found to contribute to regulating changes in cell surface adhesive properties that affect the propensity of cells to clump and to flocculate. The exact contribution of Che1 to the control of chemotaxis and flocculation in A. brasilense remains poorly understood. Here, we show that Che1 affects reversible cell-to-cell clumping, a cellular behavior in which motile cells transiently interact by adhering to one another at their nonflagellated poles before swimming apart. Clumping precedes and is required for flocculation, and both processes appear to be independently regulated. The phenotypes of a ΔaerC receptor mutant and of mutant strains lacking cheA1, cheY1, cheB1, or cheR1 (alone or in combination) or with che1 deleted show that Che1 directly mediates changes in the flagellar swimming velocity and that this behavior directly modulates the transient nature of clumping. Our results also suggest that an additional receptor(s) and signaling pathway(s) are implicated in mediating other Che1-independent changes in clumping identified in the present study. Transient clumping precedes the transition to stable clump formation, which involves the production of specific extracellular polysaccharides (EPS); however, production of these clumping-specific EPS is not directly controlled by Che1 activity. Che1-dependent clumping may antagonize motility and prevent chemotaxis, thereby maintaining cells in a metabolically favorable niche.

The Azospirillum brasilense Che1 Chemotaxis Pathway Controls Swimming Velocity, Which Affects Transient Cell-to-Cell Clumping

PubMed Central

Bible, Amber; Russell, Matthew H.

2012-01-01

The Che1 chemotaxis-like pathway of Azospirillum brasilense contributes to chemotaxis and aerotaxis, and it has also been found to contribute to regulating changes in cell surface adhesive properties that affect the propensity of cells to clump and to flocculate. The exact contribution of Che1 to the control of chemotaxis and flocculation in A. brasilense remains poorly understood. Here, we show that Che1 affects reversible cell-to-cell clumping, a cellular behavior in which motile cells transiently interact by adhering to one another at their nonflagellated poles before swimming apart. Clumping precedes and is required for flocculation, and both processes appear to be independently regulated. The phenotypes of a ΔaerC receptor mutant and of mutant strains lacking cheA1, cheY1, cheB1, or cheR1 (alone or in combination) or with che1 deleted show that Che1 directly mediates changes in the flagellar swimming velocity and that this behavior directly modulates the transient nature of clumping. Our results also suggest that an additional receptor(s) and signaling pathway(s) are implicated in mediating other Che1-independent changes in clumping identified in the present study. Transient clumping precedes the transition to stable clump formation, which involves the production of specific extracellular polysaccharides (EPS); however, production of these clumping-specific EPS is not directly controlled by Che1 activity. Che1-dependent clumping may antagonize motility and prevent chemotaxis, thereby maintaining cells in a metabolically favorable niche. PMID:22522896

A chemotactic signaling surface on CheY defined by suppressors of flagellar switch mutations.

PubMed Central

Roman, S J; Meyers, M; Volz, K; Matsumura, P

1992-01-01

CheY is the response regulator protein that interacts with the flagellar switch apparatus to modulate flagellar rotation during chemotactic signaling. CheY can be phosphorylated and dephosphorylated in vitro, and evidence indicates that CheY-P is the activated form that induces clockwise flagellar rotation, resulting in a tumble in the cell's swimming pattern. The flagellar switch apparatus is a complex macromolecular structure composed of at least three gene products, FliG, FliM, and FliN. Genetic analysis of Escherichia coli has identified fliG and fliM as genes in which mutations occur that allele specifically suppress cheY mutations, indicating interactions among these gene products. We have generated a class of cheY mutations selected for dominant suppression of fliG mutations. Interestingly, these cheY mutations dominantly suppressed both fliG and fliM mutations; this is consistent with the idea that the CheY protein interacts with both switch gene products during signaling. Biochemical characterization of wild-type and suppressor CheY proteins did not reveal altered phosphorylation properties or evidence for phosphorylation-dependent CheY multimerization. These data indicate that suppressor CheY proteins are specifically altered in the ability to transduce chemotactic signals to the switch at some point subsequent to phosphorylation. Physical mapping of suppressor amino acid substitutions on the crystal structure of CheY revealed a high degree of spatial clustering, suggesting that this region of CheY is a signaling surface that transduces chemotactic signals to the switch. Images PMID:1400175

Measurement and explanation of socioeconomic inequality in catastrophic health care expenditure: evidence from the rural areas of Shaanxi Province.

PubMed

Xu, Yongjian; Gao, Jianmin; Zhou, Zhongliang; Xue, Qinxiang; Yang, Jinjuan; Luo, Hao; Li, Yanli; Lai, Sha; Chen, Gang

2015-07-03

Policy interventions have been taken to protect households from facing unpredictable economic changes that may cause catastrophe in China. This study aims to estimate the change of overall proportion of households incurring catastrophic health care expenditure (CHE) and its income-related inequality in the rural areas of Shaanxi Province from 2008 to 2013. The data were drawn from the National Household Health Service Surveys of Shaanxi Province conducted in the years 2008 and 2013. In total, 3,217 households in 2008 and 13,085 households in 2013 were selected for analysis. A "Capacity to pay" approach was used to measure the incidence of CHE. The concentration index was employed to measure the extent of income-related inequality in CHE. A decomposition method, based on a logit model, was used to decompose the concentration index into its determining components. From 2008 to 2013, the overall proportion of households incurring CHE dropped from 17.19 % to 15.83 %, while conversely, the inequality in facing CHE strongly increased. The majority of observed inequalities in CHE were explained by household economic status and household size in 2013. In addition, the absence of commercial health insurance and having elderly members were also important contributors to inequality in CHE. Even though we used a conservative method to measure CHE, the overall proportion of households incurring CHE in Shaanxi Province is still considerably high in both years. Furthermore, there exists a strong pro-rich inequality of CHE in rural areas of Shaanxi Province. Our study suggests that narrowing the gap of household economic status, improving the anti-risk capability of small scale households, establishing prepayment mechanisms in health insurance, strengthening the depth of reimbursement and subsidising vulnerable households in Shaanxi Province are helpful for both reducing the probability of incurring CHE and the pro-rich inequality in CHE.

Cholinesterase activity in the tissues of bivalves Noah's ark shell (Arca noae) and warty venus (Venus verrucosa): characterisation and in vitro sensitivity to organophosphorous pesticide trichlorfon.

PubMed

Perić, Lorena; Ribarić, Luka; Nerlović, Vedrana

2013-08-01

Cholinesterase (ChE, EC 3.1.1.7) activity was investigated in gills and adductor muscle of two bivalve species: Arca noae and Venus verrucosa. The properties of ChEs were investigated using acetylcholine iodide (ASCh), butyrylcholine iodide (BSCh) and propionylcholine iodide (PrSCh) as substrates and eserine, BW254c51 and iso-OMPA as specific inhibitors. The highest level of ChE activity in crude tissue extracts was detected with PrSCh followed by ASCh, while values obtained with BSCh were apparently low, except in A. noae adductor muscle. The enzyme activity in A. noae gills and V. verrucosa gills and adductor muscle was significantly inhibited by BW254c51, but not with iso-OMPA. ChE activity in adductor muscle of A. noae was significantly reduced by both diagnostic inhibitors. The effect of organophosphorous pesticide trichlorfon on ChE activity was investigated in vitro in both species as well as in the gills of mussels Mytilus galloprovincialis. The highest sensitivity of ChE to trichlorfon was observed in A. noae gills and adductor muscle (IC50 1.6×10(-7)M and 1.1×10(-7)M, respectively), followed by M. galloprovincialis gills (IC50 1.0×10(-6)M) and V. verrucosa gills and adductor muscle (IC50 1.7×10(-5)M and 0.9×10(-5)M, respectively). The results of this study suggest the potential of ChE activity measurement in the tissues of A. noae as effective biomarker of OP exposure in marine environment. Copyright © 2013 Elsevier Inc. All rights reserved.

Studies of Dynamic Protein-Protein Interactions in Bacteria Using Renilla Luciferase Complementation Are Undermined by Nonspecific Enzyme Inhibition

PubMed Central

Hatzios, Stavroula K.; Ringgaard, Simon; Davis, Brigid M.; Waldor, Matthew K.

2012-01-01

The luciferase protein fragment complementation assay is a powerful tool for studying protein-protein interactions. Two inactive fragments of luciferase are genetically fused to interacting proteins, and when these two proteins interact, the luciferase fragments can reversibly associate and reconstitute enzyme activity. Though this technology has been used extensively in live eukaryotic cells, split luciferase complementation has not yet been applied to studies of dynamic protein-protein interactions in live bacteria. As proof of concept and to develop a new tool for studies of bacterial chemotaxis, fragments of Renilla luciferase (Rluc) were fused to the chemotaxis-associated response regulator CheY3 and its phosphatase CheZ in the enteric pathogen Vibrio cholerae. Luciferase activity was dependent on the presence of both CheY3 and CheZ fusion proteins, demonstrating the specificity of the assay. Furthermore, enzyme activity was markedly reduced in V. cholerae chemotaxis mutants, suggesting that this approach can measure defects in chemotactic signaling. However, attempts to measure changes in dynamic CheY3-CheZ interactions in response to various chemoeffectors were undermined by nonspecific inhibition of the full-length luciferase. These observations reveal an unexpected limitation of split Rluc complementation that may have implications for existing data and highlight the need for great caution when evaluating small molecule effects on dynamic protein-protein interactions using the split luciferase technology. PMID:22905225

Studies of dynamic protein-protein interactions in bacteria using Renilla luciferase complementation are undermined by nonspecific enzyme inhibition.

PubMed

Hatzios, Stavroula K; Ringgaard, Simon; Davis, Brigid M; Waldor, Matthew K

2012-01-01

The luciferase protein fragment complementation assay is a powerful tool for studying protein-protein interactions. Two inactive fragments of luciferase are genetically fused to interacting proteins, and when these two proteins interact, the luciferase fragments can reversibly associate and reconstitute enzyme activity. Though this technology has been used extensively in live eukaryotic cells, split luciferase complementation has not yet been applied to studies of dynamic protein-protein interactions in live bacteria. As proof of concept and to develop a new tool for studies of bacterial chemotaxis, fragments of Renilla luciferase (Rluc) were fused to the chemotaxis-associated response regulator CheY3 and its phosphatase CheZ in the enteric pathogen Vibrio cholerae. Luciferase activity was dependent on the presence of both CheY3 and CheZ fusion proteins, demonstrating the specificity of the assay. Furthermore, enzyme activity was markedly reduced in V. cholerae chemotaxis mutants, suggesting that this approach can measure defects in chemotactic signaling. However, attempts to measure changes in dynamic CheY3-CheZ interactions in response to various chemoeffectors were undermined by nonspecific inhibition of the full-length luciferase. These observations reveal an unexpected limitation of split Rluc complementation that may have implications for existing data and highlight the need for great caution when evaluating small molecule effects on dynamic protein-protein interactions using the split luciferase technology.

Reactivation of VX-inhibited cholinesterase by 2-PAM and HS-6 in rats.

PubMed

Harris, L W; Stitcher, D L

1983-01-01

Atropinized rats intoxicated with ethyl-S-2-diisopropyl aminoethyl methyl phosphonothioate (VX), 15 mg/kg iv, were divided into three groups and were treated with normal saline, iv, 30 mg/kg of 2-PAM C1, iv, and 30 mg/kg of HS-6, iv. One hr after administration of therapy they were decapitated and cholinesterase (ChE) activity was determined on blood, brain and diaphragm tissue. Both 2-PAM C1 and HS-6 markedly reactivated VX-inhibited blood and diaphragm ChE. Brain ChE activity was not significantly reactivated by either oxime. The effectiveness of these oximes in restoration of VX-inactivated ChE in vivo offers an explanation as to why conventional atropine/oxime therapy is so effective against VX intoxication.

The first evidence of cholinesterases in skin mucus of carps and its applicability as biomarker of organophosphate exposure.

PubMed

Nigam, Ashwini Kumar; Srivastava, Nidhi; Rai, Amita Kumari; Kumari, Usha; Mittal, Ajay Kumar; Mittal, Swati

2014-05-01

The presence of cholinesterase (ChE) activity in skin mucus of three carps, Cirrhinus mrigala, Labeo rohita, and Catla catla and its applicability as biomarker of the organophosphorus insecticide exposure were investigated. Biochemical characterization, using specific substrates and inhibitors, indicated that measured esterase activity in skin mucus was mainly owing to ChEs. Significant difference in the proportion of acetylcholinesterase and butyrylcholinesterase activities was observed in skin mucus of three carps. Enzyme kinetic analysis, using the substrate acetylthiocholine iodide revealed significantly high Vmax value in C. catla compared to that in L. rohita and C. mrigala. In contrast, Vmax value using the substrate butyrylthiocholine iodide was significantly high in C. mrigala than in L. rohita and C. catla. In vitro treatment of skin mucus of three carps, with the organophosphorus insecticide Nuvan®, showed strong inhibition of ChE activities. In vivo experiments conducted using C. mrigala and exposing the fish to the sublethal test concentrations (5 and 15 mg/L) of the insecticide also revealed significant inhibition of ChE activity in mucus. In C. mrigala, exposed to the sublethal test concentrations of the insecticide for 4 days and then kept for recovery for 16 days, mucus ChE activity recovered to the control level. Thus, ChE activity in skin mucus could be considered a good biomarker of the organophosphorus insecticide exposure to fish and a useful tool in monitoring environmental toxicity. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

Prospective evaluation of the impact of covert hepatic encephalopathy on quality of life and sleep in cirrhotic patients.

PubMed

Labenz, C; Baron, J S; Toenges, G; Schattenberg, J M; Nagel, M; Sprinzl, M F; Nguyen-Tat, M; Zimmermann, T; Huber, Y; Marquardt, J U; Galle, P R; Wörns, M-A

2018-06-04

Minimal hepatic encephalopathy (HE) and HE grade 1 (HE1) according to the West Haven criteria have recently been grouped as one entity named-covert HE- (CHE). Data regarding the impact of CHE on health-related quality of life (HRQoL) and sleep quality are controversial. First, to determine whether CHE affects HRQoL and sleep quality of cirrhotic patients and second, whether minimal HE (MHE) and HE1 affect HRQoL and sleep quality to a comparable extent. A total of 145 consecutive cirrhotic patients were enrolled. HE1 was diagnosed clinically according to the West Haven criteria. Critical flicker frequency and the Psychometric Hepatic Encephalopathy Score were used to detect MHE. Chronic Liver Disease Questionnaire (CLDQ) was used to assess HRQoL and Pittsburgh Sleep Quality Index (PSQI) was applied to assess sleep quality. Covert HE was detected in 59 (40.7%) patients (MHE: n = 40; HE1: n = 19). Multivariate analysis identified CHE (P < 0.001) and female gender (P = 0.006) as independent predictors of reduced HRQoL (CLDQ total score). CHE (P = 0.021), low haemoglobin (P = 0.024) and female gender (P = 0.003) were identified as independent predictors of poor sleep quality (PSQI total score). Results of CLDQ and PSQI were comparable in patients with HE1 and MHE (CLDQ: 4.6 ± 0.9 vs 4.5 ± 1.2, P = 0.907; PSQI: 11.3 ± 3.8 vs 9.9 ± 5.0, P = 0.3). Covert HE was associated with impaired HRQoL and sleep quality. MHE and HE1 affected both outcomes to a comparable extent supporting the use of CHE as a clinically useful term for patients with both entities of HE in clinical practice. © 2018 John Wiley & Sons Ltd.

In vivo and in vitro changes in neurochemical parameters related to mercury concentrations from specific brain regions of polar bears (Ursus maritimus).

PubMed

Krey, Anke; Kwan, Michael; Chan, Hing Man

2014-11-01

Mercury (Hg) has been detected in polar bear brain tissue, but its biological effects are not well known. Relationships between Hg concentrations and neurochemical enzyme activities and receptor binding were assessed in the cerebellum, frontal lobes, and occipital lobes of 24 polar bears collected from Nunavik (Northern Quebec), Canada. The concentration-response relationship was further studied with in vitro experiments using pooled brain homogenate of 12 randomly chosen bears. In environmentally exposed brain samples, there was no correlative relationship between Hg concentration and cholinesterase (ChE) activity or muscarinic acetylcholine receptor (mAChR) binding in any of the 3 brain regions. Monoamine oxidase (MAO) activity in the occipital lobe showed a negative correlative relationship with total Hg concentration. In vitro experiments, however, demonstrated that Hg (mercuric chloride and methylmercury chloride) can inhibit ChE and MAO activities and muscarinic mAChR binding. These results show that Hg can alter neurobiochemical parameters but the current environmental Hg exposure level does have an effect on the neurochemistry of polar bears from northern Canada. © 2014 SETAC.

Heterozygous Che-1 KO mice show deficiencies in object recognition memory persistence.

PubMed

Zalcman, Gisela; Corbi, Nicoletta; Di Certo, Maria Grazia; Mattei, Elisabetta; Federman, Noel; Romano, Arturo

2016-10-06

Transcriptional regulation is a key process in the formation of long-term memories. Che-1 is a protein involved in the regulation of gene transcription that has recently been proved to bind the transcription factor NF-κB, which is known to be involved in many memory-related molecular events. This evidence prompted us to investigate the putative role of Che-1 in memory processes. For this study we newly generated a line of Che-1(+/-) heterozygous mice. Che-1 homozygous KO mouse is lethal during development, but Che-1(+/-) heterozygous mouse is normal in its general anatomical and physiological characteristics. We analyzed the behavioral characteristic and memory performance of Che-1(+/-) mice in two NF-κB dependent types of memory. We found that Che-1(+/-) mice show similar locomotor activity and thigmotactic behavior than wild type (WT) mice in an open field. In a similar way, no differences were found in anxiety-like behavior between Che-1(+/-) and WT mice in an elevated plus maze as well as in fear response in a contextual fear conditioning (CFC) and object exploration in a novel object recognition (NOR) task. No differences were found between WT and Che-1(+/-) mice performance in CFC training and when tested at 24h or 7days after training. Similar performance was found between groups in NOR task, both in training and 24h testing performance. However, we found that object recognition memory persistence at 7days was impaired in Che-1(+/-) heterozygous mice. This is the first evidence showing that Che-1 is involved in memory processes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Bacterial Energy Sensor Aer Modulates the Activity of the Chemotaxis Kinase CheA Based on the Redox State of the Flavin Cofactor.

PubMed

Samanta, Dipanjan; Widom, Joanne; Borbat, Peter P; Freed, Jack H; Crane, Brian R

2016-12-09

Flagellated bacteria modulate their swimming behavior in response to environmental cues through the CheA/CheY signaling pathway. In addition to responding to external chemicals, bacteria also monitor internal conditions that reflect the availability of oxygen, light, and reducing equivalents, in a process termed "energy taxis." In Escherichia coli, the transmembrane receptor Aer is the primary energy sensor for motility. Genetic and physiological data suggest that Aer monitors the electron transport chain through the redox state of its FAD cofactor. However, direct biochemical data correlating FAD redox chemistry with CheA kinase activity have been lacking. Here, we test this hypothesis via functional reconstitution of Aer into nanodiscs. As purified, Aer contains fully oxidized FAD, which can be chemically reduced to the anionic semiquinone (ASQ). Oxidized Aer activates CheA, whereas ASQ Aer reversibly inhibits CheA. Under these conditions, Aer cannot be further reduced to the hydroquinone, in contrast to the proposed Aer signaling model. Pulse ESR spectroscopy of the ASQ corroborates a potential mechanism for signaling in that the resulting distance between the two flavin-binding PAS (Per-Arnt-Sim) domains implies that they tightly sandwich the signal-transducing HAMP domain in the kinase-off state. Aer appears to follow oligomerization patterns observed for related chemoreceptors, as higher loading of Aer dimers into nanodiscs increases kinase activity. These results provide a new methodological platform to study Aer function along with new mechanistic details into its signal transduction process. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Catastrophic healthcare expenditure and poverty related to out-of-pocket payments for healthcare in Bangladesh-an estimation of financial risk protection of universal health coverage.

PubMed

Khan, Jahangir A M; Ahmed, Sayem; Evans, Timothy G

2017-10-01

The Sustainable Development Goals target to achieve Universal Health Coverage (UHC), including financial risk protection (FRP) among other dimensions. There are four indicators of FRP, namely incidence of catastrophic health expenditure (CHE), mean positive catastrophic overshoot, incidence of impoverishment and increase in the depth of poverty occur for high out-of-pocket (OOP) healthcare spending. OOP spending is the major payment strategy for healthcare in most low-and-middle-income countries, such as Bangladesh. Large and unpredictable health payments can expose households to substantial financial risk and, at their most extreme, can result in poverty. The aim of this study was to estimate the impact of OOP spending on CHE and poverty, i.e. status of FRP for UHC in Bangladesh. A nationally representative Household Income and Expenditure Survey 2010 was used to determine household consumption expenditure and health-related spending in the last 30 days. Mean CHE headcount and its concentration indices (CI) were calculated. The propensity of facing CHE for households was predicted by demographic and socioeconomic characteristics. The poverty headcount was estimated using 'total household consumption expenditure' and such expenditure without OOP payments for health in comparison with the poverty-line measured by cost of basic need. In absolute values, a pro-rich distribution of OOP payment for healthcare was found in urban and rural Bangladesh. At the 10%-threshold level, in total 14.2% of households faced CHE with 1.9% overshoot. 16.5% of the poorest and 9.2% of the richest households faced CHE. An overall pro-poor distribution was found for CHE (CI = -0.064) in both urban and rural households, while the former had higher CHE incidences. The poverty headcount increased by 3.5% (5.1 million individuals) due to OOP payments. Reliance on OOP payments for healthcare in Bangladesh should be reduced for poverty alleviation in urban and rural Bangladesh in order to secure FRP for UHC. © The Author 2017. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Black-bellied whistling duck (Dendrocygna autumnalis) brain cholinesterase characterization and diagnosis of anticholinesterase pesticide exposure in wild populations from Mexico.

PubMed

Osten, Jaime Rendón-von; Soares, Amadeu M V M; Guilhermino, Lucia

2005-02-01

Rice is the main crop in the subbasin of the fluvial lagoon system of Palizada River (FLSPR) in the state of Campeche, Mexico. The pesticides used to control pests of this crop mainly are carbofuran, chlorpyrifos, and glyphosate. Black-bellied whistling duck (Dendrocygna autumnalis) is an ecologically and economically important species in the area. This duck is consumed by local inhabitants throughout the year, despite its potential exposure to pesticides. Due to its feeding habits, abundance, and nutritional value, D. autumnalis is a good indicator of environmental contamination and a potential route of human exposure to organophosphate and carbamate pesticides. In this study, the brain cholinesterase (ChE) in the frontal cerebral cortex of autochthonous ducks was characterized. In addition, the potential of the three locally used pesticides and mixtures to inhibit ChE activity was investigated and the exposure of the wild duck population during intensive pesticide applications in rice fields was evaluated. We found that acetylcholinesterase (AChE) seems to be the predominant ChE form in the biological fraction analyzed. Carbofuran was the most potent ChE inhibitor of D. autumnalis brain ChE activity from the three pesticides analyzed. Cholinesterase inhibition after exposure to pesticide mixtures predominantly was due to carbofuran. A decrease (p < 0.05) in AChE activity (>30%) was apparent in wild ducks compared to reference ducks, with recovery of ChE inhibition in wild ducks occurring months later when no pesticides were applied in the field. Dendrocygna autumnalis brain ChE is a suitable parameter for inclusion in biomonitoring programs for both environmental protection and human safety.

CheS-Mapper 2.0 for visual validation of (Q)SAR models

PubMed Central

2014-01-01

Background Sound statistical validation is important to evaluate and compare the overall performance of (Q)SAR models. However, classical validation does not support the user in better understanding the properties of the model or the underlying data. Even though, a number of visualization tools for analyzing (Q)SAR information in small molecule datasets exist, integrated visualization methods that allow the investigation of model validation results are still lacking. Results We propose visual validation, as an approach for the graphical inspection of (Q)SAR model validation results. The approach applies the 3D viewer CheS-Mapper, an open-source application for the exploration of small molecules in virtual 3D space. The present work describes the new functionalities in CheS-Mapper 2.0, that facilitate the analysis of (Q)SAR information and allows the visual validation of (Q)SAR models. The tool enables the comparison of model predictions to the actual activity in feature space. The approach is generic: It is model-independent and can handle physico-chemical and structural input features as well as quantitative and qualitative endpoints. Conclusions Visual validation with CheS-Mapper enables analyzing (Q)SAR information in the data and indicates how this information is employed by the (Q)SAR model. It reveals, if the endpoint is modeled too specific or too generic and highlights common properties of misclassified compounds. Moreover, the researcher can use CheS-Mapper to inspect how the (Q)SAR model predicts activity cliffs. The CheS-Mapper software is freely available at http://ches-mapper.org. Graphical abstract Comparing actual and predicted activity values with CheS-Mapper.

How to Improve Students' Comprehension Concerning the Major Terms of Functional Groups?--In the Experiment of OrCheTaboo Game

ERIC Educational Resources Information Center

Akkuzu, Nalan; Uyulgan, Melis Arzu

2016-01-01

In this research, for an effective learning of concepts in the scope of functional groups in organic chemistry, it has been developed as "Organic Chemistry Taboo (OrCheTaboo)" which is an educational activity by the researchers. The aim of this study is to analyze the effect of the game OrCheTaboo on learning of concepts related to…

Impact of Osteoarthritis on Household Catastrophic Health Expenditures in Korea.

PubMed

Kim, Hyoungyoung; Cho, Soo-Kyung; Kim, Daehyun; Kim, Dalho; Jung, Sun-Young; Jang, Eun Jin; Sung, Yoon-Kyoung

2018-05-21

Osteoarthritis (OA) is a disease of old age whose prevalence is increasing. This study explored the impact of OA on household catastrophic health expenditure (CHE) in Korea. We used data on 5,200 households from the Korea Health Panel Survey in 2013 and estimated annual living expenses and out-of-pocket (OOP) payments. Household CHE was defined when a household's total OOP health payments exceeded 10%, 20%, 30%, or 40% of the household's capacity to pay. To compare the OOP payments of households with OA individuals and those without OA, OA households were matched 1:1 with households containing a member with other chronic disease such as neoplasm, hypertension, heart disease, cerebrovascular disease, diabetes, or osteoporosis. The impact of OA on CHE was determined by multivariable logistic analysis. A total of 1,289 households were included, and households with and without OA patients paid mean annual OOP payments of $2,789 and $2,607, respectively. The prevalence of household CHE at thresholds of 10%, 20%, 30%, and 40% were higher in households with OA patients than in those without OA patients ( P < 0.001). The presence of OA patients in each household contributed significantly to CHE at thresholds of 10% (odds ratio [OR], 1.48; 95% confidence interval [CI], 1.16-1.87), 20% (OR, 1.29; 95% CI, 1.01-1.66), and 30% (OR, 1.37; 95% CI, 1.05-1.78), but not of 40% (OR, 1.17; 95% CI, 0.87-1.57). The presence of OA patients in Korean households is significantly related to CHE. Policy makers should try to reduce OOP payments in households with OA patients.

43 CFR 11.62 - Injury determination phase-injury definition.

Code of Federal Regulations, 2014 CFR

2014-10-01

... normal brain ChE activity of the wildlife species. These enzymes are in the nervous system of vertebrate... are in the nervous systems of vertebrate organisms and the rate of ChE activity is associated with the... other organs, as well as soft tissues of the gastrointestinal tract and vascular system, when comparing...

43 CFR 11.62 - Injury determination phase-injury definition.

Code of Federal Regulations, 2010 CFR

2010-10-01

... normal brain ChE activity of the wildlife species. These enzymes are in the nervous system of vertebrate... are in the nervous systems of vertebrate organisms and the rate of ChE activity is associated with the... other organs, as well as soft tissues of the gastrointestinal tract and vascular system, when comparing...

43 CFR 11.62 - Injury determination phase-injury definition.

Code of Federal Regulations, 2013 CFR

2013-10-01

... normal brain ChE activity of the wildlife species. These enzymes are in the nervous system of vertebrate... are in the nervous systems of vertebrate organisms and the rate of ChE activity is associated with the... other organs, as well as soft tissues of the gastrointestinal tract and vascular system, when comparing...

43 CFR 11.62 - Injury determination phase-injury definition.

Code of Federal Regulations, 2011 CFR

2011-10-01

... normal brain ChE activity of the wildlife species. These enzymes are in the nervous system of vertebrate... are in the nervous systems of vertebrate organisms and the rate of ChE activity is associated with the... other organs, as well as soft tissues of the gastrointestinal tract and vascular system, when comparing...

Effects on birds of fenthion aerial application for mosquito control

USGS Publications Warehouse

DeWeese, L.R.; McEwen, L.C.; Settimi, L.A.; Deblinger, R.D.

1983-01-01

Effects on birds of an aerial application of fenthion, a potent organophosphorus cholinesterase (ChE)-inhibiting insecticide, were assessed on four study sites 1.8 to 3.6 km2 in size. These sites were located within 121.5 km2 of wet meadows treated with 47 g of fenthion (AI) per ha in ultralow- volume formulation. Assessment methods were searches for sick or dead birds, measurements of brain ChE activity in specimens found dead or collected alive at different time intervals, and counts of bird populations. After treatment, 99 birds and 15 mammals were found sick or dead; 106 of these were on one site. Brain ChE activity in dead birds was depressed sufficiently to indicate that death was caused by an anti-ChE substance. Brain ChE activity in three common bird species collected alive showed the greatest reduction 2 days postspray. Two of these species had ChE activity that was still significantly (P<0.05) depressed 15 days postspray. Bird populations declined most where mortality was heaviest. Fenthion sprayed for mosquito control was life threatening to many birds inhabiting treated meadows.

CHOLINESTERASE IN DENERVATED END PLATES AND MUSCLE FIBRES

PubMed Central

Brzin, Miro; Majcen-Tkačev, Živa

1963-01-01

Parallel studies were made of cholinesterase activities and localizations in denervated rat and rabbit gastrocnemius muscle. Koelle's histochemical reaction was used for demonstrating the localization of cholinesterases. Enzyme activities in whole sliced muscle were measured by electrometric titration. The Cartesian ampulla-diver technique was used for cholinesterase activity determinations in end plate regions or in small pieces of the muscle fibre itself. No changes in the activity of cholinesterases (ChE) were found in the whole denervated muscle which would account for its chemical supersensitivity. The ChE distribution pattern was changed so that the end plate region became less active in the denervated muscle than in the normal one. The decrease in ChE activity in the end plates seems to be largely compensated for by an increase of this enzyme elsewhere in the muscle. A possible connection between the spatial spread of cholinesterase activity and the enlargement of the acetylcholine-sensitive surface is discussed. PMID:14086761

Prevalence and intensity of catastrophic health care expenditures in Iran from 2008 to 2015: a study on Iranian household income and expenditure survey.

PubMed

Yazdi-Feyzabadi, Vahid; Bahrampour, Mina; Rashidian, Arash; Haghdoost, Ali-Akbar; Akbari Javar, Mohammadreza; Mehrolhassani, Mohammad Hossein

2018-04-13

Households exposure to catastrophic health expenditure is a valuable measure to monitor financial protection in health sector payments. The present study had two aims: first, to estimate the prevalence and intensity of catastrophic health expenditures (CHE) in Iran. Second, to investigate main factors that influence the probability of CHE. CHE is defined as an occasion in which a household's out-of-pocket (OOP) spending exceeds 40% of the total income that remains after subtraction of living expenses. This study used the data from eight national repeated cross-sectional surveys on households' income and expenditure. The proportion of households facing CHE, as a prevalence measure, was estimated for rural and urban areas. The intensity of CHE was also calculated using overshoot and mean positive overshoot (MPO) measures. The factors affecting the CHE were also analyzed using logistic random effects regression model. We also used ArcMap 10.1 to display visually disparities across the country. An increasing number of Iranians has been subject to catastrophic health care costs over the study period in both rural and urban areas (CHE = 2.57% in 2008 and 3.25% in 2015). In the same period, the overshoot of CHE and the mean positive overshoot ranged from 0.26% to 0.65% and from 12.26% to 20.86%, respectively. The average absolute monetary value of OOP spending per month has been low in rural areas over the years, but the prevalence of CHE has been higher than urban areas. Generally put, rural settlement, higher income, receiving inpatient and outpatient services, and existence of elderly people in the household led to increase in CHE prevalence (p < 0.05). Interestingly, provinces with more limited geographical and cultural accessibility had the lowest CHE. According to the findings, Iran's healthcare system has failed to realize the aim of five-year national development plan regarding CHE prevalence (1% CHE prevalence according to the plan). Therefore, revision of financial health care protection policies focusing on pre-payments seems mandatory. For instance, these policies should extend the interventions that target low-income populations particularly in rural areas, provide more coverage for catastrophic medical services in basic benefit packages, and develop supplementary health insurance.

Plasma cholinesterase levels of mountain plovers (Charadrius montanus) wintering in central California, USA

USGS Publications Warehouse

Iko, W.M.; Archuleta, A.S.; Knopf, F.L.

2003-01-01

Declines of over 60% in mountain plover (Charadrius montanus) populations over the past 30 years have made it a species of concern throughout its current range and a proposed species for listing under the U.S. Endangered Species Act. Wintering mountain plovers spend considerable time on freshly plowed agricultural fields where they may potentially be exposed to anticholinesterase pesticides. Because of the population status and wintering ecology of plovers, the objectives of our study were to use nondestructive methods to report baseline plasma cholinesterase (ChE) levels in free-ranging mountain plovers wintering in California, USA, and to assess whether sampled birds showed signs of ChE inhibition related to anticholinesterase chemical exposure. We compared plasma ChE activity for mountain plovers sampled from the Carrizo Plain (an area relatively free of anticholinesterase pesticide use) with similar measures for plovers from the Central Valley (where anticholinesterase pesticides are widely used). Analyses for ChE inhibition indicated that none of the plovers had been recently exposed to these chemicals. However, mean ChE levels of plovers from the Central Valley were significantly higher (32%) than levels reported for plovers from the Carrizo Plain. This result differs from our original assumption of higher exposure risk to mountain plovers in the Central Valley but does suggest that some effect is occurring in the ChE activity of mountain plovers wintering in California.

Possible mechanisms for sensitivity to organophosphorus and carbamate insecticides in eastern screech-owls and American kestrels.

PubMed

Vyas, N B; Thiele, L A; Garland, S C

1998-07-01

Effects of a single dietary exposure to fenthion and carbofuran on the survival, feeding behavior and brain ChE activity of eastern screech-owls, Otus asio and American kestrels, Falco sparverius, were evaluated. Birds were exposed to fenthion (23.6-189.0 ppm) or carbofuran (31.7-253.6 ppm) via meatballs. Carbofuran-exposed owls ate either < or = 10% or > or = 80% of the meatball whereas all kestrels ate < or = 10% of the meatball before exhibiting acute signs of toxicity. Fenthion-exposed owls and kestrels displayed a wide spectrum of meatball consumption (< 10-100%). Significant brain ChE inhibition was observed in dead and surviving kestrels exposed to fenthion and carbofuran and dead owls exposed to fenthion (P < 0.0001). Brain ChE activity of owls exposed to carbofuran that survived was not different from that of controls (P = 0.25). Data suggest: (1) slow feeding on a carbamate-contaminated item may provide limited protection from the toxicity of the chemical at certain rates of exposure; (2) the degree of ChE inhibition at neuromuscular junctions may be critical in determining the sensitivity of a species to a carbamate insecticide; (3) sensitivity may be a function of the ChE affinity for the carbamate inhibitor; and (4) the importance of neuromuscular junction ChE depression in determining the sensitivity of an animal may be species-specific.

Possible mechanisms for sensitivity to organophosphorus and carbamate insecticides in eastern screech-owls and American kestrels

USGS Publications Warehouse

Vyas, N.B.; Thiele, L.A.; Garland, S.C.

1998-01-01

Effects of a single dietary exposure to fenthion and carbofuran on the survival, feeding behavior and brain ChE activity of eastern screech-owls, Otus asio and American kestrels, Falco sparverius, were evaluated. Birds were exposed to fenthion (23.6–189.0 ppm) or carbofuran (31.7–253.6 ppm) via meatballs. Carbofuran-exposed owls ate either ≤10% or ≥80% of the meatball whereas all kestrels ate ≤10% of the meatball before exhibiting acute signs of toxicity. Fenthion-exposed owls and kestrels displayed a wide spectrum of meatball consumption (<10–100%). Significant brain ChE inhibition was observed in dead and surviving kestrels exposed to fenthion and carbofuran and dead owls exposed to fenthion (P<0.0001). Brain ChE activity of owls exposed to carbofuran that survived was not different from that of controls (P=0.25). Data suggest: (1) slow feeding on a carbamate-contaminated item may provide limited protection from the toxicity of the chemical at certain rates of exposure; (2) the degree of ChE inhibition at neuromuscular junctions may be critical in determining the sensitivity of a species to a carbamate insecticide; (3) sensitivity may be a function of the ChE affinity for the carbamate inhibitor; and (4) the importance of neuromuscular junction ChE depression in determining the sensitivity of an animal may be species-specific.

Catastrophic health expenditure: a comparative analysis of empty-nest and non-empty-nest households with seniors in Shandong, China.

PubMed

Yang, Tingting; Chu, Jie; Zhou, Chengchao; Medina, Alexis; Li, Cuicui; Jiang, Shan; Zheng, Wengui; Sun, Liyuan; Liu, Jing

2016-07-05

The aim of this study was to compare the catastrophic health expenditure (CHE) prevalence and its determinants between empty-nest and non-empty-nest elderly households. Shandong province of China. A total of 2761 elderly households are included in the analysis. CHE incidence among elderly households was 44.9%. The CHE incidence of empty-nest singles (59.3%, p=0.000, OR=3.19) and empty-nest couples (52.9%, p=0.000, OR=2.45) are both statistically higher than that of non-empty-nest elderly households (31.4%). An inverse association was observed between CHE incidence and income level in all elderly household types. Factors including 1 or more household elderly members with non-communicable chronic diseases in the past 6 months, 1 or more elderly household members being hospitalised in the past year and lower household income, are significant risk factors for CHE in all 3 household types (p<0.05). Health insurance status was found to be a significant determinant of CHE among empty-nest singles and non-empty-nest households (p<0.05). CHE incidence among elderly households is high in China. Empty-nest households are at higher risk for CHE than non-empty-nest households. Based on these findings, we suggest that special insurance be developed to broaden the coverage of health services and heighten the reimbursement rate for empty-nest elderly in the existing health insurance schemes. Financial and social protection interventions are also essential for identified at-risk subgroups among different types of elderly households. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Catastrophic health expenditure: a comparative analysis of empty-nest and non-empty-nest households with seniors in Shandong, China

PubMed Central

Yang, Tingting; Chu, Jie; Zhou, Chengchao; Medina, Alexis; Li, Cuicui; Jiang, Shan; Zheng, Wengui; Sun, Liyuan; Liu, Jing

2016-01-01

Objective The aim of this study was to compare the catastrophic health expenditure (CHE) prevalence and its determinants between empty-nest and non-empty-nest elderly households. Setting Shandong province of China. Participants A total of 2761 elderly households are included in the analysis. Results CHE incidence among elderly households was 44.9%. The CHE incidence of empty-nest singles (59.3%, p=0.000, OR=3.19) and empty-nest couples (52.9%, p=0.000, OR=2.45) are both statistically higher than that of non-empty-nest elderly households (31.4%). An inverse association was observed between CHE incidence and income level in all elderly household types. Factors including 1 or more household elderly members with non-communicable chronic diseases in the past 6 months, 1 or more elderly household members being hospitalised in the past year and lower household income, are significant risk factors for CHE in all 3 household types (p<0.05). Health insurance status was found to be a significant determinant of CHE among empty-nest singles and non-empty-nest households (p<0.05). Conclusions CHE incidence among elderly households is high in China. Empty-nest households are at higher risk for CHE than non-empty-nest households. Based on these findings, we suggest that special insurance be developed to broaden the coverage of health services and heighten the reimbursement rate for empty-nest elderly in the existing health insurance schemes. Financial and social protection interventions are also essential for identified at-risk subgroups among different types of elderly households. PMID:27381206

The effects of chlorpyrifos on cholinesterase activity and foraging behavior in the dragonfly, Anax junius (Odonata)

USGS Publications Warehouse

Brewer, S.K.; Atchison, G.J.

1999-01-01

We examined head capsule cholinesterase (ChE) and foraging behavior in nymphs of the dragonfly, Anax junius, exposed for 24 h to 0.2, 0.6 and 1.0 ??g l-1 of the organophosphorus (OP) insecticide, chlorpyrifos [O,O-diethyl O-(3,5,6-trichloro-2-pyridyl) phosphorothioate]. The invertebrate community is an important component of the structure and function of wetland ecosystems, yet the potential effects of insecticides on wetland ecosystems are largely unknown. Our objectives were to determine if exposure to environmentally realistic concentrations of chlorpyrifos affected foraging behavior and ChE activity in head capsules of dragonfly nymphs. Nymphs were exposed to different concentrations of chlorpyrifos and different prey densities in a factorial design. ChE activities and foraging behaviors of treated nymphs were not statistically different (p ??? 0.05) from control groups. Prey density effects exerted a greater effect on dragonfly foraging than toxicant exposures. Nymphs offered higher prey densities exhibited more foraging behaviors but also missed their prey more often. High variability in ChE activities within the control group and across treated groups precluded determination of relationships between ChE and foraging behaviors. It appears that A. junius is relatively tolerant of chlorpyrifos, although the concentrations we tested have been shown in other work to adversely affect the prey base; therefore the introduction of this insecticide may have indirect adverse affects on top invertebrate predators such as Odonata.

Antileishmanial, antimalarial and antimicrobial activities of the extract and isolated compounds from Austroplenckia populnea (Celastraceae).

PubMed

Andrade, Sérgio F; da Silva Filho, Ademar A; de O Resende, Dimas; Silva, Márcio L A; Cunha, Wilson R; Nanayakkara, N P Dhammika; Bastos, Jairo Kenupp

2008-01-01

Austroplenckia populnea (Celastraceae), known as "marmelinho do campo", is used in Brazilian folk medicine as antimicrobial, anti-inflammatory, and antitumoural agent. The aim of the present work was to evaluate the antimicrobial, antileishmanial and antimalarial activities of the crude hydroalcoholic extract of A. populnea (CHE) and some of its isolated compounds. The phytochemical study of the CHE was carried out affording the isolation of methyl populnoate (1), populnoic acid (2), and stigmast-5-en-3-O-beta-(D-glucopyranoside) (3). This is the first time that the presence of compound 3 in A. populnea is reported. The results showed that the CHE presents antifungal and antibacterial activities, especially against Candida glabrata and Candida albicans, for which the CHE showed IC50 values of 0.7 microg mL(-1) and 5.5 microg mL(-1), respectively, while amphotericin B showed an IC50 value of 0.1 microg mL(-1) against both microorganisms. Compounds 1-3 were inactive against all tested microorganisms. In the antileishmanial activity test against Leishmania donovani, the CHE showed an IC50 value of 52 microg mL(-1), while compounds 2 and 3 displayed an IC50 value of 18 microg mL(-1) In the antimalarial assay against Plasmodium falciparum (D6 and W2 clones), it was observed that all evaluated samples were inactive. In order to compare the effect on the parasites with the toxicity to mammalian cells, the cytotoxicity activity of the isolated compounds was evaluated against Vero cells, showing that all evaluated samples exhibited no cytotoxicity at the maximum dose tested.

Development of square wave voltammetry method for the assessment of organophosphorus compound impact on the cholinesterase of Pheretima with 2,6-dichloroindophenol as a redox indicator.

PubMed

Qiu, Jingxia; Chen, Jin; Ma, Qianqian; Miao, Yuqing

2009-09-01

A square wave voltammetry method was developed for the assessment of organophosphorus (OPs) compound impact on the cholinesterase of Pheretima with 2,6-dichloroindophenol (2,6-DCIP) as a redox indicator. The substrate of acetylthiocholine is hydrolysed by the cholinesterase (ChE) from soil animal pheretima, and the produced thiocholine reacts with the 2,6-DCIP to give obvious shift of electrochemical signal. The inhibition of ChE was assessed by measuring the enzyme activity before and after incubating with parathion-methyl. The reduction peak current of 2,6-DCIP decreases with the time of enzymatical reaction. The ChE loses almost 32.74% activity after 10 min incubation with 1ng mL(-1) paraoxon and 54.62% with 10 microg mL(-1) paraoxon, while the activity that corresponds to 100 microg mL(-1) paraoxon was nearly completely inhibited. This method can be employed to assess the inhibition of ChE and investigate OPs impact on environmental animals.

Acute Toxicity Estimation and Operational Risk Management of Chemical Warfare Agent Exposures

DTIC Science & Technology

2004-05-01

Following absorption into the body, nerve agents bind with and inhibit the activity of cholinesterases (ChE) that are present in the blood and...other tissues. Blood ChE activity depression by itself is not considered an adverse effect but (particularly red blood cell cholinesterase (RBC-ChE...chemical, such as an organophosphate , that blocks nerve impulses by inhibiting the activity of the enzyme cholinesterase (adapted from University of

Catastrophic health expenditure and its determinants in Kenya slum communities.

PubMed

Buigut, Steven; Ettarh, Remare; Amendah, Djesika D

2015-05-14

In Kenya, where 60 to 80% of the urban residents live in informal settlements (frequently referred to as slums), out-of-pocket (OOP) payments account for more than a third of national health expenditures. However, little is known on the extent to which these OOP payments are associated with personal or household financial catastrophe in the slums. This paper seeks to examine the incidence and determinants of catastrophic health expenditure among urban slum communities in Kenya. We use a unique dataset on informal settlement residents in Kenya and various approaches that relate households OOP payments for healthcare to total expenditures adjusted for subsistence, or income. We classified households whose OOP was in excess of a predefined threshold as facing catastrophic health expenditures (CHE), and identified the determinants of CHE using multivariate logistic regression analysis. The results indicate that the proportion of households facing CHE varies widely between 1.52% and 28.38% depending on the method and the threshold used. A core set of variables were found to be key determinants of CHE. The number of working adults in a household and membership in a social safety net appear to reduce the risk of catastrophic expenditure. Conversely, seeking care in a public or private hospital increases the risk of CHE. This study suggests that a substantial proportion of residents of informal settlements in Kenya face CHE and would likely forgo health care they need but cannot afford. Mechanisms that pool risk and cost (insurance) are needed to protect slum residents from CHE and improve equity in health care access and payment.

Structural Insight inot the low Affinity Between Thermotoga maritima CheA and CheB Compared to their Escherichia coli/Salmonella typhimurium Counterparts

DOE Office of Scientific and Technical Information (OSTI.GOV)

S Park; B Crane

2011-12-31

CheA-mediated CheB phosphorylation and the subsequent CheB-mediated demethylation of the chemoreceptors are important steps required for the bacterial chemotactic adaptation response. Although Escherichia coli CheB has been reported to interact with CheA competitively against CheY, we have observed that Thermotoga maritima CheB has no detectable CheA-binding. By determining the CheY-like domain crystal structure of T. maritima CheB, and comparing against the T. maritima CheY and Salmonella typhimurium CheB structures, we propose that the two consecutive glutamates in the {beta}4/{alpha}4 loop of T. maritima CheB that is absent in T. maritima CheY and in E. coli/S. typhimurium CheB may be onemore » factor contributing to the low CheA affinity.« less

In vitro investigation of efficacy of new reactivators on OPC inhibited rat brain acetylcholinesterase.

PubMed

Atanasov, Vasil N; Petrova, Iskra; Dishovsky, Christophor

2013-03-25

Organophosphorus compounds (OPC) were developed as warfare nerve agents. They are also widely used as pesticides. The drug therapy of intoxication with OPC includes mainly combination of cholinesterase (ChE) reactivators and cholinolytics. There is no single ChE reactivator having an ability to reactivate sufficiently the inhibited enzyme due to the high variability of chemical structure of the inhibitors. The difficulties in reactivation of ChE activity and slight antidote effect regarding intoxication with some OPC are some of the reasons for continuous efforts to obtain new reactivators of ChE. The aim of the present study was to evaluate the efficacy of some ChE reactivators against OPC intoxication (tabun, paraoxon and dichlorvos) in in vitro experiments and to compare their activity to that known for some currently used oximes (obidoxime, HI-6, 2-PAM). Experiments were carried out using rat brain acetylcholinesterase (AChE). Reactivators showed different activity in the reactivation of rat brain AChE after dichlorvos, paraoxon and tabun inhibition. AChE was easier reactivated after paraoxon treatment. The best effect showed BT-07-4M, obidoxime, TMB-4 and BT-08 from the group of symmetric oximes, and Toxidin, BT-05 and BT-03 from asymmetric compounds. The reactivation of brain AChE inhibited with tabun demonstrated better activity of new compound BT-07-4M, TMB-4 and obidoxime from symmetric oximes, and BT-05 and BT-03 possessing asymmetric structure. All compounds showed low activity toward inhibition of AChE caused by dichlorvos. Comparison of two main structure types (symmetric/asymmetric) showed that the symmetric compounds reactivated better AChE, inhibited with this OPC, than asymmetric ones. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Cholinesterase activity of muscle tissue from freshwater fishes: characterization and sensitivity analysis to the organophosphate methyl-paraoxon.

PubMed

Lopes, Renato Matos; Filho, Moacelio Veranio Silva; de Salles, João Bosco; Bastos, Vera Lúcia Freire Cunha; Bastos, Jayme Cunha

2014-06-01

The biochemical characterization of cholinesterases (ChE) from different teleost species has been a critical step in ensuring the proper use of ChE activity levels as biomarkers in environmental monitoring programs. In the present study, ChE from Oreochromis niloticus, Piaractus mesopotamicus, Leporinus macrocephalus, and Prochilodus lineatus was biochemically characterized by specific substrates and inhibitors. Moreover, muscle tissue ChE sensitivity to the organophosphate pesticide methyl-paraoxon was evaluated by determining the inhibition kinetic constants for its progressive irreversible inhibition by methyl-paraoxon as well as the 50% inhibitory concentration (IC50) for 30 min for each species. The present results indicate that acetylcholinesterase (AChE) must be present in the muscle from P. mesopotamicus, L. macrocephalus, and P. lineatus and that O. niloticus possesses an atypical cholinesterase or AChE and butyrylcholinesterase (BChE). Furthermore, there is a large difference regarding the sensitivity of these enzymes to methyl-paraoxon. The determined IC50 values for 30 min were 70 nM (O. niloticus), 258 nM (P. lineatus), 319 nM (L. macrocephalus), and 1578 nM (P. mesopotamicus). The results of the present study also indicate that the use of efficient methods for extracting these enzymes, their kinetic characterization, and determination of sensitivity differences between AChE and BChE to organophosphate compounds are essential for the determination of accurate ChE activity levels for environmental monitoring programs. © 2014 SETAC.

His-Tag-Mediated Dimerization of Chemoreceptors Leads to Assembly of Functional Nanoarrays.

PubMed

Haglin, Elizabeth R; Yang, Wen; Briegel, Ariane; Thompson, Lynmarie K

2017-11-07

Transmembrane chemotaxis receptors are found in bacteria in extended hexagonal arrays stabilized by the membrane and by cytosolic binding partners, the kinase CheA and coupling protein CheW. Models of array architecture and assembly propose receptors cluster into trimers of dimers that associate with one CheA dimer and two CheW monomers to form the minimal "core unit" necessary for signal transduction. Reconstructing in vitro chemoreceptor ternary complexes that are homogeneous and functional and exhibit native architecture remains a challenge. Here we report that His-tag-mediated receptor dimerization with divalent metals is sufficient to drive assembly of nativelike functional arrays of a receptor cytoplasmic fragment. Our results indicate receptor dimerization initiates assembly and precedes formation of ternary complexes with partial kinase activity. Restoration of maximal kinase activity coincides with a shift to larger complexes, suggesting that kinase activity depends on interactions beyond the core unit. We hypothesize that achieving maximal activity requires building core units into hexagons and/or coalescing hexagons into the extended lattice. Overall, the minimally perturbing His-tag-mediated dimerization leads to assembly of chemoreceptor arrays with native architecture and thus serves as a powerful tool for studying the assembly and mechanism of this complex and other multiprotein complexes.

Anticholinesterase exposure of white-winged doves breeding in lower Rio Grande valley, Texas

USGS Publications Warehouse

Tacha, T.C.; Schacht, S.J.; George, R.R.; Hill, E.F.

1994-01-01

We studied exposure of breeding white-winged doves (Zenaida asiatica) to anticholinesterase compounds (organophosphorus and carbamate pesticides) in the Lower Rio Grande Valley (LRGV), Texas. Widespread use of organophosphorus pesticides and dove population declines prompted the study. We collected breeding adult doves in May and July 1991 (n = 28) and July 1992 (n = 33) at 6 locations. We used depression of whole-brain cholinesterase (ChE) activity (2 SD below control mean) to detect exposure; values from 4 hand-reared doves fed commercial pigeon chow served as the control. Mean brain ChE activity was lower (P lt 0.027) than the control sample at all 6 locations in 1991; 79% of the birds were diagnostic of exposure ( gt 16.1% ChE depression). Pooled 1992 field samples also were lower (P lt 0.036) than were control samples; doves from 4 of the 6 locations had brain ChE activity below (P lt 0.088) controls. Overall, 39% of 1992 doves were diagnostic of exposure to anticholinesterase compounds. Higher exposure rates in 1991 were probably due to increased use of organophosphorus pesticides. Research is needed documenting effects of sublethal exposure on white-winged dove productivity.

Relationship Between Brain and Plasma Carbaryl Levels and Cholinesterase Inhibition

EPA Science Inventory

Carbaryl is a N-methylcarbamate pesticide and, like others in this class, is a reversible inhibitor of cholinesterase (ChE) enzymes. Although studied for many years, there is a surprising lack of information relating tissue levels of carbaryl with ChE activity in the same animals...

The Effects of Exercise on Pharmacokinetics and Pharmacodynamics of Physostigmine in Rats

DTIC Science & Technology

1989-02-15

Phy ( cholinesterase activity ) are likely to be altered by exercise due to altered blood flow rates to liver and pH of muscle. During exercise...concurrent acute exercise on the ChE activity in RBC aad tissues and in blood biochemical parameters in rats. Phy has been reported to reduce the...Springfield, Illinois. Also, we have studied the effect of exercise training, Phy and training + Phy on ChE activity in RBC and tissues and on blood biochemi

Cholinesterase inhibition and acetylcholine accumulation following intracerebral administration of paraoxon in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ray, A.; Liu, J.; Karanth, S.

2009-05-01

We evaluated the inhibition of striatal cholinesterase activity following intracerebral administration of paraoxon assaying activity either in tissue homogenates ex vivo or by substrate hydrolysis in situ. Artificial cerebrospinal fluid (aCSF) or paraoxon in aCSF was infused unilaterally (0.5 {mu}l/min for 2 h) and ipsilateral and contralateral striata were harvested for ChE assay ex vivo. High paraoxon concentrations were needed to inhibit ipsilateral striatal cholinesterase activity (no inhibition at < 0.1 mM; 27% at 0.1 mM; 79% at 1 mM paraoxon). With 3 mM paraoxon infusion, substantial ChE inhibition was also noted in contralateral striatum. ChE histochemistry generally confirmed thesemore » concentration- and side-dependent effects. Microdialysates collected for up to 4 h after paraoxon infusion inhibited ChE activity when added to striatal homogenate, suggesting prolonged efflux of paraoxon. Since paraoxon efflux could complicate acetylcholine analysis, we evaluated the effects of paraoxon (0, 0.03, 0.1, 1, 10 or 100 {mu}M, 1.5 {mu}l/min for 45 min) administered by reverse dialysis through a microdialysis probe. ChE activity was then monitored in situ by perfusing the colorimetric substrate acetylthiocholine through the same probe and measuring product (thiocholine) in dialysates. Concentration-dependent inhibition was noted but reached a plateau of about 70% at 1 {mu}M and higher concentrations. Striatal acetylcholine was below the detection limit at all times with 0.1 {mu}M paraoxon but was transiently elevated (0.5-1.5 h) with 10 {mu}M paraoxon. In vivo paraoxon (0.4 mg/kg, sc) in adult rats elicited about 90% striatal ChE inhibition measured ex vivo, but only about 10% inhibition measured in situ. Histochemical analyses revealed intense AChE and glial fibrillary acidic protein staining near the cannula track, suggesting proliferation of inflammatory cells/glia. The findings suggest that ex vivo and in situ cholinesterase assays can provide very different views into enzyme-inhibitor interactions. Furthermore, the proliferation/migration of cells containing high amounts of cholinesterase just adjacent to a dialysis probe could affect the recovery and thus detection of extracellular acetylcholine in microdialysis studies.« less

Distigmine Bromide Produces Sustained Potentiation of Guinea-Pig Urinary Bladder Motility by Inhibiting Cholinesterase Activity.

PubMed

Obara, Keisuke; Chino, Daisuke; Tanaka, Yoshio

2017-01-01

Distigmine is a cholinesterase (ChE) inhibitor used for the treatment of detrusor underactivity in Japan. Distigmine's pharmacological effects are known to be long-lasting, but the duration of its effect on urinary bladder contractile function has not been fully elucidated. The present study aimed to determine these effects in relation to the plasma concentrations of distigmine and its inhibition of ChE activities in blood, plasma, and bladder tissue. Intravesical pressures were recorded in anesthetized guinea-pigs for 12 h after the intravenous administration of saline or distigmine (0.01-0.1 mg/kg). Plasma distigmine concentrations were measured by liquid chromatograph-tandem mass spectrometry (LC-MS/MS), while ChE activities were assayed using 5,5'-dithiobis(2-nitrobenzoic acid). Distigmine (0.1 mg/kg) significantly increased the maximum intravesical pressure at micturition reflex for 12 h post-administration. In contrast, plasma distigmine was only detectable for 6 h post-administration in these animals and a one-compartment model calculated an elimination half-life of 0.7 h. However, bladder and blood acetylcholinesterase activities were significantly inhibited for 12 h after distigmine administration, although plasma ChE activities were not affected. The pharmacodynamic effects of distigmine thus persisted after its elimination from the circulation, indicating that it may bind to bladder acetylcholinesterase, producing sustained enzyme inhibition and enhancement of bladder contractility.

Impact of systemic alitretinoin treatment on skin barrier gene and protein expression in patients with chronic hand eczema.

PubMed

Kumari, V; Timm, K; Kühl, A A; Heine, G; Worm, M

2016-12-01

Chronic hand eczema (CHE) is a common inflammatory skin disease that affects approximately 10% of the population. Systemic alitretinoin has been shown to be effective in patients with CHE who are refractory to topical corticosteroids. To analyse the impact of alitretinoin on the skin barrier genes and protein expression in the skin lesions of patients with CHE. Fifteen patients with CHE were treated with 30 mg daily of alitretinoin for up to 27 weeks. Disease severity was assessed using a clinical score. Skin biopsies from all the patients were evaluated before and after therapy for the expression of Ki-67, various skin barrier genes and thymic stromal lymphopoietin (TSLP) by real-time quantitative polymerase chain reaction and immunohistochemistry. After alitretinoin application, an improvement in the clinical severity of CHE was observed in the majority of patients. Analysis of skin biopsies before treatment showed a significant increase in Ki-67-positive cells in the suprabasal layer and a dysregulated expression of various skin barrier genes, such as claudin 1, loricrin, filaggrin and cytokeratin 10, which were normalized after treatment. TSLP was significantly upregulated in patients with CHE and also normalized after alitretinoin treatment and negatively correlated with filaggrin. Our data indicate that the expression of barrier genes and proteins was normalized following treatment with alitretinoin in patients with CHE. The change in expression levels of these genes correlated with the clinical efficacy, suggesting that alitretinoin exhibits a disease-modifying activity. TSLP is upregulated in CHE and seems to counteract filaggrin expression in the skin. © 2016 British Association of Dermatologists.

AGE-RELATED BRAIN CHOLINESTERASE INHIBITION KINETICS FOLLOWING IN VITRO INCUBATION WITH CHLORPYRIFOS-OXON AND DIAZINON-OXON

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kousba, Ahmed A.; Poet, Torka S.; Timchalk, Chuck

2007-01-01

Chlorpyrifos and diazinon are two commonly used organophosphorus (OP) insecticides, and their primary mechanism of action involves the inhibition of acetylcholinesterase (AChE) by their metabolites chlorpyrifos-oxon (CPO) and diazinon-oxon (DZO), respectively. The study objectives were to assess the in vitro age-related inhibition kinetics of neonatal rat brain cholinesterase (ChE) by estimating the bimolecular inhibitory rate constant (ki) values for CPO and DZO. Brain ChE inhibition and ki values following CPO and DZO incubation with neonatal Sprague-Dawley rats rat brain homogenates were determined at post natal day (PND) -5, -12 and -17 and compared with the corresponding inhibition and ki valuesmore » obtained in the adult rat. A modified Ellman method was utilized for measuring the ChE activity. Chlorpyrifos-oxon resulted in greater ChE inhibition than DZO consistent with the estimated ki values of both compounds. Neonatal brain ChE inhibition kinetics exhibited a marked age-related sensitivity to CPO, where the order of ChE inhibition was PND-5 > PND-7 > PND-17 with ki values of 0.95, 0.50 and 0.22 nM-1hr-1, respectively. In contrast, DZO did not exhibit an age-related inhibition of neonatal brain ChE, and the estimated ki value at all PND ages was 0.02 nM-1hr-1. These results demonstrated an age- and chemical-related OP-selective inhibition of rat brain ChE which may be critically important in understanding the potential sensitivity of juvenile humans to specific OP exposures.« less

Identification of polypeptides necessary for chemotaxis in Escherichia coli.

PubMed Central

Silverman, M; Simon, M

1977-01-01

Molecular cloning techniques were used to construct Escherichia coli-lambda hybrids that contained many of the genes necessary for flagellar rotation and chemotaxis. The properties of specific hybrids that carried the classical "cheA" and "cheB" loci were examined by genetic complementation and by measuring the capacity of the hybrids to direct the synthesis of specific polypeptides. The results of these tests with lambda hybrids and with a series of deletion mutations derived from the hybrids redefined the "cheA" and "cheB" regions. Six genes were resolved: cheA, cheW, cheX, cheB, cheY, and cheZ. They directed the synthesis of specific polypeptides with the following apparent molecular weights: cheA, 76,000 and 66,000; cheW, 12,000; cheX, 28,000; cheB, 38,000; cheY, 8,000; and cheZ, 24,000. The presence of another gene, cheM, was inferred from the protein synthesis experiments. The cheM gene directed the synthesis of polypeptides with apparent molecular weights of 63,000, 61,000, and 60,000. The synthesis of all of these polypeptides is regulated by the same mechanisms that regulate the synthesis of flagellar-related structural components. Images PMID:324984

[Insect cholinesterases and irreversible inhibitors. Statistical treatment of the data].

PubMed

Moralev, S N

2010-01-01

The data on sensitivity of cholinesterases (ChE) of different insects to reversible inhibitors, as well as the data on physico-chemical parameters of amino acids constituting their active centers, were treated by factor analysis and juxtaposed. It is shown that both these characteristics are related to taxonomical belonging of insects. It is revealed the "material substrate" of the factors determining inhibitor action specificity, which are specific sites in ChE active center.

Effects of pyridostigmine and cholinolytics on cholinesterase and acetylcholine in Soman poisoned rats.

PubMed

Stitcher, D L; Harris, L W; Heyl, W C; Alter, S C

1978-01-01

Soman reduced blood and brain cholinesterase (ChE) activity to less than 15% and increased cerebral acetylcholine (ACh) levels to 137.4% of control. When pyridostigmine (P) was used as a prophylactic adjunct, it reduced blood ChE activity to 31.6% of control, failed to significantly alter brain ChE activity, and protected more than 70% of the blood (but not brain enzyme) from phosphonylation by soman. Benactyzine (B) was more effective than atropine (A) in reducing cerebral ACh concentrations, while a combination of the two was more effective than either alone. A prophylaxis of P + A + B was effective in controlling ACh levels in rats poisoned with one LD50 dose of Soman. Since P did not diminish the effects of the cholinolytics on cerebral ACh, this (together with the enzyme data) suggests that the two cholinolytics alone provided the central protection.

Cholinergic and behavioral neurotoxicity of carbaryl and cadmium to larval rainbow trout (Oncorhynchus mykiss)

USGS Publications Warehouse

Beauvais, S.L.; Jones, S.B.; Parris, J.T.; Brewer, S.K.; Little, E.E.

2001-01-01

Pesticides and heavy metals are common environmental contaminants that can cause neurotoxicity to aquatic organisms, impairing reproduction and survival. Neurotoxic effects of cadmium and carbaryl exposures were estimated in larval rainbow trout (RBT; Oncorhynchus mykiss) using changes in physiological endpoints and correlations with behavioral responses. Following exposures, RBT were videotaped to assess swimming speed. Brain tissue was used to measure cholinesterase (ChE) activity, muscarinic cholinergic receptor (MChR) number, and MChR affinity. ChE activity decreased with increasing concentrations of carbaryl but not of cadmium. MChR were not affected by exposure to either carbaryl or cadmium. Swimming speed correlated with ChE activity in carbaryl-exposed RBT, but no correlation occurred in cadmium-exposed fish. Thus, carbaryl exposure resulted in neurotoxicity reflected by changes in physiological and behavioral parameters measured, while cadmium exposure did not. Correlations between behavior and physiology provide a useful assessment of neurotoxicity.

Cholinesterases and neurotoxicity as highly sensitive biomarkers for an organophosphate insecticide in a freshwater gastropod (Chilina gibbosa) with low sensitivity carboxylesterases.

PubMed

Bianco, Karina; Yusseppone, María Soledad; Otero, Sofía; Luquet, Carlos; Ríos de Molina, María Del Carmen; Kristoff, Gisela

2013-11-15

In the Upper Valley of Río Negro and Río Neuquén in Argentina, agriculture represents the second most important economic activity. Azinphos-methyl has been found in water from this region throughout the year at a maximum concentration of 22.48 μg L(-1) during the application period. Toxicological studies on local non-target species have been performed mostly on vertebrates, while mollusks, which could be more sensitive, have not been studied so far. This work aims to characterize cholinesterase (ChE) and carboxilesterase (CE) activities of Chilina gibbosa, a freshwater gastropod native to southern Argentina and Chile. These enzymes, together with neurotoxicity signals, are evaluated herein after as sensitive biomarkers of exposure to azinphos-methyl at environmentally relevant concentrations. Effects of azinphos-methyl on antioxidant defenses: glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and glutathione S-transferase (GST) are also studied in order to complete a set of biomarkers with different sensitivity and specificity, to propose C. gibbosa as a sentinel species. The highest specific activity was obtained with acetylthiocholine as substrate, followed by propionylthiocholine (83% in comparison to acetylthiocholine) and butyrylthiocholine (19%).The lowest Km and the highest efficiency for ChE were obtained with acetylthiocholine. Regarding CEs activities, a higher efficiency was obtained with p-nitrophenyl butyrate than with p-nitrophenyl acetate. Eserine produced significant inhibition of ChE activity (81% with 0.001 mM and 98% with 1mM) while iso-OMPA did not produce any significant effect on ChE. Our results show that C. gibbosa ChE is very sensitive to azinphos-methyl (CI50 0.02 μg L(-1)) while CEs are inhibited at higher concentrations (CI50 1,000 μg L(-1)). CEs have been reported to be more sensitive to OPs than ChEs in most of the aquatic invertebrates protecting the organisms from neurotoxic effects. In contrast, C. gibbosa, has ChE which are much more sensitive to azinphos-methyl than CEs and shows marked signs of neurotoxicity. Regarding antioxidant defenses, GSH levels were significantly increased by 0.02 and 20 μg L(-1) azinphos-methyl (80 and 103%, respectively), CAT activity was increased 85% only at 0.02 μg L(-1) and SOD and GST did not show any significant response. Since ChE activity, neurotoxicity signs, GSH and CAT are sensitive biomarkers of acute exposure to azinphos-methyl at environmental concentrations C. gibbosa could be included as sentinel species in monitoring programs of pesticide hazard in regions of Argentina and Chile. Copyright © 2013 Elsevier B.V. All rights reserved.

Synthesis, biological evaluation, QSAR study and molecular docking of novel N-(4-amino carbonylpiperazinyl) (thio)phosphoramide derivatives as cholinesterase inhibitors.

PubMed

Gholivand, Khodayar; Ebrahimi Valmoozi, Ali Asghar; Bonsaii, Mahyar

2014-06-01

Novel (thio)phosphoramidate derivatives based on piperidincarboxamide with the general formula of (NH2-C(O)-C5H9N)-P(X=O,S)R1R2 (1-5) and (NH2-C(O)-C5H9N)2-P(O)R (6-9) were synthesized and characterized by (31)P, (13)C, (1)H NMR, IR spectroscopy. Furthermore, the crystal structure of compound (NH2-C(O)-C5H9N)2-P(O)(OC6H5) (6) was investigated. The activities of derivatives on cholinesterases (ChE) were determined using a modified Ellman's method. Also the mixed-type mechanisms of these compounds were evaluated by Lineweaver-Burk plots. Molecular docking and quantitative structure-activity relationship (QSAR) were used to understand the relationship between molecular structural features and anti-ChE activity, and to predict the binding affinity of phosphoramido-piperidinecarboxamides (PAPCAs) to ChE receptors. From molecular docking analysis, noncovalent interactions especially hydrogen bonding as well as hydrophobic was found between PAPCAs and ChE. Based on the docking results, appropriate molecular structural parameters were adopted to develop a QSAR model. DFT-QSAR models for ChE enzymes demonstrated the importance of electrophilicity parameter in describing the anti-AChE and anti-BChE activities of the synthesized compounds. The correlation matrix of QSAR models and docking analysis confirmed that electrophilicity descriptor can control the influence of the hydrophobic properties of P=(O, S) and CO functional groups of PAPCA derivatives in the inhibition of human ChE enzymes. Copyright © 2014 Elsevier Inc. All rights reserved.

Phosphate Flow between Hybrid Histidine Kinases CheA3 and CheS3 Controls Rhodospirillum centenum Cyst Formation

PubMed Central

He, Kuang; Marden, Jeremiah N.; Quardokus, Ellen M.; Bauer, Carl E.

2013-01-01

Genomic and genetic analyses have demonstrated that many species contain multiple chemotaxis-like signal transduction cascades that likely control processes other than chemotaxis. The Che3 signal transduction cascade from Rhodospirillum centenum is one such example that regulates development of dormant cysts. This Che-like cascade contains two hybrid response regulator-histidine kinases, CheA3 and CheS3, and a single-domain response regulator CheY3. We demonstrate that cheS3 is epistatic to cheA3 and that only CheS3∼P can phosphorylate CheY3. We further show that CheA3 derepresses cyst formation by phosphorylating a CheS3 receiver domain. These results demonstrate that the flow of phosphate as defined by the paradigm E. coli chemotaxis cascade does not necessarily hold true for non-chemotactic Che-like signal transduction cascades. PMID:24367276

Biochemical and locomotor responses of Carcinus maenas exposed to the serotonin reuptake inhibitor fluoxetine.

PubMed

Mesquita, Sofia Raquel; Guilhermino, Lúcia; Guimarães, Laura

2011-10-01

The aim of this study was to assess the effects of the widely used anti-depressant fluoxetine on behaviour (locomotion), moulting, neuromuscular transmission, energy production and anti-oxidant defences' efficiency of the epibenthic crab Carcinus maenas. Crabs were individually exposed to fluoxetine concentrations for 7d. Effects on locomotion were assessed at the end of the exposure using an open field test adapted to C. maenas in the present study. Tissue samples were later collected to evaluate fluoxetine effects on physiological functions using the activity of key enzymes and other parameters as biomarkers, namely: N-acetyl-β-glucosaminidase (NAGase) in the epidermis (moulting) and the hepatopancreas; cholinesterases (ChE) in muscle (neuromuscular cholinergic transmission); NADP(+)-dependent isocitrate dehydrogenase (IDH) and lactate dehydrogenease (LDH) in muscle (energy production); glutathione S-transferases (GST) in hepatopancreas (biotransformation and oxidative stress system); glutathione reductase (GR), and glutathione peroxidade (GPx), total glutathione levels (TG) and lipid peroxidation levels in the hepatopancreas (anti-oxidant defences and oxidative damage). Because no information on C. maenas NAGase activity was previously available, its variation during the moult cycle was also investigated. The results showed that locomotion was significantly increased at fluoxetine concentrations equal or above 120 μg L⁻¹, with animals spending more time moving, walking longer distances than controls. Levels of NAGase activity were found to vary in relation to C. maenas moult cycle, but no alterations were observed after exposure to fluoxetine. Significant increases in the activity of ChE, GST and GR enzymes, and the levels of TG were found, with a lowest observed effect concentration (LOEC) of 120 μg L⁻¹. Effects on locomotion were significantly and positively correlated to those induced on ChE activity. The results raise concern when hypothesising conditions of chronic exposure in the wild. Copyright © 2011 Elsevier Ltd. All rights reserved.

Cyclic di-GMP differentially tunes a bacterial flagellar motor through a novel class of CheY-like regulators.

PubMed

Nesper, Jutta; Hug, Isabelle; Kato, Setsu; Hee, Chee-Seng; Habazettl, Judith Maria; Manfredi, Pablo; Grzesiek, Stephan; Schirmer, Tilman; Emonet, Thierry; Jenal, Urs

2017-11-01

The flagellar motor is a sophisticated rotary machine facilitating locomotion and signal transduction. Owing to its important role in bacterial behavior, its assembly and activity are tightly regulated. For example, chemotaxis relies on a sensory pathway coupling chemical information to rotational bias of the motor through phosphorylation of the motor switch protein CheY. Using a chemical proteomics approach, we identified a novel family of CheY-like (Cle) proteins in Caulobacter crescentus , which tune flagellar activity in response to binding of the second messenger c-di-GMP to a C-terminal extension. In their c-di-GMP bound conformation Cle proteins interact with the flagellar switch to control motor activity. We show that individual Cle proteins have adopted discrete cellular functions by interfering with chemotaxis and by promoting rapid surface attachment of motile cells. This study broadens the regulatory versatility of bacterial motors and unfolds mechanisms that tie motor activity to mechanical cues and bacterial surface adaptation.

Hydrogen exchange differences between chemoreceptor signaling complexes localize to functionally important subdomains.

PubMed

Koshy, Seena S; Li, Xuni; Eyles, Stephen J; Weis, Robert M; Thompson, Lynmarie K

2014-12-16

The goal of understanding mechanisms of transmembrane signaling, one of many key life processes mediated by membrane proteins, has motivated numerous studies of bacterial chemotaxis receptors. Ligand binding to the receptor causes a piston motion of an α helix in the periplasmic and transmembrane domains, but it is unclear how the signal is then propagated through the cytoplasmic domain to control the activity of the associated kinase CheA. Recent proposals suggest that signaling in the cytoplasmic domain involves opposing changes in dynamics in different subdomains. However, it has been difficult to measure dynamics within the functional system, consisting of extended arrays of receptor complexes with two other proteins, CheA and CheW. We have combined hydrogen exchange mass spectrometry with vesicle template assembly of functional complexes of the receptor cytoplasmic domain to reveal that there are significant signaling-associated changes in exchange, and these changes localize to key regions of the receptor involved in the excitation and adaptation responses. The methylation subdomain exhibits complex changes that include slower hydrogen exchange in complexes in a kinase-activating state, which may be partially consistent with proposals that this subdomain is stabilized in this state. The signaling subdomain exhibits significant protection from hydrogen exchange in complexes in a kinase-activating state, suggesting a tighter and/or larger interaction interface with CheA and CheW in this state. These first measurements of the stability of protein subdomains within functional signaling complexes demonstrate the promise of this approach for measuring functionally important protein dynamics within the various physiologically relevant states of multiprotein complexes.

Hydrogen Exchange Differences between Chemoreceptor Signaling Complexes Localize to Functionally Important Subdomains

PubMed Central

2015-01-01

The goal of understanding mechanisms of transmembrane signaling, one of many key life processes mediated by membrane proteins, has motivated numerous studies of bacterial chemotaxis receptors. Ligand binding to the receptor causes a piston motion of an α helix in the periplasmic and transmembrane domains, but it is unclear how the signal is then propagated through the cytoplasmic domain to control the activity of the associated kinase CheA. Recent proposals suggest that signaling in the cytoplasmic domain involves opposing changes in dynamics in different subdomains. However, it has been difficult to measure dynamics within the functional system, consisting of extended arrays of receptor complexes with two other proteins, CheA and CheW. We have combined hydrogen exchange mass spectrometry with vesicle template assembly of functional complexes of the receptor cytoplasmic domain to reveal that there are significant signaling-associated changes in exchange, and these changes localize to key regions of the receptor involved in the excitation and adaptation responses. The methylation subdomain exhibits complex changes that include slower hydrogen exchange in complexes in a kinase-activating state, which may be partially consistent with proposals that this subdomain is stabilized in this state. The signaling subdomain exhibits significant protection from hydrogen exchange in complexes in a kinase-activating state, suggesting a tighter and/or larger interaction interface with CheA and CheW in this state. These first measurements of the stability of protein subdomains within functional signaling complexes demonstrate the promise of this approach for measuring functionally important protein dynamics within the various physiologically relevant states of multiprotein complexes. PMID:25420045

Effects on wildlife of ethyl and methyl parathion applied to California rice fields

USGS Publications Warehouse

Custer, T.W.; Hill, E.F.; Ohlendorf, H.M.

1985-01-01

Selected rice fields on the Sacramento National Wildlife Refuge Complex were aerially sprayed one time during May or June 1982 with either ethyl (0.11 kg Al/ha) or methyl (0.84 kg AI/ha) parathion for control of tadpole shrimp, Triops longicaudatus. No sick or dead vertebrate wildlife were found or adjacent to the treated rice fields after spraying. Specimens of the following birds and mammals were assayed for brain cholinesterase (ChE) activity to determine exposure to either form of parathion; house mouse, Mus musculus; black-tailed jackrabbit, Lepus californicus; mallard, Anas platyrhynchos; ring-necked pheasant, Phasianus colchicus; American coot, Fulica americana; and red-winged blackbird, Agelaius phoeniceus. Both mice and pheasants from methyl parathion-treated fields had overall mean ChE activities that were significantly (P < 0.05) inhibited compared with controls, and 7, 40, 54 and 57% of individual blackbirds, pheasant, mice, and coots, respectively, had inhibited brain ChE activities (i.e., less than -2 SD of control mean). Although no overall species effect was detected for ethyl parathoid treatment, pheasants (43%), coots (33%), and mice (37%) had significantly inhibited brain ChE activities. Neither of the parathion treatment appeared acutely hazardous to wildlife in or adjacent to rice fields, but sufficient information on potential hazards was obtained to warrant caution in use of these chemicals, especially methyl parathion, in rice fields.

Effects of wildlife of ethyl and methyl parathion applied to California USA rice fields

USGS Publications Warehouse

Custer, T.W.; Hill, E.F.; Ohlendorf, H.M.

1985-01-01

Selected rice fields on the Sacramento National Wildlife Refuge Complex were aerially sprayed one time during May or June 1982 with either ethyl (0.11 kg Al/ha) or methyl (0.84 kg AI/ha) parathion for control of tadpole shrimp, Triops longicaudatus. No sick or dead vertebrate wildlife were found or adjacent to the treated rice fields after spraying. Specimens of the following birds and mammals were assayed for brain cholinesterase (ChE) activity to determine exposure to either form of parathion; house mouse, Mus musculus; black-tailed jackrabbit, Lepus californicus; mallard, Anas platyrhynchos; ring-necked pheasant, Phasianus colchicus; American coot, Fulica americana; and red-winged blackbird, Agelaius phoeniceus. Both mice and pheasants from methyl parathion-treated fields had overall mean ChE activities that were significantly (P < 0.05) inhibited compared with controls, and 7, 40, 54 and 57% of individual blackbirds, pheasant, mice, and coots, respectively, had inhibited brain ChE activities (i.e., less than -2 SD of control mean). Although no overall species effect was detected for ethyl parathoid treatment, pheasants (43%), coots (33%), and mice (37%) had significantly inhibited brain ChE activities. Neither of the parathion treatment appeared acutely hazardous to wildlife in or adjacent to rice fields, but sufficient information on potential hazards was obtained to warrant caution in use of these chemicals, especially methyl parathion, in rice fields.

Lack of relay toxicity in ferret hybrids fed carbaryl-treated prairie dogs.

PubMed

Orsted, K M; Dubay, S A; Raisbeck, M F; Siemion, R S; Sanchez, D A; Williams, E S

1998-04-01

Carbaryl (1-napthol methylcarbamate) is being considered for control of fleas on prairie dogs (Cynomys spp.) used in black-footed ferret (Mustela nigripes) recovery in the western United States. The potential for relay toxicity in ferrets was determined by feeding carbaryl treated prairie dogs to black-footed ferret x Siberian polecat (M. eversmanni) hybrids. Adult prairie dogs were treated topically with 2.5 g of commercial 5% carbaryl dust sold as flea powder. After 14 days prairie dogs were killed and fed to ferrets. Potential for relay toxicity was evaluated by analyzing ferret blood cholinesterase (CHe), prairie dog brain Che, and hepatic carbamate concentration. There was no difference between pre- and post-exposure blood CHe activity, nor did treated prairie dog brain CHe differ significantly from controls. Post-exposure blood CHe did not exhibit reactivation after dilution in aqueous buffer. Hepatic carbaryl concentrations were less than detection limits (50 ppb). Based on these results, we conclude that short-term use of carbaryl for flea control on prairie dogs does not pose a hazard of relay toxicity in black-footed ferrets.

Hydrogen exchange mass spectrometry of functional membrane-bound chemotaxis receptor complexes.

PubMed

Koshy, Seena S; Eyles, Stephen J; Weis, Robert M; Thompson, Lynmarie K

2013-12-10

The transmembrane signaling mechanism of bacterial chemotaxis receptors is thought to involve changes in receptor conformation and dynamics. The receptors function in ternary complexes with two other proteins, CheA and CheW, that form extended membrane-bound arrays. Previous studies have shown that attractant binding induces a small (∼2 Å) piston displacement of one helix of the periplasmic and transmembrane domains toward the cytoplasm, but it is not clear how this signal propagates through the cytoplasmic domain to control the kinase activity of the CheA bound at the membrane-distal tip, nearly 200 Å away. The cytoplasmic domain has been shown to be highly dynamic, which raises the question of how a small piston motion could propagate through a dynamic domain to control CheA kinase activity. To address this, we have developed a method for measuring dynamics of the receptor cytoplasmic fragment (CF) in functional complexes with CheA and CheW. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) measurements of global exchange of the CF demonstrate that the CF exhibits significantly slower exchange in functional complexes than in solution. Because the exchange rates in functional complexes are comparable to those of other proteins with similar structures, the CF appears to be a well-structured protein within these complexes, which is compatible with its role in propagating a signal that appears to be a tiny conformational change in the periplasmic and transmembrane domains of the receptor. We also demonstrate the feasibility of this protocol for local exchange measurements by incorporating a pepsin digest step to produce peptides with 87% sequence coverage and only 20% back exchange. This method extends HDX-MS to membrane-bound functional complexes without detergents that may perturb the stability or structure of the system.

Hydrogen Exchange Mass Spectrometry of Functional Membrane-bound Chemotaxis Receptor Complexes

PubMed Central

Koshy, Seena S.; Eyles, Stephen J.; Weis, Robert M.; Thompson, Lynmarie K.

2014-01-01

The transmembrane signaling mechanism of bacterial chemotaxis receptors is thought to involve changes in receptor conformation and dynamics. The receptors function in ternary complexes with two other proteins, CheA and CheW, that form extended membrane-bound arrays. Previous studies have shown that attractant binding induces a small (~2 Å) piston displacement of one helix of the periplasmic and transmembrane domains towards the cytoplasm, but it is not clear how this signal propagates through the cytoplasmic domain to control the kinase activity of the CheA bound at the membrane-distal tip, nearly 200 Å away. The cytoplasmic domain has been shown to be highly dynamic, which raises the question of how a small piston motion could propagate through a dynamic domain to control CheA kinase activity. To address this, we have developed a method for measuring dynamics of the receptor cytoplasmic fragment (CF) in functional complexes with CheA and CheW. Hydrogen exchange mass spectrometry (HDX-MS) measurements of global exchange of CF demonstrate that CF exhibits significantly slower exchange in functional complexes than in solution. Since the exchange rates in functional complexes are comparable to that of other proteins of similar structure, the CF appears to be a well-structured protein within these complexes, which is compatible with its role in propagating a signal that appears to be a tiny conformational change in the periplasmic and transmembrane domains of the receptor. We also demonstrate the feasibility of this protocol for local exchange measurements, by incorporating a pepsin digest step to produce peptides with 87% sequence coverage and only 20% back exchange. This method extends HDX-MS to membrane-bound functional complexes without detergents that may perturb the stability or structure of the system. PMID:24274333

Coastal heavy rainband formed along Sumatera Island, Indonesia, observed with X-band Doppler radars during HARIMAU2011 campaign

NASA Astrophysics Data System (ADS)

Mori, Shuichi; Jun-Ichi, Hamada; Hattori, Miki; Kamimera, Hideyuki; Wu, Peiming; Arbain, Ardhi A.; Lestari, Sopia; Syamsudin, Fadli; Yamanaka, Manabu D.

2013-04-01

Coastal heavy rainbands (CHeRs) are widely identified over Asian monsoon region (e.g., Western Ghats, Bay of Bengal, Gulf of Thailand, and western Philippines) by satellite observations. Some of them are explained by synoptic wind-terrain interaction (Xie et al., 2006 JC) because they are anchored along mountain ranges face to southwest direction and predominant during boreal summer southwesterly monsoon season. Most Asian megacities are located in coastal regions, thus they have much chance to be suffered from torrential rainfall embedded in CHeRs which may cause flash floods in downtown cities and landslides in mountainous regions. Moreover, rainfall amount over the coastal land varies quite largely if those CHeRs change their lateral location a little, therefore water resource management for social community is seriously sensitive to their variability. Satellite observations show that CHeRs are modified by various kinds of environmental variations, e.g., diurnal, intraseasonal, monsoonal, ENSO, and IOD. However, climatology, structure, and mechanism of CHeRs have not been examined in detail from mesoscale points of view because there are quite few studies based on ground based radar observations. Previous studies (e.g., Mori et al. 2004 MWR; Yamanaka et al. 2008 JDR; Wu et al. 2007 SOLA) showed most CHeRs in Indonesia are identified along coastlines where convective diurnal variation is predominant, and coastal heavy rain are brought mainly in the nighttime observed with a radar-profiler network deployed by Hydrometeorological ARray for Intraseasonal variation (ISV) - Monsoon AUtomonitoring (HARIMAU) project. In addition, they are confirmed even in the seasons when the wind-terrain interaction cannot explain them well. These results suggest that CHeRs are formed by not only the synoptic wind-terrain effect but also mesoscale convections which developed nocturnally everyday along coastlines. We carried out the HARIMAU2011 campaign observation over Sumatera Island, Indonesia, during 01-31 December 2011 in collaboration with CINDY and DYNAMO to study the CHeR formed along the southwestern coastline of Sumatera Island by using X-band Doppler and dual polarimetric (DP) radars, intensive soundings at two stations, disdrometers, and surface observation network. Two MJOs (MJO-2 and -3) were identified which passed over Sumatera Island during the campaign period. We divided the period into four phases: MJO-2 active (phase-I), MJO inactive (phase-II), MJO-3 active (phase-III), and MJO inactive (phase IV). CHeRs organized by a lot of mesoscale convections were observed throughout the period, however, those convections developed mainly over the coastal sea, coastal land, and both coastal sea and land, during phase-I, -II, and -III, respectively. Diurnal cycle of convections was not clear during the phase-I and -II. Whereas, that during the phase-III was clearly observed and a lot of convections were identified which migrated from the coastal land to sea during the night. Radar observations showed CHeRs were formed by both convections, a) generated originally over the coastal land in the evening and developed in the night after migrated into the sea, b) generated over the coastal sea in the night and developed independently. Environmental conditions including MJO activity and local circulations were also examined in terms of CHeR formation process.

Cholinesterase inhibition of birds inhabiting wheat fields treated with methyl parathion and toxaphene

USGS Publications Warehouse

Niethammer, K.R.; Baskett, T.S.

1983-01-01

Red-winged blackbirds (Agelaius phoeniceus) and dickcissels (Spiza americana) inhabiting wheat fields treated with 0.67 kg AI/ha methyl parathion and 1.35 kg AI/ha toxaphene showed brain cholinesterase (ChE) inhibition compared with birds inhabiting untreated fields. Maximum inhibition occurred about five days after insecticide application. ChE activities again approached normal 10 days after treatment. ChE inhibition for dickcissels and red-winged blackbirds differed significantly (p<0.05); maximum inhibition for the former species was 74%, and for the latter, 40%. These differences could not be explained by the diets of the two species, as they were similar.

Partial protection from organophosphate-induced cholinesterase inhibition by metyrapone treatment.

PubMed

Swiercz, Radosław; Lutz, Piotr; Gralewicz, Sławomir; Grzelińska, Zofia; Piasecka-Zelga, Joanna; Wąsowicz, Wojciech

2013-08-01

Organophosphates are cholinesterase (ChE) inhibitors with worldwide use as insecticides. Stress response, evidenced by a dramatic and relatively long-lasting (several hours) rise in the plasma glucocorticoid concentration is an integral element of the organophosphate (OP) poisoning symptomatology. In rodents, corticosterone (CORT) is the main glucocorticoid. There are several reports suggesting a relationship between the stressor-induced rise in CORT concentration (the CORT response) and the activity of the cerebral and peripheral ChE. Thus, it seems reasonable to presume that, in OP intoxication, the rise in plasma CORT concentration may somehow affect the magnitude of the OP-induced ChE inhibition. Metyrapone (MET) [2-methyl-1,2-di(pyridin-3-yl)propan-1-one] blocks CORT synthesis by inhibiting steroid 11β-hydroxylase, thereby preventing the CORT response. Chlorfenvinphos (CVP) [2-chloro-1-(2,4-dichlorophenyl) ethenyl diethyl phosphate] is an organophosphate insecticide still in use in some countries. The purpose of the present work was to compare the CVP-induced effects - the rise of the plasma CORT concentration and the reduction in ChE activity - in MET-treated and MET-untreated rats. Chlorfenvinphos was administered once at 0.0, 0.5, 1.0 and 3.0 mg/kg i.p. Metyrapone, at 100 mg/kg i.p., was administered five times, at 24-h intervals. The first MET dose was given two hours before CVP. The following was observed in the MET-treated rats: i) no rise in plasma CORT concentration after the CVP administration, ii) a reduced inhibition and a faster restitution of blood and brain ChE activities. The results suggest that MET treatment may confer significant protection against at least some effects of OP poisoning. The likely mechanism of the protective MET action has been discussed.

Computer-Aided Resolution of an Experimental Paradox in Bacterial Chemotaxis

PubMed Central

Abouhamad, Walid N.; Bray, Dennis; Schuster, Martin; Boesch, Kristin C.; Silversmith, Ruth E.; Bourret, Robert B.

1998-01-01

Escherichia coli responds to its environment by means of a network of intracellular reactions which process signals from membrane-bound receptors and relay them to the flagellar motors. Although characterization of the reactions in the chemotaxis signaling pathway is sufficiently complete to construct computer simulations that predict the phenotypes of mutant strains with a high degree of accuracy, two previous experimental investigations of the activity remaining upon genetic deletion of multiple signaling components yielded several contradictory results (M. P. Conley, A. J. Wolfe, D. F. Blair, and H. C. Berg, J. Bacteriol. 171:5190–5193, 1989; J. D. Liu and J. S. Parkinson, Proc. Natl. Acad. Sci. USA 86:8703–8707, 1989). For example, “building up” the pathway by adding back CheA and CheY to a gutted strain lacking chemotaxis genes resulted in counterclockwise flagellar rotation whereas “breaking down” the pathway by deleting chemotaxis genes except cheA and cheY resulted in alternating episodes of clockwise and counterclockwise flagellar rotation. Our computer simulation predicts that trace amounts of CheZ expressed in the gutted strain could account for this difference. We tested this explanation experimentally by constructing a mutant containing a new deletion of the che genes that cannot express CheZ and verified that the behavior of strains built up from the new deletion does in fact conform to both the phenotypes observed for breakdown strains and computer-generated predictions. Our findings consolidate the present view of the chemotaxis signaling pathway and highlight the utility of molecularly based computer models in the analysis of complex biochemical networks. PMID:9683468

Carqueja (Baccharis trimera) Protects against Oxidative Stress and β-Amyloid-Induced Toxicity in Caenorhabditis elegans

PubMed Central

Aparecida Paiva, Franciny; de Freitas Bonomo, Larissa; Ferreira Boasquivis, Patrícia; Borges Raposo de Paula, Igor Thadeu; Guerra, Joyce Ferreira da Costa; Mendes Leal, Wagney; Silva, Marcelo Eustáquio; Pedrosa, Maria Lúcia; Oliveira, Riva de Paula

2015-01-01

Carqueja (Baccharis trimera) is a native plant found throughout South America. Several studies have shown that Carqueja has antioxidant activity in vitro, as well as anti-inflammatory, antidiabetic, analgesic, antihepatotoxic, and antimutagenic properties. However, studies regarding its antioxidant potential in vivo are limited. In this study, we used Caenorhabditis elegans as a model to examine the antioxidant effects of a Carqueja hydroalcoholic extract (CHE) on stress resistance and lifespan and to investigate whether CHE has a protective effect in a C. elegans model for Alzheimer's disease. Here, we show for the first time, using in vivo assays, that CHE treatment improved oxidative stress resistance by increasing survival rate and by reducing ROS levels under oxidative stress conditions independently of the stress-related signaling pathways (p38, JNK, and ERK) and transcription factors (SKN-1/Nrf and DAF-16/Foxo) tested here. CHE treatment also increased the defenses against β-amyloid toxicity in C. elegans, in part by increasing proteasome activity and the expression of two heat shock protein genes. Our findings suggest a potential neuroprotective use for Carqueja, supporting the idea that dietary antioxidants are a promising approach to boost the defensive systems against stress and neurodegeneration. PMID:26236426

A Variable Active Site Residue Influences the Kinetics of Response Regulator Phosphorylation and Dephosphorylation.

PubMed

Immormino, Robert M; Silversmith, Ruth E; Bourret, Robert B

2016-10-04

Two-component regulatory systems, minimally composed of a sensor kinase and a response regulator protein, are common mediators of signal transduction in microorganisms. All response regulators contain a receiver domain with conserved active site residues that catalyze the signal activating and deactivating phosphorylation and dephosphorylation reactions. We explored the impact of variable active site position T+1 (one residue C-terminal to the conserved Thr/Ser) on reaction kinetics and signaling fidelity, using wild type and mutant Escherichia coli CheY, CheB, and NarL to represent the three major sequence classes observed across response regulators: Ala/Gly, Ser/Thr, and Val/Ile/Met, respectively, at T+1. Biochemical and structural data together suggested that different amino acids at T+1 impacted reaction kinetics by altering access to the active site while not perturbing overall protein structure. A given amino acid at position T+1 had similar effects on autodephosphorylation in each protein background tested, likely by modulating access of the attacking water molecule to the active site. Similarly, rate constants for CheY autophosphorylation with three different small molecule phosphodonors were consistent with the steric constraints on access to the phosphorylation site arising from combination of specific phosphodonors with particular amino acids at T+1. Because other variable active site residues also influence response regulator phosphorylation biochemistry, we began to explore how context (here, the amino acid at T+2) affected the influence of position T+1 on CheY autocatalytic reactions. Finally, position T+1 affected the fidelity and kinetics of phosphotransfer between sensor kinases and response regulators but was not a primary determinant of their interaction.

Reactivation of Brain Acetylcholinesterase by Monoisonitrosoacetone Increases the Therapeutic Efficacy Against Nerve Agents in Guinea Pigs

DTIC Science & Technology

2010-01-01

hese findings support previous reports that protection of ChE nzyme activity in the brain as well as in peripheral tissues with entrally acting... activity . Animals were injected s.c. with either saline (0.5ml/kg) or a 1.0× LD50 dose of GB (42.0g/kg), GF (57.0g/kg), or VX (8.0g/kg). The severity...of toxic signs of each animal was scored at 13min after nerve agent. Fifteen minutes after nerve agent injection, when the inhibition of ChE activity

Plasma Cholinesterase Activity in Female Green Turtles Chelonia mydas Nesting in Laguna de Terminos, Mexico Related to Organochlorine Pesticides in Their Eggs.

PubMed

Rivas-Hernández, Gerardo; May-Uc, Yaneli; Noreña-Barroso, Elsa; Cobos-Gasca, Víctor; Rodríguez-Fuentes, Gabriela

2018-01-01

The inhibition of cholinesterase (ChE) activity has been used as a biomarker of exposure to organophosphate and carbamate insecticides. ChE of nesting female green turtles (Chelonia mydas) were biochemically characterized using two substrates, acetylthiocholine iodide and butyrylthiocholine iodide, and three ChE inhibitors (eserine sulfate, BW284C51 and iso-OMPA). The results indicated that BChE is the predominant plasma ChE in female C. mydas, but with atypical properties that differ from those found in human BChE. Eggs from green turtles nesting at two sites in Laguna de Terminos contained µg g -1 (wet weight) quantities of organochlorine (OC) pesticides. Drins (aldrin, dieldrin, endrin, endrin ketone, endrin aldehyde) were found at the highest concentrations with no significant differences in the concentrations in eggs collected at the two sampling sites. A negative relationship was found between levels of OC pesticides in eggs and BChE activity in the plasma of female turtles laying the eggs. Since OC pesticides are not cholinesterase inhibitors, we hypothesized that this inverse relationship may be related to an antagonistic effect between OCs and organophosphate pesticides and mobilization of OCs from the fatty tissues of the female turtles into their eggs. However, further study is required to verify the hypothesis. It is also possible that other contaminants, such as petroleum hydrocarbons are responsible for the modulation of cholinesterase activity in female turtles.

Penicillium sp. as an organism that degrades endosulfan and reduces its genotoxic effects.

PubMed

Romero-Aguilar, Mariana; Tovar-Sánchez, Efrain; Sánchez-Salinas, Enrique; Mussali-Galante, Patricia; Sánchez-Meza, Juan Carlos; Castrejón-Godínez, María Luisa; Dantán-González, Edgar; Trujillo-Vera, Miguel Ángel; Ortiz-Hernández, Ma Laura

2014-01-01

Endosulfan is an organochloride and persistent pesticide that has caused concern because of its impact in the environment and its toxicity to and bioaccumulation in living organisms. In this study, we isolated an endosulfan-degrading fungus from the activated sludge from an industrial wastewater treatment plant. Through repetitive enrichment and successive subculture in media containing endosulfan as the sole carbon source, a fungus designated CHE 23 was isolated. Based on a phylogenetic analysis, strain CHE 23 was assigned to the genus Penicillium sp. In a mineral salt medium with 50 mg/l endosulfan as the sole source carbon, CHE 23 removed the added endosulfan in a period of six days. To verify the decrease in endosulfan toxicity due to the activity of the fungus, we performed genotoxicity tests trough the single cell gel electrophoresis assay or comet assay, with Eisenia fetida as the bioindicator species. This organism was exposed to the supernatants of the culture of the fungus and endosulfan. Our results indicated that the genotoxicity of endosulfan was completely reduced due the activity of this fungus. These results suggest that the Penicillium sp. CHE 23 strain can be used to degrade endosulfan residues and/or for water and soil bioremediation processes without causing toxicity problems, which are probably due to the generation of no-toxic metabolites during biodegradation.

[Effects of total glucosides of paeony on enhancing insulin sensitivity and antagonizing nonalcoholic fatty liver in rats].

PubMed

Zheng, Lin-Ying; Pan, Jing-Qiang; Lv, Jun-Hua

2008-10-01

To study the pathological changes of blood glucose, serum lipid, insulin resistance, liver function, liver cell denaturalization of total glucosides of paeony on nonalcoholic fatty liver rats caused by insulin resistance and discuss the acting mechanism. Adult SD rats were maintained on high-fat-sugar-salt diet for 56 days. In the 57th day, their fasting blood glucose (FBG) and 2-hours blood glucose after oral glucose tolerance test (OGTT-2 hBG) were mensurated, according to which and the weight the rats were divided randomly into nonalcoholic fatty liver model group, metformin group (0.2 g x kg(-1)) and total glucosides of paeony group (high dosage 0.15 g x kg(-1), low dosage 0.05 g x kg(-1)). All the rats were still administered the same diet and given different drugs by intragastric administration for 28 days. In the 29th day, all of them were killed and the blood was sampled to measure the levels of blood glucose [FBG, OGTT-2 hBG, fasting insulin (Fins)] and serum lipid [free fatty acids (FFA), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)], then the HOMA insulin resistance index (HOMA-IRI, fasting glucosexinsulin) and insulin sensitivity index (ISI) were counted. The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholinesterase (ChE), superoxide dismutase (SOD) and the contents of malondialdehyde (MDA) were measured also. Livers were weighed and collected to be observed the pathological changes. Compared with normal group, in nonalcoholic fatty liver model group the levels of Fins and IRI were increased obviously (P < 0.01), ISI were decreased (P < 0.01), FFA, TG, TC, LDL-C were increased (P < 0.01), HDL-C were decreased (P < 0.05); the content of MDA were increased (P < 0.05), the activities of SOD were decreased (P < 0.01); AST, ALT and ChE were increased (P < 0.05, or P < 0.01), the pathological changes of liver fat were severe (P < 0.01). In glucosides of paeony group and metformin group, hyperinsulinaemia and insulin resistence were resisted (P < 0.05, or P < 0.01); the levels of FFA, TG, TC, LDL-C were decreased and HDL-C were increased (P < 0.05, or P < 0.01); the activities of AST, ALT, ChE were decreased (P < 0.05, or P < 0.01) and SOD were increased (P < 0.01). The contents of MDA were decreased (P < 0.05). The levels of FBG and 2 hBG in metformin group were decreased but in total glucosides of paeony group were not decreased obviously. Total glucosides of paeony may protect liver function and modulate serum lipid for the fatty liver rats caused by insulin resistance, and its action mechanism may be concerned with enhancing insulin sensitivity and antioxidative ability, decreasing serum lipid.

The Emotional Communication in Hearing Questionnaire (EMO-CHeQ): Development and Evaluation.

PubMed

Singh, Gurjit; Liskovoi, Lisa; Launer, Stefan; Russo, Frank

2018-06-11

The objectives of this research were to develop and evaluate a self-report questionnaire (the Emotional Communication in Hearing Questionnaire or EMO-CHeQ) designed to assess experiences of hearing and handicap when listening to signals that contain vocal emotion information. Study 1 involved internet-based administration of a 42-item version of the EMO-CHeQ to 586 adult participants (243 with self-reported normal hearing [NH], 193 with self-reported hearing impairment but no reported use of hearing aids [HI], and 150 with self-reported hearing impairment and use of hearing aids [HA]). To better understand the factor structure of the EMO-CHeQ and eliminate redundant items, an exploratory factor analysis was conducted. Study 2 involved laboratory-based administration of a 16-item version of the EMO-CHeQ to 32 adult participants (12 normal hearing/near normal hearing (NH/nNH), 10 HI, and 10 HA). In addition, participants completed an emotion-identification task under audio and audiovisual conditions. In study 1, the exploratory factor analysis yielded an interpretable solution with four factors emerging that explained a total of 66.3% of the variance in performance the EMO-CHeQ. Item deletion resulted in construction of the 16-item EMO-CHeQ. In study 1, both the HI and HA group reported greater vocal emotion communication handicap on the EMO-CHeQ than on the NH group, but differences in handicap were not observed between the HI and HA group. In study 2, the same pattern of reported handicap was observed in individuals with audiometrically verified hearing as was found in study 1. On the emotion-identification task, no group differences in performance were observed in the audiovisual condition, but group differences were observed in the audio alone condition. Although the HI and HA group exhibited similar emotion-identification performance, both groups performed worse than the NH/nNH group, thus suggesting the presence of behavioral deficits that parallel self-reported vocal emotion communication handicap. The EMO-CHeQ was significantly and strongly (r = -0.64) correlated with performance on the emotion-identification task for listeners with hearing impairment. The results from both studies suggest that the EMO-CHeQ appears to be a reliable and ecologically valid measure to rapidly assess experiences of hearing and handicap when listening to signals that contain vocal emotion information.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

A fixed-time diffusion analysis method determines that the three cheV genes of Helicobacter pylori differentially affect motility

PubMed Central

Lowenthal, Andrew C.; Simon, Christopher; Fair, Amber S.; Mehmood, Khalid; Terry, Karianne; Anastasia, Stephanie; Ottemann, Karen M.

2009-01-01

Helicobacter pylori is a chemotactic bacterium that has three CheV proteins in its predicted chemotaxis signal transduction system. CheV proteins contain both CheW- and response-regulator-like domains. To determine the function of these proteins, we developed a fixed-time diffusion method that would quantify bacterial direction change without needing to define particular behaviours, to deal with the many behaviours that swimming H. pylori exhibit. We then analysed mutants that had each cheV gene deleted individually and found that the behaviour of each mutant differed substantially from wild-type and the other mutants. cheV1 and cheV2 mutants displayed smooth swimming behaviour, consistent with decreased cellular CheY-P, similar to a cheW mutant. In contrast, the cheV3 mutation had the opposite effect and the mutant cells appeared to change direction frequently. Additional analysis showed that the cheV mutants displayed aberrant behaviour as compared to the wild-type in the soft-agar chemotaxis assay. The soft-agar assay phenotype was less extreme compared to that seen in the fixed-time diffusion model, suggesting that the cheV mutants are able to partially compensate for their defects under some conditions. Each cheV mutant furthermore had defects in mouse colonization that ranged from severe to modest, consistent with a role in chemotaxis. These studies thus show that the H. pylori CheV proteins each differently affect swimming behaviour. PMID:19332820

Experiment-to-Experiment Disturbance of Microgravity Environment

NASA Technical Reports Server (NTRS)

DeLombard, Richard; Hrovat, Kenneth; McPherson, Kevin

1998-01-01

The STS-87 Shuttle mission carried the Fourth United States MicroGravity Payload (USMP-4) as one of the primary payloads. Four USMP-4 science experiments were installed on two carriers in the cargo bay of the Shuttle. The Confined Helium Experiment (CHeX), located on the aft carrier, was particularly susceptible to vibrations in several frequency ranges due to structural resonances of the CHeX apparatus and the extreme sensitivity of the sample to vibrations. Shortly after activation of the USMP-4 payload, a strong, vibratory disturbance within the susceptibility region of the CHeX apparatus was detected. After investigating the characteristics of the disturbance and the time at which it first appeared, it was deduced that the vibration was generated by cooling fans in the Isothermal Dendritic Growth Experiment (IDGE). This paper will summarize the development of the conflict, briefly describe the disturbance source, and the susceptibility of the CHeX apparatus, and summarize the results of post-mission tests of IDGE.

The reaction time of organ-forming substance in goldfish EGG and its relationship with mesodermal formation

NASA Astrophysics Data System (ADS)

Zhang, Shicui; Wu, Shangqin

1988-12-01

Fertilized goldfish eggs were dechorionated with a pair of forceps and were cut off along or a little above the equator into animal and vegetative parts at desired stages with a glass needle or ligated into two connected fragments before cleavage with baby hair loop. Some of the ligated eggs were detached by further fastening soon after ligation, and some released later at different stages (2-cell, 16-cell, 128-cell, 512-cell, mid-blastula) to let the organ-forming substance (OFS) enter the blastoderm. The cholinesterase (ChE) in the resulting embryos was assayed. The results are as follows. 1. All the 142 embryos developed from the animal hemispheres cut off or ligated off before cleavage gave rise to hyperblastula in which no ChE activity was observed. 2. All 50 embryos obtained from animal halves isolated at the 8-cell stage produced ChE. 3. Embryos developed from the eggs released before the 512-cell stage formed ChE, but the later the releasing of the hair knots, the smaller the number of ChE-producing embryos. 4. After the 512-cell stage (excluding this stage), neither ChE nor tissue differentiation occurred in the embryos developed from the unfastened eggs though their OFS flow was set free. Since ChE is thought to be a muscle-specific enzyme in the early developmental stage, it is concluded that the OFS in goldfish egg appears to be indispensable for the establishment of the mesoderm.

Mechanism of soman-induced contractions in canine tracheal smooth muscle. (Reannouncement with new availability information)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adler, M.; Moore, D.H.; Filbert, M.G.

1992-12-31

The actions of the irreversible organophosphorus cholinesterase (ChE) inhibitor soman were investigated on canine trachea smooth muscle in vitro. Concentrations of soman > or - 1 nM increased the amplitude and decay of contractions elicited by electric field stimulation. The effect on decay showed a marked dependence on stimulation frequency, undergoing a 2.4-fold increase between 3 and 60 Hz. Soman also potentiated tensions due to bath applied acetylcholine (ACh). Little or no potentiation was observed for contractions elicited by carbamylcholine, an agonist that is not hydrolyzed by ChE. Concentration of soman > or - 3 nM led to the appearancemore » of sustained contractures. These contractures developed with a delayed onset and were well correlated with ChE activity. Alkylation of muscarinic receptors by propylbenzilylcholine mustard antagonized the actions of soman on both spontaneous and electrically-evoked muscle contractions. The results are consistent with a mechanism in which the toxic actions of soman are mediated by accumulation of neurally-released ACh secondary to inhibition of ChE activity. An important factor in this accumulation is suggested to be the buffering effect of the muscarinic receptors on the efflux of ACh from the neuroeffector junction. Tracheal smooth muscle, Cholinesterase inhibitors, Muscarinic receptor, Soman, Organophosphate.« less

Che-1 gene silencing induces osteosarcoma cell apoptosis by inhibiting mutant p53 expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Ming; Wang, Dan, E-mail: danwangwdd@163.com; Li, Ning

2016-04-22

The transcriptional cofactor Che-1 is an RNA polymerase II (Pol II) which is involved in tumorigenesis, such as breast cancer and multiple myeloma. Che-1 can also regulate mutant p53 expression, which plays roles in many types of cancer. In this study, we aimed to investigate the effects and specific mechanism of Che-1 in the regulation of osteosarcoma (OS) cell growth. We found that Che-1 is highly expressed in several kinds of OS cells compared with osteoblast hFOB1.19 cells. MTT and flow cytometry assays showed that Che-1 depletion by siRNA markedly suppressed MG-63 and U2OS cell proliferation and promoted apoptosis. The chromatinmore » immunoprecipitation (ChIP) assay verified the presence of Che-1 on the p53 promoter in MG-63 and U2OS cells carrying mutant p53. Further studies showed that Che-1 depletion inhibited mutant p53 expression. Notably, our study showed that the loss of Che-1 inhibits proliferation and promotes apoptosis in MG-63 cells by decreasing the level of mutant p53. Therefore, these findings open the possibility that silencing of Che-1 will have therapeutic benefit in OS. - Highlights: • Che-1 is highly expressed in several kinds of OS cells. • Che-1 depletion suppressed MG-63 and U2OS cell growth. • Che-1 is existed in the p53 promoter in MG-63 and U2OS cells. • Che-1 depletion inhibited mutant p53 expression. • Che-1 depletion inhibits cell growth by decreasing the level of mutant p53.« less

Rosemary tea consumption results to anxiolytic- and anti-depressant-like behavior of adult male mice and inhibits all cerebral area and liver cholinesterase activity; phytochemical investigation and in silico studies.

PubMed

Ferlemi, Anastasia-Varvara; Katsikoudi, Antigoni; Kontogianni, Vassiliki G; Kellici, Tahsin F; Iatrou, Grigoris; Lamari, Fotini N; Tzakos, Andreas G; Margarity, Marigoula

2015-07-25

Our aim was to investigate the possible effects of regular drinking of Rosmarinus officinalis L. leaf infusion on behavior and on AChE activity of mice. Rosemary tea (2% w/w) phytochemical profile was investigated through LC/DAD/ESI-MS(n). Adult male mice were randomly divided into two groups: "Rosemary-treated" that received orally the rosemary tea for 4weeks and "control" that received drinking water. The effects of regular drinking of rosemary tea on behavioral parameters were assessed by passive avoidance, elevated plus maze and forced swimming tests. Moreover, its effects on cerebral and liver cholinesterase (ChE) isoforms activity were examined colorimetricaly. Phytochemical analysis revealed the presence of diterpenes, flavonoids and hydroxycinnamic derivatives in rosemary tea; the major compounds were quantitatively determined. Its consumption rigorously affected anxiety/fear and depression-like behavior of mice, though memory/learning was unaffected. ChE isoforms activity was significantly decreased in brain and liver of "rosemary treated" mice. In order to explain the tissue ChE inhibition, principal component analysis, pharmacophore alignment and molecular docking were used to explore a possible relationship between main identified compounds of rosemary tea, i.e. rosmarinic acid, luteolin-7-O-glucuronide, caffeic acid and known AChE inhibitors. Results revealed potential common pharmacophores of the phenolic components with the inhibitors. Our findings suggest that rosemary tea administration exerts anxiolytic and antidepressant effects on mice and inhibits ChE activity; its main phytochemicals may function in a similar way as inhibitors. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Purification and studies on characteristics of cholinesterases from Daphnia magna *

PubMed Central

Yang, Yan-xia; Niu, Li-zhi; Li, Shao-nan

2013-01-01

Due to their significant value in both economy and ecology, Daphnia had long been employed to investigate in vivo response of cholinesterase (ChE) in anticholinesterase exposures, whereas the type constitution and property of the enzyme remained unclear. A type of ChE was purified from Daphnia magna using a three-step procedure, i.e., Triton X-100 extraction, ammonium sulfate precipitation, and diethylaminoethyl (DEAE)-Sepharose™-Fast-Flow chromatography. According to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), molecular mass of the purified ChE was estimated to be 84 kDa. Based on substrate studies, the purified enzyme preferred butyrylthiocholine iodide (BTCh) [with maximum velocity (V max)/Michaelis constant (K m)=8.428 L/(min·mg protein)] to acetylthiocholine iodide (ATCh) [with V max/K m=5.346 L/(min·mg protein)] as its substrate. Activity of the purified enzyme was suppressed by high concentrations of either ATCh or BTCh. Inhibitor studies showed that the purified enzyme was more sensitive towards inhibition by tetraisopropylpyrophosphoramide (iso-OMPA) than by 1,5-bis(4-allyldimethylammoniumphenyl) pentan-3-one dibromide (BW284C51). Result of the study suggested that the purified ChE was more like a type of pseudocholinesterase, and it also suggested that Daphnia magna contained multiple types of ChE in their bodies. PMID:23549850

Biochemical effects of chlorpyrifos on two developmental stages of Xenopus laevis.

PubMed

Richards, Sean M; Kendall, Ron J

2002-09-01

Abstract-The effects of a 96-h static exposure to chlorpyrifos were examined in two developmental stages of larval Xenopus laevis (premetamorph and metamorph). Measures of effect included mortality, deformity, cholinesterase (ChE) activity, and DNA and protein concentration. All parameters indicated that metamorphs were more sensitive than were premetamorphs. For larvae exposed as premetamorphs, the median lethal concentration and median effective concentration were 14.6 mg/L and 1.71 mg/L; for those exposed as metamorphs, values were 0.56 mg/L and 0.24 mg/L, respectively. Cholinesterase activity was the most sensitive biochemical parameter. Exposure to chlorpyrifos at 0.01 mg/L caused significant decreases in the ChE activity of metamorphs; 0.1 mg/L significantly decreased premetamorph ChE activity. Metamorph DNA was significantly decreased at 0.1 mg/L; premetamorph DNA was not reduced until exposure to 1.0 mg/L. Whole-body protein was the least sensitive biochemical measure of effect. Premetamorphs did not experience a reduction in protein concentrations. Metamorph protein concentration was significantly decreased at 1.0 mg/L. Based on current surface water data, the most sensitive effect would not have a high probability (< or = 4.2%) of occurring in the environment.

Physiological measures of neurotoxicity of diazinon and malathion to larval rainbow trout (Oncorhynchus mykiss) and their correlation with behavioral measures

USGS Publications Warehouse

Beauvais, S.L.; Jones, S.B.; Brewer, S.K.; Little, E.E.

2000-01-01

Relations between neurotoxicants and changes in physiological parameters and behavior were investigated in larval rainbow trout (RBT; Oncorhynchus mykiss) exposed to sublethal concentrations of two organophosphate pesticides (OPs). Fish were exposed to diazinon and malathion in static-renewal experiments. After exposures for 24, 96, or 96 h, followed by 48 h of recovery, individual RBT were videotaped to assess locomotory behaviors. Brain tissue from the same fish was assayed for the physiological endpoints, cholinesterase (ChE) activity, muscarinic cholinergic receptor (MChR) number (Bmax), and MChR affinity (KD). Cholinesterase activity decreased significantly with increasing concentrations of both diazinon and malathion and differed significantly among exposure durations, with 24- and 96-h means less than 48-h recovery means. Decreases in Bmax with OP concentration were not significant for either chemical, and KDwas unaffected. Changes in swimming speed and distance were significantly correlated with changes in ChE activity for both chemicals; rate of turning was significantly correlated with ChE activity in malathion exposures. These results suggest that correlations between physiological and behavioral changes previously seen in mammals also occur in fish.

The impact of the new cooperative medical scheme on financial burden of tuberculosis patients: evidence from six counties in China.

PubMed

Xiang, Li; Pan, Yao; Hou, Shuangyi; Zhang, Hongwei; Sato, Kaori D; Li, Qiang; Wang, Jing; Tang, Shenglan

2016-01-28

Tuberculosis (TB) patients in China encounter heavy financial burdens throughout the course of their treatment and it is unclear how China's health insurance systems affect the alleviation of this burden under the integrated approach. This study aimed to measure reimbursement for TB services under the New Cooperative Medical Scheme (NCMS) in rural China and to evaluate changes in catastrophic health expenditure (CHE) caused by the reimbursement policies. Reimbursement data were obtained from routine data systems for the NCMS in Yichang (YC) and Hanzhong (HZ). 1884 TB inpatients reimbursed by NCMS from 2010 to 2012 were included. Household surveys were conducted. A total of 494 TB patients under the NCMS were selected in this paper. 12 Focus Group Discussions (FGDs) were held. We measured the impact of the NCMS by counterfactual analysis, which analyzed the financial burden alleviation. Equity was assessed by Concentration Index (CI), and disaggregated by project sites. TB inpatients were reimbursed with an effective reimbursement rate of 57.3 %. Average out-of-pocket (OOP) payments for outpatient and inpatient services after diagnosis were 1413 yuan and 430 yuan, and 3572 yuan and 3013 yuan in YC and HZ, respectively. The reimbursement level for TB outpatient care after diagnosis was very low due to a limited outpatient quota. TB patients in HZ incurred higher effective reimbursement rates, but the incidence of CHE remained higher. The reduction of CHE incidence after the NCMS showed no difference statistically (P > 0.05). The severity of CHE was alleviated slightly. CIs after reimbursement were all below zero and their absolute values were higher than those before reimbursement. Low reimbursement for TB patients could lead to heavy financial burden. Poor TB patients incurred high rates of CHE. The NCMS was found to be a protective factor for CHE, but the impact was modest and the equity of CHE did not improve. The NCMS reimbursement policies should be improved in the future to include a more comprehensive coverage of care. Supplemental programs may be necessary to expand coverage for TB care.

Catastrophic health expenditures and its inequality in elderly households with chronic disease patients in China.

PubMed

Wang, Zhonghua; Li, Xiangjun; Chen, Mingsheng

2015-01-20

Although numerous studies examine catastrophic health expenditures (CHE) worldwide, most focus on whole populations rather than specific vulnerable groups. This study analyzes the extent, associated factors and inequality of CHE in elderly household with chronic disease patients in China. Data were obtained from a nationally representative elderly household survey-the China Health and Retirement Longitudinal Study-that was conducted by the National School of Development of Peking University in 2011. An elderly household with chronic disease patients is defined by ≥ 1 chronic disease patient who is ≥ 45 years of age. CHE was measured according to the proportion of out-of-pocket health payments to non-food household expenditures. The associated factors of CHE were estimated using ordinary least square and logistic regression modeling. CHE inequality was measured according to the concentration index (CI) and its decomposition. CHE incidence and intensity were relatively high among elderly households with chronic disease patients. The main associated factors of CHE include household size, having members > 65 years, having members with ≥ 2 chronic diseases, per capita income, and elderly household members demonstrating healthcare-seeking behaviors. Healthcare insurance did not significantly affect CHE risk. Disproportionate concentration of CHE was noted among elderly households, and poor elderly households demonstrated a higher probability of experiencing CHE. Factors such as household size, per capita income, having members > 65 years, and having members with ≥ 2 chronic diseases are major and positive contributors to CHE inequality. Some inpatient and outpatient services are negatively contributed to CHE inequality,suggesting that the unequal usage of such services reduces CHE inequality among elderly households with chronic disease patients. Policy efforts should focus on improving financial protection and relieving the economic burden of disease in elderly households. The government should increase income subsidies and optimize social health insurance programs, thereby reducing CHE and alleviating CHE inequality among elderly households in China.

COMPARISON BETWEEN ELLMAN AND RADIOMETRIC METHODS FOR ASSESSING CHOLINESTERASE (CHE) INHIBITION IN RATS TREATED WITH N-METHYL CARBAMATE INSECTICIDES.

EPA Science Inventory

Carbamylated ChE is unstable and readily reactivates. This reactivation, promoted by increasing temperature and dilution, could have an impact on ex vivo ChE assays by decreasing apparent ChE inhibition. To assess the best method for measuring ChE inhibition in brain and RBCs f...

Characterizations of cholinesterases in golden apple snail (Pomacea canaliculata).

PubMed

Zou, Xiang-Hui; Xie, Heidi Qun-Hui; Zha, Guang-Cai; Chen, Vicky Ping; Sun, Yan-Jie; Zheng, Yu-Zhong; Tsim, Karl Wah-Keung; Dong, Tina Ting-Xia; Choi, Roy Chi-Yan; Luk, Wilson Kin-Wai

2014-07-01

Cholinesterases (ChEs) have been identified in vertebrates and invertebrates. Inhibition of ChE activity in invertebrates, such as bivalve molluscs, has been used to evaluate the exposure of organophosphates, carbamate pesticides, and heavy metals in the marine system. The golden apple snail (Pomacea canaliculata) is considered as one of the worst invasive alien species harmful to rice and other crops. The ChE(s) in this animal, which has been found recently, but poorly characterized thus far, could serve as biomarker(s) for environmental surveillance as well as a potential target for the pest control. In this study, the tissue distribution, substrate preference, sensitivity to ChE inhibitors, and molecular species of ChEs in P. canaliculata were investigated. It was found that the activities of both AChE and BChE were present in all test tissues. The intestine had the most abundant ChE activities. Both enzymes had fair activities in the head, kidney, and gills. The BChE activity was more sensitive to tetra-isopropylpyrophosphoramide (iso-OMPA) than the AChE. Only one BChE molecular species, 5.8S, was found in the intestine and head, whereas two AChE species, 5.8S and 11.6S, were found there. We propose that intestine ChEs of this snail may be potential biomarkers for manipulating pollutions.

Agronomic performance of new open pollinated experimental lines of broccoli (Brassica oleracea L. var. italica) evaluated under organic farming.

PubMed

Sahamishirazi, Samira; Moehring, Jens; Zikeli, Sabine; Fleck, Michael; Claupein, Wilhelm; Graeff-Hoenninger, Simone

2018-01-01

In order to develop new open pollinating cultivars of broccoli for organic farming, two experiments were conducted during fall 2015 and spring 2016. This study was aimed at comparing the agronomic performance of eleven new open pollinating breeding lines of broccoli to introduce new lines and to test their seasonal suitability for organic farming. Field experiments were carried out at the organic research station Kleinhohenheim of the University of Hohenheim (Stuttgart-Germany). Different agronomic traits total biomass fresh weight, head fresh weight, head diameter, hollow-stem, fresh weight harvest index and marketable yield were assessed together with commercial control cultivars. The data from both experiments were analyzed using a two-stage mixed model approach. In our study, genotype, growing season and their interaction had significant effects on most traits. Plants belonging to the fall growing season had bigger sizes in comparison to spring with significantly (p< 0.0001) higher biomass fresh weight. Some experimental lines had significant lower head fresh weight in spring in comparison to the fall season. The high temperature during the harvest period for the spring season affected the yield negatively through decreasing the firmness of broccoli heads. The low average minimum temperatures during the spring growing season lead to low biomass fresh weight but high fresh weight harvest index. Testing the seasonal suitability of all open pollinating lines showed that the considered fall season was better for broccoli production. However, the change in yield between the fall and the spring growing season was not significant for "Line 701" and "CHE-MIC". Considering the expression of different agronomic traits, "CHE-GRE-G", "Calinaro" and "CAN-SPB" performed the best in the fall growing season, and "CHE-GRE-G", "CHE-GRE-A", "CHE-BAL-A" and "CHE-MIC" and "Line 701" were best in the spring growing season, specifically due to the highest marketable yield and proportion of marketable heads.

Induction of reactive oxygen species-stimulated distinctive autophagy by chelerythrine in non-small cell lung cancer cells.

PubMed

Tang, Zheng-Hai; Cao, Wen-Xiang; Wang, Zhao-Yu; Lu, Jia-Hong; Liu, Bo; Chen, Xiuping; Lu, Jin-Jian

2017-08-01

Chelerythrine (CHE), a natural benzo[c]phenanthridine alkaloid, shows anti-cancer effect through a number of mechanisms. Herein, the effect and mechanism of the CHE-induced autophagy, a type II programmed cell death, in non-small cell lung cancer (NSCLC) cells were studied for the first time. CHE induced cell viability decrease, colony formation inhibition, and apoptosis in a concentration-dependent manner in NSCLC A549 and NCI-H1299 cells. In addition, CHE triggered the expression of phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II). The CHE-induced expression of LC3-II was further increased in the combination treatment with chloroquine (CQ), an autophagy inhibitor, and large amounts of red-puncta were observed in the CHE-treated A549 cells with stable expression of mRFP-EGFP-LC3, indicating that CHE induces autophagy flux. Silence of beclin 1 reversed the CHE-induced expression of LC3-II. Inhibition of autophagy remarkably reversed the CHE-induced cell viability decrease and apoptosis in NCI-H1299 cells but not in A549 cells. Furthermore, CHE triggered reactive oxygen species (ROS) generation in both cell lines. A decreased level of ROS through pretreatment with N-acetyl-L-cysteine reversed the CHE-induced cell viability decrease, apoptosis, and autophagy. Taken together, CHE induced distinctive autophagy in A549 (accompanied autophagy) and NCI-H1299 (pro-death autophagy) cells and a decreased level of ROS reversed the effect of CHE in NSCLC cells in terms of cell viability, apoptosis, and autophagy. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Brain cholinesterase reactivation as a marker of exposure to anticholinesterase pesticides: a case study in a population of yellow-legged gull Larus michahellis (Naumann, 1840) along the northern coast of Portugal.

PubMed

Santos, Cátia S A; Monteiro, Marta S; Soares, Amadeu M V M; Loureiro, Susana

2016-01-01

Between late 2010 to early 2011, an increased mortality in gulls was observed along the northern coast of Portugal, with individuals exhibiting neurologic disorders consistent with an eventual anticholinesterase pesticide poisoning event. To clarify if this mortality was related to organophosphate (OP) and/or carbamate (CB) poisoning, chemical and spontaneous cholinesterase (ChE) reactivation was tested in the brain of the yellow-legged gull (Larus michahellis). Initial brain ChE activity in L. michahellis was 40.92 ± 5.23 U/mg of protein (average ± SE). Following chemical and spontaneous reactivation, ChE activity increased in average 70.38 ± 48.59% and 131.95 ± 92.64%, respectively. ChE reactivation was found to decrease at increasing concentrations of the oxime pyridine-2-aldoxime methochloride and dilution factor, underscoring the importance of first optimizing the assay conditions prior to its use on bird species. These results suggest that birds analysed could have been exposed to OP and CB pesticide compounds and that in most cases CB exposure appeared to be the main cause of birds poisoning. These results are an important contribution to environmental monitoring as it demonstrates the suitability of L. michaellis as sentinel species of OP and CB pesticides within an urban environment.

The Influence of Study Species Selection on Estimates of Pesticide Exposure in Free-Ranging Birds

NASA Astrophysics Data System (ADS)

Borges, Shannon L.; Vyas, Nimish B.; Christman, Mary C.

2014-02-01

Field studies of pesticide effects on birds often utilize indicator species with the purpose of extrapolating to other avian taxa. Little guidance exists for choosing indicator species to monitor the presence and/or effects of contaminants that are labile in the environment or body, but are acutely toxic, such as anticholinesterase (anti-ChE) insecticides. Use of an indicator species that does not represent maximum exposure and/or effects could lead to inaccurate risk estimates. Our objective was to test the relevance of a priori selection of indicator species for a study on pesticide exposure to birds inhabiting fruit orchards. We used total plasma ChE activity and ChE reactivation to describe the variability in anti-ChE pesticide exposure among avian species in two conventionally managed fruit orchards. Of seven species included in statistical analyses, the less common species, chipping sparrow ( Spizella passerina), showed the greatest percentage of exposed individuals and the greatest ChE depression, whereas the two most common species, American robins ( Turdus migratorius) and gray catbirds ( Dumatella carolinensis), did not show significant exposure. Due to their lower abundance, chipping sparrows would have been an unlikely choice for study. Our results show that selection of indicator species using traditionally accepted criteria such as abundance and ease of collection may not identify species that are at greatest risk. Our efforts also demonstrate the usefulness of conducting multiple-species pilot studies prior to initiating detailed studies on pesticide effects. A study such as ours can help focus research and resources on study species that are most appropriate.

Evolutionary genomics suggests that CheV is an additional adaptor for accommodating specific chemoreceptors within the chemotaxis signaling complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ortega, Davi R.; Zhulin, Igor B.; Punta, Marco

Escherichia coli and Salmonella enterica are models for many experiments in molecular biology including chemotaxis, and most of the results obtained with one organism have been generalized to another. While most components of the chemotaxis pathway are strongly conserved between the two species, Salmonella genomes contain some chemoreceptors and an additional protein, CheV, that are not found in E. coli. The role of CheV was examined in distantly related species Bacillus subtilis and Helicobacter pylori, but its role in bacterial chemotaxis is still not well understood. We tested a hypothesis that in enterobacteria CheV functions as an additional adaptor linkingmore » the CheA kinase to certain types of chemoreceptors that cannot be effectively accommodated by the universal adaptor CheW. Phylogenetic profiling, genomic context and comparative protein sequence analyses suggested that CheV interacts with specific domains of CheA and chemoreceptors from an orthologous group exemplified by the Salmonella McpC protein. Structural consideration of the conservation patterns suggests that CheV and CheW share the same binding spot on the chemoreceptor structure, but have some affinity bias towards chemoreceptors from different orthologous groups. Finally, published experimental results and data newly obtained via comparative genomics support the idea that CheV functions as a "phosphate sink" possibly to off-set the over-stimulation of the kinase by certain types of chemoreceptors. Altogether, our results strongly suggest that CheV is an additional adaptor for accommodating specific chemoreceptors within the chemotaxis signaling complex.« less

Evolutionary genomics suggests that CheV is an additional adaptor for accommodating specific chemoreceptors within the chemotaxis signaling complex

DOE PAGES

Ortega, Davi R.; Zhulin, Igor B.; Punta, Marco

2016-02-04

Escherichia coli and Salmonella enterica are models for many experiments in molecular biology including chemotaxis, and most of the results obtained with one organism have been generalized to another. While most components of the chemotaxis pathway are strongly conserved between the two species, Salmonella genomes contain some chemoreceptors and an additional protein, CheV, that are not found in E. coli. The role of CheV was examined in distantly related species Bacillus subtilis and Helicobacter pylori, but its role in bacterial chemotaxis is still not well understood. We tested a hypothesis that in enterobacteria CheV functions as an additional adaptor linkingmore » the CheA kinase to certain types of chemoreceptors that cannot be effectively accommodated by the universal adaptor CheW. Phylogenetic profiling, genomic context and comparative protein sequence analyses suggested that CheV interacts with specific domains of CheA and chemoreceptors from an orthologous group exemplified by the Salmonella McpC protein. Structural consideration of the conservation patterns suggests that CheV and CheW share the same binding spot on the chemoreceptor structure, but have some affinity bias towards chemoreceptors from different orthologous groups. Finally, published experimental results and data newly obtained via comparative genomics support the idea that CheV functions as a "phosphate sink" possibly to off-set the over-stimulation of the kinase by certain types of chemoreceptors. Altogether, our results strongly suggest that CheV is an additional adaptor for accommodating specific chemoreceptors within the chemotaxis signaling complex.« less

Income related inequality and influencing factors: a study for the incidence of catastrophic health expenditure in rural China.

PubMed

Gu, Hai; Kou, Yun; Yan, Zhiwen; Ding, Yilei; Shieh, Jusheng; Sun, Jun; Cui, Nan; Wang, Qianjing; You, Hua

2017-09-20

Catastrophic health expenditure (CHE) puts a heavy disease burden on patients' families, aggravating income-related inequality. In an attempt to reduce the financial risks of rural families incurring CHE, China began the New Rural Cooperative Medical System (NCMS) on a trial basis in 2003 and has raised the reimbursement rates continuously since then. Based on statistical data about rural families in sample area of Jiangsu province, this study measures the incidence of CHE, analyzes socioeconomic inequality related to CHE, and explores the influences of the NCMS on the incidence of CHE. Statistical data were acquired from two surveys about rural health care, one conducted in 2009 and one conducted in 2010. In 2009, 1424 rural families were analyzed; in 2010, 1796 rural families were analyzed. An index of CHE is created to enable the evaluation of the associated financial risks. The concentration index and concentration curve are used to measure the income-related inequality involved in CHE. Multiple logistic regression is utilized to explore the factors that influence the incidence of CHE. The incidence of CHE decreased from 13.62% in 2009 to 7.74% in 2010. The concentration index of CHE was changed from -0.298 (2009) to -0.323 (2010). Compared with rural families in which all members were covered by the NCMS, rural families in which some members were not covered by the NCMS had a lower incidence of CHE: The odds ratio is 0.65 with a 95% confidence interval of 0.43 to 1.00. For rural families in which all members were covered by the NCMS, the increase in reimbursement rates is correlated to the decline in the incidence of CHE if other influencing factors were controlled: The odds ratio is 0.48 with a 95% confidence interval of 0.36 to 0.64. Between 2009 and 2010, the incidence rate of CHE in the sampled area decreased sharply, CHE was more concentrated among least wealthy and inequality increased during study period. As of 2010, the poorest rural families still had high risk of experiencing CHE. For rural families in which all members are covered by the NCMS, the rise in reimbursement rates reduces the probability of experiencing CHE.

Climate warming, euxinia and carbon isotope perturbations during the Carnian (Triassic) Crisis in South China

NASA Astrophysics Data System (ADS)

Sun, Y. D.; Wignall, P. B.; Joachimski, M. M.; Bond, D. P. G.; Grasby, S. E.; Lai, X. L.; Wang, L. N.; Zhang, Z. T.; Sun, S.

2016-06-01

The Carnian Humid Episode (CHE), also known as the Carnian Pluvial Event, and associated biotic changes are major enigmas of the Mesozoic record in western Tethys. We show that the CHE also occurred in eastern Tethys (South China), suggestive of a much more widespread and probably global climate perturbation. Oxygen isotope records from conodont apatite indicate a double-pulse warming event. The CHE coincided with an initial warming of 4 °C. This was followed by a transient cooling period and then a prolonged ∼7 °C warming in the later Carnian (Tuvalian 2). Carbon isotope perturbations associated with the CHE of western Tethys occurred contemporaneously in South China, and mark the start of a prolonged period of carbon cycle instability that persisted until the late Carnian. The dry-wet transition during the CHE coincides with the negative carbon isotope excursion and the temperature rise, pointing to an intensification of hydrologic cycle activities due to climatic warming. While carbonate platform shutdown in western Tethys is associated with an influx of siliciclastic sediment, the eastern Tethyan carbonate platforms are overlain by deep-water anoxic facies. The transition from oxygenated to euxinic facies was via a condensed, manganiferous carbonate (MnO content up to 15.1 wt%), that records an intense Mn shuttle operating in the basin. Significant siliciclastic influx in South China only occurred after the CHE climatic changes and was probably due to foreland basin development at the onset of the Indosinian Orogeny. The mid-Carnian biotic crisis thus coincided with several phenomena associated with major extinction events: a carbonate production crisis, climate warming, δ13 C oscillations, marine anoxia, biotic turnover and flood basalt eruptions (of the Wrangellia Large Igneous Province).

Assessment of biochemical and behavioral effects of carbaryl and methomyl in Brown-Norway rats from preweaning to senescence.

PubMed

Moser, Virginia C; Phillips, Pamela M; McDaniel, Katherine L

2015-05-04

Factors impacting life stage-specific sensitivity to chemicals include toxicokinetic and toxicodynamic changes. To evaluate age-related differences in the biochemical and behavioral impacts of two typical N-methyl carbamate pesticides, we systematically compared their dose-response and time-course in preweanling (postnatal day, PND, 18) and adult male Brown Norway rats (n=9-10/dose or time) ranging from adolescence to senescence (1, 4, 12, 24 mo). Carbaryl was administered orally at 3, 7.5, 15, or 22.5mg/kg and data were collected at 40 min after dosing, or else given at 3 or 15 mg/kg and data collected at 30, 60, 120, and 240 min. Methomyl was studied only in adult and senescent rat (4, 12, 24 mo) in terms of dose-response (0.25. 0.6, 1.25, 2.5mg/kg) and time-course (1.25mg/kg at 30, 60, 120, 240 min). Motor activity as well as brain and erythrocyte (RBC) cholinesterase (ChE) activity were measured in the same animals. In the carbaryl dose-response, PND18 rats were the most sensitive to the brain ChE-inhibiting effects of carbaryl, but 12- and 24-mo rats showed more motor activity depression even at similar levels of brain ChE inhibition. We have previously reported that brain ChE inhibition, but not motor activity effects, closely tracked carbaryl tissue levels. There were no age-related differences in methomyl-induced ChE inhibition across doses, but greater motor activity depression was again observed in the 12- and 24-mo rats. Carbaryl time-course data showed that motor activity depression reached a maximum later, and recovered slower, in the 12- and 24-mo rats compared to the younger ages; slowest recovery and maximal effects were seen in the 24-mo rats. Acetylcholinesterase sensitivity (concentration-inhibition curves) was measured in vitro using control tissues from each age. Inhibitory concentrations of carbaryl were somewhat lower in PND18, 12-, and 24-mo tissues compared to 1- and 4-mo, but there were no differences with methomyl-treated tissues. Thus, in the dose-response and time-course, there were dissociations between brain ChE inhibition and the magnitude as well as recovery of motor activity changes. The explanation for this dissociation is unclear, and is likely due to early development followed by aging-related decline in both kinetic parameters and neurological responsiveness. Copyright © 2015. Published by Elsevier Ireland Ltd.

Catastrophic health expenditure among households with members with special diseases: A case study in Kurdistan

PubMed Central

Moradi, Ghobad; Safari, Hossein; Piroozi, Bakhtiar; Qanbari, Laila; Farshadi, Salahadin; Qasri, Homan; Farhadifar, Fariba

2017-01-01

Background: One of the main goals of health systems is to protect people against financial risks associated with diseases that can be catastrophic for patients. In 2014, Health Sector Evolution Plan (HSEP) was implemented in Iran; one of the objectives of HSEP was to reduce out-of-pocket payments and provide more financial protection for people. Therefore, the present study aimed at exploring the likelihood of facing catastrophic health expenditures (CHE) among households with members suffering from dialysis, kidney transplant, or multiple sclerosis (MS) after the implementation of HSEP. Methods: A total number of 385 households were selected using stratified random sampling and were asked to complete the World Health Survey questionnaire through telephone conversations. As outlined by the World Health Organization (WHO), when household out-of-pocket expense for health services is ≥40% of its capacity to pay, then that household is considered to be facing CHE. Furthermore, determinants of CHE were identified using logistic regression. Results: The percentage of facing catastrophic health care expenditures for households with a MS, dialysis, and kidney transplant patient was 20.6%, 18.7%, and 13.8%, respectively. Results of logistic regression analysis revealed that patient’s economic status, level of education, supplementary insurance status, type of disease, multiple members with special diseases in the household, rural residence, use of inpatient, dental, and rehabilitation services were effective factors for determining the likelihood of facing CHE. Conclusion: Despite the implementation of HSEP, the percentage of CHE is still high for households that have members who suffer from special diseases. However, basic health insurance packages should be amended and more cost-sharing exemptions should be granted to provide more financial protection for the vulnerable households. PMID:29445672

Catastrophic health expenditure among households with members with special diseases: A case study in Kurdistan.

PubMed

Moradi, Ghobad; Safari, Hossein; Piroozi, Bakhtiar; Qanbari, Laila; Farshadi, Salahadin; Qasri, Homan; Farhadifar, Fariba

2017-01-01

Background: One of the main goals of health systems is to protect people against financial risks associated with diseases that can be catastrophic for patients. In 2014, Health Sector Evolution Plan (HSEP) was implemented in Iran; one of the objectives of HSEP was to reduce out-of-pocket payments and provide more financial protection for people. Therefore, the present study aimed at exploring the likelihood of facing catastrophic health expenditures (CHE) among households with members suffering from dialysis, kidney transplant, or multiple sclerosis (MS) after the implementation of HSEP. Methods: A total number of 385 households were selected using stratified random sampling and were asked to complete the World Health Survey questionnaire through telephone conversations. As outlined by the World Health Organization (WHO), when household out-of-pocket expense for health services is ≥40% of its capacity to pay, then that household is considered to be facing CHE. Furthermore, determinants of CHE were identified using logistic regression. Results: The percentage of facing catastrophic health care expenditures for households with a MS, dialysis, and kidney transplant patient was 20.6%, 18.7%, and 13.8%, respectively. Results of logistic regression analysis revealed that patient's economic status, level of education, supplementary insurance status, type of disease, multiple members with special diseases in the household, rural residence, use of inpatient, dental, and rehabilitation services were effective factors for determining the likelihood of facing CHE. Conclusion: Despite the implementation of HSEP, the percentage of CHE is still high for households that have members who suffer from special diseases. However, basic health insurance packages should be amended and more cost-sharing exemptions should be granted to provide more financial protection for the vulnerable households.

Cumulative incidence, distribution, and determinants of catastrophic health expenditure in Nepal: results from the living standards survey.

PubMed

Ghimire, Mamata; Ayer, Rakesh; Kondo, Masahide

2018-02-14

Nepal has committed to the global community to achieve universal health coverage by 2030. Nevertheless, Nepal still has a high proportion of out-of-pocket health payment and a limited risk-pooling mechanism. Out-of-pocket payment for the healthcare services could result in catastrophic health expenditure (CHE). Evidence is required to effectively channel the efforts to lower those expenses in order to achieve universal health coverage. However, little is known about CHE and its determinants in a broad national context in Nepal. Therefore, this study was conducted to explore the cumulative incidence, distribution, and determinants of CHE in Nepal. Data were obtained from the nationally representative survey, the Nepal Living Standards Survey-third undertaken in 2010/11. Information from 5988 households was used for the analyses. Households were classified as having CHE when their out-of-pocket health payment was greater than or equal to 40% of their capacity to pay. Remaining households were classified as not having CHE. Logistic regression analyses were used to identify determinants of CHE. Based on household-weighted sample, the cumulative incidence of CHE was 10.3% per month in Nepal. This incidence was concentrated in the far-western region and households in the poorer expenditure quartiles. Multivariable logistic regression revealed that households were more likely to face CHE if they; consisted of chronically ill member(s), have a higher burden of acute illness and injuries, have elderly (≥60 years) member(s), belonged to the poor expenditure quartile, and were located in the far-western region. In contrast, households were less likely to incur CHE when their household head was educated. Having children (≤5 years) in households did not significantly affect catastrophic health expenditure. This study identified a high cumulative incidence of CHE. CHE was disproportionately concentrated in the poor households and households located in the far-western region. Policy-makers should focus on prioritizing households vulnerable to CHE. Interventions to reduce economic burden of out-of-pocket healthcare payment are imperative to lower incidences of CHE among those households. Improving literacy rate might also be useful in order to lower CHE and facilitate universal health coverage.

Indian community health insurance schemes provide partial protection against catastrophic health expenditure

PubMed Central

Devadasan, Narayanan; Criel, Bart; Van Damme, Wim; Ranson, Kent; Van der Stuyft, Patrick

2007-01-01

Background More than 72% of health expenditure in India is financed by individual households at the time of illness through out-of-pocket payments. This is a highly regressive way of financing health care and sometimes leads to impoverishment. Health insurance is recommended as a measure to protect households from such catastrophic health expenditure (CHE). We studied two Indian community health insurance (CHI) schemes, ACCORD and SEWA, to determine whether insured households are protected from CHE. Methods ACCORD provides health insurance cover for the indigenous population, living in Gudalur, Tamil Nadu. SEWA provides insurance cover for self employed women in the state of Gujarat. Both cover hospitalisation expenses, but only upto a maximum limit of US$23 and US$45, respectively. We reviewed the insurance claims registers in both schemes and identified patients who were hospitalised during the period 01/04/2003 to 31/03/2004. Details of their diagnoses, places and costs of treatment and self-reported annual incomes were obtained. There is no single definition of CHE and none of these have been validated. For this research, we used the following definition; "annual hospital expenditure greater than 10% of annual income," to identify those who experienced CHE. Results There were a total of 683 and 3152 hospital admissions at ACCORD and SEWA, respectively. In the absence of the CHI scheme, all of the patients at ACCORD and SEWA would have had to pay OOP for their hospitalisation. With the CHI scheme, 67% and 34% of patients did not have to make any out-of-pocket (OOP) payment for their hospital expenses at ACCORD and SEWA, respectively. Both CHI schemes halved the number of households that would have experienced CHE by covering hospital costs. However, despite this, 4% and 23% of households with admissions still experienced CHE at ACCORD and SEWA, respectively. This was related to the following conditions: low annual income, benefit packages with low maximum limits, exclusion of some conditions from the benefit package, and use of the private sector for admissions. Conclusion CHI appears to be effective at halving the incidence of CHE among hospitalised patients. This protection could be further enhanced by improving the design of the CHI schemes, especially by increasing the upper limits of benefit packages, minimising exclusions and controlling costs. PMID:17362506

Indian community health insurance schemes provide partial protection against catastrophic health expenditure.

PubMed

Devadasan, Narayanan; Criel, Bart; Van Damme, Wim; Ranson, Kent; Van der Stuyft, Patrick

2007-03-15

More than 72% of health expenditure in India is financed by individual households at the time of illness through out-of-pocket payments. This is a highly regressive way of financing health care and sometimes leads to impoverishment. Health insurance is recommended as a measure to protect households from such catastrophic health expenditure (CHE). We studied two Indian community health insurance (CHI) schemes, ACCORD and SEWA, to determine whether insured households are protected from CHE. ACCORD provides health insurance cover for the indigenous population, living in Gudalur, Tamil Nadu. SEWA provides insurance cover for self employed women in the state of Gujarat. Both cover hospitalisation expenses, but only upto a maximum limit of US$23 and US$45, respectively. We reviewed the insurance claims registers in both schemes and identified patients who were hospitalised during the period 01/04/2003 to 31/03/2004. Details of their diagnoses, places and costs of treatment and self-reported annual incomes were obtained. There is no single definition of CHE and none of these have been validated. For this research, we used the following definition; "annual hospital expenditure greater than 10% of annual income," to identify those who experienced CHE. There were a total of 683 and 3152 hospital admissions at ACCORD and SEWA, respectively. In the absence of the CHI scheme, all of the patients at ACCORD and SEWA would have had to pay OOP for their hospitalisation. With the CHI scheme, 67% and 34% of patients did not have to make any out-of-pocket (OOP) payment for their hospital expenses at ACCORD and SEWA, respectively. Both CHI schemes halved the number of households that would have experienced CHE by covering hospital costs. However, despite this, 4% and 23% of households with admissions still experienced CHE at ACCORD and SEWA, respectively. This was related to the following conditions: low annual income, benefit packages with low maximum limits, exclusion of some conditions from the benefit package, and use of the private sector for admissions. CHI appears to be effective at halving the incidence of CHE among hospitalised patients. This protection could be further enhanced by improving the design of the CHI schemes, especially by increasing the upper limits of benefit packages, minimising exclusions and controlling costs.

Blood cholinesterase levels in a group of Malaysian blood donors.

PubMed

Chan, L; Balabaskaran, S; Delilkan, A E; Ong, L H

1994-12-01

Data on blood cholinesterase levels in the Malaysian population is lacking. The spectrophotometric method of Ellman was used to determine the red cell, plasma and whole blood cholinesterase (ChE) levels in 407 Malaysian blood donors. The mean+1SD for plasma ChE in females (n = 48) was 2.37 + 0.70 umol/min/ml and 2.76 + 0.75 umol/min/ml in males (n = 359). The mean plasma ChE in males was higher than in females (p < 0.001). The mean+1SD for red cell ChE in females was 9.01 + 1.20 umol/min/ml whereas in males it was 7.69 +1.30 umol/min/ml (the mean red cell ChE in females was higher than in males, p < 0.0001). The mean+1SD for whole blood ChE for females was 4.31+ 0.58 umol/min/ml and for males it was 4.95 + 0.71 umol/min/ml. The mean whole blood ChE in males was higher than in females (p < 0.0001). Sex influenced the plasma, red cell and whole blood ChE. In males the plasma ChE was affected by the race factor. The mean+1SD plasma ChE for the Malay, Chinese and Indian were 2.92 + 0.80, 2.73 + 0.71 and 2.61+ 0.73 respectively (p < 0.002). The age factor in males affected the red cell ChE with 7.88 + 1.32 in the (30-69) age group and 7.47 + 1.23 in the (15-29) age group (p < 0.005). The whole blood ChE in females was affected by blood groups. The mean+1SD whole blood ChE for blood groups A,B and O were 4.19 + 0.42, 3.93 + 0.46 and 4.49 + 0.62 respectively (p < 0.03). The significant difference is between the ChE of group B and O, but the ChE of group A could not be determined to be different from group B or O. These results serve as guidelines for our local population in the evaluation of cholinesterase levels with regard to pesticide poisoning, liver biosynthetic capacity and unusual sensitivity to succinylcholine.

Determination of esterase activity and characterization of cholinesterases in the reef fish Haemulon plumieri.

PubMed

Leticia, Alpuche-Gual; Gerardo, Gold-Bouchot

2008-11-01

White grunt (Haemulon plumieri) has been proposed by the Mesoamerican Barrier Reef System (MBRS) Synoptic Monitoring Program as a bioindicator species. It is in this sense that the present study has a main goal to evaluate this organism's suitability as an indicator species. Individuals were captured during three seasons at the port of Sisal, Yucatan, Mexico which is located in an area that is considered to be weakly impacted by human activities such as agriculture or industry. Both cholinesterase (ChE) and carboxylesterase (CbE) activities were measured in brain, muscle, liver and eye of sampled individuals. Results indicated that ChE and CbE activities were greatest in the brain (256.3 ± 43) and in the liver (191 ± 21), respectively. Furthermore, ChEs detected in brain, liver and muscle were characterized, and results suggested that the acetylcholinesterase (AChE) type was more abundant relative to pseudocholinesterase (BChE) which was rare. In addition, K(m) and V(max) and IC(50) values were calculated from the Michaelis-Menten equation. Finally, an additional experiment in vitro showed a significant decrease in both ChE and CbE activities when different tissues were exposed to model xenobiotics, such as benzo[a]pyrene and Chlorpyrifos. In conclusion, findings from this study confirm the potential suitability of H. plumieri as an organic pollution bioindicator species, and thus of practical use for environmental biomonitoring purposes.

Expression of cholinesterase gene(s) in human brain tissues: translational evidence for multiple mRNA species.

PubMed Central

Soreq, H; Zevin-Sonkin, D; Razon, N

1984-01-01

To resolve the origin(s) of the molecular heterogeneity of human nervous system cholinesterases (ChEs), we used Xenopus oocytes, which produce biologically active ChE when microinjected with unfractionated brain mRNA. The RNA was prepared from primary gliomas, meningiomas and embryonic brain, each of which expresses ChE activity with distinct substrate specificities and molecular forms. Sucrose gradient fractionation of DMSO-denatured mRNA from these sources revealed three size classes of ChE-inducing mRNAs, sedimenting at approximately 32S, 20S and 9S. The amounts of these different classes of ChE-inducing mRNAs varied between the three tissue sources examined. To distinguish between ChEs produced in oocytes and having different substrate specificities, their activity was determined in the presence of selective inhibitors. Both 'true' (acetylcholine hydrolase, EC 3.1.1.7) and 'pseudo' (acylcholine acylhydrolase, EC 3.1.1.8) multimeric cholinesterase activities were found in the mRNA-injected oocytes. Moreover, human brain mRNAs inducing 'true' and 'pseudo' ChE activities had different size distribution, indicating that different mRNAs might be translated into various types of ChEs. These findings imply that the heterogeneity of ChEs in the human nervous system is not limited to the post-translational level, but extends to the level of mRNA. PMID:6745236

Potential anti-cholinesterase and β-site amyloid precursor protein cleaving enzyme 1 inhibitory activities of cornuside and gallotannins from Cornus officinalis fruits.

PubMed

Bhakta, Himanshu Kumar; Park, Chan Hum; Yokozawa, Takako; Tanaka, Takashi; Jung, Hyun Ah; Choi, Jae Sue

2017-07-01

Cholinesterase (ChE) and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors are promising agents for the treatment of Alzheimer's disease (AD). In the present study, we examined the inhibitory activity of seven compounds isolated from the fruits of Cornus officinalis, cornuside, polymeric proanthocyanidins, 1,2,3-tri-O-galloyl-β-D-glucose, 1,2,3,6-tetra-O-galloyl-β-D-glucose, tellimagrandin I, tellimagrandin II, and isoterchebin, against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and BACE1. All of the compounds displayed concentration-dependent in vitro inhibitory activity toward the ChEs and BACE1. Among them, tellimagrandin II exhibited the best inhibitory activity toward ChEs, whereas the best BACE1 inhibitor was 1,2,3,6-tetra-O-galloyl-β-D-glucose. Isoterchebin and polymeric proanthocyanidins were also significant ChE inhibitors. The kinetic and docking studies demonstrated that all compounds interacted with both the catalytic active sites and the peripheral anionic sites of the ChEs and BACE1. Tellimagrandin II, isoterchebin, and the polymeric proanthocyanidins exhibited concentration-dependent inhibition of peroxynitrite-mediated protein tyrosine nitration. In conclusion, we identified significant ChE and BACE1 inhibitors from Corni Fructus that could have value as new multi-targeted compounds for anti-AD agents.

Piperine inhibits ABCA1 degradation and promotes cholesterol efflux from THP‐1‐derived macrophages

PubMed Central

Wang, Limei; Palme, Veronika; Rotter, Susanne; Schilcher, Nicole; Cukaj, Malsor; Wang, Dongdong; Ladurner, Angela; Heiss, Elke H.; Stangl, Herbert; Dirsch, Verena M.

2016-01-01

1 Scope Increased macrophage cholesterol efflux (ChE) is considered to have anti‐atherosclerotic effect counteracting cardiovascular disease. The principle pungent ingredient of the fruits of Piper nigrum, piperine, is identified in this study as a ChE inducer in THP‐1‐derived macrophages, and mechanisms underlying this effect are explored. 2 Methods and results Without affecting cell viability, piperine concentration‐dependently enhances ChE in THP‐1‐derived macrophages from 25 to 100 μM. The expression level of the key cholesterol transporter protein ATP‐binding cassette transporter A1 (ABCA1) is significantly upregulated by piperine, as revealed by western blot analyses. However, two other ChE‐mediating transporter proteins, ATP‐binding cassette transporter G1 (ABCG1) and scavenger receptor class B member 1 (SR‐B1), remain unaffected. Piperine exerts no influence on ABCA1 mRNA levels, but significantly inhibits the degradation of ABCA1, as evident by an increased half‐life of the protein in the presence of cycloheximide. Furthermore, it is found that piperine likely interferes with the calpain‐mediated ABCA1 degradation pathway and exhibits significant inhibition of calpain activity. 3 Conclusion Our findings suggest that piperine promotes ChE in THP‐1‐derived macrophages by upregulation of ABCA1, which might be mediated by inhibition of calpain activity. This novel bioactivity makes the dietary constituent piperine a good candidate to be further explored for therapeutic or preventive applications in the context of atherosclerosis. PMID:27862930

Novel brain-penetrating oximes for reactivation of cholinesterase inhibited by sarin and VX surrogates.

PubMed

Chambers, Janice E; Meek, Edward C; Chambers, Howard W

2016-06-01

Current oxime reactivators for organophosphate-inhibited cholinesterase (ChE) do not effectively cross the blood-brain barrier and therefore cannot restore brain ChE activity in vivo. Our laboratories have studied highly relevant sarin and VX surrogates, which differ from their respective nerve agents only in the leaving group and thereby leave ChE phosphylated with the same chemical moiety as sarin and VX. Our laboratories have developed novel substituted phenoxyalkyl pyridinium oximes that lead to reduced ChE inhibition in the brains of rats challenged with a high sublethal dosage of the sarin surrogate, whereas 2-PAM did not, using a paradigm designed to demonstrate brain penetration. In addition, treatment of rats with these novel oximes is associated with attenuation of seizure-like behavior compared to rats treated with 2-PAM, providing additional evidence that the oximes penetrate the blood-brain barrier. Further, some of the oximes provided 24-h survival superior to 2-PAM, and shortened the duration of seizure-like behavior when rats were challenged with lethal dosages of the sarin and VX surrogates, providing additional support for the conclusion that these oximes penetrate the brain. © 2016 New York Academy of Sciences.

Novel brain-penetrating oximes for reactivation of cholinesterase inhibited by sarin and VX surrogates

PubMed Central

Chambers, Janice E.; Meek, Edward C.; Chambers, Howard W.

2016-01-01

Current oxime reactivators for organophosphate-inhibited cholinesterase (ChE) do not effectively cross the blood–brain barrier and therefore cannot restore brain ChE activity in vivo. Our laboratories have studied highly relevant sarin and VX surrogates, which differ from their respective nerve agents only in the leaving group and thereby leave ChE phosphylated with the same chemical moiety as sarin and VX. Our laboratories have invented novel substituted phenoxyalkyl pyridinium oximes (U.S. Patent 9,227,937 B2) that lead to reduced ChE inhibition in the brains of rats challenged with a high sublethal dosage of the sarin surrogate, whereas 2-PAM did not, using a paradigm designed to demonstrate brain penetration. In addition, these novel oximes also showed an attenuation of seizure-like behavior compared to rats treated with 2-PAM, giving additional evidence of the ability of these oximes to penetrate the blood–brain barrier. Further, some of these oximes provided 24-hour survival superior to 2-PAM and shortened the duration of seizure-like behavior when rats were challenged with lethal dosages of the sarin and VX surrogates, providing additional support for the concept of these life-saving oximes penetrating the brain. PMID:27153507

Impact of chemical proportions on the acute neurotoxicity of a mixture of seven carbamates in preweanling and adult rats.

PubMed

Moser, Virginia C; Padilla, Stephanie; Simmons, Jane Ellen; Haber, Lynne T; Hertzberg, Richard C

2012-09-01

Statistical design and environmental relevance are important aspects of studies of chemical mixtures, such as pesticides. We used a dose-additivity model to test experimentally the default assumptions of dose additivity for two mixtures of seven N-methylcarbamates (carbaryl, carbofuran, formetanate, methomyl, methiocarb, oxamyl, and propoxur). The best-fitting models were selected for the single-chemical dose-response data and used to develop a combined prediction model, which was then compared with the experimental mixture data. We evaluated behavioral (motor activity) and cholinesterase (ChE)-inhibitory (brain, red blood cells) outcomes at the time of peak acute effects following oral gavage in adult and preweanling (17 days old) Long-Evans male rats. The mixtures varied only in their mixing ratios. In the relative potency mixture, proportions of each carbamate were set at equitoxic component doses. A California environmental mixture was based on the 2005 sales of each carbamate in California. In adult rats, the relative potency mixture showed dose additivity for red blood cell ChE and motor activity, and brain ChE inhibition showed a modest greater-than additive (synergistic) response, but only at a middle dose. In rat pups, the relative potency mixture was either dose-additive (brain ChE inhibition, motor activity) or slightly less-than additive (red blood cell ChE inhibition). On the other hand, at both ages, the environmental mixture showed greater-than additive responses on all three endpoints, with significant deviations from predicted at most to all doses tested. Thus, we observed different interactive properties for different mixing ratios of these chemicals. These approaches for studying pesticide mixtures can improve evaluations of potential toxicity under varying experimental conditions that may mimic human exposures.

A functional genomics approach reveals CHE as a component of the Arabidopsis circadian clock.

PubMed

Pruneda-Paz, Jose L; Breton, Ghislain; Para, Alessia; Kay, Steve A

2009-03-13

Transcriptional feedback loops constitute the molecular circuitry of the plant circadian clock. In Arabidopsis, a core loop is established between CCA1 and TOC1. Although CCA1 directly represses TOC1, the TOC1 protein has no DNA binding domains, which suggests that it cannot directly regulate CCA1. We established a functional genomic strategy that led to the identification of CHE, a TCP transcription factor that binds specifically to the CCA1 promoter. CHE is a clock component partially redundant with LHY in the repression of CCA1. The expression of CHE is regulated by CCA1, thus adding a CCA1/CHE feedback loop to the Arabidopsis circadian network. Because CHE and TOC1 interact, and CHE binds to the CCA1 promoter, a molecular linkage between TOC1 and CCA1 gene regulation is established.

Receptor-mediated protein kinase activation and the mechanism of transmembrane signaling in bacterial chemotaxis.

PubMed Central

Liu, Y; Levit, M; Lurz, R; Surette, M G; Stock, J B

1997-01-01

Chemotaxis responses of Escherichia coli and Salmonella are mediated by type I membrane receptors with N-terminal extracytoplasmic sensing domains connected by transmembrane helices to C-terminal signaling domains in the cytoplasm. Receptor signaling involves regulation of an associated protein kinase, CheA. Here we show that kinase activation by a soluble signaling domain construct involves the formation of a large complex, with approximately 14 receptor signaling domains per CheA dimer. Electron microscopic examination of these active complexes indicates a well defined bundle composed of numerous receptor filaments. Our findings suggest a mechanism for transmembrane signaling whereby stimulus-induced changes in lateral packing interactions within an array of receptor-sensing domains at the cell surface perturb an equilibrium between active and inactive receptor-kinase complexes within the cytoplasm. PMID:9405352

Central radio galaxies in groups: cavities, bubbles and the history of AGN heating

NASA Astrophysics Data System (ADS)

Giacintucci, S.; Venturi, T.; Raychaudhury, S.; Vrtilek, J.

2008-10-01

E' noto che le regioni centrali degli ammassi e gruppi di galassie costituiscono un ambiente in cui gas caldo e plasma radioemittente proveniente dalle galassie dominanti interagiscono tra loro. In particolare, si pensa che la radioemissione dell'AGN centrale ed i suoi possibili cicli di attivita', siano strettamente legati alla presenza di cavita' e "bubbles" nel gas intergalattico. Si presentera' lo status di un progetto osservativo effettuato con il Giant Metrewave Radio Telescope (GMRT, India) su di un campione di 18 gruppi di galassie, osservati a tre frequenze radio (235 MHz, 325 MHz e 610 MHz). Lo studio della morfologia radio degli AGN centrali e la relativa analisi spettrale permettono di ottenere stime sull'eta' di questi oggetti, e sulla loro energia totale, che a loro volta sono in relazione con le proprieta' X dei gruppi stessi. Per tutti gli oggetti del campione sono disponibili osservazioni Chandra di proprieta'. Per due oggetti del campione, 4C+24.36 (al centro di AWM04) e NGC741 (al centro di RSOG17) verra' presentato uno studio dettagliato.

Catastrophic health expenditure in households with chronic disease patients: A pre-post comparison of the New Health Care Reform in Shaanxi Province, China

PubMed Central

Xu, Yongjian; Ma, Jie; Wu, Na; Fan, Xiaojing; Zhang, Tao; Zhou, Zhongliang; Ren, Jianping; Chen, Gang

2018-01-01

Introduction In 2009, China officially launched the New Health Care Reform (NHCR). One important purpose of the reform was to reduce financial burden of health care through health insurance expansion and health care provider regulations. This study aimed to provide evidence on the effect of the NHCR reform on catastrophic health expenditure (CHE) by comparing the occurrence and inequality of CHE among households with chronic diseases patients before and after the reform. Methods This study used the subset of data from the 2008 and 2013 National Health Services Survey conducted in Shaanxi Province. Our sample included households with chronic diseases patients and excluded observations with key variables missing. The final sample size was 1942 households in 2008 and 7704 households in 2013. We defined CHE occurrence following the definition of the World Health Organization (WHO). The income-related inequality in CHE was measured by the concentration index. A multi-level logistic regression model was used in the study to explore the influence of the NHCR on CHE occurrence, controlling for important covariates. Results From 2008 to 2013, the occurrence rate of CHE in rural areas declined from 29.15% to 23.62%. However, the CHE rate in urban areas increased from 19.18% to 24.95%. The interaction term between year and rural/urban location was statistically significant, confirming that the influence of the NHCR on the CHE occurrence rates were heterogeneous between rural and urban areas. As for the CHE inequality, the concentration index in rural areas decreased from -0.4572 to -0.5499 with a p-value less than 0.05. This implied that the CHE occurrence inequality was increased after the implementation of the NHCR. Conclusion Our study suggested that the implementation of the NHCR might not have been effective in reducing the CHE occurrence for households with chronic disease patients. Although the occurrence of CHE of rural households had decreased, the occurrence of CHE in urban areas was higher than before. In addition, the income inequality of CHE occurrence was greater in 2013 compared to that in 2008 in rural areas. Although the reform resulted in higher insurance coverage and higher government expenditure in health care, the financial burden of health care on households did not necessarily improve. Further efforts on developing the current health insurance system and optimizing the hierarchical health care system are required to improve the protection against CHE. PMID:29547654

[Effect of Alternanthera philoxeroides on enzymic histochemistry of Oncomelania hupensis].

PubMed

Tan, Ping; Zhang, Xue-jun; Yang, Jian-ming; Zhang, Yan

2009-02-28

To investigate the mechanisms of Alternanthera philoxeroides (Mardus) Grisebach in inhibiting Oncomelania snails' locomotivity and killing effect. Uninfected snails were divided into four groups and exposed to an aqueous extract of A. philoxeroides and dechlorinated water (as control) for 12 h or 20 h, respectively. The activities of the Mg2+-adenosine triphosphatase (Mg2+-ATPase), cholinesterase (ChE), lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) in the head-foot muscles, centric ganglions, gills and liver of Oncomelania hupensis were analyzed using enzyme histochemistry technology and changes were observed under a light microscope. Statistical quantitative analysis of data of grey values was conducted on the computer-assisted image analyzing system (HPIAS-1000). The color of stained ChE in the head-foot muscles, centric ganglions and gills of the snail lightened evidently, showing a decrease of ChE activity after snails were immersed in the extract of A. philoxeroides for 12 h or 20 h. Results of grey values at different stained parts of snail, measured by the computer-assisted image analyzing system, indicated that there was a significant difference (P<0.01) between the activities of ChE in the head-foot muscles (130.95 +/- 8.08, 129.91 +/- 7.05), centric ganglions (127.43 +/- 7.27, 126.78 +/- 7.38) and gills (121.38 +/- 7.31, 126.41 +/- 8.28) from snails exposed to aqueous extract of A. philoxeroides for 12 h and 20 h and the activities of the enzyme in counter-parts (64.65 +/- 8.54, 65.18 +/- 7.96, 57.86 +/- 6.57, 50.71 +/- 6.15, 88.96 +/- 6.78 and 89.86 +/- 7.01, respectively) from control group. The activities of Mg2+-ATPase also showed a significant difference (P<0.05) in the head-foot muscles (89.91 +/- 5.08), centric ganglions (71.15 +/- 5.43) and liver (112.40 +/- 7.81) of the snail after 20 h of exposure against those in counter-parts (78.81 +/- 8.10, 60.09 +/- 6.05 and 95.50 +/- 8.35, respectively) from the control, but no significant difference (P>0.05) was shown on the activities of Mg2+-ATPase between the snails exposed for 12 h in extract of A. philoxeroides and those of control. No statistical difference (P>0.05) was found between the dechlorinated water group and the extract of A. philoxeroides group in the activities of LDH and SDH after 12 h or 20 h of exposure. The extract of A. philoxeroides rapidly inhibits ChE, and then the activity of Mg2+-ATPase, which may suppress the release and utilization of ATP in the Oncomelania snails and finally causes death of snails.

Comparative Effects of Oral Chlorpyrifos Exposure on Cholinesterase Activity and Muscarinic Receptor Binding in Neonatal and Adult Rat Heart

PubMed Central

Howard, Marcia D.; Mirajkar, Nikita; Karanth, Subramanya; Pope, Carey N.

2010-01-01

Organophosphorus (OP) pesticides elicit acute toxicity by inhibiting acetylcholinesterase (AChE), the enzyme responsible for inactivating acetylcholine (ACh) at cholinergic synapses. A number of OP toxicants have also been reported to interact directly with muscarinic receptors, in particular the M2 muscarinic subtype. Parasympathetic innervation to the heart primarily regulates cardiac function by activating M2 receptors in the sinus node, atrial-ventricular node and conducting tissues. Thus, OP insecticides can potentially influence cardiac function in a receptor–mediated manner indirectly by inhibiting acetylcholinesterase and directly by binding to muscarinic M2 receptors. Young animals are generally more sensitive than adults to the acute toxicity of OP insecticides and age related differences in potency of direct binding to muscarinic receptors by some OP toxicants have been reported. We thus compared the effects of the common OP insecticide chlorpyrifos (CPF) on functional signs of toxicity and cardiac ChE activity and muscarinic receptor binding in neonatal and adult rats. Dosages were based on acute lethality (i.e., 0.5 and 1 × LD10: neonates, 7.5 and 15 mg/kg; adults, 68 and 136 mg/kg). Dose- and time-related changes in body weight and cholinergic signs of toxicity (involuntary movements) were noted in both age groups. With 1 × LD10, relatively similar maximal reductions in ChE activity (95%) and muscarinic receptor binding (≈ 30%) were noted, but receptor binding reductions appeared earlier in adults and were more prolonged in neonates. In vitro inhibition studies indicated that ChE in neonatal tissues was markedly more sensitive to inhibition by the active metabolite of chlorpyrifos (i.e., chlorpyrifos oxon, CPO) than enzyme in adult tissues (IC50 values: neonates, 17 nM; adults, 200 nM). Chelation of free calcium with EDTA had relatively little effect on in vitro cholinesterase inhibition, suggesting that differential A-esterase activity was not responsible for the age-related difference in cholinesterase sensitivity between age groups. Pre-incubation of neonatal and adult tissues with selective inhibitors of AChE and butyrylcholinesterase (BChE) indicated that a majority (82–90%) of ChE activity in the heart of both neonates and adults was BChE. The rapid onset (by 4 hours after dosing) of changes in muscarinic receptor binding in adult heart may be a reflection of the more potent direct binding to muscarinic receptors by chlorpyrifos oxon previously reported in adult tissues. The results suggest that ChE activity (primarily BChE) in neonatal heart may be inherently more sensitive to inhibition by some anticholinesterases and that toxicologically significant binding to muscarinic receptors may be possible with acute chlorpyrifos intoxication, potentially contributing to age-related differences in sensitivity. PMID:17644233

The influence of study species selection on estimates of pesticide exposure in free-ranging birds

USGS Publications Warehouse

Borges, Shannon L.; Vyas, Nimish B.; Christman, Mary C.

2014-01-01

Field studies of pesticide effects on birds often utilize indicator species with the purpose 16 of extrapolating to other avian taxa. Little guidance exists for choosing indicator species to 17 monitor the presence and/or effects of contaminants that are labile in the environment or body, 18 but are acutely toxic, such as anticholinesterase (anti-ChE) insecticides. Use of an indicator 19 species that does not represent maximum exposure and/or effects could lead to inaccurate risk 20 estimates. Our objective was to test the relevance of a priori selection of indicator species for a 21 study on pesticide exposure to birds inhabiting fruit orchards. We used total plasma 22 cholinesterase (ChE) activity and ChE reactivation to describe the variability in anti-ChE exposure among avian species in two conventionally managed fruit orchards. Of seven 24 species included in statistical analyses, the less common species, chipping sparrow (Spizella 25 passerina), showed the greatest percentage of exposed individuals and the greatest ChE 26 depression, whereas the two most common species, American robins (Turdus migratorius) and 27 grey catbirds (Dumatella carolinensis), did not show significant exposure. Due to their lower 28 abundance, chipping sparrows would have been an unlikely choice for study. Our results show 29 that selection of indicator species using traditionally accepted criteria such as abundance and 30 ease of collection may not identify species that are at greatest risk. Our efforts also demonstrate 31 the usefulness of conducting multiple-species pilot studies prior to initiating detailed studies on 32 pesticide effects. A study such as ours can help focus research and resources on study species 33 that are most appropriate.

Diagnosis of anticholinesterase poisoning in birds: Effects of environmental temperature and underfeeding on cholinesterase activity

USGS Publications Warehouse

Rattner, B.A.

1982-01-01

Brain cholinesterase (ChE) activity has been used extensively to monitor exposure to organophosphorus (OP) and carbamate (CB) insecticides in wild birds. A series of factorial experiments was conducted to assess the extent to which noncontaminant-related environmental conditions might affect brain ChE activity and thereby confound the diagnosis of OP and CB intoxication. Underfeeding (restricting intake to 50% of control for 21 d or fasting for 1-3 d) or exposure to elevated temperature (36 + 1?C for 1 d) caused only slight reductions (10-17%) in brain AChE activity in adult male Japanese quail (Coturnix coturnix japonica). This degree of 'reduction' in brain AChE activity is considerably less than the 50% 'inhibition' criterion employed in the diagnosis of insecticide-induced mortality, but nevertheless approaches the 20% 'inhibition' level used as a conservative estimate of sublethal exposure to a known insecticide application.

Agronomic performance of new open pollinated experimental lines of broccoli (Brassica oleracea L. var. italica) evaluated under organic farming

PubMed Central

Moehring, Jens; Zikeli, Sabine; Fleck, Michael; Claupein, Wilhelm; Graeff-Hoenninger, Simone

2018-01-01

In order to develop new open pollinating cultivars of broccoli for organic farming, two experiments were conducted during fall 2015 and spring 2016. This study was aimed at comparing the agronomic performance of eleven new open pollinating breeding lines of broccoli to introduce new lines and to test their seasonal suitability for organic farming. Field experiments were carried out at the organic research station Kleinhohenheim of the University of Hohenheim (Stuttgart-Germany). Different agronomic traits total biomass fresh weight, head fresh weight, head diameter, hollow-stem, fresh weight harvest index and marketable yield were assessed together with commercial control cultivars. The data from both experiments were analyzed using a two-stage mixed model approach. In our study, genotype, growing season and their interaction had significant effects on most traits. Plants belonging to the fall growing season had bigger sizes in comparison to spring with significantly (p< 0.0001) higher biomass fresh weight. Some experimental lines had significant lower head fresh weight in spring in comparison to the fall season. The high temperature during the harvest period for the spring season affected the yield negatively through decreasing the firmness of broccoli heads. The low average minimum temperatures during the spring growing season lead to low biomass fresh weight but high fresh weight harvest index. Testing the seasonal suitability of all open pollinating lines showed that the considered fall season was better for broccoli production. However, the change in yield between the fall and the spring growing season was not significant for “Line 701” and “CHE-MIC”. Considering the expression of different agronomic traits, “CHE-GRE-G”, “Calinaro” and “CAN-SPB” performed the best in the fall growing season, and “CHE-GRE-G”, “CHE-GRE-A”, “CHE-BAL-A” and “CHE-MIC” and “Line 701” were best in the spring growing season, specifically due to the highest marketable yield and proportion of marketable heads. PMID:29738530

A Multi-Institution Study of Student Demographics and Outcomes in Chemical Engineering

ERIC Educational Resources Information Center

Lord, Susan M.; Layton, Richard A.; Ohland, Matthew W.; Brawner, Catherine E.; Long, Russell A.

2014-01-01

Using a large multi-institutional dataset, we describe demographics and outcomes for students starting in and transferring into chemical engineering (ChE). In this dataset, men outnumber women in ChE except among black students. While ChE starters graduate in ChE at rates comparable to or above their racial/ethnic population average for…

Specific radioisotopic assay for cholinesterase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Talbot, B.G.; Anderson, D.R.; Harris, L.W.

1992-02-01

The authors have developed a radiometric method (1) for measuring cholinesterase (ChE) activity that uses 0.4 N perchloric acid (PCA), instead of p-dioxane (method 2), to denature the ChE and stop hydrolysis of acetyl-1-{sup 14}C-choline (ACh). The unreacted ACh is removed by IRP-69 cationic exchange resin suspended in water, instead of dioxane. The supernatant containing the hydrolysis product, {sup 14}C-acetic acid, is mixed with nonhazardous scintillation cocktail and counted. The incubation mixture of 1 is similar to 2 and contains 0.1 ml of buffer-salt solution 0.1 ml of guinea pig whole blood (WB)-water suspension and 0.1 ml of 3 mMmore » ACh solution. Procedures 1 and 2 were compared to a titragraphic assay for ChE activity; specific activity values of WB (mmol ACh hydrolyzed/ml/hr) were found to be 137.6, 72.4 and 135.0, respectively. When {sup 14}C-acetic acid was processed through procedures 1 and 2, significantly less {sup 14}C was found in the supernatant from 2, whereas all of the expected {sup 14}C was found in the supernatant from 1, suggesting that IRP-69 resin in dioxane will remove significant amounts of {sup 14}C-acetic acid.« less

Toxicity of abate® 4E (temephos) in mallard ducklings and the influence of cold

USGS Publications Warehouse

Fleming, W.J.; Heinz, G.H.; Franson, J.C.; Rattner, B.A.

1985-01-01

Diets mixed to contain 0, 0.1, 1.0, 10 and 100 ppm temephos (determined chemically to contain less than 0.5, less than 0.5, 0.89, 6.0 and 59 ppm temephos, respectively) in an Abate® 4E formulation, were fed to mallard (Anas platyrhynchos) ducklings for 7 d. During this period, half of the ducklings in each dietary treatment group were housed in a heated brooder (39 to 41 °C) and half were housed in an unheated brooder (10 to 18°C). Mortality in all dietary groups in the unheated brooder was higher than in the heated brooder. High temephos-related mortality occurred in the 100 ppm group in the unheated brooder but not in any other diet-temperature groups. Ingestion of the 100 ppm temephos diet inhibited plasma Cholinesterase (ChE) activity and elevated plasma corticosterone concentration and creatine phosphokinase activity, but other selected plasma chemistries were not affected in a dose-related manner. Brain ChE activity was depressed only in the 100 ppm dietary groups; maximum inhibition of brain ChE activity was 48%. These findings suggest that diets containing up to 10 ppm temephos do not directly affect duckling survival during the first week of life and that the toxicity of 100 ppm temephos is markedly enhanced by cold.

Borrelia burgdorferi CheY2 Is Dispensable for Chemotaxis or Motility but Crucial for the Infectious Life Cycle of the Spirochete.

PubMed

Xu, Hui; Sultan, Syed; Yerke, Aaron; Moon, Ki Hwan; Wooten, R Mark; Motaleb, M A

2017-01-01

The requirements for bacterial chemotaxis and motility range from dispensable to crucial for host colonization. Even though more than 50% of all sequenced prokaryotic genomes possess at least one chemotaxis signaling system, many of those genomes contain multiple copies of a chemotaxis gene. However, the functions of most of those additional genes are unknown. Most motile bacteria possess at least one CheY response regulator that is typically dedicated to the control of motility and which is usually essential for virulence. Borrelia burgdorferi appears to be notably different, in that it has three cheY genes, and our current studies on cheY2 suggests that it has varied effects on different aspects of the natural infection cycle. Mutants deficient in this protein exhibit normal motility and chemotaxis in vitro but show reduced virulence in mice. Specifically, the cheY2 mutants were severely attenuated in murine infection and dissemination to distant tissues after needle inoculation. Moreover, while ΔcheY2 spirochetes are able to survive normally in the Ixodes ticks, mice fed upon by the ΔcheY2-infected ticks did not develop a persistent infection in the murine host. Our data suggest that CheY2, despite resembling a typical response regulator, functions distinctively from most other chemotaxis CheY proteins. We propose that CheY2 serves as a regulator for a B. burgdorferi virulence determinant that is required for productive infection within vertebrate, but not tick, hosts. Copyright © 2016 American Society for Microbiology.

Borrelia burgdorferi CheY2 Is Dispensable for Chemotaxis or Motility but Crucial for the Infectious Life Cycle of the Spirochete

PubMed Central

Xu, Hui; Sultan, Syed; Yerke, Aaron; Moon, Ki Hwan; Wooten, R. Mark

2016-01-01

ABSTRACT The requirements for bacterial chemotaxis and motility range from dispensable to crucial for host colonization. Even though more than 50% of all sequenced prokaryotic genomes possess at least one chemotaxis signaling system, many of those genomes contain multiple copies of a chemotaxis gene. However, the functions of most of those additional genes are unknown. Most motile bacteria possess at least one CheY response regulator that is typically dedicated to the control of motility and which is usually essential for virulence. Borrelia burgdorferi appears to be notably different, in that it has three cheY genes, and our current studies on cheY2 suggests that it has varied effects on different aspects of the natural infection cycle. Mutants deficient in this protein exhibit normal motility and chemotaxis in vitro but show reduced virulence in mice. Specifically, the cheY2 mutants were severely attenuated in murine infection and dissemination to distant tissues after needle inoculation. Moreover, while ΔcheY2 spirochetes are able to survive normally in the Ixodes ticks, mice fed upon by the ΔcheY2-infected ticks did not develop a persistent infection in the murine host. Our data suggest that CheY2, despite resembling a typical response regulator, functions distinctively from most other chemotaxis CheY proteins. We propose that CheY2 serves as a regulator for a B. burgdorferi virulence determinant that is required for productive infection within vertebrate, but not tick, hosts. PMID:27799336

Protecting patients with cardiovascular diseases from catastrophic health expenditure and impoverishment by health finance reform.

PubMed

Sun, Jing; Liabsuetrakul, Tippawan; Fan, Yancun; McNeil, Edward

2015-12-01

To compare the incidences of catastrophic health expenditure (CHE) and impoverishment, the risk protection offered by two health financial reforms and to explore factors associated with CHE and impoverishment among patients with cardiovascular diseases (CVDs) in rural Inner Mongolia, China. Cross-sectional study conducted in 2014 in rural Inner Mongolia, China. Patients with CVDs aged over 18 years residing in the sample areas for at least one year were eligible. The definitions of CHE and impoverishment recommended by WHO were adopted. The protection of CHE and impoverishment was compared between the New Cooperative Medical Scheme (NCMS) alone and NCMS plus National Essential Medicines Scheme (NEMS) using the percentage change of incidences for CHE and impoverishment. Logistic regression was used to explore factors associated with CHE and impoverishment. The incidences of CHE and impoverishment under NCMS plus NEMS were 11.26% and 3.30%, respectively, which were lower than those under NCMS alone. The rates of protection were higher among households with patients with CVDs covered by NCMS plus NEMS (25.68% and 34.65%, respectively). NCMS plus NEMS could protect the poor households more from CHE but not impoverishment. NCMS plus NEMS protected more than one-fourth of households from CHE and more than one-third from impoverishment. NCMS plus NEMS was more effective at protecting households with patients with CVDs from CHE and impoverishment than NCMS alone. An integration of NCMS with NEMS should be expanded. However, further strategies to minimise catastrophic health expenditure after this health finance reform are still needed. © 2015 John Wiley & Sons Ltd.

Organisation and Management of Continuing Higher Education: Findings of a Comparative Study in Six Countries from a German Perspective

ERIC Educational Resources Information Center

Knust, Michaela; Zawacki-Richter, Olaf; Hanft, Anke

2008-01-01

An international comparison study investigated the organisation and management of continuing higher education (CHE) in Germany, Finland, France, the United Kingdom, Austria and the United States of America. CHE is compared on the system level (boundaries between traditional study programmes and CHE, linking of CHE and vocational training,…

Chemotaxis and flagellar genes of Chromobacterium violaceum.

PubMed

Pereira, Maristela; Parente, Juliana Alves; Bataus, Luiz Artur Mendes; Cardoso, Divina das Dores de Paula; Soares, Renata Bastos Ascenço; Soares, Célia Maria de Almeida

2004-03-31

The availability of the complete genome of the Gram-negative beta-proteobacterium Chromobacterium violaceum has increasingly impacted our understanding of this microorganism. This review focuses on the genomic organization and structural analysis of the deduced proteins of the chemosensory adaptation system of C. violaceum. C. violaceum has multiple homologues of most chemotaxis genes, organized mostly in clusters in the bacterial genome. We found at least 67 genes, distributed in 10 gene clusters, involved in the chemotaxis of C. violaceum. A close examination of the chemoreceptors methyl-accepting chemotaxis proteins (MCPs), and the deduced sequences of the members of the two-component signaling system revealed canonical motifs, described as essential for the function of the deduced proteins. The chemoreceptors found in C. violaceum include the complete repertoire of such genes described in bacteria, designated as tsr, tar, trg, and tap; 41 MCP loci were found in the C. violaceum genome. Also, the C. violaceum genome includes a large repertoire of the proteins of the chemosensory transducer system. Multiple homologues of bacterial chemotaxis genes, including CheA, CheB, CheD, CheR, CheV, CheY, CheZ, and CheW, were found in the C. violaceum genome.

Interactions of the chemotaxis signal protein CheY with bacterial flagellar motors visualized by evanescent wave microscopy.

PubMed

Khan, S; Pierce, D; Vale, R D

The chemotaxis signal protein CheY of enteric bacteria shuttles between transmembrane methyl-accepting chemotaxis protein (MCP) receptor complexes and flagellar basal bodies [1]. The basal body C-rings, composed of the FliM, FliG and FliN proteins, form the rotor of the flagellar motor [2]. Phosphorylated CheY binds to isolated FliM [3] and may also interact with FliG [4], but its binding to basal bodies has not been measured. Using the chemorepellent acetate to phosphorylate and acetylate CheY [5], we have measured the covalent-modification-dependent binding of a green fluorescent protein-CheY fusion (GFP-CheY) to motor assemblies in bacteria lacking MCP complexes by evanescent wave microscopy [6]. At acetate concentrations that cause solely clockwise rotation, GFP-CheY molecules bound to native basal bodies or to overproduced rotor complexes with a stoichiometry comparable to the number of C-ring subunits. GFP-CheY did not bind to rotors lacking FIiM/FliN, showing that these subunits are essential for the association. This assay provides a new means of monitoring protein-protein interactions in signal transduction pathways in living cells.

Role of CheW protein in coupling membrane receptors to the intracellular signaling system of bacterial chemotaxis.

PubMed Central

Liu, J D; Parkinson, J S

1989-01-01

Chemotactic behavior in Escherichia coli is mediated by membrane-associated chemoreceptors that transmit sensory signals to the flagellar motors through an intracellular signaling system, which appears to involve a protein phosphorylation cascade. This study concerns the role of CheW, a cytoplasmic protein, in coupling methyl-accepting chemotaxis proteins (MCPs), the major class of membrane receptors, to the intracellular signaling system. Steady-state flagellar rotation behavior was examined in a series of strains with different combinations and relative amounts of CheW, MCPs, and other signaling components. At normal expression levels, CheW stimulated clockwise rotation, and receptors appeared to enhance this stimulatory effect. At high expression levels, MCPs inhibited clockwise rotation, and CheW appeared to augment this inhibitory effect. Since overexpression of CheW or MCP molecules had the same behavioral effect as their absence, chemoreceptors probably use CheW to modulate two distinct signals, one that stimulates and one that inhibits the intracellular phosphorylation cascade. Images PMID:2682657

Rivastigmine Alleviates Experimentally Induced Colitis in Mice and Rats by Acting at Central and Peripheral Sites to Modulate Immune Responses

PubMed Central

Shifrin, Helena; Nadler-Milbauer, Mirela; Shoham, Shai; Weinstock, Marta

2013-01-01

The cholinergic anti-inflammatory system and α7 nicotinic receptors in macrophages have been proposed to play a role in neuroimmunomodulation and in the etiology of ulcerative colitis. We investigated the ability of a cholinesterase (ChE) inhibitor rivastigmine, to improve the pathology of ulcerative colitis by increasing the concentration of extracellular acetylcholine in the brain and periphery. In combination with carbachol (10 µM), rivastigmine (1 µM) significantly decreased the release of nitric oxide, TNF-α, IL-1β and IL-6 from lipopolysaccharide-activated RAW 264.7 macrophages and this effect was abolished by α7 nicotinic receptor blockade by bungarotoxin. Rivastigmine (1 mg/kg) but not (0.5 mg/kg), injected subcutaneously once daily in BALB/c mice with colitis induced by 4% dextran sodium sulphate (DSS), reduced the disease activity index (DAI) by 60% and damage to colon structure. Rivastigmine (1 mg/kg) also reduced myeloperoxidase activity and IL-6 by >60%, and the infiltration of CD11b expressing cells by 80%. These effects were accompanied by significantly greater ChE inhibition in cortex, brain stem, plasma and colon than that after 0.5 mg/kg. Co-administration of rivastigmine (1 mg/kg) with the muscarinic antagonist scopolamine significantly increased the number of CD11b expressing cells in the colon but did not change DAI compared to those treated with rivastigmine alone. Rivastigmine 1 and 2 mg given rectally to rats with colitis induced by rectal administration of 30 mg dintrobezene sulfonic acid (DNBS) also caused a dose related reduction in ChE activity in blood and colon, the number of ulcers and area of ulceration, levels of TNF-α and in MPO activity. The study revealed that the ChE inhibitor rivastigmine is able to reduce gastro-intestinal inflammation by actions at various sites at which it preserves ACh. These include ACh released from vagal nerve endings that activates alpha7 nicotinic receptors on circulating macrophages and in brainstem neurons. PMID:23469045

Rivastigmine alleviates experimentally induced colitis in mice and rats by acting at central and peripheral sites to modulate immune responses.

PubMed

Shifrin, Helena; Nadler-Milbauer, Mirela; Shoham, Shai; Weinstock, Marta

2013-01-01

The cholinergic anti-inflammatory system and α7 nicotinic receptors in macrophages have been proposed to play a role in neuroimmunomodulation and in the etiology of ulcerative colitis. We investigated the ability of a cholinesterase (ChE) inhibitor rivastigmine, to improve the pathology of ulcerative colitis by increasing the concentration of extracellular acetylcholine in the brain and periphery. In combination with carbachol (10 µM), rivastigmine (1 µM) significantly decreased the release of nitric oxide, TNF-α, IL-1β and IL-6 from lipopolysaccharide-activated RAW 264.7 macrophages and this effect was abolished by α7 nicotinic receptor blockade by bungarotoxin. Rivastigmine (1 mg/kg) but not (0.5 mg/kg), injected subcutaneously once daily in BALB/c mice with colitis induced by 4% dextran sodium sulphate (DSS), reduced the disease activity index (DAI) by 60% and damage to colon structure. Rivastigmine (1 mg/kg) also reduced myeloperoxidase activity and IL-6 by >60%, and the infiltration of CD11b expressing cells by 80%. These effects were accompanied by significantly greater ChE inhibition in cortex, brain stem, plasma and colon than that after 0.5 mg/kg. Co-administration of rivastigmine (1 mg/kg) with the muscarinic antagonist scopolamine significantly increased the number of CD11b expressing cells in the colon but did not change DAI compared to those treated with rivastigmine alone. Rivastigmine 1 and 2 mg given rectally to rats with colitis induced by rectal administration of 30 mg dintrobezene sulfonic acid (DNBS) also caused a dose related reduction in ChE activity in blood and colon, the number of ulcers and area of ulceration, levels of TNF-α and in MPO activity. The study revealed that the ChE inhibitor rivastigmine is able to reduce gastro-intestinal inflammation by actions at various sites at which it preserves ACh. These include ACh released from vagal nerve endings that activates alpha7 nicotinic receptors on circulating macrophages and in brainstem neurons.

Coupling cosmogenic dating and magnetostratigraphy to constrain the chronological evolution of peri-Mediterranean karsts during the Messinian and the Pliocene: Example of Ardèche Valley, Southern France

NASA Astrophysics Data System (ADS)

Tassy, Aurélie; Mocochain, Ludovic; Bellier, Olivier; Braucher, Régis; Gattacceca, Jérôme; Bourlès, Didier

2013-05-01

The Ardèche River entrenches a deep canyon in the Saint Remèze plateau from Vallon-Pont-d'Arc to its confluence with the Rhône. This plateau is part of the Ardèche Cretaceous limestone plateau located at the edge of the Mid Rhône valley. It is characterized by dense multi-level cave systems, such as Saint-Marcel Cave (50 km of mapped passages) and Chauvet Cave, famous for its paleolithic paintings. Until now, and despite the absence of absolute dating, stepping of the Saint Remèze cave levels has been interpreted as the result of the Messinian salinity crisis. To clarify this interpretation, fluvial sediments of cave systems have been absolutely dated, while cave sediments have been demonstrated to be ideal for "burial dating" based on the different radioactive decay rates of the in situ-produced cosmogenic nuclides 10Be and 26Al. Combined with magnetostratigraphy and constrained by the Lower Ardèche base-level curve, this contribution provides an absolute dating for each cave level. The obtained results are consistent with the stepping per ascensum model of both surface landforms and caves for the Messinian-Pliocene eustatic cycle. Finally, this study provides evidence for a rise of the Ardèche river level to 40 m above the Pliocene abandonment surface. The second active period of the Chauvet Cave is evidenced between 2.96 and 2.18 Ma (cave filling). An absolute dating for the Pliocene abandonment surface between 1.94 and 1.77 Ma is also obtained, which brings new understandings to the geodynamic evolution of the area. The Lower Ardèche has been uplifted after the Pliocene, with a rate of 0.03 mm/year since 1.77 Ma.

CFTR is restricted to a small population of high expresser cells that provide a forskolin-sensitive transepithelial Cl- conductance in the proximal colon of the possum, Trichosurus vulpecula.

PubMed

Fan, Shujun; Harfoot, Natalie; Bartolo, Ray C; Butt, A Grant

2012-04-01

The cystic fibrosis transmembrane conductance regulator (CFTR) is central to anion secretion in both the possum and eutherian small intestine. Here, we investigated its role in the possum proximal colon, which has novel transport properties compared with the eutherian proximal colon. Despite considerable CFTR expression, high doses of the CFTR activator forskolin (EC(50)≈10 μmol l(-1)) were required for a modest, CFTR-dependent increase in short-circuit current (I(sc)) in the proximal colon. Presumably, this is because CFTR is restricted to the apical membrane of a small population of CFTR high expresser (CHE) cells in the surface and upper crypt epithelium. Furthermore, although the forskolin-stimulated I(sc) was dependent on serosal Na(+), Cl(-) and HCO(3)(-), consistent with anion secretion, inhibition of the basolateral Na-K-2Cl(-) (NKCC1) or Na-HCO(3) (pNBCe1) cotransporters did not prevent it. Therefore, although NKCC1 and pNBCe1 are expressed in the colonic epithelium they do not appear to be expressed in CHE cells. At low doses (IC(50)≈1 μmol l(-1)), forskolin also decreased the transepithelial conductance (G(T)) of the colon through inhibition of a 4,4'-diisothiocyano-2,2'-stilbenedisulphonic acid-sensitive anion conductance in the basolateral membrane of the CHE cells. This conductance is arranged in series with CFTR in the CHE cells and, therefore, the CHE cells provide a transepithelial Cl(-) conductance for passive Cl(-) absorption across the epithelium. Inhibition of the basolateral Cl(-) conductance of the CHE cells by forskolin will inhibit Na(+) absorption by restricting the movement of its counter-ion Cl(-), assisting in the conversion of the tissue from an absorptive to a secretory state.

Differential effect of Pistacia vera extracts on experimental atherosclerosis in the rabbit animal model: an experimental study

PubMed Central

2010-01-01

Background Lipid-enriched diets and oxidative stress are risk factors for the development of atherosclerosis. The effects of the methanolic (ME) and cyclohexane (CHE) extracts of the Pistacia vera nut, often included in the Mediterranean diet, were studied in the rabbit model of atherosclerosis. Methods and results Twenty-four New Zealand White rabbits received atherogenic diet (Control Group), supplemented with ME (Group ME) or CHE (Group CHE) for 3 months. Previously, a GC-MS and a UHPLC LC-DAD-ESI(-)-HRMS/MS method were developed to investigate the extracts' chemical profiles. Blood samples at baseline and monthly determined lipid profile, lipid peroxidation and liver function. The aorta, myocardium and liver were examined histologically at 3 months. Groups ME and CHE had significantly higher HDL- and non-significantly lower LDL-cholesterol median % changes from baseline than the Control Group. Triacylglycerol was significantly higher in Group CHE vs. Control. MDA values were significantly lower in Group ME vs. Control and CHE. ALT and AST were significantly higher in Group CHE vs. Control. γ-GT was lower in Group ME vs. Control. Aortic intimal thickness was significantly less in Groups ME and CHE vs. Control; Group ME atherosclerotic lesions were significantly less extensive vs. Groups Control and CHE. Only Group CHE had significant liver fatty infiltration. Conclusions During short-term administration concomitantly with atherogenic diet, both P. vera extracts were beneficial on HDL-, LDL-cholesterol and aortic intimal thickness. The ME additionally presented an antioxidant effect and significant decrease of aortic surface lesions. These results indicate that P. vera dietary inclusion, in particular its ME, is potentially beneficial in atherosclerosis management. PMID:20633299

Simulating the impact of cholinesterase-inhibiting pesticides on non-target wildlife in irrigated crops

USGS Publications Warehouse

Pisani, J.M.; Grant, W.E.; Mora, M.A.

2008-01-01

We present a simulation model for risk assessment of the impact of insecticide inhibitors of cholinesterase (ChE) applied in irrigated agricultural fields on non-target wildlife. The model, which we developed as a compartment model based on difference equations (??t = 1 h), consists of six submodels describing the dynamics of (1) insecticide application, (2) insecticide movement into floodable soil, (3) irrigation and rain, (4) insecticide dissolution in water, (5) foraging and insecticide intake from water, and (6) ChE inhibition and recovery. To demonstrate application of the model, we simulated historical and "worst-case" scenarios of the impact of ChE-inhibiting insecticides on white-winged doves (Zenaida asiatica) inhabiting natural brushland adjacent to cotton and sugarcane fields in the Lower Rio Grande Valley of Texas, USA. Only when a rain event occurred just after insecticide application did predicted levels of ChE inhibition surpass the diagnostic level of 20% exposure. The present model should aid in assessing the effect of ChE-inhibiting insecticides on ChE activity of different species that drink contaminated water from irrigated agricultural fields, and in identifying specific situations in which the juxtaposition of environmental conditions and management schemes could result in a high risk to non-target wildlife. ?? 2007 Elsevier B.V. All rights reserved.

The C. elegans che-1 gene encodes a zinc finger transcription factor required for specification of the ASE chemosensory neurons.

PubMed

Uchida, Okiko; Nakano, Hiroyuki; Koga, Makoto; Ohshima, Yasumi

2003-04-01

Chemotaxis to water-soluble chemicals such as NaCl is an important behavior of C. elegans when seeking food. ASE chemosensory neurons have a major role in this behavior. We show that che-1, defined by chemotaxis defects, encodes a zinc-finger protein similar to the GLASS transcription factor required for photoreceptor cell differentiation in Drosophila, and that che-1 is essential for specification and function of ASE neurons. Expression of a che-1::gfp fusion construct was predominant in ASE. In che-1 mutants, expression of genes characterizing ASE such as seven-transmembrane receptors, guanylate cyclases and a cyclic-nucleotide gated channel is lost. Ectopic expression of che-1 cDNA induced expression of ASE-specific marker genes, a dye-filling defect in neurons other than ASE and dauer formation.

[I direttori delle riviste vanno avanti: attenersi ai principi accademici, adottare trasparenza e rispetto e applicare le regole.

PubMed

Teixeira da Silva, Jaime A; Dobránszki, Judit

2018-05-01

Nonostante i cambiamenti in corso nell'ambito delle pubblicazioni scientifiche (STEM - scienza, tecnologia, ingegneria e medicina), è indubbio che i direttori delle riviste restano i più importanti custodi del processo editoriale. In questo articolo vengono analizzati i motivi per cui i direttori delle riviste devono continuare ad attenersi ai principi editoriali fondamentali e a utilizzare le nuove tecnologie digitali solo per dare forza al contenuto, ma non per sostituirlo nella sua qualità. Per raggiungere questo obiettivo, in un'epoca caratterizzata da controlli ed equilibri, i direttori delle riviste devono essere attentamente sorvegliati e ritenuti responsabili tanto quanto gli autori che essi stessi valutano. Qualunque scorciatoia potrebbe avere conseguenze negative e inaspettate per quella rivista che non si attenesse a tali regole, che vedrebbe intaccata la propria reputazione e che dovrebbe faticare per recuperare la fiducia dei propri lettori. Quindi, a rischio di sembrare scontati, è meglio prevenire il danno alla reputazione piuttosto che curarlo. L'unico modo per evitarlo è che i direttori delle riviste si adattino a un crescente movimento sempre più critico, che richiede maggiore trasparenza e responsabilità da parte di chi contribuisce a costruire la base delle conoscenze scientifiche e dalla società, specialmente laddove la ricerca è finanziata pubblicamente.

Does User Fee Removal Policy Provide Financial Protection from Catastrophic Health Care Payments? Evidence from Zambia

PubMed Central

Masiye, Felix; Kaonga, Oliver; Kirigia, Joses M

2016-01-01

Background Out-of-pocket payments in health care have been shown to impose significant burden on households in Sub-Saharan Africa, leading to constrained access to health care and impoverishment. In an effort to reduce the financial burden imposed on households by user fees, some countries in Sub-Saharan Africa have abolished user fees in the health sector. Zambia is one of few countries in Sub-Saharan Africa to abolish user fees in primary health care facilities with a view to alleviating financial burden of out-of-pocket payments among the poor. The main aim of this paper was to examine the extent and patterns of financial protection from fees following the decision to abolish user fees in public primary health facilities. Methods Our analysis is based on a nationally representative health expenditure and utilization survey conducted in 2014. We calculated the incidence and intensity of catastrophic health expenditure based on households’ out-of-pocket payments during a visit as a percentage of total household consumption expenditure. We further show the intensity of the problem of catastrophic health expenditure (CHE) experienced by households. Results Our analysis show that following the removal of user fees, a majority of patients who visited public health facilities benefitted from free care at the point of use. Further, seeking care at public primary health facilities is associated with a reduced likelihood of incurring CHE after controlling for economic wellbeing and other covariates. However, 10% of households are shown to suffer financial catastrophe as a result of out-of-pocket payments. Further, there is considerable inequality in the incidence of CHE whereby the poorest expenditure quintile experienced a much higher incidence. Conclusion Despite the removal of user fees at primary health care level, CHE is high among the poorest sections of the population. This study also shows that cost of transportation is mainly responsible for limiting the protective effectiveness of user fee removal on CHE among particularly poorest households. PMID:26795620

Does User Fee Removal Policy Provide Financial Protection from Catastrophic Health Care Payments? Evidence from Zambia.

PubMed

Masiye, Felix; Kaonga, Oliver; Kirigia, Joses M

2016-01-01

Out-of-pocket payments in health care have been shown to impose significant burden on households in Sub-Saharan Africa, leading to constrained access to health care and impoverishment. In an effort to reduce the financial burden imposed on households by user fees, some countries in Sub-Saharan Africa have abolished user fees in the health sector. Zambia is one of few countries in Sub-Saharan Africa to abolish user fees in primary health care facilities with a view to alleviating financial burden of out-of-pocket payments among the poor. The main aim of this paper was to examine the extent and patterns of financial protection from fees following the decision to abolish user fees in public primary health facilities. Our analysis is based on a nationally representative health expenditure and utilization survey conducted in 2014. We calculated the incidence and intensity of catastrophic health expenditure based on households' out-of-pocket payments during a visit as a percentage of total household consumption expenditure. We further show the intensity of the problem of catastrophic health expenditure (CHE) experienced by households. Our analysis show that following the removal of user fees, a majority of patients who visited public health facilities benefitted from free care at the point of use. Further, seeking care at public primary health facilities is associated with a reduced likelihood of incurring CHE after controlling for economic wellbeing and other covariates. However, 10% of households are shown to suffer financial catastrophe as a result of out-of-pocket payments. Further, there is considerable inequality in the incidence of CHE whereby the poorest expenditure quintile experienced a much higher incidence. Despite the removal of user fees at primary health care level, CHE is high among the poorest sections of the population. This study also shows that cost of transportation is mainly responsible for limiting the protective effectiveness of user fee removal on CHE among particularly poorest households.

Attention deficit hyperactivity disorder and the behavior of "Che" Guevara.

PubMed

Teive, Hélio A G; Zavala, Jorge A; Munhoz, Renato P; Lara, Diogo R; Lima, Pedro; Palmini, André

2009-09-01

Attention deficit hyperactivity disorder (ADHD) is a childhood onset neuropsychiatric disorder characterized by inattention, hyperactivity and impulsivity. ADHD is related to several co-morbidities, such as opposition defiant disorder, conduct disorder, mood and anxiety disturbances, as well as tics and Tourette's syndrome. The objective of this report is to shed an alternative light on the personality of Ernesto "Che" Guevara, discussing whether he might have had ADHD. Several published biographies of Che Guevara were reviewed. Established ADHD criteria (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), were used as a framework to evaluate Che's behaviour. In addition, we compared the main features of Che's reported behaviour to the set of abnormalities leading to the diagnosis of ADHD in adults proposed by Wender and colleagues and known as the UTAH ADHD criteria. Analysis of the most renowned biographies of Ernesto "Che" Guevara suggests that he may have had ADHD.

Effect of Chelerythrine on Intestinal Cell Turnover following Intestinal Ischemia-Reperfusion Injury in a Rat Model.

PubMed

Sukhotnik, Igor; Bitterman, Sivan; Shahar, Yoav Ben; Pollak, Yulia; Bitterman, Nir; Halabi, Salim; Coran, Arnold G; Bitterman, Arie

2017-02-01

Background  Chelerythrine (CHE) is a benzophenanthridine alkaloid that is a potent, selective, and cell-permeable protein kinase C inhibitor. The purpose of the present study was to examine the effect of CHE on intestinal recovery and enterocyte turnover after intestinal ischemia-reperfusion (IR) injury in rats. Methods  Male Sprague-Dawley rats were divided into four experimental groups: (1) sham rats underwent laparotomy, (2) sham-CHE rats underwent laparotomy and were treated with intraperitoneal CHE; (3) IR-rats underwent occlusion of both superior mesenteric artery and portal vein for 30 minutes followed by 48 hours of reperfusion, and (4) IR-CHE rats underwent IR and were treated with intraperitoneal CHE immediately before abdominal closure. Intestinal structural changes, Park injury score, enterocyte proliferation, and enterocyte apoptosis were determined 24 hours following IR. The expression of Bax, Bcl-2, p-ERK, and caspase-3 in the intestinal mucosa was determined using real Western blot and immunohistochemistry. Results  Treatment with CHE resulted in a significant decrease in Park injury score in jejunum (threefold decrease) and ileum (twofold decrease), and parallel increase in mucosal weight in jejunum and ileum, villus height in jejunum and ileum, and crypt depth in ileum compared with IR animals. IR-CHE rats also experienced a significantly lower apoptotic index in jejunum and ileum, which was accompanied by a lower Bax/Bcl2 ratio compared with IR animals. Conclusions  Treatment with CHE inhibits programmed cell death and prevents intestinal mucosal damage following intestinal IR in a rat. Georg Thieme Verlag KG Stuttgart · New York.

Effects of carbamates on whole blood cholinesterase activity: chemical protection against soman.

PubMed

Heyl, W C; Harris, L W; Stitcher, D L

1980-01-01

The toxicity (LD50) of several carbamates, all reversible inhibitors of cholinesterase (ChE), were determined in male rabbits. These include isopropyl methylphenyl carbamate (IMPC), pyridostigmine, neostigmine, benzpyrinium and physostigmine. When 1/9 of the LD50 of the above carbamates was individually combined with atropine (A) and benactyzine (B), mecamylamine (M) or chloropromazine (CPZ) and administered to rabbits in a pretreatment regimen, most animals could be protected from a 10 LD50 challenge of Soman. If CPZ, M or B was omitted from this regimen, no rabbits survived this challenge of Soman. The protection afforded against Soman was found to be related to reversible inhibition of ChE by the carbamates; reversible ChE inhibition varied with the route of injection and with the physical properties of the carbamate. Oral administration of pyridostigmine, a quaternary carbamate, provided protection for 24 hours. When the pretreatment included four components (pyridostigmine, A, M and B), the LD50 of Soman was raised 30.8 times in rabbits.

DDE increased the toxicity of parathion to coturnix quail

USGS Publications Warehouse

Ludke, J.L.

1977-01-01

Adult male Japanese quail (Coturnix coturnix) were exposed to DDE or chlordane in the diet and subsequently dosed with parathion or paraoxon. Pretreatment with 5 or 50 ppm DDE in the diet for 12 weeks resulted in increased cholinesterase (ChE) activity in plasma, but not in the brain. Dietary concentrations of 5 and 50 ppm DDE caused increased susceptibility of quail that were challenged with parathion or paraoxon. The increased mortality resulting from DDE pretreatment was reflected in brain ChE inhibition. The synergistic action of DDE was apparent after 3 days of exposure to 50 ppm DDE and 1 week of exposure to 5 ppm DDE. Birds exposed for 3 weeks to 5 or 50 ppm DDE retained their DDE-potentiated sensitivity to parathion after 2 weeks on clean diet. Chlordane pretreatment resulted in decreased susceptibility (antagonism) to parathion, but not to paraoxon dosage. Implications of differing responses in ChE and mortality among controls, DDE-, and chlordane-pretreated birds after parathion or paraoxon dosage are discussed.

Flagellar dynamics reveal the distribution of chemotactic signaling molecule CheY-P in E. coli

NASA Astrophysics Data System (ADS)

Bano, Roshni; Mears, Patrick; Chemla, Yann; Golding, Ido

E. colicells swim in a random walk consisting of ''runs'' - during which the flagella that propel the cell rotate counter-clockwise (CCW) - and ''tumbles''- during which one or more flagella rotate clockwise (CW). The tumbling frequency is modulated by the phosphorylation state of the signaling molecule CheY, which depends on the cell's environment. Phosphorylated CheY (CheY-P) binds to a flagellar motor and engenders a change in rotation state from CCW to CW. Despite advances in methods used to observe chemotactic signaling, it remains a challenge to measure the CheY-P level in cells directly. Here, we used an optical trap assay coupled with fluorescence microscopy to observe the dynamics of fluorescently labelled flagella in individual cells. By measuring the distribution of flagellar states in multi-flagellated cells and using our recent finding that each flagellar motor independently measures the cellular CheY-P concentration, we are able to extract the probability distribution of the CheY-P level in the cell. This analysis reveals the magnitude of fluctuations in chemotactic signaling in the live cell. We further investigate how this CheY-P distribution changes when cells encounter chemical gradients and perform chemotaxis. This work was supported by the National Science Foundation (NSF) through the Centre for Physics of Living Cells (CPLC).

Novel activation domain derived from Che-1 cofactor coupled with the artificial protein Jazz drives utrophin upregulation.

PubMed

Desantis, Agata; Onori, Annalisa; Di Certo, Maria Grazia; Mattei, Elisabetta; Fanciulli, Maurizio; Passananti, Claudio; Corbi, Nicoletta

2009-02-01

Our aim is to upregulate the expression level of the dystrophin related gene utrophin in Duchenne muscular dystrophy, thus complementing the lack of dystrophin functions. To this end, we have engineered synthetic zinc finger based transcription factors. We have previously shown that the artificial three-zinc finger protein named Jazz fused with the Vp16 activation domain, is able to bind utrophin promoter A and to increase the endogenous level of utrophin in transgenic mice. Here, we report on an innovative artificial protein, named CJ7, that consists of Jazz DNA binding domain fused to a novel activation domain derived from the regulatory multivalent adaptor protein Che-1/AATF. This transcriptional activation domain is 100 amino acids in size and it is very powerful as compared to the Vp16 activation domain. We show that CJ7 protein efficiently promotes transcription and accumulation of the acetylated form of histone H3 on the genomic utrophin promoter locus.

Distinct Domains of CheA Confer Unique Functions in Chemotaxis and Cell Length in Azospirillum brasilense Sp7.

PubMed

Gullett, Jessica M; Bible, Amber; Alexandre, Gladys

2017-07-01

Chemotaxis is the movement of cells in response to gradients of diverse chemical cues. Motile bacteria utilize a conserved chemotaxis signal transduction system to bias their motility and navigate through a gradient. A central regulator of chemotaxis is the histidine kinase CheA. This cytoplasmic protein interacts with membrane-bound receptors, which assemble into large polar arrays, to propagate the signal. In the alphaproteobacterium Azospirillum brasilense , Che1 controls transient increases in swimming speed during chemotaxis, but it also biases the cell length at division. However, the exact underlying molecular mechanisms for Che1-dependent control of multiple cellular behaviors are not known. Here, we identify specific domains of the CheA1 histidine kinase implicated in modulating each of these functions. We show that CheA1 is produced in two isoforms: a membrane-anchored isoform produced as a fusion with a conserved seven-transmembrane domain of unknown function (TMX) at the N terminus and a soluble isoform similar to prototypical CheA. Site-directed and deletion mutagenesis combined with behavioral assays confirm the role of CheA1 in chemotaxis and implicate the TMX domain in mediating changes in cell length. Fluorescence microscopy further reveals that the membrane-anchored isoform is distributed around the cell surface while the soluble isoform localizes at the cell poles. Together, the data provide a mechanism for the role of Che1 in controlling multiple unrelated cellular behaviors via acquisition of a new domain in CheA1 and production of distinct functional isoforms. IMPORTANCE Chemotaxis provides a significant competitive advantage to bacteria in the environment, and this function has been transferred laterally multiple times, with evidence of functional divergence in different genomic contexts. The molecular principles that underlie functional diversification of chemotaxis in various genomic contexts are unknown. Here, we provide a molecular mechanism by which a single CheA protein controls two unrelated functions: chemotaxis and cell length. Acquisition of this multifunctionality is seemingly a recent evolutionary event. The findings illustrate a mechanism by which chemotaxis function may be co-opted to regulate additional cellular functions. Copyright © 2017 American Society for Microbiology.

Distinct Domains of CheA Confer Unique Functions in Chemotaxis and Cell Length in Azospirillum brasilense Sp7

PubMed Central

Gullett, Jessica M.

2017-01-01

ABSTRACT Chemotaxis is the movement of cells in response to gradients of diverse chemical cues. Motile bacteria utilize a conserved chemotaxis signal transduction system to bias their motility and navigate through a gradient. A central regulator of chemotaxis is the histidine kinase CheA. This cytoplasmic protein interacts with membrane-bound receptors, which assemble into large polar arrays, to propagate the signal. In the alphaproteobacterium Azospirillum brasilense, Che1 controls transient increases in swimming speed during chemotaxis, but it also biases the cell length at division. However, the exact underlying molecular mechanisms for Che1-dependent control of multiple cellular behaviors are not known. Here, we identify specific domains of the CheA1 histidine kinase implicated in modulating each of these functions. We show that CheA1 is produced in two isoforms: a membrane-anchored isoform produced as a fusion with a conserved seven-transmembrane domain of unknown function (TMX) at the N terminus and a soluble isoform similar to prototypical CheA. Site-directed and deletion mutagenesis combined with behavioral assays confirm the role of CheA1 in chemotaxis and implicate the TMX domain in mediating changes in cell length. Fluorescence microscopy further reveals that the membrane-anchored isoform is distributed around the cell surface while the soluble isoform localizes at the cell poles. Together, the data provide a mechanism for the role of Che1 in controlling multiple unrelated cellular behaviors via acquisition of a new domain in CheA1 and production of distinct functional isoforms. IMPORTANCE Chemotaxis provides a significant competitive advantage to bacteria in the environment, and this function has been transferred laterally multiple times, with evidence of functional divergence in different genomic contexts. The molecular principles that underlie functional diversification of chemotaxis in various genomic contexts are unknown. Here, we provide a molecular mechanism by which a single CheA protein controls two unrelated functions: chemotaxis and cell length. Acquisition of this multifunctionality is seemingly a recent evolutionary event. The findings illustrate a mechanism by which chemotaxis function may be co-opted to regulate additional cellular functions. PMID:28416707

Sensitivity of nestling and adult starlings to dicrotophos, an organophosphate pesticide

USGS Publications Warehouse

Grue, C.E.; Shipley, B.K.

1984-01-01

The 24-hr median lethal dose (LD50) of dicrotophos (3-hydroxy-N,N-dimethyl-cis-crotonamide dimethyl phosphate) for free-living 5-day-old nestling European starlings (Sturnus vulgaris, LDso = 4.92 mg/kg body wt) was about one-half that obtained for free-living 15day-old nestlings (9.59 mg/kg) and captive adult males (8.37 mg/kg) and females (8.47 mg/ kg). Nestlings and adults with low pretreatment body weights appeared to be more vulnerable to organophosphate (OP) exposure. Brain cholinesterase (ChE) activity was severely depressed in all birds that died (74-94%); the degree of inhibition did not vary with age or sex. Inhibition of brain ChE in 5-day-old nestlings alive 24 hr post dose (X = 28-43%) was lower than that of 15-day-old (X = 55-68%) and adult (X = 55-77%) survivors. Body weights of OP-dosed birds that died were depressed an average of 20 to 46% in 5-day-olds, 7 to 20% in 15-day-olds, and 0 to 10% in adults; weight losses varied inversely with age and dosage, and directly with time to death. Average weight losses in 5- and 15-day-old survivors (X < 31 and 26%, respectively) varied directly with dose and exceeded comparable values for adults (X = 3-15%). Results suggest that (1) young nestling songbirds may be nearly twice as sensitive as adults to OPs, (2) growth of nestlings may be severely depressed following OP exposure, and (3) recovery of brain ChE activity following exposure to ChE inhibitors may be more rapid in nestlings than adults.

Neurotoxicological and statistical analyses of a mixture of five organophosphorus pesticides using a ray design.

PubMed

Moser, V C; Casey, M; Hamm, A; Carter, W H; Simmons, J E; Gennings, C

2005-07-01

Environmental exposures generally involve chemical mixtures instead of single chemicals. Statistical models such as the fixed-ratio ray design, wherein the mixing ratio (proportions) of the chemicals is fixed across increasing mixture doses, allows for the detection and characterization of interactions among the chemicals. In this study, we tested for interaction(s) in a mixture of five organophosphorus (OP) pesticides (chlorpyrifos, diazinon, dimethoate, acephate, and malathion). The ratio of the five pesticides (full ray) reflected the relative dietary exposure estimates of the general population as projected by the US EPA Dietary Exposure Evaluation Model (DEEM). A second mixture was tested using the same dose levels of all pesticides, but excluding malathion (reduced ray). The experimental approach first required characterization of dose-response curves for the individual OPs to build a dose-additivity model. A series of behavioral measures were evaluated in adult male Long-Evans rats at the time of peak effect following a single oral dose, and then tissues were collected for measurement of cholinesterase (ChE) activity. Neurochemical (blood and brain cholinesterase [ChE] activity) and behavioral (motor activity, gait score, tail-pinch response score) endpoints were evaluated statistically for evidence of additivity. The additivity model constructed from the single chemical data was used to predict the effects of the pesticide mixture along the full ray (10-450 mg/kg) and the reduced ray (1.75-78.8 mg/kg). The experimental mixture data were also modeled and statistically compared to the additivity models. Analysis of the 5-OP mixture (the full ray) revealed significant deviation from additivity for all endpoints except tail-pinch response. Greater-than-additive responses (synergism) were observed at the lower doses of the 5-OP mixture, which contained non-effective dose levels of each of the components. The predicted effective doses (ED20, ED50) were about half that predicted by additivity, and for brain ChE and motor activity, there was a threshold shift in the dose-response curves. For the brain ChE and motor activity, there was no difference between the full (5-OP mixture) and reduced (4-OP mixture) rays, indicating that malathion did not influence the non-additivity. While the reduced ray for blood ChE showed greater deviation from additivity without malathion in the mixture, the non-additivity observed for the gait score was reversed when malathion was removed. Thus, greater-than-additive interactions were detected for both the full and reduced ray mixtures, and the role of malathion in the interactions varied depending on the endpoint. In all cases, the deviations from additivity occurred at the lower end of the dose-response curves.

Detector for CheMin

NASA Image and Video Library

2012-10-30

This charged couple device CCD is part of the CheMin instrument on NASA Curiosity rover. When CheMin directs X-rays at a sample of soil, this imager, which is the size of a postage stamp, detects both the position and energy of each X-ray photon.

Chenopodium ambrosioides associated with whole body vibration exercises alters the feed intake in Wistar rats.

PubMed

Cardoso, André Luiz Bandeira Dionizio; Frederico, Éric Heleno Freire Ferreira; Guimarães, Carlos Alberto Sampaio; Almeida, Lívia Pinto; Neves, Rosane de Figueiredo; de Sá-Caputo, Danúbia Cunha; Moreira-Marconi, Eloá; Dionello, Carla de Fontoura; Morel, Danielle Soares; Paineiras-Domingos, Laisa Liane; Sousa-Gonçalves, Cintia Renata; Asad, Nasser Ribeiro; Bernardo-Filho, Mario

2017-08-31

The consequences of treatment involving the use of a natural product and whole body vibration (WBV) exercise have been investigated. The aim of the present study was to evaluate the effects of the joint treatment with an aqueous extract of Chenopodium ambrosioides and WBV on physiological parameters in rats. Wistar rats ( n =20) were divided equally into four groups: control group (CG), treated with C. ambrosioides (CHE) group, exposed to 50 Hz of mechanial vibration (VBR), and treated with C. ambrosioides and exposed to 50 Hz of mechanical vibration (VBR + CHE) daily for 6 weeks. The body mass of the animals was determined weekly, the feed intake and the stool consistency were measured daily. One day after the 6 weeks of treatment, samples of blood were collected and used for biochemical analysis. Along 6 weeks, there was an increase ( P <0.001) in the feed intake in VBR group and a decrease in the CHE group in comparison with other groups. The levels of the enzyme aspartate aminotransferase (AST) in VBR + CHE group decreased ( P <0.05) in comparison with other groups. No differences were found in body mass and stool consistency. WBV altered the feed intake without directly affecting the body mass. Moreover, WBV in association with C. ambrosioides caused alteration in the enzymatic activity of AST. © 2017 The Author(s).

A predictive computational model of the kinetic mechanism of stimulus-induced transducer methylation and feedback regulation through CheY in archaeal phototaxis and chemotaxis.

PubMed

Streif, Stefan; Oesterhelt, Dieter; Marwan, Wolfgang

2010-03-18

Photo- and chemotaxis of the archaeon Halobacterium salinarum is based on the control of flagellar motor switching through stimulus-specific methyl-accepting transducer proteins that relay the sensory input signal to a two-component system. Certain members of the transducer family function as receptor proteins by directly sensing specific chemical or physical stimuli. Others interact with specific receptor proteins like the phototaxis photoreceptors sensory rhodopsin I and II, or require specific binding proteins as for example some chemotaxis transducers. Receptor activation by light or a change in receptor occupancy by chemical stimuli results in reversible methylation of glutamate residues of the transducer proteins. Both, methylation and demethylation reactions are involved in sensory adaptation and are modulated by the response regulator CheY. By mathematical modeling we infer the kinetic mechanisms of stimulus-induced transducer methylation and adaptation. The model (deterministic and in the form of ordinary differential equations) correctly predicts experimentally observed transducer demethylation (as detected by released methanol) in response to attractant and repellent stimuli of wildtype cells, a cheY deletion mutant, and a mutant in which the stimulated transducer species is methylation-deficient. We provide a kinetic model for signal processing in photo- and chemotaxis in the archaeon H. salinarum suggesting an essential role of receptor cooperativity, antagonistic reversible methylation, and a CheY-dependent feedback on transducer demethylation.

A 36,000-Year-Old Volcanic Eruption Depicted in the Chauvet-Pont d’Arc Cave (Ardèche, France)?

PubMed Central

Nomade, Sébastien; Genty, Dominique; Sasco, Romain; Scao, Vincent; Féruglio, Valérie; Baffier, Dominique; Guillou, Hervé; Bourdier, Camille; Valladas, Hélène; Reigner, Edouard; Debard, Evelyne; Pastre, Jean–François; Geneste, Jean-Michel

2016-01-01

Among the paintings and engravings found in the Chauvet-Pont d’Arc cave (Ardèche, France), several peculiar spray-shape signs have been previously described in the Megaloceros Gallery. Here we document the occurrence of strombolian volcanic activity located 35 km northwest of the cave, and visible from the hills above the cave entrance. The volcanic eruptions were dated, using 40Ar/39Ar, between 29 ± 10 ka and 35 ± 8 ka (2σ), which overlaps with the 14C AMS and thermoluminescence ages of the first Aurignacian occupations of the cave in the Megaloceros Gallery. Our work provides the first evidence of an intense volcanic activity between 40 and 30 ka in the Bas-Vivarais region, and it is very likely that Humans living in the Ardèche river area witnessed one or several eruptions. We propose that the spray-shape signs found in the Chauvet-Pont d’Arc cave could be the oldest known depiction of a volcanic eruption, predating by more than 34 ka the description by Pliny the Younger of the Vesuvius eruption (AD 79) and by 28 ka the Çatalhöyük mural discovered in central Turkey. PMID:26745626

A 36,000-Year-Old Volcanic Eruption Depicted in the Chauvet-Pont d'Arc Cave (Ardèche, France)?

PubMed

Nomade, Sébastien; Genty, Dominique; Sasco, Romain; Scao, Vincent; Féruglio, Valérie; Baffier, Dominique; Guillou, Hervé; Bourdier, Camille; Valladas, Hélène; Reigner, Edouard; Debard, Evelyne; Pastre, Jean-François; Geneste, Jean-Michel

2016-01-01

Among the paintings and engravings found in the Chauvet-Pont d'Arc cave (Ardèche, France), several peculiar spray-shape signs have been previously described in the Megaloceros Gallery. Here we document the occurrence of strombolian volcanic activity located 35 km northwest of the cave, and visible from the hills above the cave entrance. The volcanic eruptions were dated, using 40Ar/39Ar, between 29 ± 10 ka and 35 ± 8 ka (2σ), which overlaps with the 14C AMS and thermoluminescence ages of the first Aurignacian occupations of the cave in the Megaloceros Gallery. Our work provides the first evidence of an intense volcanic activity between 40 and 30 ka in the Bas-Vivarais region, and it is very likely that Humans living in the Ardèche river area witnessed one or several eruptions. We propose that the spray-shape signs found in the Chauvet-Pont d'Arc cave could be the oldest known depiction of a volcanic eruption, predating by more than 34 ka the description by Pliny the Younger of the Vesuvius eruption (AD 79) and by 28 ka the Çatalhöyük mural discovered in central Turkey.

Synthesis and evaluation of 7-substituted coumarin derivatives as multimodal monoamine oxidase-B and cholinesterase inhibitors for the treatment of Alzheimer's disease.

PubMed

Joubert, Jacques; Foka, Germaine B; Repsold, Benjamin P; Oliver, Douglas W; Kapp, Erika; Malan, Sarel F

2017-01-05

A series of 7-substituted coumarin derivatives were designed and synthesised to display ChE and MAO-B inhibitory activity. The compounds consisted out of a coumarin structure (MAO-B inhibitor) and benzyl-, piperidine-, N-benzylpiperidine- or p-bromo-N-benzylpiperizine moiety, resembling the N-benzylpiperidine function of donepezil (ChE inhibitor), connected via an alkyl ether linkage at the 7 position. The biological assay results indicated that all the compounds (1-25) displayed selective inhibition to hMAO-B over hMAO-A, with the benzyloxy series (1-8, 10-13) showing nano-molar hMAO-B inhibition (IC 50 : 0.5-73 nM). Limited ChE inhibitory activity was however observed for the benzyloxy series with the exception of 2 and especially 3 showing selective BuChE inhibition. From this series 3 showed the best multifunctional activity (eqBuChE IC 50  = 0.96 μM, hMAO-A IC 50  = 2.13 μM, hMAO-B IC 50  = 0.0021 μM). Within the N-benzylpiperidine (16-19) and p-bromo-N-benzylpiperizine (21-24) series the compounds in general showed moderate ChE and MAO-B inhibitory activity. Of these compounds 19 was the most potent multifunctional agent showing good eeAChE and eqBuChE inhibition (IC 50  = 9.10 μM and 5.90 μM, respectively), and relatively potent and selective hMAO-B inhibition (IC 50  = 0.30 μM, SI = >33). Molecular modeling revealed that 19 was able to bind simultaneously to the CAS, mid-gorge and PAS sites of AChE and BuChE suggesting that it will be able to inhibit AChE induced Aβ aggregation. From this study, compounds that 3 and 19 can be considered as promising multifunctional lead compounds. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

32 CFR 179.6 - Procedures.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Chemical Warfare Materiel Hazard Evaluation (CHE) module. (1) The CHE module provides an evaluation of the chemical hazards associated with the physiological effects of CWM. The CHE module is used only when CWM are... used for evaluating the potential hazards posed by MC and other chemical contaminants. The HHE module...

Discovery of novel rivastigmine-hydroxycinnamic acid hybrids as multi-targeted agents for Alzheimer's disease.

PubMed

Chen, Ziwei; Digiacomo, Maria; Tu, Yalin; Gu, Qiong; Wang, Shengnan; Yang, Xiaohong; Chu, Jiaqi; Chen, Qiuhe; Han, Yifan; Chen, Jingkao; Nesi, Giulia; Sestito, Simona; Macchia, Marco; Rapposelli, Simona; Pi, Rongbiao

2017-01-05

A series of rivastigmine-caffeic acid and rivastigmine-ferulic acid hybrids were designed, synthesized, and evaluated as multifunctional agents for Alzheimer's disease (AD) in vitro. The new compounds exerted antioxidant neuroprotective properties and good cholinesterases (ChE) inhibitory activities. Some of them also inhibited amyloid protein (Aβ) aggregation. In particular, compound 5 emerged as promising drug candidates endowed with neuroprotective potential, ChE inhibitory, Aβ self-aggregation inhibitory and copper chelation properties. These data suggest that compound 5 offers an attractive starting point for further lead optimization in the drug-discovery process against AD. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Age-dependent pharmacokinetic and pharmacodynamic response in preweanling rats following oral exposure to the organophosphorus insecticide chlorpyrifos

DOE Office of Scientific and Technical Information (OSTI.GOV)

Timchalk, Chuck; Poet, Torka S.; Kousba, Ahmed A.

2006-03-01

Juvenile rats are more susceptible than adults to the acute toxicity of organophosphorus insecticides like chlorpyrifos (CPF). Age- and dose-dependent differences in metabolism may be responsible. Of importance is CYP450 activation and detoxification of CPF to CPF-oxon and 3,5,6-trichloro-2-pyridinol (TCP), as well as B-esterase (cholinesterase; ChE) and A-esterase (PON-1) detoxification of CPF-oxon to TCP. The pharmacokinetics of CPF, TCP, and the extent of blood (plasma/RBC), and brain ChE inhibition in rats were determined on postnatal days (PND) -5, -12, and -17 following oral gavage administration of 1 and 10 mg CPF/kg of body weight. For all neonatal ages the bloodmore » TCP exceeded the CPF concentration, and within each age group there was no evidence of non-linear kinetics over the dose range evaluated. Younger animals demonstrated a greater sensitivity to ChE inhibition as evident by the dose- and age-dependent inhibition of plasma, RBC, and brain ChE. Of particular importance was the observation that even in rats as young as PND-5, the CYP450 metabolic capacity was adequate to metabolize CPF to both TCP and CPF-oxon based on the detection of TCP in blood and extensive ChE inhibition (biomarker of CPF-oxon) at all ages. In addition, the increase in the blood TCP concentration ({approx}3-fold) in PND-17 rats relative to the response in the younger animals, and the higher blood concentrations of CPF in neonatal rats (1.7 to 7.5-fold) relative to adults was consistent with an increase in CYP450 metabolic capacity with age. This is the first reported study that evaluated both the pharmacokinetics of the parent pesticide, the major metabolite and the extent of ChE inhibition dynamics in the same animals as a function of neonatal age. The results suggest that in the neonatal rat, CPF was rapidly absorbed and metabolized, and the extent of metabolism was age-dependent.« less

DIFFERENTIAL PROFILES OF CHOLINESTERASE INHIBITION AND NEUROBEHAVIORAL EFFECTS IN RATS EXPOSED TO FENAMIPHOS AND PROFENOPHOS.

EPA Science Inventory

The relationship between cholinesterase (ChE) inhibition and neurobehavioral changes was examined using two ChE-inhibiting organophosphorus pesticides, fenamiphos and profenophos. Both pesticides inhibit blood ChE, yet brain ChE is relatively spared (little to no inhibition up t...

Lost Chevalier Pairs - A Followup

DTIC Science & Technology

2012-01-01

included only if they have been corrected in some manner. As a part of this check, new matches against 2MASS ( Cutrie et aL 2003) were made to the L...against 2MASS which instead found random faint pairs which agreed within search parameters. : In checking Berko’s matches, it was noticed that...CHE 1 000851.85+ 141505.7 11.0 13.2 1910.90 39.2 3.7 Che1910 00199+2633 CHE4 001956.81+263340.8 12.8 14.1 1998.02 204.0 4.16 2MASS 00204+2617 CHE6

Direct Correlation between Motile Behavior and Protein Abundance in Single Cells

PubMed Central

Gillet, Sébastien; Frankel, Nicholas W.; Weibel, Douglas B.

2016-01-01

Understanding how stochastic molecular fluctuations affect cell behavior requires the quantification of both behavior and protein numbers in the same cells. Here, we combine automated microscopy with in situ hydrogel polymerization to measure single-cell protein expression after tracking swimming behavior. We characterized the distribution of non-genetic phenotypic diversity in Escherichia coli motility, which affects single-cell exploration. By expressing fluorescently tagged chemotaxis proteins (CheR and CheB) at different levels, we quantitatively mapped motile phenotype (tumble bias) to protein numbers using thousands of single-cell measurements. Our results disagreed with established models until we incorporated the role of CheB in receptor deamidation and the slow fluctuations in receptor methylation. Beyond refining models, our central finding is that changes in numbers of CheR and CheB affect the population mean tumble bias and its variance independently. Therefore, it is possible to adjust the degree of phenotypic diversity of a population by adjusting the global level of expression of CheR and CheB while keeping their ratio constant, which, as shown in previous studies, confers functional robustness to the system. Since genetic control of protein expression is heritable, our results suggest that non-genetic diversity in motile behavior is selectable, supporting earlier hypotheses that such diversity confers a selective advantage. PMID:27599206

CheMentor Software System by H. A. Peoples

NASA Astrophysics Data System (ADS)

Reid, Brian P.

1997-09-01

CheMentor Software System H. A. Peoples. Computerized Learning Enhancements: http://www.ecis.com/~clehap; email: clehap@ecis.com; 1996 - 1997. CheMentor is a series of software packages for introductory-level chemistry, which includes Practice Items (I), Stoichiometry (I), Calculating Chemical Formulae, and the CheMentor Toolkit. The first three packages provide practice problems for students and various types of help to solve them; the Toolkit includes "calculators" for determining chemical quantities as well as the Practice Items (I) set of problems. The set of software packages is designed so that each individual product acts as a module of a common CheMentor program. As the name CheMentor implies, the software is designed as a "mentor" for students learning introductory chemistry concepts and problems. The typical use of the software would be by individual students (or perhaps small groups) as an adjunct to lectures. CheMentor is a HyperCard application and the modules are HyperCard stacks. The requirements to run the packages include a Macintosh computer with at least 1 MB of RAM, a hard drive with several MB of available space depending upon the packages selected (10 MB were required for all the packages reviewed here), and the Mac operating system 6.0.5 or later.

Opposite effects of central oxytocin and arginine vasopressin on changes in gastric motor function induced by chronic stress.

PubMed

Bülbül, Mehmet; Sinen, Osman; Gemici, Burcu; İzgüt-Uysal, V Nimet

2017-01-01

Hypothalamic oxytocin (OXT) and arginine vasopressin (AVP) are known to act oppositely on hypothalamic-pituitary-adrenal (HPA) axis, stress response and gastrointestinal (GI) motility. In rodents, exposure to restraint stress (RS) delays gastric emptying (GE), however, repeated exposure to the same stressor (chronic homotypic stress (CHS)), the delayed GE is restored to basal level, while hypothalamic OXT is upregulated. In contrast, when rats are exposed to chronic heterotypic stress (CHeS), these adaptive changes are not observed. Although the involvement of central OXT in gastric motor adaptation is partly investigated, the role of hypothalamic AVP in CHeS-induced maladaptive paradigm is poorly understood. Using in-vivo brain microdialysis in rats, the changes OXT and AVP release from hypothalamus were monitored under basal non-stressed (NS) conditions and in rats exposed to acute stress (AS), CHS and CHeS. To investigate the involvement of central endogenous OXT or AVP in CHS-induced habituation and CHeS-induced maladaptation, chronic central administration of selective OXT receptor antagonist L-371257 and selective AVP V 1b receptor antagonist SSR-149415 was performed daily. OXT was measured higher in AS and CHS group, but not in CHeS-loaded rats, whereas AVP significantly increased in rats exposed to AS and CHeS. Additionally, the response of the hypothalamic OXT- and AVP-producing cells was amplified following CHS and CHeS, respectively. In rats exposed to AS for 90min solid GE significantly delayed. The delayed-GE was completely restored to the basal level following CHS, however, it remained delayed in CHeS-loaded rats. The CHS-induced restoration was prevented by L-371257, whereas SSR-149415 abolished the CHeS-induced impaired GE. A significant correlation was observed between GE and (i) OXT in CHS-loaded rats (rho=0.61, p<0.05, positively), (ii) AVP in CHeS-loaded rats (rho=0.69, p<0.05, negatively). Under long term stressed conditions, the release of AVP and OXT from hypothalamus may vary depending on the content of the stressors. Central AVP appears to act oppositely to OXT by mediating CHeS-induced gastric motor maladaptation. Long term central AVP antagonism might be a pharmacological approach for the treatment of stress-related gastric motility disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Uptake and effects of the antimicrobial florfenicol, microplastics and their mixtures on freshwater exotic invasive bivalve Corbicula fluminea.

PubMed

Guilhermino, Lúcia; Vieira, Luís R; Ribeiro, Diogo; Tavares, Ana Sofia; Cardoso, Vera; Alves, Anabela; Almeida, José Manuel

2018-05-01

Microplastics and antimicrobials are widely spread environmental contaminants and more research on their toxicity is needed. The uptake and effects of the antimicrobial florfenicol, microplastics, and their mixtures on Corbicula fluminea were investigated. Bivalves were exposed for 96h to florfenicol (1.8 and 7.1mg/l), microplastics (0.2 and 0.7mg/l), or mixtures of the two substances. After 96h, all bivalves exposed to antimicrobial treatments had florfenicol in their body (e.g. 2±1μg/g). Microplastics were found in the gut, lumen of the digestive gland, connective tissue, hemolymphatic sinuses, and gills surface of animals. Florfenicol caused a significant inhibition of cholinesterase (ChE) activity (~32%). Animals exposed to 0.2mg/l of microplastics showed ChE activity inhibition (31%), and no other significant alterations. Mixtures caused feeding inhibition (57-83%), significant ChE inhibition (44-57%) and of isocitrate dehydrogenase activity, and increased anti-oxidant enzymes activity and lipid peroxidation levels. Overall, the results indicate that C. fluminea take up florfenicol and microplastics from the water and accumulated or at least retained it in their body for some time; both florfenicol (low ppm range) and microplastics (ppb range) were toxic to C. fluminea, with mixtures containing florfenicol and microplastics being more toxic. Thus, the risk of exposure and toxic effects of florfenicol to C. fluminea and other bivalves, and its predators increase in ecosystems contaminated with the antimicrobial and microplastics, as well as to humans consuming contaminated species from these ecosystems. Copyright © 2017 Elsevier B.V. All rights reserved.

Functional characterization of transmembrane intracellular pH regulators and mechanism of alcohol-induced intracellular acidosis in human umbilical cord blood stem cell-like cells.

PubMed

Tsai, Yi-Ting; Liu, Jah-Yao; Lee, Chung-Yi; Tsai, Chien-Sung; Chen, Ming-Hurng; Ou, Chien-Chih; Chen, Wei-Hwa; Loh, Shih-Hurng

2011-12-01

Changing intracellular pH (pHi) exerts considerable influence on many cellular functions. Different pHi regulators, such as the Na-H exchanger (NHE), Na/(Equation is included in full-text article.)symporter, and Cl/OH exchanger (CHE), have been identified in mature mammalian cells. The aims of the present study were to investigate the physiological mechanisms of pHi recovery and to further explore the effects of alcohol on the pHi in human umbilical cord blood CD34 stem cell-like cells (HUCB-CD34STs). HUCB-CD34STs were loaded with the pH-sensitive dye, 2',7'-bis(2-carboxethyl)-5(6)-carboxyfluorescein, to examine pHi. In isolated HUCB-CD34STs, we found that (1) the resting pHi is 7.03 ± 0.02; (2) 2 Na-dependent acid extruders and a Cl-dependent acid loading carrier exist and are functional; (3) alcohol functions in a concentration-dependent manner to reduce pHi and increase NHE activity, but it does not affect CHE activity; and (4) fomepizole, a specific alcohol dehydrogenase inhibitor, does not change the intracellular acidosis and NHE activity-induced by alcohol, whereas 3-amino-1, 2,4-trizole, a specific catalase inhibitor, entirely abolishes these effects. In conclusion, we demonstrate that 2 acid extruders and 1 acid loader (most likely NHE, NBC, and CHE, respectively) functionally existed in HUCB-CD34STs. Additionally, the intracellular acidosis is mainly caused by catalase-mediated alcohol metabolites, which provoke the activity of NHE.

Avian mortality events in the United States caused by anticholinesterase pesticides: A retrospective summary of National Wildlife Health Center records from 1980 to 2000

USGS Publications Warehouse

Fleischli, Margaret A.; Franson, J.C.; Thomas, N.J.; Finley, D.L.; Riley, Walter

2004-01-01

We reviewed the U.S. Geological Survey National Wildlife Health Center (NWHC) mortality database from 1980 to 2000 to identify cases of poisoning caused by organophosphorus and carbamate pesticides. From the 35,022 cases from which one or more avian carcasses were submitted to the NWHC for necropsy, we identified 335 mortality events attributed to anticholinesterase poisoning, 119 of which have been included in earlier reports. Poisoning events were classified as confirmed (n = 205) when supported by findings of ≥50% inhibition of cholinesterase (ChE) activity in brain tissue and the detection of a specific pesticide in the gastrointestinal contents of one or more carcasses. Suspected poisonings (n = 130) were defined as cases where brain ChE activity was ≥50% inhibited or a specific pesticide was identified in gastrointestinal contents. The 335 avian mortality events occurred in 42 states. Washington, Virginia, and Ohio had the highest frequency of events, with 24 (7.2%), 21 (6.3%), and 20 (6.0%) events, respectively. A total of 8877 carcasses of 103 avian species in 12 orders was recovered. Because carcass counts underestimate total mortality, this represents the minimum actual mortality. Of 24 different pesticides identified, the most frequent were famphur (n = 59; 18%), carbofuran (n = 52; 15%), diazinon (n = 40; 12%), and fenthion (n = 17; 5.1%). Falconiformes were reported killed most frequently (49% of all die-offs) but Anseriformes were found dead in the greatest numbers (64% of 8877 found dead). The majority of birds reported killed by famphur were Passeriformes and Falconiformes, with the latter found dead in 90% of famphur-related poisoning events. Carbofuran and famphur were involved in mortality of the greatest variety of species (45 and 33, respectively). Most of the mortality events caused by diazinon involved waterfowl.

CheMin Instrument Performance and Calibration on Mars

NASA Technical Reports Server (NTRS)

Vaniman, D. T.; Blake, D. F.; Morookian, J. M.; Yen, A. S.; Ming, D. W.; Morris, R. V.; Achilles, C. N.; Bish, D. L.; Chipera, S. J.; Morrison, S. M.;

National health insurance scheme: how protected are households in Oyo State, Nigeria from catastrophic health expenditure?

PubMed Central

Ilesanmi, Olayinka Stephen; Adebiyi, Akindele Olupelumi; Fatiregun, Akinola Ayoola

2014-01-01

Background: The major objective of the National Health Insurance Scheme (NHIS) in Nigeria is to protect families from the financial hardship of large medical bills. Catastrophic Health Expenditure (CHE) is rampart in Nigeria despite the take-off of the NHIS. This study aimed to determine if households enrolled in the NHIS were protected from having CHE. Methods: The study took place among 714 households in urban communities of Oyo State. CHE was measured using a threshold of 40% of monthly non-food expenditure. Descriptive statistics were done, Principal Component Analysis was used to divide households into wealth quintiles. Chi-square test and binary logistic regression were done. Results: The mean age of household respondent was 33.5 years. The median household income was 43,500 naira (290 US dollars) and the range was 7,000–680,000 naira (46.7–4,533 US dollars) in 2012. The overall median household healthcare cost was 890 naira (5.9 US dollars) and the range was 10-17,700 naira (0.1–118 US dollars) in 2012. In all, 67 (9.4%) households were enrolled in NHIS scheme. Healthcare services was utilized by 637 (82.9%) and CHE occurred in 42 (6.6%) households. CHE occurred in 14 (10.9%) of the households in the lowest quintile compared to 3 (2.5%) in the highest wealth quintile (P= 0.004). The odds of CHE among households in lowest wealth quintile is about 5 times. They had Crude OR (CI): 4.7 (1.3–16.8), P= 0.022. Non enrolled households were two times likely to have CHE, though not significant Conclusion: Households in the lowest wealth quintiles were at higher risk of CHE. Universal coverage of health insurance in Nigeria should be fast-tracked to give the expected financial risk protection and decreased incidence of CHE. PMID:24847483

National health insurance scheme: how protected are households in Oyo State, Nigeria from catastrophic health expenditure?

PubMed

Ilesanmi, Olayinka Stephen; Adebiyi, Akindele Olupelumi; Fatiregun, Akinola Ayoola

2014-05-01

The major objective of the National Health Insurance Scheme (NHIS) in Nigeria is to protect families from the financial hardship of large medical bills. Catastrophic Health Expenditure (CHE) is rampart in Nigeria despite the take-off of the NHIS. This study aimed to determine if households enrolled in the NHIS were protected from having CHE. The study took place among 714 households in urban communities of Oyo State. CHE was measured using a threshold of 40% of monthly non-food expenditure. Descriptive statistics were done, Principal Component Analysis was used to divide households into wealth quintiles. Chi-square test and binary logistic regression were done. The mean age of household respondent was 33.5 years. The median household income was 43,500 naira (290 US dollars) and the range was 7,000-680,000 naira (46.7-4,533 US dollars) in 2012. The overall median household healthcare cost was 890 naira (5.9 US dollars) and the range was 10-17,700 naira (0.1-118 US dollars) in 2012. In all, 67 (9.4%) households were enrolled in NHIS scheme. Healthcare services was utilized by 637 (82.9%) and CHE occurred in 42 (6.6%) households. CHE occurred in 14 (10.9%) of the households in the lowest quintile compared to 3 (2.5%) in the highest wealth quintile (P= 0.004). The odds of CHE among households in lowest wealth quintile is about 5 times. They had Crude OR (CI): 4.7 (1.3-16.8), P= 0.022. Non enrolled households were two times likely to have CHE, though not significant Conclusion: Households in the lowest wealth quintiles were at higher risk of CHE. Universal coverage of health insurance in Nigeria should be fast-tracked to give the expected financial risk protection and decreased incidence of CHE.

Inhibition of human carboxylesterases hCE1 and hiCE by cholinesterase inhibitors.

PubMed

Tsurkan, Lyudmila G; Hatfield, M Jason; Edwards, Carol C; Hyatt, Janice L; Potter, Philip M

2013-03-25

Carboxylesterases (CEs) are ubiquitously expressed proteins that are responsible for the detoxification of xenobiotics. They tend to be expressed in tissues likely to be exposed to such agents (e.g., lung and gut epithelia, liver) and can hydrolyze numerous agents, including many clinically used drugs. Due to the considerable structural similarity between cholinesterases (ChE) and CEs, we have assessed the ability of a series of ChE inhibitors to modulate the activity of the human liver (hCE1) and the human intestinal CE (hiCE) isoforms. We observed inhibition of hCE1 and hiCE by carbamate-containing small molecules, including those used for the treatment of Alzheimer's disease. For example, rivastigmine resulted in greater than 95% inhibition of hiCE that was irreversible under the conditions used. Hence, the administration of esterified drugs, in combination with these carbamates, may inadvertently result in decreased hydrolysis of the former, thereby limiting their efficacy. Therefore drug:drug interactions should be carefully evaluated in individuals receiving ChE inhibitors. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Inhibition of human carboxylesterases hCE1 and hiCE by cholinesterase inhibitors

PubMed Central

Tsurkan, Lyudmila G.; Hatfield, M. Jason; Edwards, Carol C.; Hyatt, Janice L.; Potter, Philip M.

2012-01-01

Carboxylesterases (CEs) are ubiquitously expressed proteins that are responsible for the detoxification of xenobiotics. They tend to be expressed in tissues likely to be exposed to such agents (e.g., lung and gut epithelia, liver) and can hydrolyze numerous agents, including many clinically used drugs. Due to the considerable structural similarity between cholinesterases (ChE) and CEs, we have assessed the ability of a series of ChE inhibitors to modulate the activity of the human liver (hCE1) and the human intestinal CE (hiCE) isoforms, We observed inhibition of hCE1 and hiCE by carbamate-containing small molecules, including those used for the treatment of Alzheimer’s disease. For example, rivastigmine resulted in greater than 95% inhibition of hiCE that was irreversible under the conditions used. Hence, the administration of esterified drugs, in combination with these carbamates, may inadvertently result in decreased hydrolysis of the former, thereby limiting their efficacy. Therefore drug:drug interactions should be carefully evaluated in individuals receiving ChE inhibitors. PMID:23123248

De novo amplification within a silent human cholinesterase gene in a family subjected to prolonged exposure to organophosphorus insecticides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prody, C.A.; Dreyfus, P.; Soreq, H.

1989-01-01

A 100-fold DNA amplification in the CHE gene, coding for serum butyrylcholinesterase (BtChoEase), was found in a farmer expressing silent CHE phenotype. Individuals homozygous for this gene display a defective serum BtChoEase and are particularly vulnerable to poisoning by agricultural organophosphorus insecticides, to which all members of this family had long been exposed. DNA blot hybridization with regional BtChoEase cDNA probes suggested that the amplification was most intense in regions encoding central sequences within BtChoEase cDNA, whereas distal sequences were amplified to a much lower extent. This is in agreement with the onion skin model, based on amplification of genesmore » in cultured cells and primary tumors. The amplification was absent in the grandparents but present at the same extent in one of their sons and in a grandson, with similar DNA blot hybridization patterns. In situ hybridization experiments localized the amplified sequences to the long arm of chromosome 3, close to the site where the authors previously mapped the CHE gene. Altogether, these observations suggest that the initial amplification event occurred early in embryogenesis, spermatogenesis, or oogenesis, where the CHE gene is intensely active and where cholinergic functioning was indicated to be physiologically necessary. These findings demonstrate a de novo amplification in apparently healthy individuals within an autosomal gene producing a target protein to an inhibitor.« less

An Age-Dependent Physiologically-Based Pharmacokinetic/Pharmacodynamic Model for the Organophosphorus Insecticide Chlorpyrifos in the Preweanling Rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Timchalk, Chuck; Kousba, Ahmed A.; Poet, Torka S.

2007-08-01

Juvenile rats are more susceptible than adults to the acute toxicity of organophosphorus insecticides like chlorpyrifos (CPF). Age- and dose-dependent differences in metabolism may be responsible. Of importance is CYP450 activation and detoxification of CPF to chlorpyrifos-oxon (CPF-oxon) and trichloropyridinol (TCP), as well as B-esterase (cholinesterase; ChE) and A-esterase (PON-1) detoxification of CPF-oxon to TCP. In the current study, a modified physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model incorporating age-dependent changes in CYP450, PON-1, and tissue ChE levels for rats was developed. In this model, age was used as a dependent function to estimate body weight which was then used to allometricallymore » scale both metabolism and tissue ChE levels. Model simulations suggest that preweanling rats are particularly sensitive to CPF toxicity, with levels of CPF-oxon in blood and brain disproportionately increasing, relative to the response in adult rats. This age-dependent non-linear increase in CPF-oxon concentration may potentially result from the depletion of non-target B-esterases, and a lower PON-1 metabolic capacity in younger animals. These results indicate that the PBPK/PD model behaves consistently with the general understanding of CPF toxicity, pharmacokinetics and tissue ChE inhibition in neonatal and adult rats. Hence, this model represents an important starting point for developing a computational model to assess the neurotoxic potential of environmentally relevant organophosphate exposures in infants and children.« less

Cellular Stoichiometry of Methyl-Accepting Chemotaxis Proteins in Sinorhizobium meliloti.

PubMed

Zatakia, Hardik M; Arapov, Timofey D; Meier, Veronika M; Scharf, Birgit E

2018-03-15

The chemosensory system in Sinorhizobium meliloti has several important deviations from the widely studied enterobacterial paradigm. To better understand the differences between the two systems and how they are optimally tuned, we determined the cellular stoichiometry of the methyl-accepting chemotaxis proteins (MCPs) and the histidine kinase CheA in S. meliloti Quantitative immunoblotting was used to determine the total amount of MCPs and CheA per cell in S. meliloti The MCPs are present in the cell in high abundance (McpV), low abundance (IcpA, McpU, McpX, and McpW), and very low abundance (McpY and McpZ), whereas McpT was below the detection limit. The approximate cellular ratio of these three receptor groups is 300:30:1. The chemoreceptor-to-CheA ratio is 23.5:1, highly similar to that seen in Bacillus subtilis (23:1) and about 10 times higher than that in Escherichia coli (3.4:1). Different from E. coli , the high-abundance receptors in S. meliloti are lacking the carboxy-terminal NWETF pentapeptide that binds the CheR methyltransferase and CheB methylesterase. Using transcriptional lacZ fusions, we showed that chemoreceptors are positively controlled by the master regulators of motility, VisNR and Rem. In addition, FlbT, a class IIA transcriptional regulator of flagellins, also positively regulates the expression of most chemoreceptors except for McpT and McpY, identifying chemoreceptors as class III genes. Taken together, these results demonstrate that the chemosensory complex and the adaptation system in S. meliloti deviates significantly from the established enterobacterial paradigm but shares some similarities with B. subtilis IMPORTANCE The symbiotic soil bacterium Sinorhizobium meliloti is of great agricultural importance because of its nitrogen-fixing properties, which enhances growth of its plant symbiont, alfalfa. Chemotaxis provides a competitive advantage for bacteria to sense their environment and interact with their eukaryotic hosts. For a better understanding of the role of chemotaxis in these processes, detailed knowledge on the regulation and composition of the chemosensory machinery is essential. Here, we show that chemoreceptor gene expression in S. meliloti is controlled through the main transcriptional regulators of motility. Chemoreceptor abundance is much lower in S. meliloti than in Escherichia coli and Bacillus subtilis Moreover, the chemoreceptor-to-kinase CheA ratio is different from that of E. coli but similar to that of B. subtilis . Copyright © 2018 American Society for Microbiology.

Disease-specific out-of-pocket and catastrophic health expenditure on hospitalization in India: Do Indian households face distress health financing?

PubMed

Kastor, Anshul; Mohanty, Sanjay K

2018-01-01

Rising non-communicable diseases (NCDs) coupled with increasing injuries have resulted in a significant increase in health spending in India. While out-of-pocket expenditure remains the major source of health care financing in India (two-thirds of the total health spending), the financial burden varies enormously across diseases and by the economic well-being of the households. Though prior studies have examined the variation in disease pattern, little is known about the financial risk to the families by type of diseases in India. In this context, the present study examines disease-specific out-of-pocket expenditure (OOPE), catastrophic health expenditure (CHE) and distress health financing. Unit data from the 71st round of the National Sample Survey Organization (2014) was used for this study. OOPE is defined as health spending on hospitalization net of reimbursement, and CHE is defined as household health spending exceeding 10% of household consumption expenditure. Distress health financing is defined as a situation when a household has to borrow money or sell their property/assets or when it gets contributions from friends/relatives to meet its health care expenses. OOPE was estimated for 16 selected diseases and across three broad categories- communicable diseases, NCDs and injuries. Multivariate logistic regression was used to understand the determinants of distress financing and CHE. Mean OOPE on hospitalization was INR 19,210 and was the highest for cancer (INR 57,232) followed by heart diseases (INR 40,947). About 28% of the households incurred CHE and faced distress financing. Among all the diseases, cancer caused the highest CHE (79%) and distress financing (43%). More than one-third of the inpatients reported distressed financing for heart diseases, neurological disorders, genito urinary problems, musculoskeletal diseases, gastro-intestinal problems and injuries. The likelihood of incurring distress financing was 3.2 times higher for those hospitalized for cancer (OR 3.23; 95% CI: 2.62-3.99) and 2.6 times for tuberculosis patients (OR 2.61; 95% CI: 2.06-3.31). A large proportion of households who had reported distress financing also incurred CHE. Free treatment for cancer and heart diseases is recommended for the vulnerable sections of the society. Risk-pooling and social security mechanisms based on contributions from both households as well as the central and state governments can reduce the financial burden of diseases and avert households from distress health financing.

Comparative shotgun proteomic analysis of Clostridium acetobutylicum from butanol fermentation using glucose and xylose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sivagnanam, Kumaran; Raghavan, Vijaya G. S.; Shah, Manesh B

2011-01-01

Background: Butanol is a second generation biofuel produced by Clostridium acetobutylicum through acetonebutanol- ethanol (ABE) fermentation process. Shotgun proteomics provides a direct approach to study the whole proteome of an organism in depth. This paper focuses on shotgun proteomic profiling of C. acetobutylicum from ABE fermentation using glucose and xylose to understand the functional mechanisms of C. acetobutylicum proteins involved in butanol production. Results: We identified 894 different proteins in C. acetobutylicum from ABE fermentation process by two dimensional - liquid chromatography - tandem mass spectrometry (2D-LC-MS/MS) method. This includes 717 proteins from glucose and 826 proteins from the xylosemore » substrate. A total of 649 proteins were found to be common and 22 significantly differentially expressed proteins were identified between glucose and xylose substrates. Conclusion: Our results demonstrate that flagellar proteins are highly up-regulated with glucose compared to xylose substrate during ABE fermentation. Chemotactic activity was also found to be lost with the xylose substrate due to the absence of CheW and CheV proteins. This is the first report on the shotgun proteomic analysis of C. acetobutylicum ATCC 824 in ABE fermentation between glucose and xylose substrate from a single time data point and the number of proteins identified here is more than any other study performed on this organism up to this report.« less

Interaction of Chelerythrine with Keyhole Limpet Hemocyanin: a Fluorescence Spectroscopy and Molecular Docking Study

NASA Astrophysics Data System (ADS)

Zhong, M.; Long, R. Q.; Wang, Y. H.; Chen, C. L.

2018-05-01

The quenching mechanism between chelerythrine (CHE) and keyhole limpet hemocyanin (KLH) was investigated using fluorescence spectroscopy and molecular docking. The experiments were conducted at three different temperatures (293, 298, and 303 K). The results revealed that the intrinsic fluorescence of KLH was strongly quenched by CHE through a static quenching mechanism. The thermodynamic parameters (ΔG, ΔH, and ΔS) of the interaction were calculated, indicating that the interaction between CHE and KLH was spontaneous and that van der Waals forces and hydrogen bond formation played major roles in the binding process. The intrinsic fluorescence of the tyrosine and tryptophan residues in KLH was studied by synchronous fluorescence, which suggested that CHE changed the conformation of KLH. Finally, molecular docking was used to obtain detailed information on the binding sites and binding affinities between CHE and KLH.

MSL Chemistry and Mineralogy X-Ray Diffraction X-Ray Fluorescence (CheMin) Instrument

NASA Technical Reports Server (NTRS)

Zimmerman, Wayne; Blake, Dave; Harris, William; Morookian, John Michael; Randall, Dave; Reder, Leonard J.; Sarrazin, Phillipe

2013-01-01

This paper provides an overview of the Mars Science Laboratory (MSL) Chemistry and Mineralogy Xray Diffraction (XRD), X-ray Fluorescence (XRF) (CheMin) Instrument, an element of the landed Curiosity rover payload, which landed on Mars in August of 2012. The scientific goal of the MSL mission is to explore and quantitatively assess regions in Gale Crater as a potential habitat for life - past or present. The CheMin instrument will receive Martian rock and soil samples from the MSL Sample Acquisition/Sample Processing and Handling (SA/SPaH) system, and process it utilizing X-Ray spectroscopy methods to determine mineral composition. The Chemin instrument will analyze Martian soil and rocks to enable scientists to investigate geophysical processes occurring on Mars. The CheMin science objectives and proposed surface operations are described along with the CheMin hardware with an emphasis on the system engineering challenges associated with developing such a complex instrument.

Butyryl-cholinesterase is related to muscle mass and strength. A new biomarker to identify elderly subjects at risk of sarcopenia.

PubMed

Cacciatore, Francesco; Della-Morte, David; Basile, Claudia; Curcio, Francesco; Liguori, Ilaria; Roselli, Mario; Gargiulo, Gaetano; Galizia, Gianluigi; Bonaduce, Domenico; Abete, Pasquale

2015-01-01

To determine the relationship between Butyryl-cholinesterase (α-glycoprotein synthesized in the liver, b-CHE) and muscle mass and strength. Muscle mass by bioimpedentiometer and muscle strength by grip strength were evaluated in 337 elderly subjects (mean age: 76.2 ± 6.7 years) admitted to comprehensive geriatric assessment. b-CHE levels were lower in sarcopenic than in nonsarcopenic elderly subjects (p < 0.01). Linear regression analysis demonstrated that b-CHE is linearly related with grip strength and muscular mass both in men and women (r = 0.45 and r = 0.33, p < 0.01; r = 0.55 and r = 0.39, p < 0.01; respectively). Multivariate analysis confirms this analysis. b-CHE is related to muscle mass and strength in elderly subjects. Thus, b-CHE may be considered to be a fair biomarker for identifying elderly subjects at risk of sarcopenia.

Age-related differences in acute neurotoxicity produced by mevinphos, monocrotophos, dicrotophos, and phosphamidon.

PubMed

Moser, Virginia C

2011-01-01

Age-related differences in the acute neurotoxicity of cholinesterase (ChE)-inhibiting pesticides have been well-studied for a few organophosphates, but not for many others. In this study, we directly compared dose-responses using brain and red blood cell (RBC) ChE measurements, along with motor activity, for mevinphos, monocrotophos, dicrotophos, and phosphamidon. Long-Evans hooded male rats were tested as adults and at postnatal day (PND) 17; PND11 pups were also tested with dicrotophos only. All chemicals were administered via oral gavage and tests were conducted at times intended to span peak behavioral and ChE effects. All OPs tested produced a rapid onset and recovery from the behavioral effects. There were age-related differences in the inhibition of brain, but not necessarily RBC, ChE. Mevinphos was clearly more toxic, up to 4-fold, to the young rat. On the other hand, monocrotophos, dicrotophos, and phosphamidon were somewhat more toxic to the young rat, but the magnitude of the differences was < 2-fold lower. Motor activity was consistently decreased in adults for all chemicals tested; however, there was more variability with the pups and clear age-related differences were only observed for mevinphos. These data show that three of these four OPs were only moderately more toxic in young rats, and further support findings that age-related differences in pesticide toxicity are chemical-specific. Published by Elsevier Inc.

Zectran fed orally to mice...cholinesterase levels in blood determined

Treesearch

Jean Marie Lang; Raymond R. Miskus

1967-01-01

Zectran, a carbamate insecticide, is being field-tested against the spruce budworm. Taken in sufficient quantity, it can induce cholinesterase (ChE) inhibition in mammals. In laboratory experiments, Zectran was fed orally to mice. Results indicated that maximum ChE inhibition occurred 15 to 30 minutes after ingestion of Zectran, and that a ChE test is unreliable in the...

Simulating cholinesterase inhibition in birds caused by dietary insecticide exposure

USGS Publications Warehouse

Corson, M.S.; Mora, M.A.; Grant, W.E.

1998-01-01

We describe a stochastic simulation model that simulates avian foraging in an agricultural landscape to evaluate factors affecting dietary insecticide exposure and to predict post-exposure cholinesterase (ChE) inhibition. To evaluate the model, we simulated published field studies and found that model predictions of insecticide decay and ChE inhibition reasonably approximated most observed results. Sensitivity analysis suggested that foraging location usually influenced ChE inhibition more than diet preferences or daily intake rate. Although organophosphorus insecticides usually caused greater inhibition than carbamate insecticides, insecticide toxicity appeared only moderately important. When we simulated impact of heavy insecticide applications during breeding seasons of 15 wild bird species, mean maximum ChE inhibition in most species exceeded 20% at some point. At this level of inhibition, birds may experience nausea and/or may exhibit minor behavioral changes. Simulated risk peaked in April–May and August–September and was lowest in July. ChE inhibition increased with proportion of vegetation in the diet. This model, and ones like it, may help predict insecticide exposure of and sublethal ChE inhibition in grassland animals, thereby reducing dependence of ecological risk assessments on field studies alone.

The Effect of Butin on the Vitiligo Mouse Model Induced by Hydroquinone.

PubMed

Huo, Shi-Xia; Wang, Qiong; Liu, Xin-Min; Ge, Chun-Hui; Gao, Li; Peng, Xiao-Ming; Yan, Ming

2017-05-01

Vernonia anthelmintica (L.) Willd has been traditionally used in the treatment of vitiligo in Uyghur medicine. This study used butin, the main component of V. anthelmintica, to study the influence on hydroquinone-induced vitiligo in mice. The animals were randomly divided into six groups: control, model, 8-methoxypsoralen (8-MOP, 4.25 mg/kg), and butin (0.425, 4.25, and 42.5 mg/kg) groups. The number of melanin-containing hair follicles, basal layer melanocytes, melanin-containing epidermal cells, the expression of tyrosinase (TYR) and tyrosinase-related protein-1 (TRP-1), the malondialdehyde (MDA), and cholinesterase (CHE) activity in serum were measured. Our results indicated that compared with the model group, the melanin-containing hair follicles, the expression of TYR and TRP-1 increased, the activity of CHE decreased after treatment with 8-MOP and all doses of butin (p < 0.05, p < 0.01), the basal layer melanocytes and melanin-containing epidermal cells increased significantly after treatment with butin 4.25 and 42.5 mg/kg (p < 0.05, p < 0.01), and the MDA activity decreased after using butin 4.25 and 42.5 mg/kg and 8-MOP (p < 0.05, p < 0.01). Our results support the use of butin on vitiligo, and its possible mechanisms may be related to increase the TYR and TRP-1 protein expression and decrease the activity of MDA and CHE in hydroquinone-induced vitiligo model in mice. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Identification of a novel alternative splicing variant of hemocyanin from shrimp Litopenaeus vannamei.

PubMed

Zhao, Shan; Lu, Xin; Zhang, Yueling; Zhao, Xianliang; Zhong, Mingqi; Li, Shengkang; Lun, Jingsheng

2013-01-01

Recent evidences suggest that invertebrates express families of immune molecules with high levels of sequence diversity. Hemocyanin is an important non-specific immune molecule present in the hemolymph of both mollusks and arthropods. In the present study, we characterized a novel alternative splicing variant of hemocyanin (cHE1) from Litopenaeus vannamei that produced mRNA transcript of 2579 bp in length. The isoform contained two additional sequences of 296 and 267 bp in the 5'- and 3'-terminus respectively, in comparison to that of wild type hemocyanin (cHE). Sequence of cHE1 shows 100% identity to that of hemocyanin genomic DNA (HE, which does not form an open reading frame), suggesting that cHE1 might be an alternative splicing variant due to intron retention. Moreover, cHE1 could be detected by RT-PCR from five tissues (heart, gill, stomach, intestine and brain), and from shrimps at stages from nauplius to mysis larva. Further, cHE1 mRNA transcripts were significantly increased in hearts after 12h of infection with Vibrio parahemolyticus or poly I: C, while no significant difference in the transcript levels of hepatopancreas cHE was detected in the pathogen-treated shrimps during the period. In summary, these studies suggested a novel splicing variant of hemocyanin in shrimp, which might be involved in shrimp resistance to pathogenic infection. Copyright © 2013 Elsevier B.V. All rights reserved.

Evaluation of Student Reflection as a Route to Improve Oral Communication

ERIC Educational Resources Information Center

Mineart, Kenneth P.; Cooper, Matthew E.

2016-01-01

This study describes the use of guided self-reflection and peer feedback activities to improve student oral communication in a large ChE class (n ~ 100) setting. Student performance tracked throughout an experimental semester indicated both reflection activities accelerated improvement in oral communication over control; student perception of the…

SOS System Induction Inhibits the Assembly of Chemoreceptor Signaling Clusters in Salmonella enterica

PubMed Central

Irazoki, Oihane; Mayola, Albert; Campoy, Susana; Barbé, Jordi

2016-01-01

Swarming, a flagellar-driven multicellular form of motility, is associated with bacterial virulence and increased antibiotic resistance. In this work we demonstrate that activation of the SOS response reversibly inhibits swarming motility by preventing the assembly of chemoreceptor-signaling polar arrays. We also show that an increase in the concentration of the RecA protein, generated by SOS system activation, rather than another function of this genetic network impairs chemoreceptor polar cluster formation. Our data provide evidence that the molecular balance between RecA and CheW proteins is crucial to allow polar cluster formation in Salmonella enterica cells. Thus, activation of the SOS response by the presence of a DNA-injuring compound increases the RecA concentration, thereby disturbing the equilibrium between RecA and CheW and resulting in the cessation of swarming. Nevertheless, when the DNA-damage decreases and the SOS response is no longer activated, basal RecA levels and thus polar cluster assembly are reestablished. These results clearly show that bacterial populations moving over surfaces make use of specific mechanisms to avoid contact with DNA-damaging compounds. PMID:26784887

SOS System Induction Inhibits the Assembly of Chemoreceptor Signaling Clusters in Salmonella enterica.

PubMed

Irazoki, Oihane; Mayola, Albert; Campoy, Susana; Barbé, Jordi

2016-01-01

Swarming, a flagellar-driven multicellular form of motility, is associated with bacterial virulence and increased antibiotic resistance. In this work we demonstrate that activation of the SOS response reversibly inhibits swarming motility by preventing the assembly of chemoreceptor-signaling polar arrays. We also show that an increase in the concentration of the RecA protein, generated by SOS system activation, rather than another function of this genetic network impairs chemoreceptor polar cluster formation. Our data provide evidence that the molecular balance between RecA and CheW proteins is crucial to allow polar cluster formation in Salmonella enterica cells. Thus, activation of the SOS response by the presence of a DNA-injuring compound increases the RecA concentration, thereby disturbing the equilibrium between RecA and CheW and resulting in the cessation of swarming. Nevertheless, when the DNA-damage decreases and the SOS response is no longer activated, basal RecA levels and thus polar cluster assembly are reestablished. These results clearly show that bacterial populations moving over surfaces make use of specific mechanisms to avoid contact with DNA-damaging compounds.

A comparison of serum cholinesterase methods : II.

DOT National Transportation Integrated Search

1972-03-01

Among aerial applicator personnek, the primary value of the periodic blood cholinesterase (ChE) assays is the detection of pesticide poisoning indicated by a decrease in the enzyme activity since the previous (or pre-season) assay. Comparison of thes...

14th EuCheMS International Conference on Chemistry and the Environment ICCE 2013: IEC-WTC, Barcelona, Spain, 25-28 June 2013.

PubMed

Luis, Santiago V; Jover, Eric

2014-10-01

The 14th European Association of Chemical and Molecular Sciences (EuCheMS) International Conference on Chemistry and the Environment (ICCE 2013) took place on 25-28 June 2013 at the IEC and the WTC in Barcelona, Spain. The ICCE is a well-established biannual conference organized by the Division of Chemistry and the EuCheMS.

Catastrophic Health Expenditure of Chronic Diseases: Evidence from Hamadan, Iran

PubMed Central

Rezapour, Aziz; Vahedi, Sajad; Khiavi, Farzad Faraji; Esmaeilzadeh, Firooz; Javan-Noughabi, Javad; Rajabi, Abdolhalim

2017-01-01

Background: Chronic noncommunicable diseases (NCDs) could increase the risk of catastrophic health expenditure (CHE). The present study aims to analyze CHE among households with and without chronic NCDs in Hamedan. Methods: In this cross-sectional study, 780 households’ patients, who were being discharged from hospitals in Hamedan, were selected using a proportional stratified random sampling method. Required data were collected through interview and observation using World Health Organization standard questionnaire. A household with chronic NCDs is defined as the one with ≥1 chronic disease patient. Both descriptive and analytical statistics, as well as different approaches and thresholds, were used to study CHE among households. Results: The households with chronic disease had higher incidence and intensity of CHE in all approaches and threshold. This result was shown through distributive-sensitive measures. The Regression analysis revealed that lower economic status, lower household size, and high utilization of health care were associated with the CHE incidence and intensity in the households with chronic NCDs in Hamedan. Conclusions: There is a high degree of CHE were caused by chronic NCDs. By thoughtful reconsideration in health-care financing, along with addressing relevant socioeconomic factors, the health system of Iran could cope with financial adversities caused by chronic NCDs. PMID:29291041

Effect of Post-Traumatic Stress Disorder on Cognitive Function and Covert Hepatic Encephalopathy Diagnosis in Cirrhotic Veterans.

PubMed

Burroughs, Thomas K; Wade, James B; Ellwood, Michael S; Fagan, Andrew; Heuman, Douglas M; Fuchs, Michael; Bajaj, Jasmohan S

2018-02-01

In veterans, post-traumatic stress disorder (PTSD) is often associated with substance abuse, which in turn can lead to cirrhosis. Cirrhotic patients are prone to cognitive impairment, which is typically due to covert hepatic encephalopathy (CHE), but can also be affected by PTSD. The aim was to define the impact of PTSD on cognitive performance and the diagnosis of CHE in cirrhotic patients. Outpatient veterans with cirrhosis underwent two separate modalities for CHE cognitive testing [Psychometric Hepatic Encephalopathy Scale (PHES) and Inhibitory Control Test (ICT)]. ICT tests for inhibitory control and response inhibition, while PHES tests for attention and psychomotor speed. Comparisons were made between patients with/without PTSD. Multivariable logistic regression with CHE on PHES and CHE on ICT as dependent variables including prior OHE, demographics, PTSD and psychotropic medications was performed. Of 402 patients with cirrhosis, 88 had evidence of PTSD. Fifty-five of these were on psychoactive medications, 15 were undergoing psychotherapy, while no specific PTSD-related therapy was found in 28 patients. Cirrhotic patients with/without PTSD were statistically similar on demographics and cirrhosis severity, but cirrhotic subjects with PTSD had a higher frequency of alcoholic cirrhosis etiology and psychotropic drug use. PTSD cirrhosis had higher ICT lure and switching errors (NCT-B response), but on regression, there was no significant impact of PTSD on CHE diagnosis using either the ICT or PHES. Veterans with cirrhosis and PTSD have a higher frequency of psychotropic drug use and alcoholic cirrhosis etiology. CHE diagnosis using PHES or ICT is not affected by concomitant PTSD.

Health services financing and delivery: analysis of policy options for Dubai, United Arab Emirates

PubMed Central

Hamidi, Samer

2015-01-01

Introduction A national health account (NHA) provides a systematic approach to mapping the flow of health sector funds within a specified health system over a defined time period. This article attempts to present a profile of health system financing in Dubai, United Arab Emirates using data from NHAs, and to compare the functional structures of financing schemes in Dubai with schemes in Qatar and selected member countries of the Organization for Economic Cooperation and Development (OECD). Methods The author analyzed secondary data published in NHAs of Dubai and Qatar and data collected by the OECD countries and publicly available from Eurostat (Statistical Office of the European Union) of 25 OECD countries for comparative analysis. All health financing indicators used were as defined in the international System of Health Accounts (SHA). Results In Dubai, spending on inpatient care was the highest-costing component, with 30% of current health expenditures (CHE). Spending on outpatient care was the second highest-costing component and accounted for about 23% of the CHE. Household spending accounted for about 22% of CHE (equivalent to US$187 per capita), compared to an average of 20% of CHE of OECD countries. Dubai spent 0.02% of CHE on long-term care, compared to an average of 11% of CHE of OECD countries. Dubai spent about 6% of CHE on prevention and public health services, compared to an average of 3.2% of CHE of OECD countries. Conclusion The findings point to potential opportunities for growth and improvement in several health policy issues in Dubai, including increasing focus and funding of preventive services; shifting from inpatient care to day surgery, outpatient, and home-based services and strengthening long-term care; and introducing cost-containment measures for pharmaceuticals. More investment in the translation of NHA data into policy is suggested for future researchers. PMID:25750545

All optical experimental design for neuron excitation, inhibition, and action potential detection

NASA Astrophysics Data System (ADS)

Walsh, Alex J.; Tolstykh, Gleb; Martens, Stacey; Sedelnikova, Anna; Ibey, Bennett L.; Beier, Hope T.

2016-03-01

Recently, infrared light has been shown to both stimulate and inhibit excitatory cells. However, studies of infrared light for excitatory cell inhibition have been constrained by the use of invasive and cumbersome electrodes for cell excitation and action potential recording. Here, we present an all optical experimental design for neuronal excitation, inhibition, and action potential detection. Primary rat neurons were transfected with plasmids containing the light sensitive ion channel CheRiff. CheRiff has a peak excitation around 450 nm, allowing excitation of transfected neurons with pulsed blue light. Additionally, primary neurons were transfected with QuasAr2, a fast and sensitive fluorescent voltage indicator. QuasAr2 is excited with yellow or red light and therefore does not spectrally overlap CheRiff, enabling imaging and action potential activation, simultaneously. Using an optic fiber, neurons were exposed to blue light sequentially to generate controlled action potentials. A second optic fiber delivered a single pulse of 1869nm light to the neuron causing inhibition of the evoked action potentials (by the blue light). When used in concert, these optical techniques enable electrode free neuron excitation, inhibition, and action potential recording, allowing research into neuronal behaviors with high spatial fidelity.

Athletes’ Selected Micro-Activities on Turf Fields: Utilizing Extant Videography for Quantification of Events During Soccer, American Football, and Field Hockey Play

EPA Science Inventory

Concerns have been recently raised about the potential exposures of athletes to chemicals when playing on synthetic turf fields. Previous research has shown that micro-activities (i.e., hand-to mouth and skin-to-surface contacts) are important factors in people’s exposures to che...

Immigrants and the US Army: A Study in Readiness and the American Dream

DTIC Science & Technology

2016-05-26

Immigrants and the US Army: A Study in Readiness and the American Dream A Monograph by LTC Che T. Arosemena...Approval Page Name of Candidate: LTC Che T. Arosemena Monograph Title: Immigrants and the US Army: A Study in Readiness and the American Dream Approved by...Abstract Immigrants and the US Army: A Study in Readiness and the American Dream , by LTC Che T. Arosemena, USA, 71

DECREASED HEART RATE IS ASSOCIATED WITH CARBAMATE-INDUCED ACTIVATION OF PRO-INFLAMMATORY SERUM PROTEINS.

EPA Science Inventory

Previously we reported that chlorpyrifos (CHP), an irreversible cholinesterase (ChE) inhibitor, induces hypertension in rats. Concomitant with hypertension, we found an increase in C-reactive protein, macrophage inflammatory protein-2 , monocyte chemotactic protein-5 and interfer...

ISCO'S LONG-TERM IMPACT ON AQUIFER CONDITIONS AND MICROBIAL ACTIVITY

EPA Science Inventory

Permanganate has been successfully used in in-situ chemical oxidation (ISCO) to transform a wide range of organic contaminants under diverse geologic and geochemical conditions. Here, a critical analysis is presented of several technical issues commonly raised during in-situ che...

Cholinesterase and glutathione S-transferase activities of three mollusc species from the NW Portuguese coast in relation to the 'Prestige' oil spill.

PubMed

Tim-Tim, Ana L S; Morgado, Fernando; Moreira, Susana; Rangel, Rui; Nogueira, António J A; Soares, Amadeu M V M; Guilhermino, Lúcia

2009-12-01

In November 2002, the tanker 'Prestige' released about 19,000 tonnes of a heavy fuel oil (no. 6) before sinking with about 58,000 tonnes of its cargo, 135 miles from Cabo Finisterra (Spain). A considerable part of the released fuel oil reached the Galician coast, causing a heavy black tide and an ecological disaster. Although the black tide did not reach the NW coast of Portugal, it is possible that some of the fuel oil or its components also arrived to this area directly through the sea water and/or indirectly through the food chain. Therefore, the aim of this study was to investigate possible changes in two widely used biomarkers, the activity of the enzymes cholinesterases (ChE) and glutathione S-transferases (GST), of three molluscs (Mytilus galloprovincialis, Nucella lapillus and Monodonta lineata) from wild populations of the NW Portuguese coast in relation to the 'Prestige' oil spill. Molluscs were collected seasonally before (autumn 2002) and after (winter 2002/2003), spring and summer 2003) the oil spill at several sites along the Portuguese NW coast. Enzymatic activities determined before the accident were compared with those determined at different times after the oil spill taking into consideration abiotic factors. Information from different parameters was integrated by Redundancy Analysis and Principal Response Curves (PRC). Results show that GST and ChE activities were influenced by abiotic factors. Despite this influence, the results of PRC analysis also suggest that some of the fuel oil reached the NW Portuguese coast changing the patterns of ChE and GST activities of local populations of rocky shore species. Furthermore, the present study highlights the need of long-term monitoring with wild populations to assess both historical and punctual effects of pollution in the marine environment.

Cost-effectiveness of oral alitretinoin in patients with severe chronic hand eczema - a long-term analysis from a Swiss perspective

PubMed Central

2010-01-01

Background The impact on patients suffering from chronic hand eczema (CHE) is enormous, as no licensed systemic treatment option with proven efficacy for CHE is available. Alitretinoin is a novel agent which showed high clinical efficacy in patients with severe, refractory CHE. We assessed the cost-effectiveness of alitretinoin for CHE patient treatment from a Swiss third party payer perspective. A further objective of this study was to determine the burden of disease in Switzerland. Methods A long-term Markov cohort simulation model was used to estimate direct medical costs (€) and clinical effectiveness (quality adjusted life years, QALYs) of treating severe CHE patients with alitretinoin. Comparison was against the standard treatment of supportive care (optimised emollient therapy). Information on response rates were derived from a randomized controlled clinical trial. Costs were considered from the perspective of the Swiss health system. Swiss epidemiological data was derived from official Swiss Statistic institutions. Results Annual costs of alitretinoin treatment accounted for €2'212. After a time horizon of 22.4 years, average remaining long-term costs accounted for €42'208 or €38'795 in the alitretinoin and the standard treatment arm, respectively. Compared with the standard therapy, the addition of alitretinoin yielded an average gain of 0.230 QALYs at the end of the simulation. Accordingly, the incremental cost-effectiveness ratio resulted in €14'816/QALY gained. These results were robust to changes in key model assumptions. Conclusion The therapy for CHE patients is currently insufficient. In our long-term model we identified the treatment with alitretinoin as a cost-effective alternative for the therapy of CHE patients in Switzerland. PMID:20579358

Reprint of: Quantitative proteomic analysis reveals that chemotaxis is involved in chlortetracycline resistance of Aeromonas hydrophila.

PubMed

Li, Wanxin; Ali, Farman; Cai, Qilan; Yao, Zujie; Sun, Lina; Lin, Wenxiong; Lin, Xiangmin

2018-05-30

In recent years, Aeromonas hydrophila, which has been classified as a food borne pathogen, has presented with increased levels of antibiotic resistance, with the mechanisms of this resistance being poorly understood. In this study, iTRAQ coupled mass spectrometry was employed to compare differentially expressed proteins in chlortetracycline (CTC) resistant A. hydrophila relative to a control strain. Result showed that a total of 234 differential proteins including 151 down-regulated and 83 up-regulated were identified in chlortetracycline resistance strain. Bioinformatics analysis showed that chemotaxis related proteins, such as CheA-2, CheR-3, CheW-2, EnvZ, PolA, FliS and FliG were down-regulated in addition to previously reported tricarboxylic acid cycle (TCA) related proteins also being down-regulated. A subset of identified differentially expressed proteins was then further validated via Western blotting. Exogenous metabolite combined with CTC further enhanced the bacterial susceptibilities to CTC in A. hydrophila. Furthermore, a bacterial survival capability assay showed that several chemotaxis related mutants, such as ΔcheR-3 and ΔAHA_0305, may affect the antimicrobial susceptibility of A. hydrophila. Overall, these findings contribute to a further understanding of the mechanism of CTC resistance in A. hydrophila and may contribute to the development of more effective future treatments. A. hydrophila is a well-known fish pathogenic bacterium and has presented with increasing levels of antibiotic resistance, with the mechanisms of this resistance being poorly understood. Our current study compared the differentially expression proteins between chlortetracycline (CTC) resistant and control stains via an iTARQ-based quantitative proteomics method. Chemotaxis related proteins were down-regulated in CTC resistant strain but exogenous metabolite addition increased bacterial susceptibility in A.hydrophila. Significantly, chemotaxis related genes depletion affected antimicrobial susceptibilities of A.hydrophila indicating the role of chemotaxis process in antibiotics resistance. Copyright © 2018 Elsevier B.V. All rights reserved.

The impact of out-of-pocket payments for dental care on household finances in low and middle income countries.

PubMed

Bernabé, Eduardo; Masood, Mohd; Vujicic, Marko

2017-01-23

Dental care is extremely costly and beyond most people means in developing countries. The primary aim of this study was to determine the impact of out-of-pocket payments for dental care on household finances in 40 low and middle income countries. A second aim was to compare the burden of payments for dental care with that for other health services. We used data from 174,257 adults, aged 18 years and above, who reported their total and itemized household expenditure in the past four weeks as part of the World Health Surveys. The financial burden on households was measured using the catastrophic health expenditure (CHE) and impoverishment approaches. A household was classified as facing CHE if it spent 40% or more of its capacity to pay, and as facing impoverishment if it fell below the country-specific poverty line after spending on health care was subtracted from household expenditure. The odds of experiencing CHE and impoverishment due to expenditure on dental care were estimated from two-level logistic regression models, controlling for various individual- and country-level covariates. Households that paid for dental care had 1.88 (95% Confidence Interval: 1.78-1.99) greater odds of incurring CHE and 1.65 (95% CI: 1.52-1.80) greater odds of facing impoverishment, after adjustment for covariates. Furthermore, the impact of paying for dental care was lower than that for medications or drugs, inpatient care, outpatient care and laboratory tests but similar to that of health care products, traditional medicine and other health services. Households with recent dental care spending were more likely to use a large portion of their disposable income and fall below the poverty line. Policy makers ought to consider including dental care as part of universal health care and advocate for the inclusion of dental care coverage in health insurance packages.

Characterization of Cell Surface and EPS Remodeling of Azospirillum brasilense Chemotaxis-like 1 Signal Transduction Pathway mutants by Atomic Force Microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Billings, Amanda N; Siuti, Piro; Bible, Amber

2011-01-01

To compete in complex microbial communities, bacteria must quickly sense environmental changes and adjust cellular functions for optimal growth. Chemotaxis-like signal transduction pathways are implicated in the modulation of multiple cellular responses, including motility, EPS production, and cell-to-cell interactions. Recently, the Che1 chemotaxis-like pathway from Azospirillum brasilense was shown to modulate flocculation. In A. brasilense, cell surface properties, including EPS production, are thought to play a direct role in promoting flocculation. Using atomic force microscopy (AFM), we have detected distinct changes in the surface morphology of flocculating A. brasilense Che1 mutant strains that are absent in the wild type strain.more » Whereas the wild type strain produces a smooth mucosal extracellular matrix, the flocculating Che1 mutant strains produce distinctive extracellular fibril structures. Further analyses using flocculation inhibition and lectin-binding assays suggest that the composition of EPS components in the extracellular matrix differs between the cheA1 and cheY1 mutants, despite an apparent similarity in the macroscopic floc structures. Collectively, these data indicate that mutations in the Che1 pathway that result in increased flocculation are correlated with distinctive changes in the extracellular matrix structure produced by the mutants, including likely changes in the EPS structure and/or composition.« less

Assessing dimethoate contamination in temperate and tropical climates: potential use of biomarkers in bioassays with two chironomid species.

PubMed

Domingues, Inês; Guilhermino, Lúcia; Soares, Amadeu M V M; Nogueira, António J A

2007-08-01

This study was conducted to investigate the potential use of biomarkers in bioassays with chironomids to assess contamination by pesticides in temperate and tropical climates. Two species of midge were studied, the widespread Chironomus riparius and the tropical Kiefferulus calligaster (Kieffer, 1911). Preliminary studies included investigations of the effects of temperature on larval development and the influence of larval age on normal variability of cholinesterase (ChE) and glutathione S-transferase (GST) activities and protein content. In the second phase, the influence of two abiotic factors particularly important in tropical conditions (temperature and oxygen concentration) and of the organophosphorous (OP) insecticide dimethoate on biochemical and conventional endpoints was investigated. Results showed that K. calligaster is morphologically and physiologically similar to C. riparius and for both, the time of larval development decreases with the increase of temperature. Moreover, 3rd and 4th instars appeared to be the most suitable for biomarkers determinations. ChE activity seems to be valuable biomarker regarding temperature and dissolved oxygen (DO) variations, while some caution should be taken when using GST as an environmental biomarker, since it shows some dependence of these parameters. C. riparius was more sensitive to dimethoate than K. calligaster suggesting that the use of bioassays with the former species in tropical conditions may overestimate the toxicity of OP pesticides to autochthonous species. When testing sub-lethal effects of dimethoate to C. riparius, ChE activity showed to be a very sensitive parameter detecting significant effects at the lowest concentration that caused emergence delay of larvae, suggesting that it is an ecologically relevant parameter.

Laboratory measurements of biomarkers and individual performances in Chironomus xanthus to evaluate pesticide contamination of sediments in a river of southeastern Brazil.

PubMed

Printes, Liane Biehl; Fernandes, Marisa Narciso; Espíndola, Evaldo Luiz Gaeta

2011-03-01

This study aimed at evaluating biomarkers, individual and population responses in the native Chironomus xanthus to assess the toxicity of pesticide-contaminated sediments from the Monjolinho River (Southeast Brazil). We measured cholinesterase (ChE) and glutathione S-transferase activities (GST), as biomarkers and survival, individual growth and adult emergence, as individual performances. There was no response of the ChE activity and a tendency to decreased GST activity in contaminated sites, but this was generally not statistically significant. Therefore, there was no association of the biomarker responses with exposure to sediment containing pesticides. In contrast, ash free dry mass was significantly increased and male emergence was decreased in C. xanthus exposed to the same sediments. In conclusion, the selected biomarkers were not sensitive and specific enough to detect and anticipate effects of pesticide contamination at the levels measured in the study area. Nevertheless, individual performances alterations pointed to potential pollution problems and possible ecological consequences. Copyright © 2010 Elsevier Inc. All rights reserved.

Efficient Computation of Sparse Matrix Functions for Large-Scale Electronic Structure Calculations: The CheSS Library.

PubMed

Mohr, Stephan; Dawson, William; Wagner, Michael; Caliste, Damien; Nakajima, Takahito; Genovese, Luigi

2017-10-10

We present CheSS, the "Chebyshev Sparse Solvers" library, which has been designed to solve typical problems arising in large-scale electronic structure calculations using localized basis sets. The library is based on a flexible and efficient expansion in terms of Chebyshev polynomials and presently features the calculation of the density matrix, the calculation of matrix powers for arbitrary powers, and the extraction of eigenvalues in a selected interval. CheSS is able to exploit the sparsity of the matrices and scales linearly with respect to the number of nonzero entries, making it well-suited for large-scale calculations. The approach is particularly adapted for setups leading to small spectral widths of the involved matrices and outperforms alternative methods in this regime. By coupling CheSS to the DFT code BigDFT, we show that such a favorable setup is indeed possible in practice. In addition, the approach based on Chebyshev polynomials can be massively parallelized, and CheSS exhibits excellent scaling up to thousands of cores even for relatively small matrix sizes.

Cholinesterase Confabs and Cousins: Approaching Forty Years

PubMed Central

Taylor, Palmer; De Jaco, Antonella; Comoletti, Davide; Miller, Meghan; Camp, Shelley

2013-01-01

In the past four decades of cholinesterase (ChE) research, we have seen substantive evolution of the field from one centered around substrate and inhibitor kinetic profiles and compound characterizations to the analysis of ChE structure, first through the gene families and then by x-ray crystallographic determinations of the free enzymes and their complexes and conjugates. Indeed, these endeavors have been facilitated by recombinant DNA technologies, structure determinations and parallel studies in related proteins in the α/β-hydrolase fold family. This approach has not only contributed to a fundamental understanding of structure and function of a large family of hydrolase-like proteins possessing functions other than catalysis, but also has been used to develop new practical strategies for scavenging and antidotal activity in cases of organophosphate insecticide or nerve agent exposure. PMID:23085121

ISCO'S LONG-TERM IMPACT ON AQUIFER CONDITIONS AND MICROBIAL ACTIVITY (ABSTRACT)

EPA Science Inventory

Permanganate has been successfully used in in-situ chemical oxidation (ISCO) to transform a wide range of organic contaminants under diverse geologic and geochemical conditions. Here, a critical analysis is presented of several technical issues commonly raised during in-situ che...

BRAIN ACONITASE ACTIVITY IN SPONTANEOUSLY HYPERTENSIVE (SHR) AND WISTAR-KYOTO (WKY) RATS.

EPA Science Inventory

Animal models of susceptibility are critical for human health risk assessment. Previous studies indicate that spontaneously hypertensive (SHR) rats are more sensitive than Wistar-Kyoto (WKY) rats to the cholinesterase (ChE) inhibitors such as carbaryl and chlorpyrifos. This diffe...

Protection against soman and sarin exposure by transdermal physostigmine and scopolamine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meshulam, Y.; Davidovici, R.; Levy, A.

1993-05-13

The purpose of this study was to evaluate the prophylactic efficacy of physostigmine (physo), administered via sustained release (SR) methods, with and without scopolamine, against soman and sarin exposure in guinea-pigs. Transdermal physo pad (3 sq cm/kg; 60-80 ug/sq cm), containing a vehicle based on propionic acid, was applied onto the dorsal back of the animals, 24 hours before exposure to the cholinesterase (ChE) inhibitors. At the time of exposure, physo concentrations in brain and plasma were 3.6 ng/g and 4.1 ng/ml respectively. Brain and whole blood ChE activity were inhibited to 70% and 57% of their original activity. Transdermalmore » physo by itself protected up to 70% of the animals exposed to 1.5 LD(50) of soman or sarin (100% mortality was recorded in the control group). Combining transdermal physo with Scopoderm (by Ciba Geigy Inc.) provided full protection against 1.5 LD(50).« less

Insurgent Safe Havens: Can We Win the Fight?

DTIC Science & Technology

2011-03-08

N/A. 14. ABSTRACT Theorists of Guerilla Warfare like Mao Tse -tung, T.E. Lawrence, and Che Guevara suggest some form of sanctuary is necessary for... Tse -tung, T.E. Lawrence, and Che Guevara suggest some form of sanctuary is necessary for any insurgency to be successful; history shows this to be...wru·fru·e, T.E. Lawrence, Mao Tse -tung and Che Guevara recdgnized the need for sanctuaries as a critical element of their insurgent campaigns; each

Destination Innovation: Episode 4 CheMin

NASA Image and Video Library

2012-08-02

Destination Innovation is a new series that explores the research, science and other projects underway at the NASA Ames Research Center. Episode 4 focuses on the CheMin instrument aboard the Mars Science Laboratory, NASA' s latest robotic explorer to visit Mars. CheMin, short for 'Chemistry and Mineralogy,' was developed at NASA Ames Research Center and is one of 10 instruments aboard the rover Curiosity. The instrument is an x-ray diffractometer, which will be able to identify minerals in the Martial rock and soil.

Estimation of plasma tacrine concentrations using an in vitro cholinesterase inhibition assay

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moriearty, P.L.; Kenny, W.; Kumar, V.

THA (9-amino, 1,2,3,4-tetrahydroacridine; tacrine) is currently under study as a cholinesterase (ChE) inhibitor in Alzheimer disease. In this study, a sensitive radiometric assay for THA inhibition of human plasma ChE, suitable for detection of effects of orally administered drug, is described. The assay is sensitive in a range of 4-50 ng/ml plasma. Reversibility of the inhibition permits distinguishing of drug effects on ChE from changes in amount of enzyme synthesized during treatment.

My Martian Moment - Episode 1 - David Blake and CheMin

NASA Image and Video Library

2015-09-25

Ames' David Blake developed the Chemistry and Mineralogy instrument, or CheMin for short, which is currently operating on NASA's Curiosity Mars rover. It identifies and measures the abundance of various minerals on the Martian surface. The instrument is built around a highly compact X-ray diffraction unit, the first of its kind to operate on a planet besides Earth. CheMin can quickly analyze soil samples, helping scientists understand the composition and history of the Martian surface.

Dead and dying Brazilian free-tailed bats (Tadarida brasiliensis) from Texas: Rabies and pesticide exposure

USGS Publications Warehouse

Clark, Donlad R.; Lollar, Amanda; Cowman, Deborah

1996-01-01

Twenty-three dead and dying Brazilian free-tailed bats from roosts in downtown Mineral Wells, Palo Pinto County, Texas, were tested for rabies and for anticholinesterase (antiChE) effects of or- ganophosphorus (OP) and carbamate pesticides. Seventeen of the 23 bats tested positive for rabies. The cause of death or dying in five of the nonrabid bats is unknown; however, one of the six nonrabid bats had a ChE activity level equivalent to only 27% of the control mean and may have been exposed to a pes- ticide. Three bats (including the bat with depressed ChE) contained sufficient ingesta to analyze for an- tiChE compounds, but no antiChE compounds could be identified in the samples. Exposure may be dermal and pulmonary as well as dietary. It is feasible that other bat deaths not explained by rabies were attributable to a pesticide but missed due to postmortem reactivation of the ChE enzyme. The largest group of rabid bats was young males (13 of 17, 76.5%), and the largest group of nonrabid bats was older females (3 of 6, 50%). All older females were nonrabid, perhaps survivors of the disease in previous years. Rabid bats had a lower mean fat index and weighed less than nonrabid bats. Four bats (not includ- ing the low ChE bat) showed external bleeding, and none was rabid; thus the incidence of bleeding was greater among nonrabid bats than among rabid bats. The four affected bats came from roosts in three different buildings, making a roost-treatment with an anticoagulant chemical seem unlikely.

Distinct Effect of Benzalkonium Chloride on the Esterase and Aryl Acylamidase Activities of Butyrylcholinesterase.

PubMed

Jaganathan; Boopathy

2000-08-01

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) from vertebrates, other than their predominant acylcholine hydrolase (esterase) activity, display a genuine aryl acylamidase activity (AAA) capable of hydrolyzing the synthetic substrate o-nitroacetanilide to o-nitroaniline. This AAA activity is strongly inhibited by classical cholinesterase (ChE) inhibitors. In the present study, benzalkonium chloride (BAC), a cationic detergent widely used as a preservative in pharmaceutical preparations, has been shown to distinctly modulate the esterase and AAA activities of BChEs. The detergent BAC was able to inhibit the esterase activity of human serum and horse serum BChEs and AChEs from electric eel and human erythrocyte. The remarkable property of BAC was its ability to profoundly activate the AAA activity of human serum and horse serum BChEs but not the AAA activity of AChEs. Thus BAC seem to preferentially activate the AAA activity of BChEs alone. Results of the study using the ChE active site-specific inhibitor diisopropyl phosphorofluoridate indicated that BAC binds to the active site of ChEs. Furthermore, studies using a structural homolog of BAC indicated that the alkyl group of BAC is essential not only for its interaction with ChEs but also for its distinct effect on the esterase and AAA activities of BChEs. This is the first report of a compound that inhibits the esterase activity, while simultaneously activating the AAA activity, of BChEs. Copyright 2000 Academic Press.

The neurochemical and behavioral effects of the novel cholinesterase–monoamine oxidase inhibitor, ladostigil, in response to L-dopa and L-tryptophan, in rats

PubMed Central

Sagi, Yotam; Driguès, Noam; Youdim, Moussa B H

2005-01-01

The novel drugs, ladostigil (TV3326) and TV3279, are R and S isomers, respectively, derived from a combination of the carbamate cholinesterase (ChE) inhibitor, rivastigmine, and the pharmacophore of the monoamine oxidase (MAO) B inhibitor, rasagiline. They were developed for the treatment of comorbidity of dementia with Parkinsonism. In the present study, we determined the effects of these drugs on both aminergic neurotransmitter levels and motor behavioral activity in naïve and in L-dopa- or L-tryptophan-induced rats. Chronic treatment of rats with ladostigil (52 mg kg−1 for 21 days) inhibited hippocampal and striatal MAO A and B activities by >90%, increased striatal levels of dopamine and serotonin, and inhibited striatal ChE activity by ∼50%. Chronic TV3279 (26 mg kg−1 for 21 days) similarly inhibited ∼50% of striatal ChE activity, but did not affect MAO activity or amine levels. In sharp contrast to the inductive effect of the MAO A/B inhibitor, tranylcypromine (TCP), on stereotyped hyperactivity in response to L-dopa (50 mg kg−1) or L-tryptophan (100 mg kg−1), ladostigil completely inhibited these behavioral hyperactivity syndromes. Accordingly, acute rivastigmine (2 mg kg−1) and chronic TV3279 abolished the ability of TCP to initiate L-dopa-induced hyperactivity, while scopolamine (0.5 mg kg−1) reversed the inhibitory effect of chronic ladostigil on L-dopa-induced hyperactivity, suggesting that ladostigil may attenuate successive locomotion by activating central cholinergic muscarinic receptors. Finally, while chronic ladostigil administration to naïve rats resulted in preserved spontaneous motor behavior, acute treatment with ladostigil decreased motor performance, compared to control animals. In contrast, chronic as well as acute treatments with TV3279 reduced spontaneous motor activity. Thus, the aminergic potentiation by ladostigil may counteract its cholinergic inhibitory effect on spontaneous motor behavior. Our results suggest that potentiation of both aminergic and cholinergic transmission systems by ladostigil contributes equally to motor behavior performance, which is substantially impaired in comorbidity of dementia with Parkinsonism including dementia with Lewy bodies (DLB). PMID:16086033

Characterization of cell surface and extracellular matrix remodeling of Azospirillum brasilense chemotaxis-like 1 signal transduction pathway mutants by atomic force microscopy.

PubMed

Edwards, Amanda Nicole; Siuti, Piro; Bible, Amber N; Alexandre, Gladys; Retterer, Scott T; Doktycz, Mitchel J; Morrell-Falvey, Jennifer L

2011-01-01

To compete in complex microbial communities, bacteria must sense environmental changes and adjust cellular functions for optimal growth. Chemotaxis-like signal transduction pathways are implicated in the regulation of multiple behaviors in response to changes in the environment, including motility patterns, exopolysaccharide production, and cell-to-cell interactions. In Azospirillum brasilense, cell surface properties, including exopolysaccharide production, are thought to play a direct role in promoting flocculation. Recently, the Che1 chemotaxis-like pathway from A. brasilense was shown to modulate flocculation, suggesting an associated modulation of cell surface properties. Using atomic force microscopy, distinct changes in the surface morphology of flocculating A. brasilense Che1 mutant strains were detected. Whereas the wild-type strain produces a smooth mucosal extracellular matrix after 24 h, the flocculating Che1 mutant strains produce distinctive extracellular fibril structures. Further analyses using flocculation inhibition, lectin-binding assays, and comparison of lipopolysaccharides profiles suggest that the extracellular matrix differs between the cheA1 and the cheY1 mutants, despite an apparent similarity in the macroscopic floc structures. Collectively, these data indicate that disruption of the Che1 pathway is correlated with distinctive changes in the extracellular matrix, which likely result from changes in surface polysaccharides structure and/or composition. FEMS Microbiology Letters © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. No claim to original US government works.

Scienza dei servizi

NASA Astrophysics Data System (ADS)

Cavenago, Dario; Mezzanzanica, Mario

I servizi sono oramai centrali nella vita sociale di ogni Paese. L'aspettativa di ogni attore sociale, sia esso cittadino/utente e/o istituzione, è quella di ricevere da uno scambio che ha alla base un servizio un contributo che si caratterizza per una qualità intrinseca. Il mantenimento di tale promessa richiede all'azienda erogatrice un forte coinvolgimento, nel disegno del servizio, degli utenti ed una capacità di gestione della conoscenza; ciò è particolarmente significativo per quei servizi che si caratterizzano per una forte personalizzazione o complessità progettuale. Disegnare un servizio, metterlo in produzione e gestirne l'erogazione ha una complessità variabile in base al grado di coinvolgimento dei destinati ed alle dimensioni critiche che esprimono le condizioni di fattibilità di un servizio di qualità appropriato alle attese degli utilizzatori. Ugualmente la globalizzazione dell'economia e la scarsità delle risorse ha portato l'attenzione, ai fini della sostenibilità delle condizioni sopra richiamate, di una ricerca di modelli e strumenti che permettano una valutazione e una standardizzazione dei processi di produzione ed erogazione secondo condizioni di economicità. Tali primi e sintetici elementi hanno condotto diversi attori istituzionali, grandi imprese ed università attraverso i loro centri di ricerca, ad una azione di riflessione sul grado di "ingegnerizzazione" dei processi sottesi alla erogazione dei servizi ed in particolare ai servizi che attuano le politiche dei grandi settori di base dell'economia di una Nazione: educazione, sanità, sociale, sviluppo infrastrutture ecc.

Amorphous Phase Characterization Through X-Ray Diffraction Profile Modeling: Implications for Amorphous Phases in Gale Crater Rocks and Soils

NASA Technical Reports Server (NTRS)

Achilles, C. N.; Downs, G. W.; Downs, R. T.; Morris, R. V.; Rampe, E. B.; Ming, D. W.; Chipera, S. J.; Blake, D. F.; Vaniman, D. T.; Bristow, T. F.;

Space Station Freedom CHeCS overview. [Crew Health Care System

NASA Technical Reports Server (NTRS)

Boyce, Joey B.

1990-01-01

The current status, progress, and future plans for development of the Crew Health Care System (CHeCS) for the International Space Station Freedom are presented. Essential operational biomedical support requirements for the astronauts, including medical care, environmental habitat monitoring, and countermeasures for the potentially maladaptive physiological effects of space flight will be provided by the CHeCS. Three integral parts will make up the system: a health maintenance facility, an environmental health system, and the exercise countermeasures facility. Details of each of the major systems and their subsystems are presented.

New Manning System Field Evaluation

DTIC Science & Technology

1986-03-01

tckovics Un,!,d LTC Larry H. tng.anam, Ph.D. zust n - Farts R. Ki~rk.land, Ph.0. CharLene S. Lewis, Ph.D. David H. MarLowe, h.D ByDlstribuatoflf LTC James...parcticipacing agencies) wich an updaCe of WTAZ&’s current HMS research accivicies; (Z) Co raise Issues chac varranc, discassson among Che agencies...provides a summacy of che uniCs Chac have compLeced Che first LcecaCIon of ch•e Soldier VILL quesctona~ve as weLil as projeccLons .or cthe second and

Direction of flagellar rotation in bacterial cell envelopes.

PubMed Central

Ravid, S; Eisenbach, M

1984-01-01

Cell envelopes with functional flagella, isolated from wild-type strains of Escherichia coli and Salmonella typhimurium by formation of spheroplasts with penicillin and subsequent osmotic lysis, demonstrate counterclockwise (CCW)-biased rotation when energized with an electron donor for respiration, DL-lactate. Since the direction of flagellar rotation in bacteria is central to the expression of chemotaxis, we studied the cause of this bias. Our main observations were: (i) spheroplasts acquired a clockwise (CW) bias if instead of being lysed they were further incubated with penicillin; (ii) repellents temporarily caused CW rotation of tethered bacteria and spheroplasts but not of their derived cell envelopes; (iii) deenergizing CW-rotating cheV bacteria by KCN or arsenate treatment caused CCW bias; (iv) cell envelopes isolated from CW-rotating cheC and cheV mutants retained the CW bias, unlike envelopes isolated from cheB and cheZ mutants, which upon cytoplasmic release lost this bias and acquired CCW bias; and (v) an inwardly directed, artificially induced proton current rotated tethered envelopes in CCW direction, but an outwardly directed current was unable to rotate the envelopes. It is concluded that (i) a cytoplasmic constituent is required for the expression of CW rotation (or repression of CCW rotation) in strains which are not defective in the switch; (ii) in the absence of this cytoplasmic constituent, the motor is not reversible in such strains, and it probably is mechanically constricted so as to permit CCW sense of rotation only; (iii) the requirement of CW rotation for ATP is not at the level of the motor or the switch but at one of the preceding functional steps of the chemotaxis machinery; (iv) the cheC and cheV gene products are associated with the cytoplasmic membrane; and (v) direct interaction between the switch-motor system and the repellent sensors is improbable. Images PMID:6370958

Specific radioisotopic assay for cholinesterase. Technical report, December 1987-March 1988

DOE Office of Scientific and Technical Information (OSTI.GOV)

Talbot, B.G.; Anderson, D.R.; Harris, L.W.

1990-05-01

The radiometric method (I) for measuring ChE activity was modified to preclude the use of p-dioxane, a hazardous material. The modified procedure (II) uses 0.4 N perchloric acid (PCA), instead of p-dioxane, to denature the ChE and stop hydrolysis of 14C-acetylcholine (ACh). The unreacted substrate (ACh) is removed by cationic exchange resin suspended in water. The supernatant (acidic water solution) containing the product of hydrolysis, 14C-acetic acid, is mixed with nonhazardous scintillation cocktail and counted. The incubation mixture (37 degrees C) for II is similar to I and is composed of 0.1 ml of buffer-salt solution (pH 7.8), 0.1 mlmore » of guinea pig whole blood (WB)-water suspension and 0.1 ml of 3mM ACh solution.« less

Case histories of bald eagles and other raptors killed by organophosphorus insecticides topically applied to livestock

USGS Publications Warehouse

Henny, C.J.; Kolbe, E.J.; Hill, E.F.; Blus, L.J.

1987-01-01

Since 1982 when secondary poisoning of a red-tailed hawk (Buteo jamaicensis) was documented following the recommended use of famphur applied topically to cattle, the Patuxent Wildlife Research Center has tested dead birds of prey for poisoning by famphur and other pour-on organophosphorus (OP) insecticides. Brain cholinesterase (ChE) activity was first determined, then if ChE was depressed greater than or equal to 50%, stomach and/or crop contents were evaluated for anti-ChE compounds. This report presents the circumstances surrounding the OP-caused deaths of eight bald eagles (Haliaeetus leucocephalus), two red-tailed hawks, and one great horned owl (Bubo virginianus) between March 1984 and March 1985. OP poisoning of raptors by pour-on insecticides in the United States is widespread, but its magnitude is unknown.

Case histories of bald eagles and other raptors killed by organophosphorus insecticides topically applied to livestock.

PubMed

Henny, C J; Kolbe, E J; Hill, E F; Blus, L J

1987-04-01

Since 1982 when secondary poisoning of a red-tailed hawk (Buteo jamaicensis) was documented following the recommended use of famphur applied topically to cattle, the Patuxent Wildlife Research Center has tested dead birds of prey for poisoning by famphur and other pour-on organophosphorus (OP) insecticides. Brain cholinesterase (ChE) activity was first determined, then if ChE was depressed greater than or equal to 50%, stomach and/or crop contents were evaluated for anti-ChE compounds. This report presents the circumstances surrounding the OP-caused deaths of eight bald eagles (Haliaeetus leucocephalus), two red-tailed hawks, and one great horned owl (Bubo virginianus) between March 1984 and March 1985. OP poisoning of raptors by pour-on insecticides in the United States is widespread, but its magnitude is unknown.

Thirsk during CHeCS medical emergency training

NASA Image and Video Library

2009-07-02

ISS020-E-016866 (2 July 2009) --- Canadian Space Agency astronaut Robert Thirsk, Expedition 20 flight engineer, participates in Crew Health Care Systems (CHeCS) medical emergency training in the Destiny laboratory of the International Space Station.

Use of lambda pMu bacteriophages to isolate lambda specialized transducing bacteriophages carrying genes for bacterial chemotaxis.

PubMed

Kondoh, H; Paul, B R; Howe, M M

1980-09-01

A general method for constructing lambda specialized transducing phages is described. The method, which is potentially applicable to any gene of Escherichia coli, is based on using Mu DNA homology to direct the integration of a lambda pMu phage near the genes whose transduction is desired. With this method we isolated a lambda transducing phage carrying all 10 genes in the che gene cluster (map location, 41.5 to 42.5 min). The products of the cheA and tar genes were identified by using transducing phages with amber mutations in these genes. It was established that tar codes for methyl-accepting chemotaxis protein II (molecular weight, 62,000) and that cheA codes for two polypeptides (molecular weights, 76,000 and 66,000). Possible origins of the two cheA polypeptides are discussed.

Azospirillum brasilense Chemotaxis Depends on Two Signaling Pathways Regulating Distinct Motility Parameters

PubMed Central

Mukherjee, Tanmoy; Kumar, Dhivya; Burriss, Nathan; Xie, Zhihong

2016-01-01

ABSTRACT The genomes of most motile bacteria encode two or more chemotaxis (Che) systems, but their functions have been characterized in only a few model systems. Azospirillum brasilense is a motile soil alphaproteobacterium able to colonize the rhizosphere of cereals. In response to an attractant, motile A. brasilense cells transiently increase swimming speed and suppress reversals. The Che1 chemotaxis pathway was previously shown to regulate changes in the swimming speed, but it has a minor role in chemotaxis and root surface colonization. Here, we show that a second chemotaxis system, named Che4, regulates the probability of swimming reversals and is the major signaling pathway for chemotaxis and wheat root surface colonization. Experimental evidence indicates that Che1 and Che4 are functionally linked to coordinate changes in the swimming motility pattern in response to attractants. The effect of Che1 on swimming speed is shown to enhance the aerotactic response of A. brasilense in gradients, likely providing the cells with a competitive advantage in the rhizosphere. Together, the results illustrate a novel mechanism by which motile bacteria utilize two chemotaxis pathways regulating distinct motility parameters to alter movement in gradients and enhance the chemotactic advantage. IMPORTANCE Chemotaxis provides motile bacteria with a competitive advantage in the colonization of diverse niches and is a function enriched in rhizosphere bacterial communities, with most species possessing at least two chemotaxis systems. Here, we identify the mechanism by which cells may derive a significant chemotactic advantage using two chemotaxis pathways that ultimately regulate distinct motility parameters. PMID:27068592

Azospirillum brasilense Chemotaxis Depends on Two Signaling Pathways Regulating Distinct Motility Parameters.

PubMed

Mukherjee, Tanmoy; Kumar, Dhivya; Burriss, Nathan; Xie, Zhihong; Alexandre, Gladys

2016-06-15

The genomes of most motile bacteria encode two or more chemotaxis (Che) systems, but their functions have been characterized in only a few model systems. Azospirillum brasilense is a motile soil alphaproteobacterium able to colonize the rhizosphere of cereals. In response to an attractant, motile A. brasilense cells transiently increase swimming speed and suppress reversals. The Che1 chemotaxis pathway was previously shown to regulate changes in the swimming speed, but it has a minor role in chemotaxis and root surface colonization. Here, we show that a second chemotaxis system, named Che4, regulates the probability of swimming reversals and is the major signaling pathway for chemotaxis and wheat root surface colonization. Experimental evidence indicates that Che1 and Che4 are functionally linked to coordinate changes in the swimming motility pattern in response to attractants. The effect of Che1 on swimming speed is shown to enhance the aerotactic response of A. brasilense in gradients, likely providing the cells with a competitive advantage in the rhizosphere. Together, the results illustrate a novel mechanism by which motile bacteria utilize two chemotaxis pathways regulating distinct motility parameters to alter movement in gradients and enhance the chemotactic advantage. Chemotaxis provides motile bacteria with a competitive advantage in the colonization of diverse niches and is a function enriched in rhizosphere bacterial communities, with most species possessing at least two chemotaxis systems. Here, we identify the mechanism by which cells may derive a significant chemotactic advantage using two chemotaxis pathways that ultimately regulate distinct motility parameters. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Developing antibodies from cholinesterase derived from prokaryotic expression and testing their feasibility for detecting immunogen content in Daphnia magna.

PubMed

Liu, Hong-cui; Yuan, Bing-qiang; Li, Shao-nan

2016-02-01

To yield cholinesterase (ChE) from prokaryotic expression, the ChE gene that belongs to Daphnia magna was amplified by reverse transcription-polymerase chain reaction (RT-PCR) using forward primer 5'-CCCYGGNGCSAT GATGTG-3' and reverse primer 5'-GYAAGTTRGCCCAATATCT-3'. To express the gene, one sequence of the amplified DNA, which was able to encode a putative protein containing two conserved carboxylesterase domains, was connected to the prokaryotic expression vector PET-29a(+). The recombinant vector was transformed into Escherichia coil BL21 (DE3). Protein expression was induced by isopropy-D-thiogalactoside. The expressed ChE was used as an immunogen to immunize BALB/c mice. The obtained antibodies were tested for their specificity towards crude enzymes from species such as Alona milleri, Macrobrachium nipponense, Bombyx mori, Chironomus kiiensis, Apis mellifera, Eisenia foetida, Brachydanio rerio, and Xenopus laevis. Results indicated that the antibodies had specificity suitable for detecting ChE in Daphnia magna. A type of indirect and non-competitive enzyme-linked immunosorbent assay (IN-ELISA) was used to test the immunoreactive content of ChE (ChE-IR) in Daphina magna. The detection limit of the IN-ELISA was found to be 14.5 ng/ml at an antiserum dilution of 1:22 000. Results from tests on Daphnia magna exposed to sublethal concentrations of triazophos indicated a maximal induction of 57.2% in terms of ChE-IR on the second day after the animals were exposed to a concentration of 2.10 μg/L triazophos. Testing on animals acclimatized to a temperature of 16 °C indicated that ChE-IR was induced by 16.9% compared with the ChE-IR content detected at 21 °C, and the rate of induction was 25.6% at 10 °C. The IN-ELISA was also used to test the stability of ChE-IR in collected samples. Repeated freezing and thawing had no influence on the outcome of the test. All these results suggest that the polyclonal antibodies developed against the recombinant ChE are as efficient as those developed against the native ChE in detecting ChE content in Daphnia magna.

Developing antibodies from cholinesterase derived from prokaryotic expression and testing their feasibility for detecting immunogen content in Daphnia magna *

PubMed Central

Liu, Hong-cui; Yuan, Bing-qiang; Li, Shao-nan

2016-01-01

To yield cholinesterase (ChE) from prokaryotic expression, the ChE gene that belongs to Daphnia magna was amplified by reverse transcription-polymerase chain reaction (RT-PCR) using forward primer 5'-CCCYGGNGCSAT GATGTG-3' and reverse primer 5'-GYAAGTTRGCCCAATATCT-3'. To express the gene, one sequence of the amplified DNA, which was able to encode a putative protein containing two conserved carboxylesterase domains, was connected to the prokaryotic expression vector PET-29a(+). The recombinant vector was transformed into Escherichia coil BL21 (DE3). Protein expression was induced by isopropy-D-thiogalactoside. The expressed ChE was used as an immunogen to immunize BALB/c mice. The obtained antibodies were tested for their specificity towards crude enzymes from species such as Alona milleri, Macrobrachium nipponense, Bombyx mori, Chironomus kiiensis, Apis mellifera, Eisenia foetida, Brachydanio rerio, and Xenopus laevis. Results indicated that the antibodies had specificity suitable for detecting ChE in Daphnia magna. A type of indirect and non-competitive enzyme-linked immunosorbent assay (IN-ELISA) was used to test the immunoreactive content of ChE (ChE-IR) in Daphina magna. The detection limit of the IN-ELISA was found to be 14.5 ng/ml at an antiserum dilution of 1:22 000. Results from tests on Daphnia magna exposed to sublethal concentrations of triazophos indicated a maximal induction of 57.2% in terms of ChE-IR on the second day after the animals were exposed to a concentration of 2.10 μg/L triazophos. Testing on animals acclimatized to a temperature of 16 °C indicated that ChE-IR was induced by 16.9% compared with the ChE-IR content detected at 21 °C, and the rate of induction was 25.6% at 10 °C. The IN-ELISA was also used to test the stability of ChE-IR in collected samples. Repeated freezing and thawing had no influence on the outcome of the test. All these results suggest that the polyclonal antibodies developed against the recombinant ChE are as efficient as those developed against the native ChE in detecting ChE content in Daphnia magna. PMID:26834012

Evaluation of effect of hybrid bioartificial liver using end-stage liver disease model

PubMed Central

Liu, Qing; Duan, Zhong-Ping; Huang, Chun; Zhao, Chun-Hui

2004-01-01

AIM: To study the role of hybrid bioartificial liver (HBL) in clearing proinflammatory cytokines and endotoxin in patients with acute and sub-acute liver failure and the effects of HBL on systemic inflammatory syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). METHODS: Five cases with severe liver failure (3 acute and 2 subacute) were treated with HBL. The clinical signs and symptoms, total bilirubin (TBIL), serum ammonia, endotoxin TNF-α, IL-6 and prothrombin activity (PTA), cholinesterase (CHE) were recorded before, during and after treatment. The end-stage liver disease (MELD) was used for the study. RESULTS: Two patients were bridged for spontaneous recovery and 1 patient was bridged for OLT successfully. Another 2 patients died on d 8 and d 21. The spontaneous recovery rate was 30.0%. PTA and CHE in all patients were significantly increased (P < 0.01), while the serum TBIL, endotoxin,TNF-α, IL-6 were decreased. MELD score (mean 43.6) predicted 100% deaths within 3 mo before treatment with HBL. After treatment with HBL, four out of 5 patients had decreased MELD scores (mean 36.6). The MELD score predicted 66% mortalities. CONCLUSION: The proinflammatory cytokines (TNFα, IL-6 and endotoxin)can be significantly removed by hybrid bioartificial liver and HBL appears to be effective in blocking SIRS and MODS in patients with acute and sub-acute liver failure. MELD is a reliable measure for predicting short-term mortality risk in patients with end-stage liver disease. The prognostic result also corresponds to clinical outcome. PMID:15112365

A technician monitors the CHeX, a USMP-4 experiment which will be flown on STS-87, in the SSPF

NASA Technical Reports Server (NTRS)

1997-01-01

United States Microgravity Payload-4 (USMP-4) experiments are prepared to be flown on Space Shuttle mission STS-87 in the Space Station Processing Facility at Kennedy Space Center (KSC). Here, a technician is monitoring the Confined Helium Experiment, or CHeX, that will use microgravity to study one of the basic influences on the behavior and properties of materials by using liquid helium confined between silicon disks. CHeX and several other experiments are scheduled for launch aboard STS-87 on Nov. 19 from KSC.

Adaptation Mechanism of the Aspartate Receptor: Electrostatics of the Adaptation Subdomain Play a Key Role in Modulating Kinase Activity†

PubMed Central

Starrett, Diane J.; Falke, Joseph J.

2010-01-01

The aspartate receptor of the Escherichia coli and Salmonella typhimurium chemotaxis pathway generates a transmembrane signal that regulates the activity of the cytoplasmic kinase CheA. Previous studies have identified a region of the cytoplasmic domain that is critical to receptor adaptation and kinase regulation. This region, termed the adaptation subdomain, contains a high density of acidic residues, including specific glutamate residues that serve as receptor adaptation sites. However, the mechanism of signal propagation through this region remains poorly understood. This study uses site-directed mutagenesis to neutralize each acidic residue within the subdomain to probe the hypothesis that electrostatics in this region play a significant role in the mechanism of kinase activation and modulation. Each point mutant was tested for its ability to regulate chemotaxis in vivo and kinase activity in vitro. Four point mutants (D273N, E281Q, D288N, and E477Q) were found to superactivate the kinase relative to the wild-type receptor, and all four of these kinase-activating substitutions are located along the same intersubunit interface as the adaptation sites. These activating substitutions retained the wild-type ability of the attractant-occupied receptor to inhibit kinase activity. When combined in a quadruple mutant (D273N/E281Q/D288N/E477Q), the four charge-neutralizing substitutions locked the receptor in a kinase-superactivating state that could not be fully inactivated by the attractant. Similar lock-on character was observed for a charge reversal substitution, D273R. Together, these results implicate the electrostatic interactions at the intersubunit interface as a major player in signal transduction and kinase regulation. The negative charge in this region destabilizes the local structure in a way that enhances conformational dynamics, as detected by disulfide trapping, and this effect is reversed by charge neutralization of the adaptation sites. Finally, two substitutions (E308Q and E463Q) preserved normal kinase activation in vitro but blocked cellular chemotaxis in vivo, suggesting that these sites lie within the docking site of an adaptation enzyme, CheR or CheB. Overall, this study highlights the importance of electrostatics in signal transduction and regulation of kinase activity by the cytoplasmic domain of the aspartate receptor. PMID:15683239

RELATIONSHIPS BETWEEN TISSUE LEVELS OF CARBARYL, A PROTOTYPICAL CARBAMATE PESTICIDE, AND CHOLINESTERASE INHIBITION IN LONG EVANS RATS.

EPA Science Inventory

As part of an effort to link pharmacokinetics with biochemical and physiological endpoints, the relationships between cholinesterase (ChE) activity and tissue levels of a prototypical N-methyl carbamate pesticide were examined. In a dose-response study, carbaryl (0, 3, 7.5, 15, 3...

Efficacy of novel phenoxyalkyl pyridinium oximes as brain-penetrating reactivators of cholinesterase inhibited by surrogates of sarin and VX.

PubMed

Chambers, Janice E; Chambers, Howard W; Funck, Kristen E; Meek, Edward C; Pringle, Ronald B; Ross, Matthew K

2016-11-25

Pyridinium oximes are strong nucleophiles and many are effective reactivators of organophosphate-inhibited cholinesterase (ChE). However, the current oxime reactivators are ineffective at crossing the blood-brain barrier and reactivating brain ChE in the intact organism. Our laboratories have developed a series of substituted phenoxyalkyl pyridinium oximes (US patent 9,227,937 B2) with the goal of identifying reactivators effective in crossing the blood-brain barrier. The first 35 of the series were found to have similar in vitro efficacy as reactivators of ChE inhibited by a sarin surrogate (phthalimidyl isopropyl methylphosphonate, PIMP) or a VX surrogate (nitrophenyl ethyl methylphosphonate, NEMP) in bovine brain preparations as previously observed in rat brain preparations. A number of these novel oximes have shown the ability to decrease the level of ChE inhibition in the brains of rats treated with a high sublethal dosage of either a sarin surrogate (nitrophenyl isopropyl methylphosphonate, NIMP) or the VX surrogate NEMP. Levels of reactivation at 2 h after oxime administration were up to 35% while the currently approved therapeutic, 2-PAM, yielded no reduction in brain ChE inhibition. In addition, there was evidence of attenuation of seizure-like behavior with several of the more effective novel oximes, but not 2-PAM. Therefore these novel oximes have demonstrated an ability to reactivate inhibited ChE in brain preparations from two species and in vivo data support their ability to enter the brain and provide a therapeutic action. These novel oximes have the potential to be developed into improved antidotes for nerve agent therapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Effectiveness of school-based interventions to prevent traffic accidents: an overview of secondary literature].

PubMed

Guerriero, Chiara; Verdina, Federico; Ferri, Chiara; Pizzaguerra, Martina; Silvestri, Silvia; Tober, Nastassja; Ristagno, Quenya; Costa, Alessandro; Cerasuolo, Michele; Faggiano, Fabrizio; Allara, Elias

2016-01-01

INTRODUZIONE: gli incidenti stradali sono l'ottava causa di morte al mondo e la prima tra i giovani di 15-29 anni. In Italia il Piano nazionale sicurezza stradale raccomanda l'educazione scolastica per la prevenzione degli incidenti stradali; ad oggi non esistono documenti che raccolgano evidenze di efficacia sugli interventi educativi stradali e le rapportino al contesto italiano. OBIETTIVI: riassumere e discutere ciò che è noto in letteratura riguardo agli interventi scolastici per la prevenzione degli incidenti stradali. METODI: sono state ricercate linee guida e revisioni sistematiche usando i seguenti criteri di inclusione: popolazione di età inferiore ai 25 anni di entrambi i sessi; interventi scolastici di educazione stradale; effetti su indicatori primari di esito come riduzione degli incidenti stradali, astinenza dalla guida sotto l'effetto di alcol e dall'accettare passaggi in macchina da guidatori che sono sotto l'effetto di alcol; effetti su indicatori secondari di esito come conoscenze e competenze sui comportamenti di guida sicura. RISULTATI: sono state identificate due revisioni sistematiche. L'educazione stradale nelle scuole non mostra evidenza di efficacia (rischio relativo 1,03; IC95% 0,98-1,08) nel ridurre gli incidenti. Programmi scolastici più specifici mostrano risultati solo in parte convincenti per l'adozione di comportamenti sicuri come l'astinenza dal guidare sotto l'effetto di alcol e dall'accettare passaggi in macchina da guidatori che sono sotto l'effetto di alcol. DISCUSSIONE: le revisioni incluse non hanno trovato programmi efficaci nella riduzione degli incidenti stradali o dei fattori che possano determinarli. Nell'attesa di studi più recenti, appare opportuno promuovere l'implementazione di interventi misti, scolastici e di comunità, che hanno mostrato maggiori prove di efficacia.

Variations in catastrophic health expenditure estimates from household surveys in India

PubMed Central

Dandona, Rakhi; Dandona, Lalit

2013-01-01

Abstract Objective To assess the comparability of out-of-pocket (OOP) payment and catastrophic health expenditure (CHE) estimates from different household surveys in India. Methods Data on CHE, outpatient and inpatient OOP payments and other expenditure from all major national or multi-state surveys since 2000 were compared. These included two consumer expenditure surveys (the National Sample Survey for 2004–05 [NSS 2004–05] and 2009–10 [NSS 2009–10]) and three health-focused surveys (the World Health Survey 2003 [WHS 2003]; the National Sample Survey on Morbidity, Health Care and the Condition of the Aged 2004 [NSS 2004]; and the Study on Global Ageing and Adult Health 2007–08 [SAGE 2007–08]). All but the NSS 2004–05 and the NSS 2009–10 used different questionnaires. Findings CHE estimates from WHS 2003 and SAGE 2007–08 were twice as high as those from NSS 2004–05, NSS 2009–10 and NSS 2004. Inpatient OOP payment estimates were twice as high in WHS 2003 and SAGE 2007–08 because in these surveys a much higher proportion of households reported such payments. However, estimates of expenditures on other items were half as high in WHS 2003 as in the other surveys because a very small number of items was used to capture these expenditures. Conclusion The wide variations observed in CHE and OOP payment estimates resulted from methodological differences. Survey methods used to assess CHE in India need to be standardized and validated to accurately track CHE and assess the impact of recent policies to reduce it. PMID:24115796

Exposure of free-flying birds to anticholinesterase insecticides in two conventionally managed fruit orchards

USGS Publications Warehouse

Borges, S.L.

2002-01-01

Conventionally managed orchards receive extensive applications of anticholinesterase (anti-ChE) insecticides throughout the growing season. Because many avian species make use of these environments for nesting and foraging, they may receive substantial exposure to anti-ChEs. The model used to assess avian risk in these environments is highly simplified, and indicator species used in risk studies may misrepresent the risk of the species in the field. A better understanding of avian risk is needed, and should begin with a closer examination o# their exposure in these environments. Exposure of free-flying birds was examined in two conventional orchards during the nesting seasons of 1999 and 2000. Our goal was to demonstrate the influences of species and chemical differences on the exposure we observed. Plasma ChE activity and ChE reactivation were used to identify exposure in multiple species following anti-ChE applications (applied singly and in mixtures). Chipping sparrows (Spizella passerina), American goldfinches (Carduelis tristis), and American robins (Turdus migratorius) demonstrated significant ChE activity depression in 1999 (p 0.005), and only chipping sparrows demonstrated significant depression in 2000 (p = 0.0002). These three species demonstrated the highest proportion of exposed individuals among all species examined in both years. Because many chemicals were simultaneously present in each orchard, chemical influences on the exposure we observed could not be discerned. This work does demonstrate, however, that avian species differ significantly in their exposure, and that chipping sparrows demonstrated the greatest exposure among the species analyzed. These results underscore the need for multiple species studies and for choosing indicator species on a biologically relevant basis.

Environmental contaminants in Texas, USA, wetland reptiles: Evaluation using blood samples

USGS Publications Warehouse

Clark, D.R.; Bickham, J.W.; Baker, D.L.; Cowman, D.F.

2000-01-01

Four species of reptiles (diamondback water snake [Nerodia rhombifer], blotched water snake [N. erythrogaster], cottonmouth [Agkistrodon piscivorus], and red-eared slider [Trachemys scripta]) were collected at two contaminated and three reference sites in Texas, USA. Old River Slough has received intensive applications of agricultural chemicals since the 1950s. Municipal Lake received industrial arsenic wastes continuously from 1940 to 1993. Blood samples were analyzed for organochlorines, potentially toxic elements, genetic damage, and plasma cholinesterase (ChE). Dichlorodiphenyldichloroethylene (DDE) concentrations reached as high as 3.0 ppm (wet weight) in whole blood of a diamondback water snake at Old River Slough, a level probably roughly equivalent to the maximum concentration found in plasma of peregrine falcons (Falco peregrinus) in 1978 to 1979 when DDE peaked in this sensitive species. Possible impacts on diamondback water snakes are unknown, but at least one diamondback water snake was gravid when captured, indicating active reproduction. Arsenic was not found in red-eared sliders (only species sampled) from Municipal Lake. Red-eared sliders of both sexes at Old River Slough showed declining levels of ChE with increasing mass, suggesting a life-long decrease of ChE levels. Possible negative population consequences are unknown, but no evidence was found in body condition (mass relative to carapace length) that red-eared sliders at either contaminated site were harmed.

CORRELATING NEUROBEHAVIORAL PERFORMANCE WITH BIOMARKERS OF ORGANOPHOSPHOROUS PESTICIDE EXPOSURE

PubMed Central

Rohlman, Diane S.; Anger, W Kent; Lein, Pamela J

2011-01-01

There is compelling evidence that adverse neurobehavioral effects are associated with occupational organophosphorous pesticide (OP) exposure in humans. Behavioral studies of pesticide applicators, greenhouse workers, agricultural workers and farm residents exposed repeatedly over months or years to low levels of OPs reveal a relatively consistent pattern of neurobehavioral deficits. However, only two studies have demonstrated a link between neurobehavioral performance and current biomarkers of OP exposure including blood cholinesterase (ChE) activity and urinary levels of OP metabolites. A variety of reasons may explain why so few studies have reported such correlations, including differing individual and group exposure histories, differing methodologies for assessing behavior and exposure, and lack of a reliable index of exposure. Alternatively, these data may suggest that current biomarkers (ChE, urine metabolites) are neither predictive nor diagnostic of the neurobehavioral effects of chronic OP pesticide exposures. This review focuses on the evidence that neurobehavioral performance deficits are associated with occupational OP pesticide exposure and concludes that research needs to return to the basics and rigorously test the relationships between neurobehavioral performance and both current (ChE and urine metabolites) and novel (eg, inflammation and oxidative stress) biomarkers using human and animal models. The results of such studies are critically important because OP pesticides are widely and extensively used throughout the world, including situations where exposure controls and personal protective equipment are not routinely used. PMID:21182866

Design, synthesis and evaluation of novel tacrine-coumarin hybrids as multifunctional cholinesterase inhibitors against Alzheimer's disease.

PubMed

Xie, Sai-Sai; Wang, Xiao-Bing; Li, Jiang-Yan; Yang, Lei; Kong, Ling-Yi

2013-06-01

A series of tacrine-coumarin hybrids (8a-t) were designed, synthesized and evaluated as multifunctional cholinesterase (ChE) inhibitors against Alzheimer's disease (AD). The screening results showed that most of them exhibited a significant ability to inhibit ChE and self-induced β-amyloid (Aβ) aggregation, and to act as metal chelators. Especially, 8f displayed the greatest ability to inhibit acetylcholinesterase (AChE, IC50 = 0.092 μM) and Aβ aggregation (67.8%, 20 μM). It was also a good butyrylcholinesterase inhibitor (BuChE, IC50 = 0.234 μM) and metal chelator. Besides, kinetic and molecular modeling studies indicated that 8f was a mixed-type inhibitor, binding simultaneously to active, peripheral and mid-gorge sites of AChE. These results suggested that 8f might be an excellent multifunctional agent for AD treatment. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Demonstrating the Open Data Repository's Data Publisher: The CheMin Database

NASA Astrophysics Data System (ADS)

Stone, N.; Lafuente, B.; Bristow, T.; Pires, A.; Keller, R. M.; Downs, R. T.; Blake, D.; Dateo, C. E.; Fonda, M.

2018-04-01

The Open Data Repository's Data Publisher aims to provide an easy-to-use software tool that will allow researchers to create and publish database templates and related data. The CheMin Database developed using this framework is shown as an example.

A CheR/CheB fusion protein is involved in cyst cell development and chemotaxis in Azospirillum brasilense Sp7.

PubMed

Wu, Lixian; Cui, Yanhua; Hong, Yuanyuan; Chen, Sanfeng

2011-12-20

We here report the sequence and functional analysis of cstB of Azospirillum brasilense Sp7. The predicted cstB contains C-terminal two PAS domains and N-terminal part which has similarity with CheB-CheR fusion protein. cstB mutants had reduced swarming ability compared to that of A. brasilense wild-type strain, implying that cstB was involved in chemotaxis in A. brasilense. A microscopic analysis revealed that cstB mutants developed mature cyst cells more quickly than wild type, indicating that cstB is involved in cyst formation. cstB mutants were affected in colony morphology and the production of exopolysaccharides (EPS) which are essential for A. brasilense cells to differentiate into cyst-like forms. These observations suggested that cstB was a multi-effector involved in cyst development and chemotaxis in A. brasilense. Copyright © 2010 Elsevier GmbH. All rights reserved.

Elettrodinamica classica

NASA Astrophysics Data System (ADS)

Lechner, Kurt

Nella scoperta della Relatività Ristretta l'Elettrodinamica, rappresentando una teoria relativistica per eccellenza, ha giocato un ruolo fondamentale. Il principio di relativit` a einsteiniana, che afferma che tutte le leggi della fisica devono avere la stessa forma in tutti i sistemi di riferimento inerziali, è emerso con forza da questa teoria ed è andato consolidandosi sempre di più, man mano che le nostre conoscenze del mondo microscopico sono diventate più complete: tutte le interazioni fondamentali rispettano infatti tale principio. Il modo più semplice ed elegante per implementarlo — difatti l'unico di un'utilità concreta — è rappresentato dal paradigma della covarianza a vista nell'ambito del calcolo tensoriale. Questo paradigma è stato applicato con successo a tutte le teorie di carattere fondamentale, come le teorie che descrivono le quattro interazioni fondamentali e le più speculative teorie di superstringa, e mantiene la sua piena efficacia anche in teoria quantistica. La nostra esposizione dell'Elettrodinamica classica si baserà dunque a ragione su questo paradigma.

Determination of cadmium in seawater by chelate vapor generation atomic fluorescence spectrometry

NASA Astrophysics Data System (ADS)

Sun, Rui; Ma, Guopeng; Duan, Xuchuan; Sun, Jinsheng

2018-03-01

A method for the determination of cadmium in seawater by chelate vapor generation (Che-VG) atomic fluorescence spectrometry is described. Several commercially available chelating agents, including ammonium pyrrolidine dithiocarbamate (APDC), sodium dimethyl dithiocarbamate (DMDTC), ammonium dibutyl dithiophosphate (DBDTP) and sodium O,O-diethyl dithiophosphate (DEDTP), are compared with sodium diethyldithiocarbamate (DDTC) for the Che-VG of cadmium, and results showed that DDTC and DEDTP had very good cadmium signal intensity. The effect of the conditions of Che-VG with DDTC on the intensity of cadmium signal was investigated. Under the optimal conditions, 85 ± 3% Che-VG efficiency is obtained for cadmium. The detection limit (3σ) obtained in the optimal conditions was 0.19 ng ml- 1. The relative standard deviation (RSD, %) for ten replicate determinations at 2 ng ml- 1 Cd was 3.42%. The proposed method was successfully applied to the ultratrace determination of cadmium in seawater samples by the standard addition method.

X-Ray Diffraction for In-Situ Mineralogical Analysis of Planetesimals.

NASA Astrophysics Data System (ADS)

Sarrazin, P.; Blake, D. F.; Dera, P.; Downs, R. T.; Taylor, J.

2017-12-01

X-ray diffraction (XRD) is a general purpose technique for definitive, quantitative mineralogical analysis. When combined with XRF data for sample chemistry, XRD analyses yield as complete a characterization as is possible by any spacecraft-capable techniques. The MSL CheMin instrument, the first XRD instrument flown in space, has been used to establish the quantitative mineralogy of the Mars global soil, to discover the first habitable environment on another planet, and to provide the first in-situ evidence of silicic volcanism on Mars. CheMin is now used to characterize the depositional and diagenetic environments associated with the mudstone sediments of lower strata of Mt. Sharp. Conventional powder XRD requires samples comprised of small grains presented in random orientations. In CheMin, sample cells are vibrated to cause loose powder to flow within the cell, driven by granular convection, which relaxes the requirement for fine grained samples. Nevertheless, CheMin still requires mechanisms to collect, crush, sieve and deliver samples before analysis. XTRA (Extraterrestrial Regolith Analyzer) is an evolution of CheMin intended to analyze fines in as-delivered surface regolith, without sample preparation. Fine-grained regolith coats the surfaces of most airless bodies in the solar system, and because this fraction is typically comminuted from the rocky regolith, it can often be used as a proxy for the surface as a whole. HXRD (Hybrid-XRD) is concept under development to analyze rocks or soils without sample preparation. Like in CheMin, the diffracted signal is collected with direct illumination CCD's. If the material is sufficiently fine-grained, a powder XRD pattern of the characteristic X-ray tube emission is obtained, similar to CheMin or XTRA. With coarse grained crystals, the white bremsstrahlung radiation of the tube is diffracted into Laue patterns. Unlike typical Laue applications, HXRD uses the CCD's capability to distinguish energy and analyze the "colors" of each Laue spot, which enable phase identification. The concept was demonstrated with prototypes and dedicated crystallographic software was developed for identification the minerals responsible for the Laue patterns. High TRL subsystems are under development for future deployment opportunities of these new XRD instruments.

Astrobiological Significance of Definitive Mineralogical Analysis of Martian Surface Samples Using the CheMin XRD/XRF Instrument

NASA Technical Reports Server (NTRS)

Feldman, S. M.; Blake, D. F.; Sarrazin, P.; Bish, D. L.; Chipera, S. J.; Vaniman, D. T.; Collins, S.

2004-01-01

The search for evidence of habitability, or of extant or extinct life on Mars, will initially be a search for evidence of past or present conditions supportive of life. The three key requirements for the emergence of life are thought to be liquid water; a suitable energy source; and chemical building blocks. CheMin is a miniaturized XRD/XRF (X-Ray diffraction / X-ray fluorescence) instrument which has been developed for definitive mineralogic analysis of soils and rocks on the Martian surface. The CheMin instrument can provide information that is highly relevant to each of these habitability requirements as summarized below.

Kommunikation mit Mitarbeitern

NASA Astrophysics Data System (ADS)

Spychala, Anne; Fleischmann, Jürgen

Kommunikation ist der Austausch von Nachrichten und Informationen zwischen Mitarbeitern eines Unternehmens (O'Hair et al. 1997). Dieser Austausch kann persönlich, aber z.B. auch per Telefon, E-Mail oder durch Computersysteme erfolgen. In diesem Kapitel betrachten wir die persönliche Kommunikation zwischen Vorgesetzten und Mitarbeitern. Zur persönlichen Kommunikation mit Mitarbeitern zählen sowohl formelle Gespräche mit Mitarbeitern als auch eher informelle Gespräche zwischen Tür und Angel. Die Gespräche können dabei mit einzelnen Mitarbeitern (z.B. jährliches Mitarbeitergespräch) oder mit Gruppen von Mitarbeitern (z.B. regelmäßige Projekt- oder Teambesprechungen) stattfinden.

Dischi (E Jet) Nelle Stelle Massicce Giovani

NASA Astrophysics Data System (ADS)

Cesaroni, Riccardo

2017-11-01

In questo contributo verrà discussa l'importanza dei dischi e jet ad essi asso- ciati per la formazione delle stelle di tipo spettrale OB e verranno presentati i risultati recentemente ottenuti con ALMA in questo ambito. In particolare mostr- eremo che la struttura del disco sembra risentire della complessità dell'ambiente circostante e che la probabilità di rivelare un disco attorno alle stelle di più alta massa è massima in una fase evolutiva intermedia. Infine discuteremo la possibilità che il fenomeno di accrescimento dal disco sulla stella possa avvenire in maniera discontinua mediante "burst", probabilmente dovuti ad instabilità nel disco.

Chemotactic Signaling by Single-Chain Chemoreceptors

PubMed Central

Mowery, Patricia; Ames, Peter; Reiser, Rebecca H.; Parkinson, John S.

2015-01-01

Bacterial chemoreceptors of the methyl-accepting chemotaxis protein (MCP) family operate in commingled clusters that enable cells to detect and track environmental chemical gradients with high sensitivity and precision. MCP homodimers of different detection specificities form mixed trimers of dimers that facilitate inter-receptor communication in core signaling complexes, which in turn assemble into a large signaling network. The two subunits of each homodimeric receptor molecule occupy different locations in the core complexes. One subunit participates in trimer-stabilizing interactions at the trimer axis, the other lies on the periphery of the trimer, where it can interact with two cytoplasmic proteins: CheA, a signaling autokinase, and CheW, which couples CheA activity to receptor control. As a possible tool for independently manipulating receptor subunits in these two structural environments, we constructed and characterized fused genes for the E. coli serine chemoreceptor Tsr that encoded single-chain receptor molecules in which the C-terminus of the first Tsr subunit was covalently connected to the N-terminus of the second with a polypeptide linker. We showed with soft agar assays and with a FRET-based in vivo CheA kinase assay that single-chain Tsr~Tsr molecules could promote serine sensing and chemotaxis responses. The length of the connection between the joined subunits was critical. Linkers nine residues or shorter locked the receptor in a kinase-on state, most likely by distorting the native structure of the receptor HAMP domain. Linkers 22 or more residues in length permitted near-normal Tsr function. Few single-chain molecules were found as monomer-sized proteolytic fragments in cells, indicating that covalently joined receptor subunits were responsible for mediating the signaling responses we observed. However, cysteine-directed crosslinking, spoiling by dominant-negative Tsr subunits, and rearrangement of ligand-binding site lesions revealed subunit swapping interactions that will need to be taken into account in experimental applications of single-chain chemoreceptors. PMID:26709829

Misura della sezione d'urto totale e Dello scattering elastico all'energia Nel centro di massa di $$\\sqrt{s}=1.8$$ TeV (in Italian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paoletti, Riccardo

La produzione di eventi elastici è stata misurata al Collider Tevatron del Fermi National Accelerator Laboratory (Batavia. 11.~ U .S.A.) alla energia nel centro di massa. di √s = 1800 GeV, nell'intervallo 0.06 < I t I< 0.24. Sono forniti dettagli sull'esperimento CDF che ha compiuto la misura e sui criteri di selezione degli eventi.

Examining inequities in incidence of catastrophic health expenditures on different healthcare services and health facilities in Nigeria.

PubMed

Onwujekwe, Obinna; Hanson, Kara; Uzochukwu, Benjamin

2012-01-01

There is limited evidence about levels of socio-economic and other differences in catastrophic health spending in Nigeria and in many sub-Saharan African countries. The study estimated the level of catastrophic healthcare expenditures for different healthcare services and facilities and their distribution across socioeconomic status (SES) groups. The study took place in four Local Government Areas in southeast Nigeria. Data were collected using interviewer-administered questionnaires administered to 4873 households. Catastrophic health expenditures (CHE) were measured using a threshold of 40% of monthly non-food expenditure. We examined both total monthly health expenditure and disaggregated expenditure by source and type of care. The average total household health expenditure per month was 2354 Naira ($19.6). For outpatient services, average monthly expenditure was 1809 Naira ($15.1), whilst for inpatient services it was 610 Naira ($5.1). Higher health expenditures were incurred by urban residents and the better-off SES groups. Overall, 27% of households incurred CHE, higher for poorer socioeconomic groups and for rural residents. Only 1.0% of households had a member that was enrolled in a health insurance scheme. The worse-off households (the poorest SES and rural dwellers) experienced the highest burden of health expenditure. There was almost a complete lack of financial risk protection. Health reform mechanisms are needed to ensure universal coverage with financial risk protection mechanisms.

Examining Inequities in Incidence of Catastrophic Health Expenditures on Different Healthcare Services and Health Facilities in Nigeria

PubMed Central

Onwujekwe, Obinna; Hanson, Kara; Uzochukwu, Benjamin

2012-01-01

Objective There is limited evidence about levels of socio-economic and other differences in catastrophic health spending in Nigeria and in many sub-Saharan African countries. The study estimated the level of catastrophic healthcare expenditures for different healthcare services and facilities and their distribution across socioeconomic status (SES) groups. Methods The study took place in four Local Government Areas in southeast Nigeria. Data were collected using interviewer-administered questionnaires administered to 4873 households. Catastrophic health expenditures (CHE) were measured using a threshold of 40% of monthly non-food expenditure. We examined both total monthly health expenditure and disaggregated expenditure by source and type of care. Results The average total household health expenditure per month was 2354 Naira ($19.6). For outpatient services, average monthly expenditure was 1809 Naira ($15.1), whilst for inpatient services it was 610 Naira ($5.1). Higher health expenditures were incurred by urban residents and the better-off SES groups. Overall, 27% of households incurred CHE, higher for poorer socioeconomic groups and for rural residents. Only 1.0% of households had a member that was enrolled in a health insurance scheme. Conclusion The worse-off households (the poorest SES and rural dwellers) experienced the highest burden of health expenditure. There was almost a complete lack of financial risk protection. Health reform mechanisms are needed to ensure universal coverage with financial risk protection mechanisms. PMID:22815828

On the Application of Simple Experiments to the Teaching of ChE Thermodynamics

ERIC Educational Resources Information Center

McNeil, Kenneth M.

1978-01-01

This article describes the undergraduate ChE thermodynamics course at Drexel University and the reasons for incorporating a series of laboratory experiments into the course. Included is a list of lecture topics and a description of each of the experiments. (BB)

Disegno dello studio genomico, ambientale, microbiomico e metabolomico sulla celiachia: un approccio al futuro della prevenzione personalizzata della celiachia

PubMed Central

SERENA, GLORIA; LEONARD, MAUREEN M.; CAMHI, STEPHANIE; HUEDO-MEDINA, TANIA B.; FASANO, ALESSIO

2017-01-01

Riassunto Negli ultimi anni abbiamo assistito a un fiorire di novità cliniche e scientifiche sulla celiachia (CE), ma forse la novità più importante che influenzerà il futuro della ricerca e della clinica in questo campo riguarda la storia naturale della malattia. Per molti anni si è creduto che la predisposizione genetica e l’esposizione al glutine fossero necessarie e sufficienti allo sviluppo della CE. Studi recenti, però suggeriscono che la perdita di tolleranza al glutine possa apparire in qualsiasi momento della vita a seguito di altri elementi. Inoltre, diversi fattori ambientali conosciuti per il loro ruolo nell’influenzare la composizione della microflora intestinale sono anche stati considerati legati allo sviluppo della CE. Tra questi fattori sono inclusi la modalità di parto, la dieta dell’infante e l’uso di antibiotici. A tutt’oggi, nessuno studio longitudinale di ampia scala ha determinato se e come la composizione del microbioma e il suo profilo metabolomico possano influenzare la perdita di tolleranza al glutine e il successivo sviluppo della CE in soggetti geneticamente predisposti. In questo articolo descriviamo uno studio prospettico, multicentrico e longitudinale su infanti a rischio per la CE che utilizzerà diverse tecniche per approfondire il ruolo che il microbioma intestinale ha durante i primi passaggi dello sviluppo della malattia autoimmune. PMID:27362724

Design, synthesis, pharmacological evaluation, QSAR analysis, molecular modeling and ADMET of novel donepezil-indolyl hybrids as multipotent cholinesterase/monoamine oxidase inhibitors for the potential treatment of Alzheimer's disease.

PubMed

Bautista-Aguilera, Oscar M; Esteban, Gerard; Bolea, Irene; Nikolic, Katarina; Agbaba, Danica; Moraleda, Ignacio; Iriepa, Isabel; Samadi, Abdelouahid; Soriano, Elena; Unzeta, Mercedes; Marco-Contelles, José

2014-03-21

The design, synthesis, and pharmacological evaluation of donepezil-indolyl based amines 7-10, amides 12-16, and carboxylic acid derivatives 5 and 11, as multipotent ASS234 analogs, able to inhibit simultaneously cholinesterase (ChE) and monoamine oxidase (MAO) enzymes for the potential treatment of Alzheimer's disease (AD), is reported. Theoretical studies using 3D-Quantitative Structure-Activity Relationship (3D-QSAR) was used to define 3D-pharmacophores for inhibition of MAO A/B, AChE, and BuChE enzymes. We found that, in general, and for the same substituent, amines are more potent ChE inhibitors (see compounds 12, 13 versus 7 and 8) or equipotent (see compounds 14, 15 versus 9 and 10) than the corresponding amides, showing a clear EeAChE inhibition selectivity. For the MAO inhibition, amides were not active, and among the amines, compound 14 was totally MAO A selective, while amines 15 and 16 were quite MAO A selective. Carboxylic acid derivatives 5 and 11 showed a multipotent moderate selective profile as EeACE and MAO A inhibitors. Propargylamine 15 [N-((5-(3-(1-benzylpiperidin-4-yl)propoxy)-1-methyl-1H-indol-2-yl)methyl)prop-2-yn-1-amine] resulted in the most potent hMAO A (IC50 = 5.5 ± 1.4 nM) and moderately potent hMAO B (IC50 = 150 ± 31 nM), EeAChE (IC50 = 190 ± 10 nM), and eqBuChE (IC50 = 830 ± 160 nM) inhibitor. However, the analogous N-allyl and the N-morpholine derivatives 16 and 14 deserve also attention as they show an attractive multipotent profile. To sum up, donepezil-indolyl hybrid 15 is a promising drug for further development for the potential prevention and treatment of AD. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Modeling Biotransformation Using In Vitro Data on Parent-Metabolite Pairs within the ToxCast Phase I Chemical Set

EPA Science Inventory

A major focus in toxicology research is the development of new in vitro methods to predict in vivo chemical toxicity. Within the EPA ToxCast program, a broad range of in vitro biochemical and cellular assays have been deployed to profile the biological activity of 320 Phase I che...

CHOLINESTERASE INHIBITION AND HYPOTHERMIA FOLLOWING EXPOSURE TO BINARY MIXTURES OF ANTICHOLINESTERASE AGENTS: LACK OF EVIDENCE FOR CAUSE-AND-EFFECT

EPA Science Inventory

Dose-additivity has been the default assumption in risk assessments of pesticides with a common mechanism of action but it has been suspected that there could be non-additive effects. Inhibition of plasma cholinesterase (ChE) activity and hypothermia were used as benchmarks of e...

Cholinesterase Inhibition and Depression of the Photic After Discharge of Flash Evoked Potentials Following Acute or Repeated Exposures to a Mixture of Carbaryl and Propoxur

EPA Science Inventory

While information exists regarding inhibition of cholinesterase (ChE) activity, little is known about neurophysiological changes produced by a mixture of N-methyl carbamate pesticides. Previously, we reported that acute treatment with propoxur or carbaryl decreased the duration o...

Reading Strategies: Issues in the Computerization of Machiavelli's "Il demonio che prese moglie".

ERIC Educational Resources Information Center

Morgan, Leslie Zarker

1994-01-01

The ideal computer-based foreign language reading program must include cognitive background, a learning taxonomy, sound computer design, and knowledge of what is needed for the specific language. Machiavelli's "Il demonia che prese moglie" is chosen for study due to its historical interest. (63 references) (CK)

Cooperative Education in New Mexico.

ERIC Educational Resources Information Center

New Mexico Commission on Higher Education.

In 1988, the State Legislature created the New Mexico Cooperative Program to develop and expand cooperative education (co-op) programs. The Commission on Higher Education (CHE) was designated to help institutions establish and expand programs and collect information. For reporting purposes, CHE required that, in order to be considered co-op, work…

Fan filter cleaning on the CHeCS AAA in the US Lab

NASA Image and Video Library

2009-05-05

ISS019-E-013710 (5 May 2009) --- Japan Aerospace Exploration Agency (JAXA) astronaut Koichi Wakata, Expedition 19/20 flight engineer, cleans a fan filter on the Crew Health Care System Avionics Air Assembly (CHeCS AAA) in the Destiny laboratory of the International Space Station.

Mineralogy by X-ray Diffraction on Mars: The Chemin Instrument on Mars Science Laboratory

NASA Technical Reports Server (NTRS)

Vaniman, D. T.; Bristow, T. F.; Bish, D. L.; Ming, D. W.; Blake, D. F.; Morris, R. V.; Rampe, E. B.; Chipera, S. J.; Treiman, A. H.; Morrison, S. M.;

The effect of river dynamics induced by the Messinian Salinity Crisis on karst landscape and caves: Example of the Lower Ardèche river (mid Rhône valley)

NASA Astrophysics Data System (ADS)

Mocochain, Ludovic; Audra, Philippe; Clauzon, Georges; Bellier, Olivier; Bigot, Jean-Yves; Parize, Olivier; Monteil, Philippe

2009-05-01

The karstic canyon of Lower Ardèche is located in the Middle Rhône valley, which is directly tributary to the Mediterranean Sea. The Rhône River is emblematic of the Messinian Salinity Crisis (MSC) impact on landscape morphology. Along the edge of the Saint-Remèze Plateau, the Rhône valley displays four benchmark levels generated by the MSC: the Pre-evaporitic abandonment surface (1), the Messinian erosional surface (2), the Marine/non-marine surface of the Pliocene ria (3) and the Pliocene abandonment surface (4). The study of these benchmark levels allows us to reconstruct the evolution of the regional base level over the last 6 Ma. We obtain a curve for base-level evolution that provides a geodynamic reference, which is used to investigate the morphogenesis of the Saint-Remèze karstic plateau. The Ardèche River downcuts the Saint-Remèze Plateau in a deep canyon, from Vallon-Pont-d'Arc to the West, to its confluence with the Rhône to the East. Several abandoned valleys are present along the western edge of the Saint-Remèze Plateau at the inlet of the Ardèche canyon. In these abandoned valleys, the fluvial deposits are related to several periods, from the Pliocene onwards. They provide important insights into the fluvial dynamics: a 160 m-thick aggradation sequence infilled the Ardèche canyon during the Pliocene. This aggrading river caused the first lateral shifting, as an aggradation epigenesis. This first infilling shows that the Ardèche canyon already existed before the Pliocene. Secondly, it has been demonstrated that the Ardèche Canyon is downcut into the Pre-evaporitic surface of the Saint-Remèze Plateau, dated to 5.45 Ma [Martini, J., 2005. Etude des paléokarsts des environs de Saint-Remèze (Ardèche, France): mise en évidence d'une rivière souterraine fossilisée durant la crise de salinité messinienne. Karstologia 45-46, 1-18]. Consequently, the canyon downcutting is entirely due to the MSC, and occurred during a time span of only 100 000 years. Based on these observations, it is possible to elucidate the curve of the regional base-level evolution. Hence, we are able to propose a new interpretation of the geomorphological evolution of the Saint-Remèze karstic plateau and its cave levels for the last 6 Ma. The cave levels consist in underground short-cuts of the surface meanders. They mainly developed during the Pliocene aggradation cycle. The Chauvet Cave, famous for its Palaeolithic paintings, corresponds to one of these underground short-cuts. The aggradation period ends at the end of the Pliocene with long high-level riverbed stability. It favours the development of large low gradient surfaces as pediments. The complete Messinian-Pliocene eustatic cycle is responsible for the downcutting of the Ardèche canyon and its infilling during the Pliocene. Consequently, karst developed according to the base-level oscillations, as low gradient surfaces and as cave levels. For the study of the peri-Mediterranean caves and karst areas, we propose to apply the Lower Ardèche valley evolution model, based on the base-level oscillations during and after the MSC.

Sarcolemmal mechanisms for pHi recovery from alkalosis in the guinea-pig ventricular myocyte

PubMed Central

Leem, Chae-Hun; Vaughan-Jones, Richard D

1998-01-01

The mechanism of pHi recovery from an intracellular alkali load (induced by acetate prepulse or by reduction/removal of ambient PCO2) was investigated using intracellular SNARF fluorescence in the guinea-pig ventricular myocyte. In Hepes buffer (pHo 7.40), pHi recovery was inhibited by removal of extracellular Cl−, but not by removal of Na+o or elevation of K+o. Recovery was unaffected by the stilbene drug DIDS (4,4-diisothiocyanatostilbene-disulphonic acid), but was slowed dose dependently by the stilbene drug DBDS (dibenzamidostilbene-disulphonic acid). In 5 % CO2/HCO3− buffer (pHo 7.40), pHi recovery was faster than in Hepes buffer. It consisted of an initial rapid recovery phase followed by a slow phase. Much of the rapid phase has been attributed to CO2-dependent buffering. The slow phase was inhibited completely by Cl− removal but not by Na+o removal or K+o elevation. At a test pHi of 7.30 in CO2/HCO3− buffer, the slow phase was inhibited 70 % by DIDS. The mean DIDS-inhibitable acid influx was equivalent in magnitude to the HCO3−-stimulated acid influx. Similarly, the DIDS-insensitive influx was equivalent to that estimated in Hepes buffer. We conclude that two independent sarcolemmal acid-loading carriers are stimulated by a rise of pHi and account for the slow phase of recovery from an alkali load. The results are consistent with activation of a DIDS-sensitive Cl−-HCO3− anion exchanger (AE) to produce HCO3− efflux, and a DIDS-insensitive Cl−-OH− exchanger (CHE) to produce OH− efflux. H+-Cl− co-influx as the alternative configuration for CHE is not, however, excluded. The dual acid-loading system (AE plus CHE), previously shown to be activated by a fall of extracellular pH, is thus activated by a rise of intracellular pH. Activity of the dual-loading system is therefore controlled by pH on both sides of the cardiac sarcolemma. PMID:9575297

Wolf-Rayet spin at low metallicity and its implication for black hole formation channels

NASA Astrophysics Data System (ADS)

Vink, Jorick S.; Harries, Tim J.

2017-07-01

Context. The spin of Wolf-Rayet (WR) stars at low metallicity (Z) is most relevant for our understanding of gravitational wave sources, such as GW 150914, and of the incidence of long-duration gamma-ray bursts (GRBs). Two scenarios have been suggested for both phenomena: one of them involves rapid rotation and quasi-chemical homogeneous evolution (CHE) and the other invokes classical evolution through mass loss in single and binary systems. Aims: The stellar spin of WR stars might enable us to test these two scenarios. In order to obtain empirical constraints on black hole progenitor spin we infer wind asymmetries in all 12 known WR stars in the Small Magellanic Cloud (SMC) at Z = 1 / 5 Z⊙ and within a significantly enlarged sample of single and binary WR stars in the Large Magellanic Cloud (LMC at Z = 1 / 2 Z⊙), thereby tripling the sample of Vink from 2007. This brings the total LMC sample to 39, making it appropriate for comparison to the Galactic sample. Methods: We measured WR wind asymmetries with VLT-FORS linear spectropolarimetry, a tool that is uniquely poised to perform such tasks in extragalactic environments. Results: We report the detection of new line effects in the LMC WN star BAT99-43 and the WC star BAT99-70, along with the well-known WR LBV HD 5980 in the SMC, which might be undergoing a chemically homogeneous evolution. With the previous reported line effects in the late-type WNL (Ofpe/WN9) objects BAT99-22 and BAT99-33, this brings the total LMC WR sample to four, I.e. a frequency of 10%. Perhaps surprisingly, the incidence of line effects amongst low Z WR stars is not found to be any higher than amongst the Galactic WR sample, challenging the rotationally induced CHE model. Conclusions: As WR mass loss is likely Z-dependent, our Magellanic Cloud line-effect WR stars may maintain their surface rotation and fulfill the basic conditions for producing long GRBs, both via the classical post-red supergiant or luminous blue variable channel, or resulting from CHE due to physics specific to very massive stars.

Critical thresholds of liver function parameters for ketosis prediction in dairy cows using receiver operating characteristic (ROC) analysis.

PubMed

Sun, Yuhang; Wang, Bo; Shu, Shi; Zhang, Hongyou; Xu, Chuang; Wu, Ling; Xia, Cheng

2015-01-01

Fatty liver syndrome and ketosis are important metabolic disorders in high-producing cows during early lactation with fatty liver usually preceding ketosis. To date, parameters for early prediction of the risk of ketosis have not been investigated in China. To determine the predictive value of some parameters on the risk of ketosis in China. In a descriptive study, 48 control and 32 ketotic Holstein Friesian cows were randomly selected from one farm with a serum β-hydroxybutyrate (BHBA) concentration of 1.20 mmol/L as cutoff point. The risk prediction thresholds for ketosis were determined by receiver operating characteristic (ROC) analysis. In line with a high BHBA concentration, blood glucose concentration was significantly lower in ketotic cows compared to control animals (2.77 ± 0.24 versus 3.34 ± 0.03 mmol/L; P = 0.02). Thresholds were more than 0.76 mmol/L for nonesterified fatty acids (NEFA, with 65% sensitivity and 92% specificity), more than 104 U/L for aspartate aminotransferase (AST, 74% and 85%, respectively), less than 140 U/L for cholinesterase (CHE, 75% and 59%, respectively), and more than 3.3 µmol/L for total bilirubin (TBIL, 58% and 83%, respectively). There were significant correlations between BHBA and glucose (R = -4.74), or CHE (R = -0.262), BHBA and NEFA (R = 0.520), or AST (R = 0.525), or TBIL (R = 0.278), or direct bilirubin (DBIL, R = 0.348). AST, CHE, TBIL and NEFA may be useful parameters for risk prediction of ketosis. This study might be of value in addressing novel directions for future research on the connection between ketosis and liver dysfunction.

Financial protection in health in Turkey: the effects of the Health Transformation Programme.

PubMed

Yardim, Mahmut S; Cilingiroglu, Nesrin; Yardim, Nazan

2014-03-01

Financial protection should be the principal objective of any health system. Commonly used indicators for financial protection are out-of-pocket (OOP) payments as a share of total health expenditure and the amount of households driven into poverty by catastrophic health expenditures (CHEs). In the last decade, OOP health payments consisted of approximately one-fifth of the health finance resources in Turkey. Until the year 2008, Turkish health system covered different public and private financing programmes as well as different types of service provision. After 2008, universal financial coverage became a part of the Health Transformation Programme (HTP). This study aimed to evaluate the financial protection in health in the era of health reforms in Turkey between 2003 and 2009. Household expenditures were derived from nationally representative Turkish Household Budget Surveys (HBSs), 2003, 2006 and 2009. Proportion of households facing CHE and impoverishment are calculated by using the methodology proposed by Ke Xu. Probability of incurring and volume of OOP spending were assessed across the health insurance groups by two-part model approach using logistic and OLS regression methods. Our findings showed that the probability of incurring and volume of OOP spending increased gradually in publicly insured households between 2003 and 2009. However, there was a diminishing trend in CHE in Turkey during the period under consideration. The official data showing an ∼3-fold increase in per capita health care use since 2003 and our study findings on decreasing CHE in this period can be interpreted as positive impact of HTP. On the other hand, increased household consumption as a share of OOP health payment and the deterioration in the progressivity of OOP spending in this period should be monitored closely.

Dose-additivity modeling for acute and repeated exposure to a mixture of N-methycarbamate Pesticides

EPA Science Inventory

The toxicity of N-methylcarbamate pesticides is attributed to the reversible inhibition of cholinesterase (ChE) enzymes in the central and peripheral nervous system. The inhibition of ChE following a single exposure to this class of pesticides has been modeled using a dose-additi...

Application of a Curriculum Hierarchy Evaluation (CHE) Model to Sequentially Arranged Tasks.

ERIC Educational Resources Information Center

O'Malley, J. Michael

A curriculum hierarchy evaluation (CHE) model was developed by combining a transfer paradigm with an aptitude-treatment-task interaction (ATTI) paradigm. Positive transfer was predicted between sequentially arranged tasks, and a programed or nonprogramed treatment was predicted to interact with aptitude and with tasks. Eighteen four and five…

The chemotaxis-like Che1 pathway has an indirect role in adhesive cell properties of Azospirillum brasilense.

PubMed

Siuti, Piro; Green, Calvin; Edwards, Amanda Nicole; Doktycz, Mitchel J; Alexandre, Gladys

2011-10-01

The Azospirillum brasilense chemotaxis-like Che1 signal transduction pathway was recently shown to modulate changes in adhesive cell surface properties that, in turn, affect cell-to-cell aggregation and flocculation behaviors rather than flagellar-mediated chemotaxis. Attachment to surfaces and root colonization may be functions related to flocculation. Here, the conditions under which A. brasilense wild-type Sp7 and che1 mutant strains attach to abiotic and biotic surfaces were examined using in vitro attachment and biofilm assays combined with atomic force microscopy and confocal microscopy. The nitrogen source available for growth is found to be a major modulator of surface attachment by A. brasilense and could be promoted in vitro by lectins, suggesting that it depends on interaction with surface-exposed residues within the extracellular matrix of cells. However, Che1-dependent signaling is shown to contribute indirectly to surface attachment, indicating that distinct mechanisms are likely underlying flocculation and attachment to surfaces in A. brasilense. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Amorphous Analogs of Martian Global Soil: Pair Distribution Function Analyses and Implications for Scattering Models of Chemin X-ray Diffraction Data

NASA Technical Reports Server (NTRS)

Achilles, C. N.; Bish, D. L.; Rampe, E. B.; Morris, R. V.

2015-01-01

Soils on Mars have been analyzed by the Mars Exploration Rovers (MER) and most recently by the Mars Science Laboratory (MSL) rover. Chemical analyses from a majority of soil samples suggest that there is a relatively uniform global soil composition across much of the planet. A soil site, Rocknest, was sampled by the MSL science payload including the CheMin X-ray diffractometer and the Alpha Particle X-ray Spectrometer (APXS). Che- Min X-ray diffraction (XRD) data revealed crystalline phases and a broad, elevated background, indicating the presence of amorphous or poorly ordered materials (Fig 1). Based on the chemical composition of the bulk soil measured by APXS and the composition of crystalline phases derived from unit-cell parameters determined with CheMin data, the percentages of crystalline and amorphous phases were calculated at 51% and 49%, respectively. Attempts to model the amorphous contribution to CheMin XRD patterns were made using amorphous standards and full-pattern fitting methods and show that the broad, elevated background region can be fitted by basaltic glass, allophane, and palagonite. However, the modeling shows only that these phases have scattering patterns similar to that for the soil, not that they represent unique solutions. Here, we use pair distribution function (PDF) analysis to determine the short-range order of amorphous analogs in martian soils and better constrain the amorphous material detected by CheMin.

[Atmospheric non-methane hydrocarbons near plants of crude oil first treatment].

PubMed

Bustaffa, Elisa; De Marinis Loiotile, Annamaria; Farella, Genoveffa; Petraccone, Stefania; De Gennaro, Gianluigi; Bianchi, Fabrizio

2016-01-01

La continua espansione delle attività di perforazione ai fini dell'estrazione petrolifera in prossimità di aree abitate ha fatto sì che negli ultimi anni l'attenzione si focalizzasse sull'impatto di questo processo fortemente industrializzato sulla salute pubblica. Le comunità che vivono nei dintorni di impianti di questo tipo devono, infatti, fronteggiare diversi problemi, quali l'inquinamento atmosferico e acustico, la contaminazione del suolo e delle acque sotterranee, il traffico dei camion da e verso il sito, incidenti e malfunzionamenti all'interno dell'impianto. In questo contesto, la valutazione del rischio per la salute è ostacolata dal fatto che l'esposizione alle sostanze chimiche presenti non può essere valutata in via definitiva, poiché non sempre si è a conoscenza di tutti i composti immessi nell'ambiente né delle loro concentrazioni, per non parlare del problema delle coesposizioni ad altri inquinanti. Nonostante l'oramai conclamato e vasto interesse generato da questo argomento, ad oggi esistono pochi studi basati su popolazioni riguardanti gli effetti sulla salute delle comunità che vivono in prossimità dei siti di perforazione ed estrazione; ciò genera la necessità di condurre campagne di monitoraggio mirate e studi epidemiologici che verifichino l'eventuale esistenza e natura di pattern di malattie associati a tali attività. La presente rassegna bibliografica individua, quindi, i principali inquinanti atmosferici presenti in prossimità di un impianto di primo trattamento del greggio e cerca di fornire un quadro generale delle loro potenziali sorgenti e caratteristiche.

Sequence comparison of phoR, gyrB, groEL, and cheA genes as phylogenetic markers for distinguishing Bacillus amyloliquefaciens and B. subtilis and for identifying Bacillus strain B29.

PubMed

Yu, C; Jin, J; Meng, L-Q; Xia, H-H; Yuan, H-F; Wang, J; Yu, D-S; Zhao, X-Y; Sha, C-Q

2017-05-20

Given the close genetic relationship between Bacillus amyloliquefaciens and B. subtilis, distinguishing the two solely based on their physiological and biochemical characteristics and 16S rRNA sequences is difficult. Molecular identification was used to discover suitable genes for distinguishing the two bacteria, and to identify the bio-controlling strain B29, due to molecular identification has been paid more and more attention. The similarity of four genes, cheA, gyrB, groEL and phoR, of the two species was compared by the software BLASTN and MAGA, and phylogenetic tree was constructed. The B29 strain was re-identified by using the screened genes. The similarities of the four genes, gyrB, groEL, cheA and phoR, of the two species were 93-95%, 82-84%, 76-78% and 76-77%, respectively. The homologies of the four genes of the strain B29 and the strains of B. amyloliquefaciens strains were more than 95%. We determined how well the phoR and cheA genes could be used to differentiate B. amyloliquefacien and B. subtilis. The previously isolated biological control strain B29, initially classified as B. subtilis, was re-classified as B. amyloliquefaciens. Our data indicate that other than the phoR gene, the cheA gene might be a useful phylogenetic marker for differentiating B. subtilis and B. amyloliquefaciens.

SAM-Like Evolved Gas Analyses of Phyllosilicate Minerals and Applications to SAM Analyses of the Sheepbed Mudstone, Gale Crater, Mars

NASA Technical Reports Server (NTRS)

McAdam, A. C.; Franz, H. B.; Mahaffy, P. R.; Eigenbrode, J. L.; Stern, J. C.; Brunner, B.; Sutter, B.; Archer, P. D.; Ming , D. W.; Morris, R. V.;

Sigma Factor Regulated Cellular Response in a Non-solvent Producing Clostridium beijerinckii Degenerated Strain: A Comparative Transcriptome Analysis

PubMed Central

Zhang, Yan; Jiao, Shengyin; Lv, Jia; Du, Renjia; Yan, Xiaoni; Wan, Caixia; Zhang, Ruijuan; Han, Bei

2017-01-01

Clostridium beijerinckii DG-8052, derived from NCIMB 8052, cannot produce solvent or form spores, a phenomenon known as degeneration. To explore the mechanisms of degeneration at the gene level, transcriptomic profiles of the wild-type 8052 and DG-8052 strains were compared. Expression of 5168 genes comprising 98.6% of the genome was assessed. Interestingly, 548 and 702 genes were significantly up-regulated in the acidogenesis and solventogenesis phases of DG-8052, respectively, and mainly responsible for the phosphotransferase system, sugar metabolic pathways, and chemotaxis; meanwhile, 699 and 797 genes were significantly down-regulated, respectively, and mainly responsible for sporulation, oxidoreduction, and solventogenesis. The functions of some altered genes, including 286 and 333 at the acidogenesis and solventogenesis phases, respectively, remain unknown. Dysregulation of the fermentation machinery was accompanied by lower transcription levels of glycolysis rate-limiting enzymes (pfk and pyk), and higher transcription of cell chemotaxis genes (cheA, cheB, cheR, cheW, and cheY), controlled mainly by σ54 at acidogenesis. Meanwhile, abnormal spore formation was associated with repressed spo0A, sigE, sigF, sigG, and sigK which are positively regulated by σ70, and correspondingly inhibited expression of CoA-transferase at the solventogenesis phase. These findings indicated that morphological and physiological changes in the degenerated Clostridium strain may be related to altered expression of sigma factors, providing valuable targets for strain development of Clostridium species. PMID:28194137

Pathways to catastrophic health expenditure for acute coronary syndrome in Kerala: ‘Good health at low cost’?

PubMed Central

2012-01-01

Background Universal health coverage through the removal of financial and other barriers to access, particularly for people who are poor, is a global priority. This viewpoint describes the many pathways to catastrophic health expenditure (CHE) for patients with Acute Coronary Syndrome (ACS) based on two case studies and the thematic analysis of field notes regarding 210 patients and their households from a study based in Kerala, India. Discussion There is evidence of the severe financial impact of non-communicable diseases (NCDs), which is in contradiction to the widely acclaimed Kerala model: Good health at low cost. However, it is important to look beyond the out-of-pocket expenditure (OOPE) and CHE to the possible pathways and identify the triggers that make families vulnerable to CHE. The identified pathways include a primary and secondary loop. The primary pathway describes the direct path by which families experience CHE. These include: 1) factors related to the pre-event period that increase the likelihood of experiencing CHE, such as being from the lower socio-economic strata (SES), past financial losses or loans that leave families with no financial shock absorber at the time of illness; 2) factors related to the acute event, diagnosis, treatment and hospitalization and expenditures incurred for the same and; 3) factors related to the post-event period such as loss of gainful employment and means of financing both the acute period and the long-term management particularly through distress financing. The secondary pathway arises from the primary and includes: 1) the impact of distress financing and; 2) the long- and short- term consequences of CHE. These factors ultimately result in a vicious cycle of debt and poverty through non-compliance and repeat acute events. Summary This paper outlines the direct and indirect pathways by which patients with ACS and their families are trapped in a vicious cycle of debt and poverty. It also contradicts the prevailing impression that only low-income families are susceptible to CHE, distress financing and their aftermaths and underscores the need for a deeper understanding at the micro-level, if Kerala and India as a whole are to undertake the difficult exercise of achieving universal health coverage to successfully tackle its growing NCD burden. PMID:22537240

DEPRESSION OF THE PHOTIC AFTER DISCHARGE OF FLASH EVOKED POTENTIALS BY PHYSOSTIGMINE, CARBARYL AND PROPOXUR AND THE RELATIONSHIP TO INHIBITION OF BRAIN CHOLINESTERASE

EPA Science Inventory

The effects of N-methyl carbamate pesticides on the photic after discharge (PhAD) of flash evoked potentials (FEPs) and the relationship between inhibition of brain cholinesterase (ChE) activity and the PhAD were evaluated. FEPs were recorded in Long Evans rats treated with physo...

Mineralogy of an active eolian sediment from the Namib dune, Gale crater, Mars

NASA Astrophysics Data System (ADS)

Achilles, C. N.; Downs, R. T.; Ming, D. W.; Rampe, E. B.; Morris, R. V.; Treiman, A. H.; Morrison, S. M.; Blake, D. F.; Vaniman, D. T.; Ewing, R. C.; Chipera, S. J.; Yen, A. S.; Bristow, T. F.; Ehlmann, B. L.; Gellert, R.; Hazen, R. M.; Fendrich, K. V.; Craig, P. I.; Grotzinger, J. P.; Des Marais, D. J.; Farmer, J. D.; Sarrazin, P. C.; Morookian, J. M.

2017-11-01

The Mars Science Laboratory rover, Curiosity, is using a comprehensive scientific payload to explore rocks and soils in Gale crater, Mars. Recent investigations of the Bagnold Dune Field provided the first in situ assessment of an active dune on Mars. The Chemistry and Mineralogy (CheMin) X-ray diffraction instrument on Curiosity performed quantitative mineralogical analyses of the <150 μm size fraction of the Namib dune at a location called Gobabeb. Gobabeb is dominated by basaltic minerals. Plagioclase, Fo56 olivine, and two Ca-Mg-Fe pyroxenes account for the majority of crystalline phases along with minor magnetite, quartz, hematite, and anhydrite. In addition to the crystalline phases, a minimum 42 wt % of the Gobabeb sample is X-ray amorphous. Mineralogical analysis of the Gobabeb data set provides insights into the origin(s) and geologic history of the dune material and offers an important opportunity for ground truth of orbital observations. CheMin's analysis of the mineralogy and phase chemistry of modern and ancient Gale crater dune fields, together with other measurements by Curiosity's science payload, provides new insights into present and past eolian processes on Mars.

Seasonal distribution of bird populations at the Patuxent Research Refuge

USGS Publications Warehouse

Hoffman, D.J.; Henny, C.J.; Hill, E.F.; Keith, J.A.; Grove, R.A.

2000-01-01

High concentrations of mercury from past mining activities have accumulated in the food chain of fish-eating birds nesting along the mid to lower Carson River. Activities of nine plasma and tissue enzymes, and concentrations of other plasma and tissue constituents were measured for black-crowned night-heron, Nycticorax nycticorax, (BCNH) and snowy egret, Egretta thula, (SE) nestlings from two high mercury sites and one low mercury site. Geometric mean blood Hg concentrations for BCNHs at the high mercury sites were 2.6 and 2.8 ppm (ww) and 0.6 ppm at the low mercury site. Blood concentrations for SEs were 3.6 and 1.9 ppm at the high mercury sites and 0.7 ppm at the low mercury site. In BCNHs plasma glutathione peroxidase (GSH peroxidase) activity was lower in both high mercury sites relative to the low mercury site. Butyryl cholinesterase (BuChe), ALT, glutathione reductase (GSSG-reductase) and LDH-L activities were lower in one high mercury site. In SEs significant differences were lower BuChe and LDH-L, but elevated GGT activities. Evidence of renal stress in both species at high mercury sites included increased plasma uric acid, blood urea nitrogen, and creatinine concentrations as well as oxidative stress in the kidney tissue itself where oxidized glutathione increased. A number of the mercury site-related effects, including decreased plasma GSH-peroxidase and hepatic G-6-PDH activities, higher GSSG-reductase activity, and lower hepatic concentrations of reduced thiols have been reported in methylmercury feeding studies with great egrets and mallards. These findings suggest the utility of herons and egrets for monitoring mercury sites.

Examples of Best Practice 2. Holocaust Education as a Universal Challenge

ERIC Educational Resources Information Center

Kalisman, Raya

2010-01-01

The Center for Humanistic Education (CHE) engages high-school students and teachers from the Arab and Jewish sectors in an examination of connections between the Holocaust, personal and social morals, and implications for present Israeli society. Since 1997, CHE has been working regularly with about 25 Jewish and Arab high schools, engaging about…

Travel as a Ritual toward Transformative Consciousness: Juxtaposing Che Guevara's Biography and Teacher Candidates' Narratives

ERIC Educational Resources Information Center

Lea, YiShan

2013-01-01

This article discusses the development of critical consciousness by examining the biographical-narratives in relationship to the experiential accounts on travel. Biographical narratives are important cultural texts filled with history and cultural nuances. The biography of Ernesto Che Guevara has resonated with readers and viewers from around the…

McArthur rotates the CHeCS rack back into position after cleaning the AAA fan

NASA Image and Video Library

2005-12-01

ISS012-E-09931 (1 December 2005) --- Astronaut William S. (Bill) McArthur Jr., Expedition 12 commander and NASA space station science officer, rotates the Crew Health Care System (CHeCS) rack back into position after cleaning the Avionics Air Assembly fan in the Destiny laboratory of the International Space Station.

Writing "Che" Writing: Apocryphal Diaries and the Deconstruction of Guevara's Myth

ERIC Educational Resources Information Center

Weiser, Frans

2013-01-01

Ernesto "Che" Guevara's iconic photograph has taken on mythical proportions since his death. Though his image has ironically been exploited by the apparatus of capitalism against which he fought, his translation into a symbol has assured that his foothold within popular culture remains largely unassailable. While recent films and…

McArthur rotates the CHeCS Rack during Expedition 12

NASA Image and Video Library

2005-12-09

ISS012-E-10806 (9 December 2005) --- Astronaut William S. (Bill) McArthur Jr., Expedition 12 commander and NASA space station science officer, rotates the Crew Health Care System (CHeCS) rack in order to access the Avionics Air Assembly (AAA) air ducts during in-flight maintenance (IFM) in the Destiny laboratory of the International Space Station.

The Development of the Chemin Mineralogy Instrument and Its Deployment on Mars (and Latest Results from the Mars Science Laboratory Rover Curiosity)

NASA Technical Reports Server (NTRS)

Blake, David F.

2014-01-01

The CheMin instrument (short for "Chemistry and Mineralogy") on the Mars Science Laboratory rover Curiosity is one of two "laboratory quality" instruments on board the Curiosity rover that is exploring Gale crater, Mars. CheMin is an X-ray diffractometer that has for the first time returned definitive and fully quantitative mineral identifications of Mars soil and drilled rock. I will describe CheMin's 23-year development from an idea to a spacecraft qualified instrument, and report on some of the discoveries that Curiosity has made since its entry, descent and landing on Aug. 6, 2012, including the discovery and characterization of the first habitable environment on Mars.

In vitro test systems supporting the development of improved pest control methods: a case study with chemical mixtures and bivalve biofoulers.

PubMed

Silva, Carlos; Nunes, Bruno; Nogueira, António Ja; Gonçalves, Fernando; Pereira, Joana L

2016-11-01

Using the bivalve macrofouler Corbicula fluminea, the suitability of in vitro testing as a stepping stone towards the improvement of control methods based on chemical mixtures was addressed in this study. In vitro cholinesterase (ChE) activity inhibition following single exposure of C. fluminea tissue to four model chemicals (the organophosphates dimethoate and dichlorvos, copper and sodium dodecyl phosphate [SDS]) was first assessed. Consequently, mixtures of dimethoate with copper and dichlorvos with SDS were tested and modelled; mixtures with ChE revealed synergistic interactions for both chemical pairs. These synergic combinations were subsequently validated in vivo and the increased control potential of these selected combinations was verified, with gains of up to 50% in C. fluminea mortality relative to corresponding single chemical treatments. Such consistency supports the suitability of using time- and cost-effective surrogate testing platforms to assist the development of biofouling control strategies incorporating mixtures.

KSC-2011-7941

NASA Image and Video Library

2011-11-25

CAPE CANAVERAL, Fla. – David Blake, NASA principal investigator for the Chemistry and Mineralogy (CheMin) investigation by the Curiosity rover, demonstrates the experiment for the media in NASA Kennedy Space Center's Press Site auditorium in Florida during prelaunch activities for the agency’s Mars Science Laboratory (MSL) launch. CheMin is designed to analyze powdered rock and soil samples by identifying and quantifying their mineral content using X-ray diffraction, a first for a mission to Mars. The car-sized Martian rover, Curiosity, has 10 science instruments designed to search for signs of life, including methane, and help determine if the gas is from a biological or geological source. Liftoff of MSL aboard a United Launch Alliance Atlas V rocket from Space Launch Complex-41 on Cape Canaveral Air Force Station is planned during a launch window which extends from 10:02 a.m. to 11:45 a.m. EST on Nov. 26. For more information, visit http://www.nasa.gov/msl. Photo credit: NASA/Kim Shiflett

KSC-2011-7942

NASA Image and Video Library

2011-11-25

CAPE CANAVERAL, Fla. – David Blake, NASA principal investigator for the Chemistry and Mineralogy (CheMin) investigation by the Curiosity rover, explains the experiment to the media in NASA Kennedy Space Center's Press Site auditorium in Florida during prelaunch activities for the agency’s Mars Science Laboratory (MSL) launch. CheMin is designed to analyze powdered rock and soil samples by identifying and quantifying their mineral content using X-ray diffraction, a first for a mission to Mars. The car-sized Martian rover, Curiosity, has 10 science instruments designed to search for signs of life, including methane, and help determine if the gas is from a biological or geological source. Liftoff of MSL aboard a United Launch Alliance Atlas V rocket from Space Launch Complex-41 on Cape Canaveral Air Force Station is planned during a launch window which extends from 10:02 a.m. to 11:45 a.m. EST on Nov. 26. For more information, visit http://www.nasa.gov/msl. Photo credit: NASA/Kim Shiflett

Quantum-mechanics-derived 13Cα chemical shift server (CheShift) for protein structure validation

PubMed Central

Vila, Jorge A.; Arnautova, Yelena A.; Martin, Osvaldo A.; Scheraga, Harold A.

2009-01-01

A server (CheShift) has been developed to predict 13Cα chemical shifts of protein structures. It is based on the generation of 696,916 conformations as a function of the φ, ψ, ω, χ1 and χ2 torsional angles for all 20 naturally occurring amino acids. Their 13Cα chemical shifts were computed at the DFT level of theory with a small basis set and extrapolated, with an empirically-determined linear regression formula, to reproduce the values obtained with a larger basis set. Analysis of the accuracy and sensitivity of the CheShift predictions, in terms of both the correlation coefficient R and the conformational-averaged rmsd between the observed and predicted 13Cα chemical shifts, was carried out for 3 sets of conformations: (i) 36 x-ray-derived protein structures solved at 2.3 Å or better resolution, for which sets of 13Cα chemical shifts were available; (ii) 15 pairs of x-ray and NMR-derived sets of protein conformations; and (iii) a set of decoys for 3 proteins showing an rmsd with respect to the x-ray structure from which they were derived of up to 3 Å. Comparative analysis carried out with 4 popular servers, namely SHIFTS, SHIFTX, SPARTA, and PROSHIFT, for these 3 sets of conformations demonstrated that CheShift is the most sensitive server with which to detect subtle differences between protein models and, hence, to validate protein structures determined by either x-ray or NMR methods, if the observed 13Cα chemical shifts are available. CheShift is available as a web server. PMID:19805131

CHeCS: International Space Station Medical Hardware Catalog

NASA Technical Reports Server (NTRS)

2008-01-01

The purpose of this catalog is to provide a detailed description of each piece of hardware in the Crew Health Care System (CHeCS), including subpacks associated with the hardware, and to briefly describe the interfaces between the hardware and the ISS. The primary user of this document is the Space Medicine/Medical Operations ISS Biomedical Flight Controllers (ISS BMEs).

Incorporation of Data Analysis throughout the ChE Curriculum Made Easy with DataFit

ERIC Educational Resources Information Center

Brenner, James R.

2007-01-01

At Florida Tech, we have incorporated DataFit from Oakdale Engineering throughout the entire curriculum, beginning with ChE 1102, an eight-week, one-day-per-week, two-hour, one-credit-hour, second-semester Introduction to Chemical Engineering course in a hands-on computer classroom. Our experience is that students retain data analysis concepts…

Lista dei caratteri macroscopici per l’identificazione dei legni

Treesearch

Flavio Ruffinatto; Alan Crivellaro; Alex C. Wiedenhoeft

2016-01-01

L’identificazione dei legni costituisce il primo passo per ottenere conoscenze indispensabili in molti ambiti di studio. Ad esempio, prima di eseguire il restauro di un manufatto di interesse culturale è indispensabile conoscere il nome dei legni che lo compongono. Oppure, nel caso in cui si sospetti che un legno protetto da convenzioni internazionali sia stato...

Lessons Learned from the Crew Health Care System (CHeCS) Rack 1 Environmental Control and Life Support (ECLS) Design

NASA Technical Reports Server (NTRS)

Williams, David E.

2006-01-01

This paper will provide an overview of the International Space Station (ISS) Environmental Control and Life Support (ECLS) design of the Crew Health Care System (CHeCS) Rack 1 and it will document some of the lessons that have been learned to date for the ECLS equipment in this rack.

Brain cholinesterase inhibition in songbirds from pecan groves sprayed with phosaline and disulfoton

USGS Publications Warehouse

White, D.H.; Seginak, J.T.

1990-01-01

Disulfoton at 0.83 kg/ha caused moderate to severe brain cholinesterase (ChE) depression in 11 of 15 blue jays collected in pecan groves 6-7 hr after the application. Phosalone at 0.83 kg/ha to pecan groves caused only slight ChE inhibition in a few blue jays and red-bellied woodpeckers.

X-Ray Diffraction Reference Intensity Ratios of Amorphous and Poorly Crystalline Phases: Implications for CheMin on the Mars Science Laboratory

NASA Technical Reports Server (NTRS)

Morris, R. V.; Achilles, C. N.; Chipera, S. J.; Ming, D. W.; Rampe, E. B.

2013-01-01

The CheMin instrument on the Mars Science Laboratory (MSL) rover Curiosity is an X-ray diffraction (XRD) and X-ray fluorescence (XRF) instrument capable of providing the mineralogical and chemical compositions of rocks and soils on the surface of Mars. CheMin uses a microfocus X-ray tube with a Co target, transmission geometry, and an energy-discriminating X-ray sensitive CCD to produce simultaneous 2-D XRD patterns and energy-dispersive X-ray histograms from powdered samples. Piezoelectric vibration of the cell is used to randomize the sample to reduce preferred orientation effects. Instrument details are provided in [1, 2, 3]. Analyses of rock and soil samples by the Mars Exploration Rovers (MER) show nanophase ferric oxide (npOx) is a significant component of the Martian global soil [4] and is thought to be one of the major contributing phases that the Curiosity rover will encounter if a soil sample is analyzed in Gale Crater. Because of the nature of this material, npOx will likely contribute to an X-ray amorphous or short-order component of a XRD pattern measured by the CheMin instrument.

Effects of Liner Length and Attenuation on NASA Langley Impedance Eduction

NASA Technical Reports Server (NTRS)

Jones, M. G.; Watson, W. R.

2016-01-01

This study explores the effects of liner length and attenuation on the CHE (convected Helmholtz equation) impedance eduction method, in which the surface impedance of an acoustic liner is inferred through an iterative process based on repeated solutions to the convected Helmholtz equation. Wire mesh-over-honeycomb and perforate-over-honeycomb acoustic liners are tested in the NASA Langley Grazing Flow Impedance Tube, and the resultant data are processed using two impedance eduction methods. The first is the CHE method, and the second is a direct method (labeled the KT method) that uses the Kumaresan and Tufts algorithm to compute the impedance directly. The CHE method has been extensively used for acoustic liner evaluation, but experiences anomalous behavior under some test conditions. It is postulated that the anomalies are related to the liner length and/or attenuation. Since the KT method only employs data measured over the length of the liner, it is expected to be unaffected by liner length. A comparison of results achieved with the two impedance eduction methods is used to explore the interactive effects of liner length and attenuation on the CHE impedance eduction method.

Rigorous derivation of porous-media phase-field equations

NASA Astrophysics Data System (ADS)

Schmuck, Markus; Kalliadasis, Serafim

2017-11-01

The evolution of interfaces in Complex heterogeneous Multiphase Systems (CheMSs) plays a fundamental role in a wide range of scientific fields such as thermodynamic modelling of phase transitions, materials science, or as a computational tool for interfacial flow studies or material design. Here, we focus on phase-field equations in CheMSs such as porous media. To the best of our knowledge, we present the first rigorous derivation of error estimates for fourth order, upscaled, and nonlinear evolution equations. For CheMs with heterogeneity ɛ, we obtain the convergence rate ɛ 1 / 4 , which governs the error between the solution of the new upscaled formulation and the solution of the microscopic phase-field problem. This error behaviour has recently been validated computationally in. Due to the wide range of application of phase-field equations, we expect this upscaled formulation to allow for new modelling, analytic, and computational perspectives for interfacial transport and phase transformations in CheMSs. This work was supported by EPSRC, UK, through Grant Nos. EP/H034587/1, EP/L027186/1, EP/L025159/1, EP/L020564/1, EP/K008595/1, and EP/P011713/1 and from ERC via Advanced Grant No. 247031.

Characterization of acetylcholinesterase-inhibition by itopride.

PubMed

Iwanaga, Y; Kimura, T; Miyashita, N; Morikawa, K; Nagata, O; Itoh, Z; Kondo, Y

1994-11-01

Itopride is a gastroprokinetic benzamide derivative. This agent inhibited both electric eel acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BuChE). The IC50 of itopride with AChE (2.04 +/- 0.27 microM) was, however, 100-fold less than that with BuChE, whereas in the case of neostigmine with AChE (11.3 +/- 3.4 nM), it was 10-fold less. The recovery of AChE activity inhibited by 10(-7) M neostigmine was partial, but that inhibited by up to 3 x 10(-5) M itopride was complete when the reaction mixture was subjected to ultrafiltration. Double reciprocal plots of the experimental data showed that both Km and Vmax were affected by itopride, suggesting that the inhibition is a "mixed" type, although primarily being an uncompetitive one. The inhibitory effect of itopride on cholinesterase (ChE) activity in guinea pig gastrointestine was much weaker than that on pure AChE. However, in the presence of a low dose of diisopropyl fluorophosphate, just enough to inhibit BuChE but not AChE, the IC50s of itopride against ChE activities were found to be about 0.5 microM. In conclusion, itopride exerts reversible and a "mixed" type of inhibition preferably against AChE. The IC50 of itopride for electric eel and guinea pig gastrointestinal AChE inhibition was 200 times and 50 times as large as that of neostigmine, respectively.

Phyllosilicate analysis capabilities of the CheMin mineralogical instrument on the Mars Science Laboratory (MSL '11) Curiosity Rover

NASA Astrophysics Data System (ADS)

Blake, D. F.; Bish, D. L.; Vaniman, D. T.; Chipera, S.; Bristow, T. F.; Sarrazin, P.

2011-12-01

The CheMin mineralogical instrument on the MSL '11 Curiosity rover will return quantitative X-ray diffraction data (XRD) from scooped soil samples and drilled rock powders collected from the Mars surface. Samples of 45-65 mm3 from material sieved to <150 μm will be delivered through a funnel to one of 27 reuseable sample cells (five additional cells on the sample wheel contain diffraction or fluorescence standards). Sample cells are 8-mm diameter discs with 7-μm thick Mylar or Kapton windows spaced 170 μm apart. Within this volume, the sample is shaken by piezoelectric vibration at sonic frequencies, causing the powder to flow past a narrow, collimated X-ray beam in random orientations over the course of an analysis. In this way, diffraction patterns exhibiting little to no preferred orientation can be obtained even from minerals normally exhibiting strong preferred orientation such as phyllosilicates. Individual analyses will require several hours over one or more Mars sols. For typical well-ordered minerals, CheMin has a Minimum Detection Limit (MDL) of <3% by mass, an accuracy of better than 15% and a precision of better than 10% for phases present in concentrations >4X MDL (12%). The resolution of the diffraction patterns is 0.30 degrees 2θ, and the angular measurement range is 4-55 degrees 2θ. With this performance, CheMin can identify and distinguish a number of clay minerals. For example, discrimination between 1:1 phyllosilicates (such as the kaolin minerals), with repeat distances of ~7Å, and smectites (e.g., montmorillonite, nontronite, saponite), with repeat distances from 10-15Å, is straightforward. However, it is important to note that the variety of treatments used in terrestrial laboratories to aid in discrimination of clay minerals will not be accessible on Mars (e.g., saturation with ethylene glycol vapor, heat treatments). Although these treatments will not be available on Mars, dehydration within the CheMin instrument could be used to advantage in discriminating between phyllosilicate minerals that exhibit different dehydration behavior, such as chlorite vs. smectite. In addition, it should be possible to identify the hydrated kaolin mineral, halloysite. The lowest-angle diffraction peak from 10.1Å hydrated halloysite occurs at ~10.2 degrees 2θ with Co radiation and is easily detectable; the mineral may readily dehydrate to ~7Å, making its identification possible based on this transition. Examples will be shown of clay mineral analysis using CheMin IV, a prototype of the CheMin flight instrument.

Mineralogy of Eolian Sands at Gale Crater

NASA Technical Reports Server (NTRS)

Achilles, C. N.; Vaniman, D. T.; Blake, D. F.; Bristow, T. F.; Rampe, E. B.; Ming, D. W.; Chipera, S. J.; Morris, R. V.; Morrison, S. M.; Downs, R. T.;

TIME COURSE AND DOSE RESPONSE ASSESSMENT OF CHOLINESTERASE (CHE) INHIBITION IN ADULT RATS TREATED ACUTELY WITH CARBARYL, METHOMYL, METHIOCARB, OXAMYL, OR PROPOXUR.

EPA Science Inventory

To compare the toxicity of 5 N-methyl carbamates, the time course and dose response profiles for ChE inhibition were established for each. For the time course comparison, adult male Long Evans rats (n=5 dose group) were dosed orally with either carbaryl (CB; 30 mg/kg in corn oi...

Fincke unbolts the front panel of the CHeCS Rack for inspection and cleaning during Expedition 9

NASA Image and Video Library

2004-09-16

ISS009-E-23061 (16 September 2004) --- Astronaut Edward M. (Mike) Fincke, Expedition 9 NASA ISS science officer and flight engineer, uses a drill to unfasten a panel on the CHeCS Rack in the Destiny laboratory of the International Space Station (ISS). Fincke was about to perform an inspection of the Avionics Air Assembly.

McArthur removes AAA clamps and ducts inside the CHeCS Rack during Expedition 12

NASA Image and Video Library

2005-12-09

ISS012-E-10817 (9 December 2005) --- Astronaut William S. (Bill) McArthur Jr., Expedition 12 commander and NASA space station science officer, opens the back panel of the Crew Health Care System (CHeCS) rack and removes the Avionics Air Assembly (AAA) air ducts during in-flight maintenance (IFM) in the Destiny laboratory of the International Space Station.

Novitskiy participates in a CHeCS medical contingency drill in the U.S. Laboratory

NASA Image and Video Library

2012-11-26

ISS034-E-005260 (26 Nov. 2012) --- Russian cosmonaut Oleg Novitskiy, Expedition 34 flight engineer, participates in a Crew Health Care System (CHeCS) medical contingency drill in the Destiny laboratory of the International Space Station. This drill gives crew members the opportunity to work as a team in resolving a simulated medical emergency onboard the space station.

Shkaplerov participates in a CHeCS Medical Contingency Drill in the U.S. Laboratory

NASA Image and Video Library

2011-12-16

ISS030-E-012600 (16 Dec. 2011) --- Russian cosmonaut Anton Shkaplerov, Expedition 30 flight engineer, participates in a Crew Health Care System (CHeCS) medical contingency drill in the Destiny laboratory of the International Space Station. This drill gives crew members the opportunity to work as a team in resolving a simulated medical emergency onboard the space station.

Novitskiy participates in a CHeCS medical contingency drill in the U.S. Laboratory

NASA Image and Video Library

2012-11-26

ISS034-E-005266 (26 Nov. 2012) --- Russian cosmonaut Oleg Novitskiy, Expedition 34 flight engineer, participates in a Crew Health Care System (CHeCS) medical contingency drill in the Destiny laboratory of the International Space Station. This drill gives crew members the opportunity to work as a team in resolving a simulated medical emergency onboard the space station.

Does the National Health Insurance Scheme provide financial protection to households in Ghana?

PubMed

Kusi, Anthony; Hansen, Kristian Schultz; Asante, Felix A; Enemark, Ulrika

2015-08-15

Excessive healthcare payments can impede access to health services and also disrupt the welfare of households with no financial protection. Health insurance is expected to offer financial protection against health shocks. Ghana began the implementation of its National Health Insurance Scheme (NHIS) in 2004. The NHIS is aimed at removing the financial barrier to healthcare by limiting direct out-of-pocket health expenditures (OOPHE). The study examines the effect of the NHIS on OOPHE and how it protects households against catastrophic health expenditures. Data was obtained from a cross-sectional representative household survey involving 2,430 households from three districts across Ghana. All OOPHE associated with treatment seeking for reported illness in the household in the last 4 weeks preceding the survey were analysed and compared between insured and uninsured persons. The incidence and intensity of catastrophic health expenditures (CHE) among households were measured by the catastrophic health payment method. The relative effect of NHIS on the incidence of CHE in the household was estimated by multiple logistic regression analysis. About 36% of households reported at least one illness during the 4 weeks period. Insured patients had significantly lower direct OOPHE for out-patient and in-patient care compared to the uninsured. On financial protection, the incidence of CHE was lower among insured households (2.9%) compared to the partially insured (3.7%) and the uninsured (4.0%) at the 40% threshold. The incidence of CHE was however significantly lower among fully insured households (6.0%) which sought healthcare from NHIS accredited health facilities compared to the partially insured (10.1%) and the uninsured households (23.2%). The likelihood of a household incurring CHE was 4.2 times less likely for fully insured and 2.9 times less likely for partially insured households relative to being uninsured. The NHIS has however not completely eliminated OOPHE for the insured and their households. The NHIS has significant effect in reducing OOPHE and offers financial protection against CHE for insured individuals and their households though they still made some out-of-pocket payments. Efforts should aim at eliminating OOPHE for the insured if the objective for establishing the NHIS is to be achieved.

Design, synthesis, and pharmacological evaluation of 2-amino-5-nitrothiazole derived semicarbazones as dual inhibitors of monoamine oxidase and cholinesterase: effect of the size of aryl binding site.

PubMed

Tripathi, Rati K P; M Sasi, Vishnu; Gupta, Sukesh K; Krishnamurthy, Sairam; Ayyannan, Senthil R

2018-12-01

A series of 2-amino-5-nitrothiazole derived semicarbazones were designed, synthesised and investigated for MAO and ChE inhibition properties. Most of the compounds showed preferential inhibition towards MAO-B. Compound 4, (1-(1-(4-Bromophenyl)ethylidene)-4-(5-nitrothiazol-2-yl)semicarbazide) emerged as lead candidate (IC 50  = 0.212 µM, SI = 331.04) against MAO-B; whereas compounds 21 1-(5-Bromo-2-oxoindolin-3-ylidene)-4-(5-nitrothiazol-2-yl)semicarbazide (IC 50  = 0.264 µM) and 17 1-((4-Chlorophenyl) (phenyl)methylene)-4-(5-nitrothiazol-2-yl)semicarbazide (IC 50  = 0.024 µM) emerged as lead AChE and BuChE inhibitors respectively; with activity of compound 21 almost equivalent to tacrine. Kinetic studies indicated that compound 4 exhibited competitive and reversible MAO-B inhibition while compounds 21 and 17 showed mixed-type of AChE and BuChE inhibition respectively. Docking studies revealed that these compounds were well-accommodated within MAO-B and ChE active sites through stable hydrogen bonding and/or hydrophobic interactions. This study revealed the requirement of small heteroaryl ring at amino terminal of semicarbazone template for preferential inhibition and selectivity towards MAO-B. Our results suggest that 5-nitrothiazole derived semicarbazones could be further exploited for its multi-targeted role in development of anti-neurodegenerative agents. [Formula: see text] A library of 2-amino-5-nitrothiazole derived semicarbazones (4-21) was designed, synthesised and evaluated for in vitro MAO and ChE inhibitory activity. Compounds 4, 21 and 17 (shown) have emerged as lead MAO-B (IC 50 :0.212 µM, competitive and reversible), AChE (IC 50 :0.264 µM, mixed and reversible) and BuChE (IC 50 :0.024 µM, mixed and reversible) inhibitor respectively. SAR studies disclosed several structural aspects significant for potency and selectivity and indicated the role of size of aryl binding site in potency and selectivity towards MAO-B. Antioxidant activity and neurotoxicity screening results further suggested their multifunctional potential for the therapy of neurodegenerative diseases.

CheNER: a tool for the identification of chemical entities and their classes in biomedical literature.

PubMed

Usié, Anabel; Cruz, Joaquim; Comas, Jorge; Solsona, Francesc; Alves, Rui

2015-01-01

Small chemical molecules regulate biological processes at the molecular level. Those molecules are often involved in causing or treating pathological states. Automatically identifying such molecules in biomedical text is difficult due to both, the diverse morphology of chemical names and the alternative types of nomenclature that are simultaneously used to describe them. To address these issues, the last BioCreAtIvE challenge proposed a CHEMDNER task, which is a Named Entity Recognition (NER) challenge that aims at labelling different types of chemical names in biomedical text. To address this challenge we tested various approaches to recognizing chemical entities in biomedical documents. These approaches range from linear Conditional Random Fields (CRFs) to a combination of CRFs with regular expression and dictionary matching, followed by a post-processing step to tag those chemical names in a corpus of Medline abstracts. We named our best performing systems CheNER. We evaluate the performance of the various approaches using the F-score statistics. Higher F-scores indicate better performance. The highest F-score we obtain in identifying unique chemical entities is 72.88%. The highest F-score we obtain in identifying all chemical entities is 73.07%. We also evaluate the F-Score of combining our system with ChemSpot, and find an increase from 72.88% to 73.83%. CheNER presents a valid alternative for automated annotation of chemical entities in biomedical documents. In addition, CheNER may be used to derive new features to train newer methods for tagging chemical entities. CheNER can be downloaded from http://metres.udl.cat and included in text annotation pipelines.

Does HIV services decentralization protect against the risk of catastrophic health expenditures?: some lessons from Cameroon.

PubMed

Boyer, Sylvie; Abu-Zaineh, Mohammad; Blanche, Jérôme; Loubière, Sandrine; Bonono, Renée-Cécile; Moatti, Jean-Paul; Ventelou, Bruno

2011-12-01

Scaling up antiretroviral treatment (ART) through decentralization of HIV care is increasingly recommended as a strategy toward ensuring equitable access to treatment. However, there have been hitherto few attempts to empirically examine the performance of this policy, and particularly its role in protecting against the risk of catastrophic health expenditures (CHE). This article therefore seeks to assess whether HIV care decentralization has a protective effect against the risk of CHE associated with HIV infection. DATA SOURCE AND STUDY DESIGN: We use primary data from the cross-sectional EVAL-ANRS 12-116 survey, conducted in 2006-2007 among a random sample of 3,151 HIV-infected outpatients followed up in 27 hospitals in Cameroon. DATA COLLECTION AND METHODS: Data collected contain sociodemographic, economic, and clinical information on patients as well as health care supply-related characteristics. We assess the determinants of CHE among the ART-treated patients using a hierarchical logistic model (n = 2,412), designed to adequately investigate the separate effects of patients and supply-related characteristics. Expenditures for HIV care exceed 17 percent of household income for 50 percent of the study population. After adjusting for individual characteristics and technological level, decentralization of HIV services emerges as the main health system factor explaining interclass variance, with a protective effect on the risk of CHE. The findings suggest that HIV care decentralization is likely to enhance equity in access to ART. Decentralization appears, however, to be a necessary but insufficient condition to fully remove the risk of CHE, unless other innovative reforms in health financing are introduced. © Health Research and Educational Trust.

The Ricor K508 cryocooler operational experience on Mars

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, Dean L.; Lysek, Mark J.; Morookian, John Michael

The Mars Science Laboratory (Curiosity) landed successfully on Mars on August 5, 2012, eight months after launch. The chosen landing site of Gale Crater, located at 4.5 degrees south latitude, 137.4 degrees east longitude, has provided a much more benign environment than was originally planned for during the critical design and integration phases of the MSL Project when all possible landing sites were still being considered. The expected near-surface atmospheric temperatures at the Gale Crater landing site during Curiosity's primary mission (1 Martian year or 687 Earth days) are from −90°C to 0°C. However, enclosed within Curiosity's thermal control fluidmore » loops the Chemistry and Mineralogy (CheMin) instrument is maintained at approximately +20°C. The CheMin instrument uses X-ray diffraction spectroscopy to make precise measurements of mineral constituents of Mars rocks and soil. The instrument incorporated the commercially available Ricor K508 Stirling cycle cryocooler to cool the CCD detector. After several months of brushing itself off, stretching and testing out its subsystems, Curiosity began the exploration of the Mars surface in October 2012. The CheMin instrument on the Mars Science Laboratory (MSL) received its first soil sample from Curiosity on October 24, and successfully analyzed its first soil sample. After a brief review of the rigorous Ricor K508 cooler qualification tests and life tests based on the original MSL environmental requirements this paper presents final pre-launch instrument integration and testing results, and details the operational data of the CheMin cryocooler, providing a snapshot of the resulting CheMin instrument analytical data.« less

Effects of Kapton Sample Cell Windows on the Detection Limit of Smectite: Implications for CheMin on the Mars Science Laboratory Mission

NASA Technical Reports Server (NTRS)

Achilles, C. N.; Ming, Douglas W.; Morris, R. V.; Blake, D. F.

2012-01-01

The CheMin instrument on the Mars Science Laboratory (MSL) rover Curiosity is an X-ray diffraction (XRD) and X-ray fluorescence (XRF) instrument capable of providing the mineralogical and chemical compositions of rocks and soils on the surface of Mars. CheMin uses a microfocus X-ray tube with a Co target, transmission geometry, and an energy-discriminating X-ray sensitive CCD to produce simultaneous 2-D XRD patterns and energy-dispersive X-ray histograms from powdered samples. CheMin has two different window materials used for sample cells -- Mylar and Kapton. Instrument details are provided elsewhere. Fe/Mg-smectite (e.g., nontronite) has been identified in Gale Crater, the MSL future landing site, by CRISM spectra. While large quantities of phyllosilicate minerals will be easily detected by CheMin, it is important to establish detection limits of such phases to understand capabilities and limitations of the instrument. A previous study indicated that the (001) peak of smectite at 15 Ang was detectable in a mixture of 1 wt.% smectite with olivine when Mylar is the window material for the sample cell. Complications arise when Kapton is the window material because Kapton itself also has a diffraction peak near 15 Ang (6.8 deg 2 Theta). This study presents results of mineral mixtures of smectite and olivine to determine smectite detection limits for Kapton sample cells. Because the intensity and position of the smectite (001) peak depends on the hydration state, we also analyzed mixtures with "hydrated" and "dehydrated"h smectite to examine the effects of hydration state on detection limits.

Communication and respect for people with dementia: student learning (CARDS) - the development and evaluation of a pilot of an education intervention for pre-qualifying healthcare students.

PubMed

Wood, Julia Helen; Alushi, Ledia; Hammond, John A

2016-04-01

Dementia is an international health priority and healthcare students need to be prepared to work with people living with dementia. There is a paucity of the literature describing appropriate educational interventions for pre-qualifying healthcare students and even fewer that are evaluated. Based on available evidence, an education program was developed aiming to increase students' knowledge and confidence in working with people with dementia (PWD). An introductory program (IP) of classroom sessions and workshops was followed by a volunteer care home experience (CHE) (4 × 3 h). Piloted with physiotherapy (IP n = 55; CHE n = 6) and nursing students (IP n = 20; CHE n = 7), using a survey design, knowledge, and perceived confidence for working with PWD were measured at four time points; baseline, after the IP, after the CHE, and six months later. The data were analyzed using paired t-tests or non-parametric equivalents. Knowledge scores increased after the IP (Time 1-2, p < 0.001, n = 48) and increases were retained after six months (Time 1-4, p < 0.001, n = 40). Perceived confidence increased at six months follow up (Time 1-4, p < 0.001, n = 40) with peaks after the IP (Time 1-2, p < 0.001, n = 47) and CHE (Time 2-3, p = 0.004, n = 13). Physiotherapy and nursing students did not differ on knowledge, but nursing students were more confident at baseline and after the IP. Prior experience equated with greater confidence but no more knowledge. Findings indicate that students' knowledge and confidence to work with PWD improves after this educational intervention, with confidence improving more when supplemented by experience.

Detection Limit of Smectite by Chemin IV Laboratory Instrument: Preliminary Implications for Chemin on the Mars Science Laboratory Mission

NASA Technical Reports Server (NTRS)

Archilles, Cherie; Ming, D. W.; Morris, R. V.; Blake, D. F.

2011-01-01

The CheMin instrument on the Mars Science Laboratory (MSL) is an miniature X-ray diffraction (XRD) and X-ray fluorescence (XRF) instrument capable of detecting the mineralogical and elemental compositions of rocks, outcrops and soils on the surface of Mars. CheMin uses a microfocus-source Co X-ray tube, a transmission sample cell, and an energy-discriminating X-ray sensitive CCD to produce simultaneous 2-D XRD patterns and energy-dispersive X-ray histograms from powdered samples. CRISM and OMEGA have identified the presence of phyllosilicates at several locations on Mars including the four candidate MSL landing sites. The objective of this study was to conduct preliminary studies to determine the CheMin detection limit of smectite in a smectite/olivine mixed mineral system.

Three-dimensional structure of homodimeric cholesterol esterase-ligand complex at 1.4 Å resolution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pletnev, V.; Addlagatta, A.; Wawrzak, Z.

2010-03-08

The three-dimensional structure of a Candida cylindracea cholesterol esterase (ChE) homodimer (534 x 2 amino acids) in complex with a ligand of proposed formula C{sub 23}H{sub 48}O{sub 2} has been determined at 1.4 {angstrom} resolution in space group P1 using synchrotron low-temperature data. The structure refined to R = 0.136 and R{sub free} = 0.169 and has revealed new stereochemical details in addition to those detected for the apo- and holo-forms at 1.9 and 2.0 {angstrom} resolution, respectively [Ghosh et al. (1995), Structure, 3, 279-288]. The cholesterol esterase structure is a dimer with four spatially separated interfacial contact areas andmore » two symmetry-related pairs of openings to an internal intradimer cavity. Hydrophobic active-site gorges in each subunit face each other across a central interfacial cavity. The ChE subunits have carbohydrate chains attached to their Asn314 and Asn351 residues, with two ordered N-acetyl-D-glucosoamine moieties visible at each site. The side chains of 14 residues have two alternative conformations with occupancy values of 0.5 {+-} 0.2. For each subunit the electron density in the enzyme active-site gorge is well modeled by a C{sub 23}-chain fatty acid.« less

CHeCS (Crew Health Care Systems): International Space Station (ISS) Medical Hardware Catalog. Version 10.0

NASA Technical Reports Server (NTRS)

2011-01-01

The purpose of this catalog is to provide a detailed description of each piece of hardware in the Crew Health Care System (CHeCS), including subpacks associated with the hardware, and to briefly describe the interfaces between the hardware and the ISS. The primary user of this document is the Space Medicine/Medical Operations ISS Biomedical Flight Controllers (ISS BMEs).

Burbank participates in a CHeCS Medical Contingency Drill in the U.S. Laboratory

NASA Image and Video Library

2011-12-16

ISS030-E-012613 (16 Dec. 2011) --- NASA astronaut Dan Burbank (foreground), Expedition 30 commander, and Russian cosmonaut Anton Shkaplerov, flight engineer, participate in a Crew Health Care System (CHeCS) medical contingency drill in the Destiny laboratory of the International Space Station. This drill gives crew members the opportunity to work as a team in resolving a simulated medical emergency onboard the space station.

Burbank participates in a CHeCS Medical Contingency Drill in the U.S. Laboratory

NASA Image and Video Library

2011-12-16

ISS030-E-012609 (16 Dec. 2011) --- NASA astronaut Dan Burbank (foreground), Expedition 30 commander, and Russian cosmonaut Anton Shkaplerov, flight engineer, participate in a Crew Health Care System (CHeCS) medical contingency drill in the Destiny laboratory of the International Space Station. This drill gives crew members the opportunity to work as a team in resolving a simulated medical emergency onboard the space station.

Ivanishin participates in a CHeCS Medical Contingency Drill in the U.S. Laboratory

NASA Image and Video Library

2011-12-16

ISS030-E-012604 (16 Dec. 2011) --- Russian cosmonauts Anatoly Ivanishin (foreground) and Anton Shkaplerov, both Expedition 30 flight engineers, participate in a Crew Health Care System (CHeCS) medical contingency drill in the Destiny laboratory of the International Space Station. This drill gives crew members the opportunity to work as a team in resolving a simulated medical emergency onboard the space station.

Pragmatic Idealism: Ernesto Che Guevaras Strategic Choice for Bolivia

DTIC Science & Technology

2017-06-01

that the guerrilla foco could be used as an inspiration to the masses, and that, by its very existence, people would be encouraged to support and join...Paperwork Reduction Project (0704-0188) Washington DC 20503. 1. AGENCY USE ONLY (Leave blank) 2. REPORT DATE June 2017 3. REPORT TYPE AND...strategic, and psychological factors meant to achieve a specific end. 14. SUBJECT TERMS Che, Guevara, guerrilla warfare, Cuba, Bolivia

Negotiating and Appropriating the "One Person, One Language" Policy within the Complex Reality of a Multilingual Crèche in Strasbourg

ERIC Educational Resources Information Center

Caporal-Ebersold, Eloise; Young, Andrea

2016-01-01

The aim of this article is to analyse the early childhood education and care (ECEC) language policy in the city of Strasbourg, focusing on an ethnographic case study of a newly established bilingual English-French crèche in the city. In France, establishing an early childhood education structure--more specifically, a day care centre catering to…

The first X-ray diffraction measurements on Mars.

PubMed

Bish, David; Blake, David; Vaniman, David; Sarrazin, Philippe; Bristow, Thomas; Achilles, Cherie; Dera, Przemyslaw; Chipera, Steve; Crisp, Joy; Downs, R T; Farmer, Jack; Gailhanou, Marc; Ming, Doug; Morookian, John Michael; Morris, Richard; Morrison, Shaunna; Rampe, Elizabeth; Treiman, Allan; Yen, Albert

2014-11-01

The Mars Science Laboratory landed in Gale crater on Mars in August 2012, and the Curiosity rover then began field studies on its drive toward Mount Sharp, a central peak made of ancient sediments. CheMin is one of ten instruments on or inside the rover, all designed to provide detailed information on the rocks, soils and atmosphere in this region. CheMin is a miniaturized X-ray diffraction/X-ray fluorescence (XRD/XRF) instrument that uses transmission geometry with an energy-discriminating CCD detector. CheMin uses onboard standards for XRD and XRF calibration, and beryl:quartz mixtures constitute the primary XRD standards. Four samples have been analysed by CheMin, namely a soil sample, two samples drilled from mudstones and a sample drilled from a sandstone. Rietveld and full-pattern analysis of the XRD data reveal a complex mineralogy, with contributions from parent igneous rocks, amorphous components and several minerals relating to aqueous alteration. In particular, the mudstone samples all contain one or more phyllosilicates consistent with alteration in liquid water. In addition to quantitative mineralogy, Rietveld refinements also provide unit-cell parameters for the major phases, which can be used to infer the chemical compositions of individual minerals and, by difference, the composition of the amorphous component.

Adverse effects of metal exposure on chemotaxis towards water-soluble attractants regulated mainly by ASE sensory neuron in nematode Caenorhabditis elegans.

PubMed

Xing, Xiaojuan; Du, Min; Zhang, Yanfen; Wang, Dayong

2009-01-01

Chemotaxis to water-soluble attractants is mainly controlled by ASE sensory neuron whose specification is regulated by che-1 in Caenorhabditis elegans. Our data suggested that exposure to high concentrations of metals, such as Pb, Cu, Ag, and Cr, would result in severe defects of chemotaxis to water-soluble attractants of NaCl, cAMP, and biotin. Moreover, the morphology of ASE neuron structures as observed by relative fluorescent intensities and relative size of fluorescent puncta of cell bodies, relative lengths of sensory endings in ASE neurons, and the expression patterns of che-1 were obviously altered in metal exposed animals when they meanwhile exhibited obvious chemotaxis defects to water-soluble attractants. In addition, the dendrite morphology could be noticeably changed in animals exposed to 150 micromol/L of Pb, Cu, and Ag. Furthermore, we observed significant decreases of chemotaxis to water-soluble attractants in Pb exposed che-1 mutant at concentrations more than 2.5 micromol/L, and in Cu, Ag, and Cr exposed che-1 mutant at concentrations more than 50 micromol/L. Therefore, impairment of the ASE neuron structures and functions may largely contribute to the appearance of chemotaxis defects to water-soluble attractants in metal exposed nematodes.

Protective efficacy of six immunogenic recombinant proteins of Vibrio anguillarum and evaluation them as vaccine candidate for flounder (Paralichthys olivaceus).

PubMed

Xing, Jing; Xu, Hongsen; Wang, Yang; Tang, Xiaoqian; Sheng, Xiuzhen; Zhan, Wenbin

2017-06-01

Vibrio anguillarum is a severe bacterium that causes terminal haemorrhagic septicaemia in freshwater and marine fish. Virulence-associated proteins play an important role in bacterial pathogenicity and could be applied for immunoprophylaxis. In this study, six antigenic proteins from V. anguillarum were selected and the immune protective efficacy of their recombinant proteins was investigated. VirA, CheR, FlaC, OmpK, OmpR and Hsp33 were recombinantly produced and the reactions of recombinant proteins to flounder-anti-V. anguillarum antibodies (fV-ab) were detected, respectively. Then the recombinant proteins were injected to fish, after immunization, the percentages of surface membrane immunoglobulin-positive (sIg+) cell in lymphocytes, total antibodies, antibodies against V. anguillarum, antibodies against recombinant proteins and relative percent survival (RPS) were analyzed, respectively. The results showed that all the recombinant proteins could react to fV-ab, proliferate sIg + cells in lymphocytes and induce production of total antibodies, specific antibodies against V. anguillarum or the recombinant proteins; the RPS of rVirA, rCheR, rFlaC, rOmpK, rOmpR and rHsp33 against V. anguillarum was 70.27%, 27.03%, 16.22%, 62.16%, 45.95% and 81.08%, respectively. The results revealed that rHsp33, rVirA and rOmpK have good protections against V. anguillarum and could be vaccine candidates against V. anguillarum. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mineralogy of Rocks and Sediments at Gale Crater, Mars

NASA Astrophysics Data System (ADS)

Achilles, Cherie; Downs, Robert; Blake, David; Vaniman, David; Ming, Doug; Rampe, Elizabeth; Morris, Dick; Morrison, Shaunna; Treiman, Allan; Chipera, Steve; Yen, Albert; Bristow, Thomas; Craig, Patricia; Hazen, Robert; Crisp, Joy; Grotzinger, John; Des Marias, David; Farmer, Jack; Sarrazin, Philippe; Morookian, John Michael

2017-04-01

The Mars Science Laboratory rover, Curiosity, is providing in situ mineralogical, geochemical, and sedimentological assessments of rocks and soils in Gale crater. Since landing in 2012, Curiosity has traveled over 15 km, providing analyses of mudstones and sandstones to build a stratigraphic history of the region. The CheMin X-ray diffraction (XRD) instrument is the first instrument on Mars to provide quantitative mineralogical analyses of drilled powders and scooped sediment based on X-ray crystallography. CheMin identifies and determines mineral abundances and unit-cell parameters of major crystalline phases, and identifies minor phases at abundances >1 wt%. In conjunction with elemental analyses, CheMin-derived crystal chemistry allows for the first calculations of crystalline and amorphous material compositions. These mineralogy, crystal chemistry, and amorphous chemistry datasets are playing central roles in the characterization of Gale crater paleoenvironments. CheMin has analyzed 17 rock and sediment samples. In the first phase of the mission, Curiosity explored the sedimentary units of Aeolis Palus (Bradbury group), including two mudstones from Yellowknife Bay. CheMin analyses of the Yellowknife Bay mudstones identified clay minerals among an overall basaltic mineral assemblage. These mineralogical results, along with imaging and geochemical analyses, were used to characterize an ancient lacustrine setting that is thought to have once been a habitable environment. Following the investigations of the Bradbury group, Curiosity arrived at the lower reaches of Aeolis Mons, commonly called Mt. Sharp. A strategic sample campaign was initiated, drilling bedrock at <25 m elevation intervals in order to compile a comprehensive stratigraphic column of Mt. Sharp sedimentary units. Two formations have been sampled thus far, the lower-most Murray formation and the Stimson formation, which lies unconformably over the Murray. The Stimson formation is a cross-bedded sandstone interpreted as ancient, lithified eolian dunes. The mineralogy of this sandstone is dominated by plagioclase, pyroxene, magnetite and X-ray amorphous phases. Adjacent to fractures, light-toned, halo-like zones are thought to result from significant aqueous alteration of the primary sandstone and show decreased abundances of feldspar and pyroxene, and an increase in the amorphous component, specifically high-silica phases. The Murray formation is the most sampled stratigraphic unit in Gale crater. Composed mainly of finely laminated mudstones and interpreted as lacustrine deposits, the mineralogy of Murray rocks reveals a complex aqueous history. Within the lower Murray strata, CheMin identified clay minerals, crystalline and amorphous silica, hematite, magnetite, and jarosite. The mineralogy suggests a paleolake that experienced variable redox conditions and sediment influx from multiple sources. Younger Murray strata have high abundances of clay minerals, hematite, and calcium sulfate but show lower variability in mineralogy compared to the older bedforms. CheMin's identification of tridymite in one of the Murray mudstone samples led to the first in situ identification of silicic volcanism on Mars. This presentation will discuss the mineralogy of sedimentary samples analyzed by CheMin and how these data are used to characterize the depositional and diagenetic environment of Gale crater's long-lived lake system.

Financial protection effects of modification of China's New Cooperative Medical Scheme on rural households with chronic diseases.

PubMed

Wang, Jing; Chen, Lina; Ye, Ting; Zhang, Zhiguo; Ma, Jingdong

2014-07-15

Several years have passed since the rural New Cooperative Medical Scheme (NCMS) in China was established and policies kept continuous improvement. Its policies on chronic diseases vary by county but have certain shared characteristics. Following this modification of medical insurance policy, this study reassesses the provision of insurance against expenditure on chronic diseases in rural areas, and analyzes its effect on impoverishment. We conducted an empirical study using multi-stage stratified random sampling. We surveyed 1,661 rural households in three provinces and analyzed the responses from 1,525 households that participated in NCMS, using descriptive and logistic regression analysis. The NCMS has reduced the prevalence of poverty and catastrophic health expenditure (CHE), as measured by out-of-pocket (OOP) payments exceeding 40% of total household expenditure, by decreasing medical expenditure. It provides obvious protection to households which include someone with chronic diseases. However, these households continue to face a higher financial risk than those without anyone suffering from chronic diseases. Variables about health service utilization and OOP payment differed significantly between households with or without people suffering from chronic disease. And CHE risk is commonly associated with household income, the number of family members with chronic diseases, OOP payment of outpatient and inpatient service in all three provinces. To reduce CHE risk for these households, it is critical to decrease OOP payments for health services by enhancing the effective reimbursement level of NCMS and strictly regulating the providers' behaviors. We recommend that a combinatory changes should be made to the rural health insurance scheme in China to improve its effect. These include improving the NCMS benefit package by broadening the catalogue of drugs and treatments covered, decreasing or abolishing deductible and increasing the reimbursement ratio of outpatient services for people with chronic diseases, together with expansion of insurance fund, and modifying health providers' behaviors by payment reform.

Ford and Novitskiy participate in a CHeCS Medical Contingency Drill in the U.S. Laboratory

NASA Image and Video Library

2012-11-26

ISS034-E-005268 (26 Nov. 2012) --- NASA astronaut Kevin Ford (background), Expedition 34 commander; and Russian cosmonaut Oleg Novitskiy, flight engineer, participate in a Crew Health Care System (CHeCS) medical contingency drill in the Destiny laboratory of the International Space Station. This drill gives crew members the opportunity to work as a team in resolving a simulated medical emergency onboard the space station.

Novitskiy and Tarelkin both participate in a CHeCS medical contingency drill in the U.S. Laboratory

NASA Image and Video Library

2012-11-26

ISS034-E-005261 (26 Nov. 2012) --- Russian cosmonauts Oleg Novitskiy (left) and Evgeny Tarelkin, both Expedition 34 flight engineers, participate in a Crew Health Care System (CHeCS) medical contingency drill in the Destiny laboratory of the International Space Station. This drill gives crew members the opportunity to work as a team in resolving a simulated medical emergency onboard the space station.

Covert and Overt Hepatic Encephalopathy: Diagnosis and Management

PubMed Central

Patidar, Kavish R.; Bajaj, Jasmohan S.

2015-01-01

Hepatic encephalopathy (HE) is part of a spectrum of neurocognitive changes in cirrhosis. HE is divided into two broad categories based on severity, covert (CHE) and overt (CHE). CHE has a significant impact on a patient’s quality of life, driving performances, and has recently been associated with increased hospitalizations and death. Likewise, OHE is associated with increased rates of hospitalizations and mortality, and poor quality of life. Given its significant burden on patients, care takers, and the health care system, it’s imperative for early diagnosis and management. In addition, a focus should also be directed on patient and family member education on the disease progression and adherence to medications. Treatment strategies include the use of non-absorbable disaccharides, antibiotics (i.e. rifaximin), and potentially probiotics. Other therapies currently under further investigation include: L-ornithine-L-aspartate, ornithine phenylacetate, glycerol phenylbutyrate, molecular adsorbent recirculating system, and albumin infusion. PMID:26164219

IL TRAPIANTO ORTOTOPICO DEL FEGATO

PubMed Central

STARZL, THOMAS E.

2010-01-01

E’ormai noto che esiste la possibilità rivoluzionaria di utilizzare il fegato per il trattamento della stadio terminale delle epatopatie. Nel gennaio 1980 si celebra il decimo anna di sopravvivenza con fegato trapiantato (la più lunga della letteratura) di un paziente da noi trattato. Si tratta di uno dei 12 malati sottoposti a trapianto e seguiti per più di 5 anni. La nota positiva di questa tipo di trattamento è rappresentata dall’eccellente tenore di vita che i pazienti conducono e dalla riabilitazione sociale e professionale. La nota negativa è data, invece, dal fatto che i buoni risultati non vengono raggiunti con regolarità e non possono essere previsti con esattezza. In questa breve rassegna considereremo la esperienza da noi fatta presso l’Università di Denver nel Colorado, mettendo in risalto le cause dell’elevata mortalità precoce e le prospettive future di questa mezzo terapeutico. PMID:21572898

Catastrophic Health Expenditure Among Colorectal Cancer Patients and Families: A Case of Malaysia.

PubMed

Azzani, Meram; Yahya, Abqariyah; Roslani, April Camilla; Su, Tin Tin

2017-09-01

This study aimed to estimate the cost of colorectal cancer (CRC) management and to explore the prevalence and determinants of catastrophic health expenditure (CHE) among CRC patients and their families arising from the costs of CRC management. Data were collected prospectively from 138 CRC patients. Patients were interviewed by using a structured questionnaire at the time of the diagnosis, then at 6 months and 12 months following diagnosis. Simple descriptive methods and multivariate binary logistic regression were used in the analysis. The mean cost of managing CRC was RM8306.9 (US$2595.9), and 47.8% of patients' families experienced CHE. The main determinants of CHE were the economic status of the family and the likelihood of the patient undergoing surgery. The results of this study strongly suggest that stakeholders and policy makers should provide individuals with financial protection against the consequences of cancer, a costly illness that often requires prolonged treatment.

cDNA-AFLP analysis of differential gene expression related to cell chemotactic and encystment of Azospirillum brasilense.

PubMed

Li, Huamin; Cui, Yanhua; Wu, Lixian; Tu, Ran; Chen, Sanfeng

2011-12-20

Our previous study indicated org35 was involved in chemotaxis and interacted with nitrogen fixation transcriptional activator NifA via PAS domain. In order to reveal the role of org35 in nitrogen regulation, the downstream target genes of org35 were identified. We here report differentially expressed genes in org35 mutants comparing with wild type Sp7 by means of cDNA-AFLP. Four up-regulated transcript-derived fragments (TDFs) homologues of chemotaxis transduction proteins were found, including CheW, methyl-accepting chemotaxis protein and response regulator CheY-like receiver. Three distinct TDFs (AB46, AB58 and AB63) were similar to PHB de-polymerase C-terminus, cell shape-determining protein and flagellin domain protein. And 11 TDFs showed similarities with signal transduction proteins, including homologous protein of the nitrogen regulation protein NtrY and nitrate/nitrite response regulator protein NarL. These data suggested that the Azospirillum brasilense org35 was a multi-effecter and involved in chemotaxis, cyst development and regulation of nitrogen fixation. Copyright © 2010 Elsevier GmbH. All rights reserved.

Sublethal landrin toxicity: Behavioral and physiological effects on captive vultures

USGS Publications Warehouse

Forthman-Quick, D.L.; Hill, E.F.

1988-01-01

Use of conditioned taste aversion (CTA) has been proposed to reduce consumption of California condor (Gymnogyps californianus) eggs by ravens (Corvus corax). Although landrin has induced aversions in ravens and other birds, no data were available on behavioral and physiological effects of landrin on condors, non-target birds that might consume treated eggs. Because condors are endangered, we selected taxonomically related surrogates to approximate the effects on condors of acute oral doses of landrin. Seven black vultures (Coragyps atratus), 2 turkey vultures (Cathartes aura), and 2 king vultures (Sarcoramphus papa) received landrin and placebo treatments 1 week apart. Plasma cholinesterase (ChE) activity was monitored at zero, 3, and 24 hours posttreatment, and behavioral observations were made for 2 hours posttreatment. The doses tested were nonlethal, and ChE levels approached normal within 24 hours after treatment. Only the frequency of vomiting differed statistically between the placebo and landrin treatment. We conclude that with appropriate precautions, landrin can be used in applications of CTA to discourage consumption of condor eggs by ravens, while posing no apparent risk to reintroduced condors.

BRAIN CHOLINESTERASE INHIBITION AND DEPRESSION OF THE PHOTIC AFTER DISCHARGE (PHAD) OF FLASH EVOKED POTENTIALS (FEPS) IN LONG EVANS RATS FOLLOWING ACUTE OR REPEATED EXPOSURES TO A MIXTURE OF CARBARYL AND PROPOXUR.

EPA Science Inventory

Carbaryl and propoxur are N-methyl carbamate pesticides (NMCs) which are part of the EPA’s cumulative risk assessments for NMCs. These NMCs inhibit cholinesterase (ChE) activity and may lead to cholinergic disruption of CNS function. We used decreases in the PhAD of FEPs to indic...

Tick Salivary Cholinesterase: A Probable Immunomodulator of Host-parasite Interactions.

PubMed

Temeyer, Kevin B; Tuckow, Alexander P

2016-05-01

The southern cattle tick, Rhipicephalus (Boophilus) microplus (Canestrini), is the most economically important cattle ectoparasite in the world. Rhipicephalus microplus and Rhipicephalus annulatus (Say) continue to threaten U.S. cattle producers despite eradication and an importation barrier based on inspection, dipping of imported cattle in organophosphate (OP) acaricide, and quarantine of infested premises. OP acaricides inhibit acetylcholinesterase (AChE), essential to tick central nervous system function. Unlike vertebrates, ticks possess at least three genes encoding AChEs, differing in amino acid sequence and biochemical properties. Genomic analyses of R. microplus and the related tick, Ixodes scapularis, suggest that ticks contain many genes encoding different AChEs. This work is the first report of a salivary cholinesterase (ChE) activity in R. microplus, and discusses complexity of the cholinergic system in ticks and significance of tick salivary ChE at the tick-host interface. It further provides three hypotheses that the salivary ChE plausibly functions 1) to reduce presence of potentially toxic acetylcholine present in the large bloodmeal imbibed during rapid engorgement, 2) to modulate the immune response (innate and/or acquired) of the host to tick antigens, and 3) to influence transmission and establishment of pathogens within the host animal. Ticks are vectors for a greater number and variety of pathogens than any other parasite, and are second only to mosquitoes (owing to malaria) as vectors of serious human disease. Saliva-assisted transmission (SAT) of pathogens is well-known; however, the salivary components participating in the SAT process remain to be elucidated. Published by Oxford University Press on behalf of Entomological Society of America 2016. This work is written by US Government employees and is in the public domain in the US.

Two cholinesterase inhibitors trigger dissimilar effects on behavior and body weight in C57BL/6 mice: The case of chlorpyrifos and rivastigmine.

PubMed

Basaure, Pia; Peris-Sampedro, Fiona; Cabré, Maria; Reverte, Ingrid; Colomina, Maria Teresa

2017-02-01

Cholinesterases (ChE) are common targets of organophosphate (OP) pesticides and play a critical role in the pathology of some dementias. While chlorpyrifos (CPF) remains one of the most commonly used OPs in the world, numerous investigations have reported its neurotoxic potential and highlighted behavioral disturbances upon its administration. Rivastigmine currently serves to treat Alzheimer's disease, but it may induce cholinergic overstimulation in non-demented individuals. The present investigation aimed to compare the acute and delayed effects caused by both ChE inhibitors in adult C57BL/6 male mice. The animals were daily fed either a standard, a CPF- (5mg/kg body weight) or a rivastigmine-supplemented diet (1 or 2mg/kg body weight) for 8 weeks. After the treatment, we established an 8-week washout period to assess recovery. ChE enzyme activity, biomarkers, physical effects, and behavioral alterations were evaluated at different time points during the exposure and after the washout period. Both rivastigmine doses induced a time-dependent weight increase. CPF and rivastigmine inhibited brain acetylcholinesterase following an isoform-specific pattern. As for behavioral assessment, CPF negatively modulated learning strategies and impaired memory in a Barnes maze task at the end of the exposure. On the other hand, the low dose of rivastigmine improved memory recall at the end of the washout period in a Morris water maze. Indeed, our results endorse the positive effects of low doses of rivastigmine following a drug-free period in young mice. Therefore, doses and periodicity of treatment to improve cognition in elderly people upon rivastigmine administration should be revised. Copyright © 2016 Elsevier B.V. All rights reserved.

Distortion product otoacoustic emissions as non-invasive biomarkers and predictors of soman-induced central neurotoxicity: a preliminary study.

PubMed

Job, Agnès; Baille, Valérie; Dorandeu, Frédéric; Pouyatos, Benoît; Foquin, Annie; Delacour, Claire; Denis, Josiane; Carpentier, Pierre

2007-09-05

The organophosphorus nerve agent soman is an irreversible cholinesterase (ChE) inhibitor that can produce long-lasting seizures and brain damage in which the neurotransmitters acetylcholine and glutamate are involved. These same neurotransmitters play key-roles in the auditory function. It was then assumed that exploring the hearing function may provide markers of the central events triggered by soman intoxication. In the present study, distortion product otoacoustic emissions (DPOAEs), a non-invasive audiometric method, were used to monitor cochlear functionality in rats administered with a moderate dose of soman (45 microg/kg). DPOAEs were investigated either 4h or 24h post-challenge. In parallel, the effects of soman on whole blood and brain ChE activity and on brain histology were also studied. The first main result is that DPOAE intensities were significantly decreased 4h post-soman and returned to baseline at 24h. The amplitude changes were well related to the severity of symptoms, with the greatest change being recorded in the rats that survived long-lasting convulsions. The second main result is that baseline DPOAEs recorded 8 days before soman appear to predict the severity of symptoms produced by the intoxication. Indeed, the lowest baseline DPOAEs corresponded to the occurrence of long-lasting convulsions and brain damage and to the greatest inhibition in central ChE. These results thus suggest that DPOAEs represent a promising non-invasive tool to assess and predict the central consequences of nerve agent poisoning. Further investigations will be carried out to assess the potential applications and the limits of this non-invasive method.

Short infrared laser pulses block action potentials in neurons

NASA Astrophysics Data System (ADS)

Walsh, Alex J.; Tolstykh, Gleb P.; Martens, Stacey L.; Ibey, Bennett L.; Beier, Hope T.

2017-02-01

Short infrared laser pulses have many physiological effects on cells including the ability to stimulate action potentials in neurons. Here we show that short infrared laser pulses can also reversibly block action potentials. Primary rat hippocampal neurons were transfected with the Optopatch2 plasmid, which contains both a blue-light activated channel rhodopsin (CheRiff) and a red-light fluorescent membrane voltage reporter (QuasAr2). This optogenetic platform allows robust stimulation and recording of action potential activity in neurons in a non-contact, low noise manner. For all experiments, QuasAr2 was imaged continuously on a wide-field fluorescent microscope using a Krypton laser (647 nm) as the excitation source and an EMCCD camera operating at 1000 Hz to collect emitted fluorescence. A co-aligned Argon laser (488 nm, 5 ms at 10Hz) provided activation light for CheRiff. A 200 mm fiber delivered infrared light locally to the target neuron. Reversible action potential block in neurons was observed following a short infrared laser pulse (0.26-0.96 J/cm2; 1.37-5.01 ms; 1869 nm), with the block persisting for more than 1 s with exposures greater than 0.69 J/cm2. Action potential block was sustained for 30 s with the short infrared laser pulsed at 1-7 Hz. Full recovery of neuronal activity was observed 5-30s post-infrared exposure. These results indicate that optogenetics provides a robust platform for the study of action potential block and that short infrared laser pulses can be used for non-contact, reversible action potential block.

Effect of methylparaben in Artemia franciscana.

PubMed

Comeche, Amparo; Martín-Villamil, María; Picó, Yolanda; Varó, Inma

2017-09-01

In this study, the toxicity of methylparaben (MeP) an emerging contaminant, was analysed in the sexual species Artemia franciscana, due to its presence in coastal areas and marine saltworks in the Mediterranean region. The acute toxicity (24h-LC 50 ) of MeP in nauplii was tested and its chronic effect (9days) evaluated by measuring survival and growth under two sublethal concentrations (0.0085 and 0.017mg/L). Also, the effect on several key enzymes involved in: antioxidant defences (catalase (CAT) and gluthathion-S-transferase (GST)), neural activity (cholinesterase (ChE)) and xenobiotic biotransformation (carboxylesterase (CbE), was assessed after 48h under sublethal exposure. The results of acute exposure indicate that MeP is harmful to A. franciscana (24h-LC 50 =36.7mg/L). MeP causes a decrease in CAT activity after 48h exposure to both concentration tested, that points out at the oxidative stress effect of MeP in A. franciscana. However, no significant effect on ChE, CbE and GST activities was found. In addition, MeP does not affect survival and growth in chronic exposure at the sublethal concentrations tested. The results of this study indicate that MeP is not a threat for A. franciscana under the experimental conditions used. Additional studies should be done considering long-term exposure and reproduction studies to analyse the potential risk of MeP as emerging contaminant in marine and hypersaline environments. Published by Elsevier Inc.

Assessment of biological effects of pollutants in a hyper eutrophic tropical water body, Lake Beira, Sri Lanka using multiple biomarker responses of resident fish, Nile tilapia (Oreochromis niloticus).

PubMed

Pathiratne, Asoka; Pathiratne, K A S; De Seram, P K C

2010-08-01

Biomarkers measured at the molecular and cellular level in fish have been proposed as sensitive "early warning" tools for biological effect measurements in environmental quality assessments. Lake Beira is a hypertrophic urban water body with a complex mixture of pollutants including polycyclic aromatic hydrocarbons (PAHs) and Microcystins. In this study, a suite of biomarker responses viz. biliary fluorescent aromatic compounds (FACs), hepatic ethoxyresorufin O-deethylase (EROD) and glutathione S-transferase (GST), brain and muscle cholinesterases (ChE), serum sorbitol dehydrogenase (SDH), and liver histology of Oreochromis niloticus, the dominant fish inhabiting this tropical Lake were evaluated to assess the pollution exposure and biological effects. Some fish sampled in the dry periods demonstrated prominent structural abnormalities in the liver and concomitant increase in serum SDH and reduction in hepatic GST activities in comparison to the control fish and the fish sampled in the rainy periods. The resident fish with apparently normal liver demonstrated induction of hepatic EROD and GST activities and increase in biliary FACs irrespective of the sampling period indicating bioavailability of PAHs. Muscle ChE activities of the resident fish were depressed significantly indicating exposure to anticholinesterase substances. The results revealed that fish populations residing in this Lake is under threat due to the pollution stress. Hepatic abnormalities in the fish may be mainly associated with the pollution stress due to recurrent exposure to PAHs and toxigenic Microcystis blooms in the Lake.

Evaluating mineralogy at terrestrial analogs for early Mars: Detection and characterization of clays with XRD and investigation of iron substitution in natroalunite

NASA Astrophysics Data System (ADS)

Beckerman, Laura Grace

The Mars Science Laboratory (MSL) Curiosity rover is equipped with CheMin, the first x-ray diffraction (XRD) instrument on Mars, for in situ mineralogy as part of its mission to seek evidence of past habitability at Gale Crater. Detection and characterization of hydrated minerals like clays and sulfates provides crucial insight into Mars' early geochemistry. For example, clays are often interpreted as having formed in lacustrine environments at neutral pHs, while sulfates such as jarosite are evidence of acid sulfate alteration. However, CheMin's inability to remove non-clay minerals and to preferentially orient samples may pose significant challenges to clay detection and characterization at Gale Crater. To evaluate the effect of particle size separation (<0.2 microm), removal of non-clay minerals, preferred orientation, and ethylene glycol solvation on XRD analyses of clays, we used both a CheMin analog instrument and a traditional laboratory XRD to identify clays in acid sulfate altered basalt from Mars analog sites in Costa Rica. We detected kaolinite in four of the fourteen samples studied, one of which also contained montmorillonite. Kaolinite was not detected in two samples with the analog instrument prior to clay isolation. These results suggest that CheMin may miss detection of some clays at Gale Crater, which could affect interpretations of early Mars' habitability. Mistaking iron-rich natroalunite (Na[Al,Fe]3(SO4) 2(OH)6) for jarosite (KFe3(SO4) 2(OH)6) could also impact interpretations of early Mars, as natroalunite can form over a broader range of pH, water:rock ratios, and redox conditions than can jarosite. To determine if iron-rich natroalunite is a common alteration product at Mars analog sites, we assessed iron content in natroalunite from Costa Rica. We detected up to 30% iron substitution in natroalunite at diverse geochemical settings. We also evaluated the feasibility of using XRD or Raman spectroscopy for in situ iron-rich natroalunite detection, and determined that CheMin on Curiosity and the Raman Laser Spectrometer on the upcoming ExoMars rover could detect natroalunite with ≥25% iron substitution. Distinguishing between iron-rich natroalunite and jarosite with CheMin could aid in interpreting geochemical conditions and habitability at Gale Crater.

Calorimetria nucleare in collisioni tra ioni pesanti ad energie intermedie

NASA Astrophysics Data System (ADS)

Spezzi, L.

2002-07-01

Nel presente lavoro di tesi ci si e' occupati di uno studio sistematico di misure di temperatura ed energia di eccitazione in sistemi nucleari formati in reazioni tra ioni pesanti ad energie intermedie. La temperatura a stata misurata tramite due diversi metodi: rapporto tra le rese di isotopi che differiscono di uno stesso numero di nucleoni ( d/t-3He/4He , 3He/4He -6Li/7Li) - temperatura isotopica -, e rapporto tra le popolazioni degli stati eccitati in frammenti instabili (5Li e 6Li) che decadono in particelle leggere in coincidenza - temperatura di emissione. Le misure in esame sono state effettuate presso i Laboratori Nazionali del Sud per i sistemi 93Nb+93Nb, 93Nb+116,124Sn, 116,120Sn+116,124Sn e 116Sn+93Nb ad energie comprese tra 17 e 40 A MeV. L'apparato di rivelazione era costituito da un odoscopio ad alta granularite (96 telescopi Si (50micron)-Si(300micron)-CsI(Tl) ) e basse soglie di rivelazione, utilizzato sia per identificare risonanze in frammenti eccitati che per misure di rese di isotopi di frammenti con 2<=Z<=6, e dal multirivelatore FIASCO che, grazie alla misura contemporanea di posizione e tempo di volo dei frammenti provenienti dal proiettile (PLF - Projectile Like Fragments) e dal bersaglio (TLF - Target Like Fragment), e' stato utilizzato per misurare direttamente l'energia di eccitazione del sistema in studio. Analisi precedenti, condotte nell'ambito di varie collaborazioni, hanno messo in evidenza la possible esistenza di una transizione di fase liquido-gas del primo ordine nella materia nucleare. In tale contesto, ci siamo occupati di una verifica della curva calorica nucleare, ovvero della correlazione esistente fra temperatura ed energia di eccitazione del sistema, indagando, nel contempo, sulla sua dipendenza dalla massa del sistema che si frammenta. Si e' effettuato, inoltre, un confronto fra i due diversi metodi di misura della temperatura (temperatura isotopica e di emissione): l'andamento plateau-like della curva calorica e' stato confermato sia dalle temperature isotopiche che dalle temperature di emissione. Le "temperature limite", ovvero quelle relative all'andamento plateau-like della curva calorica, misurate per i vari sistemi studiati, sono state confrontate con quelle attualmente disponibili in letteratura, confermando la dipendenza dalla massa del sistema di tale grandezza.

Combining Random Gene Fission and Rational Gene Fusion To Discover Near-Infrared Fluorescent Protein Fragments That Report on Protein–Protein Interactions

PubMed Central

2015-01-01

Gene fission can convert monomeric proteins into two-piece catalysts, reporters, and transcription factors for systems and synthetic biology. However, some proteins can be challenging to fragment without disrupting function, such as near-infrared fluorescent protein (IFP). We describe a directed evolution strategy that can overcome this challenge by randomly fragmenting proteins and concomitantly fusing the protein fragments to pairs of proteins or peptides that associate. We used this method to create libraries that express fragmented IFP as fusions to a pair of associating peptides (IAAL-E3 and IAAL-K3) and proteins (CheA and CheY) and screened for fragmented IFP with detectable near-infrared fluorescence. Thirteen novel fragmented IFPs were identified, all of which arose from backbone fission proximal to the interdomain linker. Either the IAAL-E3 and IAAL-K3 peptides or CheA and CheY proteins could assist with IFP fragment complementation, although the IAAL-E3 and IAAL-K3 peptides consistently yielded higher fluorescence. These results demonstrate how random gene fission can be coupled to rational gene fusion to create libraries enriched in fragmented proteins with AND gate logic that is dependent upon a protein–protein interaction, and they suggest that these near-infrared fluorescent protein fragments will be suitable as reporters for pairs of promoters and protein–protein interactions within whole animals. PMID:25265085

Combining random gene fission and rational gene fusion to discover near-infrared fluorescent protein fragments that report on protein-protein interactions.

PubMed

Pandey, Naresh; Nobles, Christopher L; Zechiedrich, Lynn; Maresso, Anthony W; Silberg, Jonathan J

2015-05-15

Gene fission can convert monomeric proteins into two-piece catalysts, reporters, and transcription factors for systems and synthetic biology. However, some proteins can be challenging to fragment without disrupting function, such as near-infrared fluorescent protein (IFP). We describe a directed evolution strategy that can overcome this challenge by randomly fragmenting proteins and concomitantly fusing the protein fragments to pairs of proteins or peptides that associate. We used this method to create libraries that express fragmented IFP as fusions to a pair of associating peptides (IAAL-E3 and IAAL-K3) and proteins (CheA and CheY) and screened for fragmented IFP with detectable near-infrared fluorescence. Thirteen novel fragmented IFPs were identified, all of which arose from backbone fission proximal to the interdomain linker. Either the IAAL-E3 and IAAL-K3 peptides or CheA and CheY proteins could assist with IFP fragment complementation, although the IAAL-E3 and IAAL-K3 peptides consistently yielded higher fluorescence. These results demonstrate how random gene fission can be coupled to rational gene fusion to create libraries enriched in fragmented proteins with AND gate logic that is dependent upon a protein-protein interaction, and they suggest that these near-infrared fluorescent protein fragments will be suitable as reporters for pairs of promoters and protein-protein interactions within whole animals.

Covert Hepatic Encephalopathy: Can My Patient Drive?

PubMed Central

Shaw, Jawaid; Bajaj, Jasmohan S

2016-01-01

Liver cirrhosis is a public health problem and hepatic encephalopathy (HE) is one of its main complications, which can be either overt meaning thereby evident and readily diagnosed, or covert/minimal (CHE) needing psychometric testing for diagnosis. Patients with CHE hepatic encephalopathy have deficits in multiple domains including visuo-spatial assessment, attention, response inhibition, working memory, along with psychomotor speed to name a few areas. These patients have poor navigational skills, get fatigued easily and demonstrate poor insight into their driving deficits. The combination of all these leads them to have poor driving skills leading to traffic violations and crashes as demonstrated not only on the simulation testing but also in real life driving events. There are multiple psychometric tests for CHE testing but these are not easily available and there is no uniform consensus on the gold standard testing as of yet. It does not automatically connote that all patients who test positive on driving simulation testing are unfit to drive. The physicians are encouraged to take driving history from the patient and the care- givers on every encounter and focus their counseling efforts more on patients with recent history of traffic crashes, with abnormal simulation studies and history of alcohol cessation within last year. As physicians are not trained to determine fitness to drive, their approach towards CHE patients in regards to driving restrictions should be driven by ethical principles while as respecting the local laws. PMID:28027071

Species clarification of Isaria isolates used as biocontrol agents against Diaphorina citri (Hemiptera: Liviidae) in Mexico.

PubMed

Gallou, Adrien; Serna-Domínguez, María G; Berlanga-Padilla, Angélica M; Ayala-Zermeño, Miguel A; Mellín-Rosas, Marco A; Montesinos-Matías, Roberto; Arredondo-Bernal, Hugo C

2016-03-01

Entomopathogenic fungi belonging to the genus Isaria (Hypocreales: Cordycipitaceae) are promising candidates for microbial control of insect pests. Currently, the Mexican government is developing a biological control program based on extensive application of Isaria isolates against Diaphorina citri (Hemiptera: Liviidae), a vector of citrus huanglongbing disease. Previous research identified three promising Isaria isolates (CHE-CNRCB 303, 305, and 307; tentatively identified as Isaria fumosorosea) from Mexico. The goal of this work was to obtain a complete morphological and molecular characterization of these isolates. Comparative analysis of morphology established that the isolates showed similar characteristics to Isaria javanica. Multi-gene analysis confirmed the morphological identification by including the three isolates within the I. javanica clade. Additionally, this work demonstrated the misidentifications of three other Isaria isolates (CHE-CNRCB 310 and 324: I. javanica, formerly I. fumosorosea; CHE-CNRCB 393: I. fumosorosea, formerly Isaria farinosa), underlying the need for a full and correct characterization of an isolate before developing a biological control program. Finally, the inter-simple sequence repeat (ISSR) genotyping method revealed that the CHE-CNRCB 303, 305, and 307 isolates belong to three different genotypes. This result indicates that ISSR markers could be used as a tool to monitor their presence in field conditions. Copyright © 2015 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

X-Ray Diffraction on Mars: Scientific Discoveries Made by the CheMin Instrument

NASA Technical Reports Server (NTRS)

Rampe, E. B.; Blake, D. F.; Ming, D. W.; Bristow, T. F.

2017-01-01

The Mars Science Laboratory Curiosity landed in Gale crater in August 2012 with the goal to identify and characterize habitable environments on Mars. Curiosity has been studying a series of sedimentary rocks primarily deposited in fluviolacustrine environments approximately 3.5 Ga. Minerals in the rocks and soils on Mars can help place further constraints on these ancient aqueous environments, including pH, salinity, and relative duration of liquid water. The Chemistry and Mineralogy (CheMin) X-ray diffraction and X-ray fluorescence instrument on Curiosity uses a Co X-ray source and charge-coupled device detector in transmission geometry to collect 2D Debye-Scherrer ring patterns of the less than 150 micron size fraction of drilled rock powders or scooped sediments. With an angular range of approximately 2.52deg 20 and a 20 resolution of approximately 0.3deg, mineral abundances can be quantified with a detection limit of approximately 1-2 wt. %. CheMin has returned quantitative mineral abundances from 16 mudstone, sandstone, and aeolian sand samples so far. The mineralogy of these samples is incredibly diverse, suggesting a variety of depositional and diagenetic environments and different source regions for the sediments. Results from CheMin have been essential for reconstructing the geologic history of Gale crater and addressing the question of habitability on ancient Mars.

Mineralogical Results from the Mars Science Laboratory Rover Curiosity

NASA Technical Reports Server (NTRS)

Blake, David Frederick.

2017-01-01

NASA's CheMin instrument, the first X-ray Diffractometer flown in space, has been operating on Mars for nearly five years. CheMin was first to establish the quantitative mineralogy of the Mars global soil (1). The instrument was next used to determine the mineralogy of a 3.7 billion year old lacustrine mudstone, a result that, together with findings from other instruments on the MSL Curiosity rover, documented the first habitable environment found on another planet (2). The mineralogy of this mudstone from an ancient playa lake was also used to derive the maximum concentration of CO2 in the early Mars atmosphere, a surprisingly low value that calls into question the current theory that CO2 greenhouse warming was responsible for the warm and wet environment of early Mars. CheMin later identified the mineral tridymite, indicative of silica-rich volcanism, in mudstones of the Murray formation on Mt. Sharp. This discovery challenges the paradigm of Mars as a basaltic planet and ushers in a new chapter of comparative terrestrial planetology (3). CheMin is now being used to systematically sample the sedimentary layers that comprise the lower strata of Mt. Sharp, a 5,000 meter sequence of sedimentary rock laid down in what was once a crater lake, characterizing isochemical sediments that through their changing mineralogy, document the oxidation and drying out of the Mars in early Hesperian time.

Investigations Using Laboratory Testbeds to Interpret Flight Instrument Datasets from Mars Robotic Missions

NASA Technical Reports Server (NTRS)

Ming, D. W.; Morris, R. V.; Sutter, B.; Archer, P. D., Jr.; Achilles, C. N.

2012-01-01

The Astromaterials Research and Exploration Science Directorate at the NASA Johnson Space Center (JSC) has laboratory instrumentation that mimic the capabilities of corresponding flight instruments to enable interpretation of datasets returned from Mars robotic missions. The lab instruments have been and continue to be applied to datasets for the Moessbauer Spectrometer (MB) on the Mars Exploration Rovers (MER), the Thermal & Evolved Gas Analyzer (TEGA) on the Mars Phoenix Scout, the CRISM instrument on the Mars Reconnaissance Orbiter Missions and will be applied to datasets for the Sample Analysis at Mars (SAM), Chemistry and Mineralogy (CheMin) and Chemistry & Camera (ChemCam) instruments onboard the Mars Science Laboratory (MSL). The laboratory instruments can analyze analog samples at costs that are substantially lower than engineering models of flight instruments, but their success to enable interpretation of flight data depends on how closely their capabilities mimic those of the flight instrument. The JSC lab MB instruments are equivalent to the MER instruments except without flight qualified components and no reference channel Co-57 source. Data from analog samples were critical for identification of Mg-Fe carbonate at Gusev crater. Fiber-optic VNIR spectrometers are used to obtain CRISM-like spectral data over the range 350-2500 nm, and data for Fephyllosilicates show irreversible behavior in the electronic transition region upon dessication. The MB and VNIR instruments can be operated within chambers where, for example, the absolute H2O concentration can be measured and controlled. Phoenix's TEGA consisted of a calorimeter coupled to a mass spectrometer (MS). The JSC laboratory testbed instrument consisted of a differential scanning calorimeter (DSC) coupled to a MS configured to operate under total pressure (12 mbar), heating rate (20 C/min), and purge gas composition (N2) analogous to the flight TEGA. TEGA detected CO2 release at both low (400-680 C) and high (725-820 C) temperature and an endothermic reaction in concert with the high temperature release. The high-temperature thermal decomposition is consistent with calcite, dolomite, or ankerite, (3-6 wt.%) or any combination of these phase based upon laboratory testbed experiments. Recent laboratory experiments suggest that the low temperature CO2 release was caused by a reaction between calcium carbonate and hydrated magnesium perchlorate; although, CO2 release by the oxidation of organic materials and Fe-/Mg-rich carbonates cannot be ruled out. MSL landed in Gale crater on August 5, 2012. Although numerous analog samples have been analyzed on the JSC laboratory testbeds, no SAM, CheMin, or ChemCam analyses have been acquired by MSL to date. The JSC SAM laboratory testbed consists of a thermal analyzer coupled with a MS configured to operate under total pressure (30 mbar), heating rate (35 C/min), and purge gas composition (He) analogous to the flight SAM. The CheMin and ChemCam laboratory testbeds were developed and built by inXitu, Inc. and Los Alamos National Laboratory, respectively, to acquire datasets relevant to the MSL CheMin and ChemCam flight instruments.

THE GALACTIC R CORONAE BOREALIS STARS: THE C{sub 2} SWAN BANDS, THE CARBON PROBLEM, AND THE {sup 12}C/{sup 13}C RATIO

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hema, B. P.; Pandey, Gajendra; Lambert, David L., E-mail: hema@iiap.res.in, E-mail: pandey@iiap.res.in, E-mail: dll@astro.as.utexas.edu

2012-03-10

Observed spectra of R Coronae Borealis (RCB) and hydrogen-deficient carbon (HdC) stars are analyzed by synthesizing the C{sub 2} Swan bands (1, 0), (0, 0), and (0, 1) using our detailed line list and the Uppsala model atmospheres. The (0, 1) and (0, 0) C{sub 2} bands are used to derive the {sup 12}C abundance, and the (1, 0) {sup 12}C{sup 13}C band to determine the {sup 12}C/{sup 13}C ratios. The carbon abundance derived from the C{sub 2} Swan bands is about the same for the adopted models constructed with different carbon abundances over the range 8.5 (C/He = 0.1%)more » to 10.5 (C/He = 10%). Carbon abundances derived from C I lines are about a factor of four lower than the carbon abundance of the adopted model atmosphere over the same C/He interval, as reported by Asplund et al., who dubbed the mismatch between adopted and derived C abundance as the 'carbon problem'. In principle, the carbon abundances obtained from C{sub 2} Swan bands and that assumed for the model atmosphere can be equated for a particular choice of C/He that varies from star to star. Then, the carbon problem for C{sub 2} bands is eliminated. However, such C/He ratios are in general less than those of the extreme helium stars, the seemingly natural relatives to the RCB and HdC stars. A more likely solution to the C{sub 2} carbon problem may lie in a modification of the model atmosphere's temperature structure. The derived carbon abundances and the {sup 12}C/{sup 13}C ratios are discussed in light of the double degenerate and the final flash scenarios.« less

Transmission X-ray Diffraction (XRD) Patterns Relevant to the MSL Chemin Amorphous Component: Sulfates And Silicates

NASA Technical Reports Server (NTRS)

Morris, R. V.; Rampe, E. B.; Graff, T. G.; Archer, P. D., Jr.; Le, L.; Ming, D. W.; Sutter, B.

2015-01-01

The Mars Science Laboratory (MSL) CheMin instrument on the Curiosity rover is a transmission X-ray diffractometer (Co-Kalpha radiation source and a approx.5deg to approx.52deg 2theta range) where the analyzed powder samples are constrained to have discrete particle diameters <150 microns by a sieve. To date, diffraction patterns have been obtained for one basaltic soil (Rocknest (RN)) and four drill fines of coherent rock (John Klein (JK), Cumberland (CB), Windjana (WJ), and Confidence Hills (CH)). The CheMin instrument has detected and quantified the abundance of both primary igneous (e.g., feldspar, olivine, and pyroxene) and secondary (e.g., Ca-sulfates, hematite, akaganeite, and Fe-saponite) minerals. The diffraction patterns of all CheMin samples are also characterized by a broad diffraction band centered near 30deg 2theta and by increasing diffraction intensity (scattering continuum) from approx.15deg to approx.5deg, the 2theta minimum. Both the broad band and the scattering continuum are attributed to the presence of an XRD amorphous component. Estimates of amorphous component abundance, based on the XRD data itself and on mass-balance calculations using APXS data crystalline component chemistry derived from XRD data, martian meteorites, and/or stoichiometry [e.g., 6-9], range from approx.20 wt.% to approx.50 wt.% of bulk sample. The APXSbased calculations show that the amorphous component is rich in volatile elements (esp. SO3) and is not simply primary basaltic glass, which was used as a surrogate to model the broad band in the RN CheMin pattern. For RN, the entire volatile inventory (except minor anhydrite) is assigned to the amorphous component because no volatile-bearing crystalline phases were reported within detection limits [2]. For JK and CB, Fesaponite, basanite, and akaganeite are volatile-bearing crystalline components. Here we report transmission XRD patterns for sulfate and silicate phases relevant to interpretation of MSL-CheMin XRD amorphous components.

Type of Inflammation Differentially Affects Expression of Interleukin 1β and 6, Tumor Necrosis Factor-α and Toll-Like Receptors in Subclinical Endometritis in Mares

PubMed Central

Szóstek, Anna Z.; Gajos, Katarzyna; Kozdrowski, Roland; Nowak, Marcin; Okuda, Kiyoshi

2016-01-01

Mares that fail to conceive or lose their embryos, without showing typical signs of clinical endometritis, should be suspected of subclinical endometritis (SE). In this study, the question was addressed: does SE fully activate selected mechanisms of innate immunity in mares? For this aim, expression of mRNAs for Toll-like Receptor 2 and 4 (TLR 2/4), interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor α (TNF) was examined in control mares versus either mares suffering from chronic endometritis (ChE) or subacute suppurative endometritis (SSE). The concentrations of IL-1β, IL-6 and TNF-α in supernatants from endometrial tissue cultures after 4 h incubation were measured using the enzyme immunoassay (EIA) method. Eighty-two warmblood mares, of known breeding history, were enrolled in this study. Based on histopathological assessment, mares were classified as suffering from ChE, SSE or as being healthy. In addition, immuno-localization of both TLR2 and TLR4 as well as TNF-α was investigated in the equine endometria. The mRNA expression of TLR2 (P < 0.01), IL-1β (P < 0.0001), IL-6 (P < 0.0001) and TLR4 and TNF (P < 0.05) was up-regulated in endometria of mares suffering from SSE compared with unaffected mares. Concentrations of IL-6 and TNF-α were increased only in mares exhibiting SSE, compared with unaffected (P < 0.01 for both) and ChE mares (P < 0.05 for both). Immuno-localization of TNF-α and TLRs was confirmed, both in unaffected and SE-affected endometria, and was present in the luminal and glandular epithelia and stromal cells. The severity of inflammation impacts the immune response and fosters activation of innate immunity mechanisms, as observed in the endometria of mares. The intracellular localization of TLRs and TNF-α in the endometria indicates a key role of endometrial epithelial and stromal cells in the immune response and inflammation. PMID:27152525

Whole Blood Robotic Cholinesterase Assay for Organophosphate Exposure - Testing Soldiers, First Responders, and Civilians in the Field and Laboratory

DTIC Science & Technology

2004-12-01

inhibited by selective (e.g. huperzine A ) and non-selective (carbamate) inhibitors (e.g. pyridostigmine bromide, PB). Both studies supported Federal...week). Huperzine A was well tolerated by these patients and warrants study as a future prophylaxis for OP poisoning. Due to the documented use...reversal of ChE inhibition by PB). 3.4 Measurement of huperzine A induced ChE inhibi- tion (RBC-AChE): Aliquots of whole blood from twelve healthy

KSC-97PC1457

NASA Image and Video Library

1997-09-15

United States Microgravity Payload-4 (USMP-4) experiments are prepared to be flown on Space Shuttle mission STS-87 in the Space Station Processing Facility at Kennedy Space Center (KSC). Here, a technician is monitoring the Confined Helium Experiment, or CHeX, that will use microgravity to study one of the basic influences on the behavior and properties of materials by using liquid helium confined between silicon disks. CHeX and several other experiments are scheduled for launch aboard STS-87 on Nov. 19 from KSC

Exploring Electrical and Magnetic Resonances from Coherently Correlated Long-Lived Radical Pairs towards Development of Negative Refractive-Index Materials

DTIC Science & Technology

2015-01-03

Dissociation in Perovskite Solar Cells Yu-Che Hsiao, Ting Wu, Mingxing Li, and Bin Hu Advanced Materials, DOI: 10.1002/adma.201405946, 2015 2...Electrode Interface and Donor/Acceptor Interface via Charge Dissociation in Organic Solar Cells at Device-Operating Condition Ting Wu, Yu-Che Hsiao...exchange energy at donor:acceptor interfaces in organic solar cells Mingxing Li, Hongfeng Wang, Lei He, Huidong Zang, Hengxing Xu, and Bin Hu Appl

Postnatal chlorpyrifos exposure and apolipoprotein E (APOE) genotype differentially affect cholinergic expression and developmental parameters in transgenic mice.

PubMed

Basaure, Pia; Guardia-Escote, Laia; Cabré, Maria; Peris-Sampedro, Fiona; Sánchez-Santed, Fernando; Domingo, José L; Colomina, Maria Teresa

2018-05-03

Chlorpyrifos (CPF) is one of the most commonly used organophosphate pesticides in the world. Our previous results described that apolipoprotein E (APOE) polymorphisms are a source of individual differences in susceptibility to CPF. The aim of this study was to assess the physical and biochemical effects of postnatal exposure to CPF in the apoE targeted replacement mouse model. Mice were exposed to CPF at 0 or 1 mg/kg/day from postnatal day 10-15. Physical development, plasma and forebrain cholinesterase (ChE) activity and gene expression in liver and forebrain were evaluated. CPF exposure delays physical maturation and decreases the expression of choline acetyltransferase, α4-subunit and the α7 receptor. CPF decreases the expression of vesicular acetylcholine transporter (VAChT) mRNA in the forebrain only in apoE3 mice. The expression of paraoxonase-2 in the forebrain was also influenced by APOE genotype and CPF. Differences between genotypes were observed in litter size, ChE activity, expression of butyrylcholinesterase and paraoxonase-1 in liver and variants of acetylcholinesterase, VAChT and the α7 receptor in the forebrain. These results support that there are different vulnerabilities to postnatal CPF exposure according to the APOE polymorphism, which in turn affects the cholinergic system and defenses to oxidative stress. Copyright © 2018 Elsevier Ltd. All rights reserved.

Orthene? toxicity to little brown bats (Myotis lucifugus): Acetylcholinesterase inhibition, coordination loss, and mortality

USGS Publications Warehouse

Clark, D.R.; Rattner, B.A.

1987-01-01

The 24-h LD50 of Orhene (active ingredient acephate, acetylphosphoramidothioic acid o,s-dimethyl ester, CAS 30560-19-1) to little brown bats (Myotis lucifugus) was high (> 1,500 mg acephate/kg) and at least several times greater than the LD50 for mice (Mus musculus) (720 mg/kg). Twenty-four hours after dosing, all surviving mice appeared behaviorally normal, but 9 of 30 surviving bats could not right themselves when placed on their backs. When dead and incapacitated bats were combined to calculate an ED50 (median effective dose), the resultant estimate (687 mg/kg) did not differ (p > 0.05) from the LD50 for mice. Serum cholinesterase (ChE) activity in control bats was 3.2 times greater than in mice. The relationship between the naturally high level of ChE and the relative tolerance of bats to organophosphorus insecticides is unexplained. Toxicity of Orthene was clearly less than that reported elsewhere for methyl parathion (phosphorothioic acid o,o-dimethyl o-[4-nitrophenyl] ester, CAS 298-00-0). This finding may be useful in selection of a chemical for agricultural use, but conclusions about the safety of Orthene to this bat species, or to others, must remain tentative until confirmed by studies under field conditions. Because bats are long-lived with low reproductive rates and slow recruitment, any additional mortality in the wild could be critical to population survival.

Novel Organophosphate Ligand O-(2-Fluoroethyl)-O-(p-Nitrophenyl)Methylphosphonate: Synthesis, Hydrolytic Stability and Analysis of the Inhibition and Reactivation of Cholinesterases.

PubMed

Chao, Chih-Kai; Ahmed, S Kaleem; Gerdes, John M; Thompson, Charles M

2016-11-21

The organophosphate O-(2-fluoroethyl)-O-(p-nitrophenyl) methyphosphonate 1 is the first-in-class, fluorine-18 radiolabeled organophosphate inhibitor ([ 18 F]1) of acetylcholinesterase (AChE). In rats, [ 18 F]1 localizes in AChE rich regions of the brain and other tissues where it likely exists as the (CH 3 )( 18 FCH 2 CH 2 O)P(O)-AChE adduct (ChE-1). Characterization of this adduct would define the inhibition mechanism and subsequent postinhibitory pathways and reactivation rates. To validate this adduct, the stability (hydrolysis) of 1 and ChE-1 reactivation rates were determined. Base hydrolysis of 1 yields p-nitrophenol and (CH 3 ) (FCH 2 CH 2 O)P(O)OH with pseudo first order rate constants (k obsd ) at pH 7.4 (PBS) of 3.25 × 10 -4 min -1 (t 1/2 = 35.5 h) at 25 °C and 8.70 × 10 -4 min -1 (t 1/2 = 13.3 h) at 37 °C. Compound 1 was a potent inhibitor of human acetylcholinesterase (HuAChE; k i = 7.5 × 10 5 M -1 min -1 ), electric eel acetylcholinesterase (EEAChE) (k i = 3.0 × 10 6 M -1 min -1 ), and human serum butyrylcholinesterase (HuBChE; 1.95 × 10 5 M -1 min -1 ). Spontaneous and oxime-mediated reactivation rates for the (CH 3 ) (FCH 2 CH 2 O)P(O)-serine ChE adducts using 2-PAM (10 μM) were (a) HuAChE 8.8 × 10 -5 min -1 (t 1/2 = 131.2 h) and 2.41 × 10 -2 min -1 (t 1/2 = 0.48 h), (b) EEAChE 9.32 × 10 -3 min -1 (t 1/2 = 1.24 h) and 3.33 × 10 -2 min -1 (t 1/2 = 0.35 h), and (c) HuBChE 1.16 × 10 -4 min -1 (t 1/2 = 99.6 h) and 4.19 × 10 -2 min -1 (t 1/2 = 0.27 h). All ChE-1 adducts undergo rapid and near complete restoration of enzyme activity following addition of 2-PAM (30 min), and no aging was observed for either reactivation process. The fast reactivation rates and absence of aging of ChE-1 adducts are explained on the basis of the electron-withdrawing fluorine group that favors the nucleophilic reactivation processes but disfavors cation-based dealkylation aging mechanisms. Therefore, the likely fate of radiolabeled compound 1 in vivo is the formation of (CH 3 )(FCH 2 CH 2 O)P(O)-serine adducts and monoacid (CH 3 )(FCH 2 CH 2 O)P(O)OH from hydrolysis and reactivation.

Sulphur-bearing Compounds Detected by MSL SAM Evolved Gas Analysis of Materials from Yellowknife Bay, Gale Crater, Mars

NASA Technical Reports Server (NTRS)

McAdam, A. C.; Franz, H. B.; Archer, P. D. Jr.; Sutter, B.; Eigenbrode, J. L.; Freissinet, C.; Atreya, S. K.; Bish, D. L.; Blake, D. F.; Brunner, A.;

ELECTRON MICROSCOPIC LOCALIZATION OF ACETYLCHOLINESTERASE AND NONSPECIFIC CHOLINESTERASE AT THE NEUROMUSCULAR JUNCTION BY THE GOLD-THIOCHOLINE AND GOLD-THIOLACETIC ACID METHODS

PubMed Central

Davis, Richard; Koelle, George B.

1967-01-01

By means of the gold-thiocholine (AuThCh) and gold-thiolacetic acid (AuThAc) methods, it has been demonstrated electron microscopically that acetylcholinesterase (AChE) is located at the prejunctional axoplasmic membrane and the postjunctional sarcoplasmic membrane, including the full lengths of its invaginations, at the motor end plate of mouse intercostal muscle. Nonspecific cholinesterase (ChE) is present in relatively low concentrations at the same sites, and in greater concentrations in the teloglial Schwann sheath cells. Significant amounts of reaction product appeared in the junctional cleft only after prolonged incubation with both methods. The identification of AChE and ChE was confirmed by the use of appropriate concentrations of several selective inhibitors. In confirmation of previous studies by light microscopy, the AuThCh method is more specific for AChE and ChE, whereas the AuThAc method allows greater accuracy of localization. PMID:6033530

[Un processo che può gettare luce sulla cosiddetta 'paura di sé' nel disturbo ossessivo-compulsivo: l'Identificazione Retrospettiva delle Motivazioni e delle Inclinazioni].

PubMed

Mannino, Gherardo; Guerini, Rossella

2018-01-01

RIASSUNTO. Al fine di comprendere meglio la psicopatologia del disturbo ossessivo-compulsivo (DOC), in anni recenti è stata prestata una crescente attenzione alla cosiddetta "paura di sé" (fear of self), vale a dire la paura che le persone con DOC nutrono di ospitare dentro di sé aspetti inaccettabili. Tuttavia, l'esatta dinamica di questo fenomeno ancora non è chiara: di conseguenza, allo scopo di delucidarla meglio, sarà qui descritto uno specifico processo psicologico denominato Identificazione Retrospettiva delle Motivazioni e delle Inclinazioni (IRMI). Quando un paziente con DOC valuta in qualche modo come inaccettabile una propria esperienza interna (pensieri, emozioni, immagini mentali, ecc.) o un proprio comportamento, identificherà retrospettivamente le presunte motivazioni/inclinazioni negative che sarebbero state all'origine di quell'esperienza o comportamento. L'IRMI non solo aiuta a comprendere meglio il fenomeno della "paura di sé", ma possiede anche importanti implicazioni per la terapia.

Comments on "Determination and Analysis of the Theoretical Production of a Bucket Wheel Excavator" / Uwagi I Komentarze Do Pracy: "Określanie I Analiza Teoretycznej Wydajności Pracy Koparki Wielonaczyniowej Kołowej"

NASA Astrophysics Data System (ADS)

Bošnjak, Srđan M.

2015-03-01

This paper comments on the recently published work dealing with the problem in the determination of the theoretical output of the bucket wheel excavator. It also includes remarks on the inadequacy in the problem approach and highlights the mistakes in the mathematical model. This work emphasizes the demand for a much wider and deeper approach to the problem of determining the output of the bucket wheel excavator. Opublikowany niedawno artykuł autorstwa Che i Chena (2014) poświecony jest ważnej kwestii jaką jest określenie teoretycznej wydajności koparki kołowej wielonaczyniowej. W załączonym przeglądzie literatury Che i Chen (2014) nie umieścili pozycji odnoszących się do metod urabiania, parametrów pracy koparki oraz teoretycznej wydajności wydobycia i być może to właśnie jest przyczyną pewnych niedokładności powstałych w trakcie rozwiązywania problemu. Intencją autora obecnej publikacji było: • Odniesienie się do krytycyzmu wyrażonego przez Che i Chena (2014) dotyczącego procedury obliczania prędkości w ruchu łukowym podanej w cytowanej literaturze przedmiotu (Pajer i in., 1971; Vetrov, 1971; Rasper, 1975; Durst i Vogt, 1988); • Zbadanie różnic pomiędzy procedurą określania teoretycznej wydajności zaproponowaną w pracy Che i Chena (2014) a odpowiednimi rozwiązaniami podanymi w literaturze; • Określenie prawidłowości i stosowalności teorii zaprezentowanej w pracy Che i Chena (2014) poprzez porównanie wyników uzyskanych z wykorzystaniem ich teorii oraz teorii podanych w wymienionych pozycjach literatury. W rozdziale 2 pracy (Che i Chen 2014) zatytułowanym " Uprzednio stosowane metody określania teoretycznej wydajności pracy koparki kołowej wielonaczyniowej" autorzy nie podali głównych odniesień literaturowych z których zaczerpnięte zostały równania (1)-(6)**. Ponadto, nie podali charakterystyki modelu działania koparki, na podstawie którego wyprowadzone zostały rzeczone równania, co stanowi poważne przeoczenie. Che i Chen (2014) kwestionują prawidłowość równania (6), lecz przedstawione w niniejszej pracy analizy i uwagi prowadzą do następujących wniosków: • Stwierdzenie w pracy (Che i Chen 2014) że równanie (6) nie uwzględnia wpływu tmax i h nie jest prawdziwe. Dowód: Równanie (6'). • Stwierdzenie że równanie (6) nie uwzględnia wpływu R_s^' - "...czyli obrotowego promienia działania..." (Che i Chen 2014) jest prawdziwe, w przeciwnym razie równanie (6) byłoby nieprawdziwe. Równanie (6) uwzględnia odpowiedni promień zdefiniowany w równaniu (i), które jest prawdziwe. Dowód: Równanie (6'). W rozdziale 2 pracy (Che i Chen 2014) zatytułowanym: "Analiza teoretycznej wydajności koparki kołowej wielonaczyniowej" kierując się błędnymi wnioskami odnośnie niedokładności równania (6) autorzy podjęli próbę skorygowania powyższej niedokładności, by w ten sposób poprawić istniejącą teorię, W trakcie realizacji koncepcji wykorzystania równania (11) do zdefiniowania zasad rządzących zmianą prędkości kątowej wysięgnika Che i Chen (2014) popełnili błąd. Przyjęli oni mianowicie, że wyrażenie (14), otrzymane dla górnego przekroju wykopu e odnosić się będzie także do wszystkich przekrojów, dla całej wysokości wrębu. Pominęli w ten sposób fakt iż prędkość w ruchu łukowym wysięgnika nie jest wielkością stałą, patrz: równania (f) i (f'), i przyjęli jej wartość maksymalną, równanie (f'). Dlatego też równania (15), (16), (18) i (19) nie są prawidłowe. Wszystkie wejściowe dane obliczeniowe a także sposób ich zapisu (Tabela 1) zostały zaczerpnięte z pracy (Che i Chen 2014). Ponadto, zaprezentowane dane o pracy koparki wielonaczyniowej SchRs wykorzystywanej w kopalni "Zukunft" w Reńskim Zagłębiu Węglowym, zaczerpnięto z pracy (Durst i Vogt 1988). Osiągnięcia badań teoretycznych Che i Chen (2014, strona 289) przedstawione dla konkretnej koparki wielonaczyniowej kołowej eksploatowanej w kopalni odkrywkowej lignitu w Reńskim Zagłębiu Węglowym ..." (Che i Chen 2014). Obliczenia głębokości wrębu i prędkości kątowej wysięgnika oraz teoretycznej wydajności pracy przeprowadzono na cztery sposoby, co obrazuje Tabela 2: • Wariant 1 - z wykorzystaniem teorii rozwiniętej przez Che i Chena (2014, strona 289); • Wariant 2 różni się od Wariantu 1 tylko zasadą określającą zmiany prędkości kątowej, i.e. określona jest ona wzorem: "...zasada 1/cosφ (Che i Chen 2014, strona 289); • Wariant 3 wykorzystuje znane równania podane w cytowanej literaturze przedmiotu (Durst i Vogt, 1988; Pajer i in., 1971; Rasper, 1975); • Wariant 4 różni od Wariantu 3 wyłącznie wyrażenie określające głębokości wrębu, w Wariancie 4 zastosowane zostało wyrażenie pozwalające na dokładne obliczenie głębokości wrębu. Zaprezentowane wyniki prowadzą do następujących wniosków: • Maksymalna teoretycznie obliczona wydajność dla wszystkich wariantów jest niższa od wartości maksymalnej otrzymanej przy wykorzystaniu równania (s), tak więc nie zachodzi niebezpieczeństwo nadmiernego przeciążenia łyżki, jak to zostało stwierdzone w pracy Che i Chena (2014); • Maksymalne teoretycznie wyliczone wydajności dla wariantu 1 i 2 należy odrzucić z powodu błędu w definicji promienia odniesienia Re, określonego równaniem (I), co zostało szczegółowo omówione w rozdziale 3 tej pracy; • Gdy teoretyczna wydajność obliczana jest w oparciu o dokładny wzór na głębokość wrębu (Wariant 4), otrzymujemy nieco wyższe wartości niż w Wariancie 3. Procentowo, różnica ta jest mniejsza niż 1% dla 0 ≤ φ ≤ 50.8°, poniżej 2% dla 0 ≤ φ ≤ 64.5° i poniżej 3% dla 0 ≤ φ ≤ 75.6° (rys. 11). Maksymalna wartość (5.9%) osiągana jest dla φ = 80°. Z punktu widzenia zastosowań inżynierskich, taki poziom błędu jest dopuszczalny, zwłaszcza gdy uwzględni się jego rozkład w zakresie 0 ≤ φ ≤ 80°, oraz fakt że błąd ten sprawia, że ryzyko zagrożenia maleje. • Obniżenie teoretycznej wydajności po tym jak prędkość kątowa osiąga wartość maksymalną (rys. 9): ".... jest akceptowalne ponieważ odnosi się do niewielkiej tylko części całkowitej objętości przenoszonego materiału" (Durst & Vogt, 1988, strona 46). Publikacja autorstwa Che i Chena (2014) jest godną uwagi próbą ulepszenia istniejącej teorii opisującej działanie koparek kołowych wielonaczyniowych. Jednakże, uwzględniając przedstawione uwagi i komentarze, nasuwają się następujące spostrzeżenia: • Badany problem jest nie jest problemem nowym i bogata literatura przedmiotu powinna była zostać uwzględniona; • Matematyczne wzory zawierają błędy, które nieuchronnie prowadzą do nieprawidłowych wniosków. Celem niniejszej pracy było zwrócenie uwagi na potrzebę zastosowania znacznie szerszego podejścia do problemu obliczania wydajności koparek kołowych wielonaczyniowych niż podejście zaproponowane w pracy Che i Chena (2014).

Physical Effects of Beach Nourishment on Sea Turtle Nesting, Delray Beach, Florida. Environmental Impact Research Program.

DTIC Science & Technology

1987-10-01

Turtles (Cheidra serptina)," Canadian Journal of Zoology, Vol 62, pp 2401-2403. Hendrickson, J. R. 1958. " The Green Turtle , CheZonia mydas (Linn.), in...sea turtle nests in the United States are located in beaches that have been nourished or renourished. Questions have been raised about how physical...changes In the beaches will affect the nesting activities of these sea turtles that use nourished beaches for nesting.’) This study was conducted to

Applied Sciences Department (R&D) Patents; a Compilation

DTIC Science & Technology

1978-12-28

References Cited the first ampoule so that the two ampoules can he bro- UNITED STATES PATENTS ken simultaneously, and, upon mixing of the chemilu...Che-V222/541 miluminescent material and the other ampoule con-.tains an activator material. The almpoules can be bro-(561 References Cited ken by...Eaminer.-Robe" F. Stshl Aimmweys- Edgar J. broere. Ii. H Loach . and Paul S. isat `PYROTECHNCIGNALING ID E 1cER IT4 COMtPiOm WA!Eft EACTII’tIGN11M 4

Multitarget-directed tricyclic pyridazinones as G protein-coupled receptor ligands and cholinesterase inhibitors.

PubMed

Pau, Amedeo; Catto, Marco; Pinna, Giovanni; Frau, Simona; Murineddu, Gabriele; Asproni, Battistina; Curzu, Maria M; Pisani, Leonardo; Leonetti, Francesco; Loza, Maria Isabel; Brea, José; Pinna, Gérard A; Carotti, Angelo

2015-06-01

By following a multitarget ligand design approach, a library of 47 compounds was prepared, and they were tested as binders of selected G protein-coupled receptors (GPCRs) and inhibitors of acetyl and/or butyryl cholinesterase. The newly designed ligands feature pyridazinone-based tricyclic scaffolds connected through alkyl chains of variable length to proper amine moieties (e.g., substituted piperazines or piperidines) for GPCR and cholinesterase (ChE) molecular recognition. The compounds were tested at three different GPCRs, namely serotoninergic 5-HT1A, adrenergic α1A, and dopaminergic D2 receptors. Our main goal was the discovery of compounds that exhibit, in addition to ChE inhibition, antagonist activity at 5-HT1A because of its involvement in neuronal deficits typical of Alzheimer's and other neurodegenerative diseases. Ligands with nanomolar affinity for the tested GPCRs were discovered, but most of them behaved as dual antagonists of α1A and 5-HT1A receptors. Nevertheless, several compounds displaying this GPCR affinity profile also showed moderate to good inhibition of AChE and BChE, thus deserving further investigations to exploit the therapeutic potential of such unusual biological profiles. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Assessment of Enzyme Inhibition: A Review with Examples from the Development of Monoamine Oxidase and Cholinesterase Inhibitory Drugs.

PubMed

Ramsay, Rona R; Tipton, Keith F

2017-07-15

The actions of many drugs involve enzyme inhibition. This is exemplified by the inhibitors of monoamine oxidases (MAO) and the cholinsterases (ChE) that have been used for several pharmacological purposes. This review describes key principles and approaches for the reliable determination of enzyme activities and inhibition as well as some of the methods that are in current use for such studies with these two enzymes. Their applicability and potential pitfalls arising from their inappropriate use are discussed. Since inhibitor potency is frequently assessed in terms of the quantity necessary to give 50% inhibition (the IC 50 value), the relationships between this and the mode of inhibition is also considered, in terms of the misleading information that it may provide. Incorporation of more than one functionality into the same molecule to give a multi-target-directed ligands (MTDLs) requires careful assessment to ensure that the specific target effects are not significantly altered and that the kinetic behavior remains as favourable with the MTDL as it does with the individual components. Such factors will be considered in terms of recently developed MTDLs that combine MAO and ChE inhibitory functions.

Pesticides and amphibian population declines in California, USA

USGS Publications Warehouse

Sparling, Donald W.; Fellers, Gary M.; McConnell, Laura L.

2001-01-01

Several species of anuran amphibians have undergone drastic population declines in the western United States over the last 10 to 15 years. In California, the most severe declines are in the Sierra Mountains east of the Central Valley and downwind of the intensely agricultural San Joaquin Valley. In contrast, coastal and more northern populations across from the less agrarian Sacramento Valley are stable or declining less precipitously. In this article, we provide evidence that pesticides are instrumental in declines of these species. Using Hyla regilla as a sentinel species, we found that cholinesterase (ChE) activity in tadpoles was depressed in mountainous areas east of the Central Valley compared with sites along the coast or north of the Valley. Cholinesterase was also lower in areas where ranid population status was poor or moderate compared with areas with good ranid status. Up to 50% of the sampled population in areas with reduced ChE had detectable organophosphorus residues, with concentrations as high as 190 ppb wet weight. In addition, up to 86% of some populations had measurable endosulfan concentrations and 40% had detectable 4,4'- dichlorodiphenyldichloroethylene, 4,4'-DDT, and 2,4'-DDT residues.

The hydrological consequences of human impact in the Lublin Region

NASA Astrophysics Data System (ADS)

Michalczyk, Zdzisław; Mięsiak-Wójcik, Katarzyna; Sposób, Joanna; Turczyński, Marek

2012-01-01

The Lublin Region is an area where local transformations in the natural environment, including the hydrosphere, occur. They result from the impact of agriculture, industry as well as water supply and sewage disposal. These activities lead to changes in the water network resulting from land improvement works, channel straightening and water runoff acceleration, as well as to the formation of local, both point and diffuse sources, of water pollution. The consequences of human impact are manifested in local transformations of the quality or quantity of water resources. As a result of intense groundwater draw-off, hydrogeological conditions are transformed, which is reflected in the persistence of depression cones of varied size and depth, noticeable in the vicinity of water intakes for Lublin, Chełm, Zamość and Kraśnik. The lowering of the first-level groundwater table also occurs as a consequence of the drainage of chalk and marl mine workings in Chełm and Rejowiec, whereas in the area of the hard coal mine both shallow and deep groundwater was transformed. It is important to indicate the consequences of human impact changes of water conditions as the hydrosphere resources should be used according to the principles of sustainable development.

Zur chemie der marsoberfläche

USGS Publications Warehouse

Keil, Klaus; Clark, Benton C.; Baird, A.K.; Toulmin, Priestley; Rose, Harry J.

1978-01-01

Analyses of 13 samples of Martian surface materials with the Viking X-ray fluorescence spectrometers show SiO2 similar to that of terrestrial mafic rocks, whereas Fe2O3, Cl, and S are higher and Al2O3, K2O, Rb, Sr, Y, and Zr are lower. Low totals suggest presence of CO2, H2O, and Na2O. Duricrust fragments are higher in S than fines, but samples from both landing sites are surprisingly similar. We suggest that Martian surface materials are aeolian deposits of complex mixtures of weathering products of maficultramafic rocks, possibly consisting of iron-rich clays, sulfates, iron oxides, carbonates, and chlorides.

Revolutionary Learning, Biodiversity, and Transformative Action. Essay Review of "Learning in Social Action: A Contribution To Understanding Informal Education" by Griff Foley; "Transformative Learning: Educational Vision for the Twenty-First Century" by Edmund O'Sullivan; and "Che Guevara, Paulo Freire and the Pedagogy of Revolution" by Peter McLaren.

ERIC Educational Resources Information Center

Mayo, Peter

2001-01-01

Three books, published 1999-2000, map out a vision of education as a vehicle for human emancipation and global transformation. Their approaches to presenting the "big picture" differ, focusing on case studies of learning through local social action; the impact of Che Guevara and Paulo Freire on liberation discourse worldwide; and comprehensive…

Dissolution Rates of Allophane, FE-Containing Allophane, and Hisingerite and Implications for Gale Crater, Mars

NASA Technical Reports Server (NTRS)

Ralston, S. J.; Hausrath, E. M.; Tschauner, O.; Rampe, E. B.; Christoffersen, R.

2018-01-01

Investigations with the CheMin Xray Diffractometer (XRD) onboard the Curiosity rover in Gale Crater demonstrate that all rock and soil samples measured to date contain approximately 15-70 weight percentage X-ray amorphous materials. The diffuse scattering hump from the X-ray amorphous materials in CheMin XRD patterns can be fit with a combination of allophane, ferrihydrite, and rhyolitic and basaltic glass. Because of the iron-rich nature of Mars' surface, Fe-rich poorly-crystalline phases, such as hisingerite, may be present in addition to allophane.

The Amorphous Component in Martian Basaltic Soil in Global Perspective from MSL and MER Missions

NASA Technical Reports Server (NTRS)

Morris, R. V.; Ming, D. W.; Blake, D. F.; Vaniman, D. T.; Bish, D. L.; Chipera, S. J.; Downs, R. T.; Gellert, R.; Treiman, A. H.; Yen, A. S.;

NASA Ames Science Instrument Launches Aboard New Mars Rover (CheMin)

NASA Image and Video Library

2011-11-23

When NASA's Mars Science Laboratory lands in a region known as Gale Crater in August of 2012, it will be poised to carry out the most sophisticated chemical analysis of the Martian surface to date. One of the 10 instruments on board the rover Curiosity will be CheMin - short for chemistry and mineralogy. Developed by Ames researcher David Blake and his team, it will use new technology to analyze and identify minerals in the Martian rocks and soil. Youtube: NASA Ames Scientists Develop MSL Science Instrument

Oral administration of pyridostigmine bromide and huperzine A protects human whole blood cholinesterases from ex vivo exposure to soman.

PubMed

Gordon, Richard K; Haigh, Julian R; Garcia, Gregory E; Feaster, Shawn R; Riel, Michael A; Lenz, David E; Aisen, Paul S; Doctor, Bhupendra P

2005-12-15

Cholinesterases (ChEs) are classified as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) according to their substrate specificity and sensitivity to selected inhibitors. The activities of AChE in red blood cells (RBC-AChE) and BChE in serum can be used as potential biomarkers of suppressed and/or heightened activity in the central and peripheral nervous systems. Exposure to organophosphate (OP) chemical warfare agents (CWAs), pesticides, anesthetics, and a variety of drugs such as cocaine, as well as some neurodegenerative and liver disease states, selectively reduces AChE or BChE activity. In humans, the toxicity of pesticides is well documented. Therefore, blood cholinesterase activity can be exploited as a tool for confirming exposure to these agents and possible treatments. Current assays for measurement of RBC-AChE and serum BChE require several labor-intensive processing steps, suffer from wide statistical variation, and there is no inter-laboratory conversion between methods. These methods, which determine only the serum BChE or RBC-AChE but not both, include the Ellman, radiometric, and deltapH (modified Michel) methods. In contrast, the Walter Reed Army Institute of Research Whole Blood (WRAIR WB, US Patent #6,746,850) cholinesterase assay rapidly determines the activity of both AChE and BChE in unprocessed (uncentrifuged) whole blood, uses a minimally invasive blood sampling technique (e.g., blood from a finger prick), and is semi-automated for high-throughput using the Biomek 2000 robotic system. To date, the WRAIR whole blood assay was used to measure AChE and BChE activities in human blood from volunteers in FDA clinical trials. In the first FDA study, 24 human subjects were given either 30 mg PB orally (n = 19) or placebo (n = 5). Blood samples were obtained pre-dosing and 2.5, 5, 8, and 24 h post-dosing. The samples were analyzed for AChE and BChE activity using the WRAIR WB robotic system, and for PB concentration by HPLC. We found that maximal inhibition of AChE (26.2%) and concentration of PB (17.1 ng/mL) occurred at 2.5 h post-PB dosing. AChE activity returned to almost 100% of pre-dose values by 6 h. A dose-dependent linear correlation was found between the amount of PB measured in the blood and the inhibition of AChE. Following soman (GD) exposure, recovered AChE activity was similar to levels that were reversibly protected by the PB administration. Therefore, the WRAIR ChE WB data clearly supports the conclusion that PB is an effective pre-treatment drug for nerve agent exposure (GD). In the second FDA human study for the treatment of Alzheimer's disease, the WRAIR ChE WB assay was used to determine the RBC-AChE and serum BChE profile of healthy elderly volunteers receiving Huperzine A. Huperzine A is a plant-derived reversible and selective AChE inhibitor compared to BChE, and is a more potent inhibitor of AChE than PB. Huperzine A is available as a nutraceutical, a natural supplement reported to improve memory, and has a variety of neuroprotective effects. Individuals received an increasing dose regimen of huperzine A (final dose 200 microg after 4 weeks), which produced more than 50% inhibition of RBC-AChE. Huperzine A was well tolerated by these patients at doses that sequestered more RBC-AChE than PB, and thus warrants further study as a prophylaxis for OP poisoning in addition to Alzheimer's therapy. Due to the documented use of OPs by terrorists and in warfare around the globe, Federal, State, and local authorities need a reliable, fast, inexpensive, and standard method for confirming such an assault in order to initiate appropriate containment, decontamination, and treatment measures. This assay is ideal for prescreening military personnel for atypical ChE activities that would preclude their deployment to areas of potential CWA exposure. The WRAIR WB ChE assay will fulfill the requirement for rapid and reliable monitoring of such exposure in military and civilian populations.

Mineralogy of Mudstone at Gale Crater, Mars: Evidence for Dynamic Lacustrine Environments

NASA Technical Reports Server (NTRS)

Rampe, E. B.; Ming, D. W.; Grotzinger, J. P.; Morris, R. V.; Blake, D. F.; Vaniman, D. T.; Bristow, T. F.; Yen, A. S.; Chipera, S. J.; Morrison, S. M.;

Performing Mineral Hydration Experiments in the CheMin Diffractometer on Mars

NASA Technical Reports Server (NTRS)

Vaniman, D. T.; Yen, A. S.; Rampe, E. B.; Blake, D. F.; Chipera, S. J.; Morookian, J. M.; Ming, D. W.; Bristow, T. F.; Morris, R. V.; Geller, R.;

PHARMACOKINETIC AND PHARMACODYNAMIC INTERACTION FOR A BINARY MIXTURE OF CHLORPYRIFOS AND DIAZINON IN THE RAT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Timchalk, Chuck; Poet, Torka S.; Hinman, Melissa N.

2005-05-15

Chlorpyrifos (CPF) and diazinon (DZN) are two commonly used organophosphorus (OP) insecticides and potential exists for concurrent exposures. The primary neurotoxic effects from OP pesticide exposures result from the inhibition of acetylcholinesterase (AChE) by their oxon metabolites. The pharmacokinetic and pharmacodynamic impact of acute binary exposures to CPF and DZN in rats were evaluated in this study. Rats were orally administered CPF, DZN or a CPF/DZN mixture (0, 15, 30 or 60 mg/kg) and blood (plasma and RBC), and brain were collected at 0, 3, 6, 12 and 24 h post-dosing, urine was also collected at 24 h. Chlorpyrifos, DZNmore » and their respective metabolites 3,5,6-trichloro-2-pyridinol (TCP) and 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMHP) were quantified in blood and/or urine and cholinesterase (ChE) inhibition was measured in brain, RBCs and plasma. Co-exposure to CPF/DZN at 15/15 mg/kg, did not appreciably alter the pharmacokinetics of CPF, DZN or their metabolites in blood; whereas, a 60/60 mg/kg dose resulted in a transient increase in Cmax, AUC, and decreased clearance of both compounds, likely due to competition between CPF and DZN for CYP450 metabolism. At lower doses, most likely to be encountered in occupational or environmental exposures, the pharmacokinetics were linear. A dose-dependent inhibition of ChE was noted in tissues for both the single and co-exposures. The overall potency for ChE inhibition was greater for CPF than DZN and the binary mixture response appeared to be strongly influenced by CPF. A comparison of the ChE binary response at the low dose (15 mg/kg), where there were no apparent pharmacokinetic interactions, suggested that the overall ChE response was additive. These are the first reported experiments we are aware of that characterize both the pharmacokinetic and pharmacodynamic interactions between CPF and DZN in the rat, and will be used to further develop a binary physiologically based pharmacokinetic and pharmacodynamic model for mixtures.« less

Decreased Astrocytic Thrombospondin-1 Secretion After Chronic Ammonia Treatment Reduces the Level of Synaptic Proteins: In Vitro and In Vivo Studies

PubMed Central

Jayakumar, A. R.; Tong, X. Y.; Curtis, K. M.; Ruiz-Cordero, R.; Shamaladevi, N.; Abuzamel, M.; Johnstone, J.; Gaidosh, G.; Rama Rao, K.V.; Norenberg, M. D.

2014-01-01

Chronic hepatic encephalopathy (CHE) is a major complication in patients with severe liver disease. Elevated blood and brain ammonia levels have been implicated in its pathogenesis, and astrocytes are the principal neural cells involved in this disorder. Since defective synthesis and release of astrocytic factors have been shown to impair synaptic integrity in other neurological conditions, we examined whether thrombospondin-1 (TSP-1), an astrocytic factor involved in the maintenance of synaptic integrity, is also altered in CHE. Cultured astrocytes were exposed to ammonia (NH4Cl, 0.5–2.5 mM) for 1–10 days, and TSP-1 content was measured in cell extracts and culture media. Astrocytes exposed to ammonia exhibited a reduction in intra- and extracellular TSP-1 levels. Exposure of cultured neurons to conditioned media (CM) from ammonia-treated astrocytes showed a decrease in synaptophysin, PSD95 and synaptotagmin levels. CM from TSP-1 overexpressing astrocytes that were treated with ammonia, when added to cultured neurons, reversed the decline in synaptic proteins. Recombinant TSP-1 similarly reversed the decrease in synaptic proteins. Metformin, an agent known to increase TSP-1 synthesis in other cell types also reversed the ammonia-induced TSP-1 reduction. Likewise, we found a significant decline in TSP-1 level in cortical astrocytes, as well as a reduction in synaptophysin content in vivo in a rat model of CHE. These findings suggest that TSP-1 may represent an important therapeutic target for CHE. PMID:25040426

Orientation in a crowded environment: can King Penguin (Aptenodytes patagonicus) chicks find their creches after a displacement?

PubMed

Nesterova, Anna P; Mardon, Jérôme; Bonadonna, Francesco

2009-01-01

For seabird species, the presence of conspecifics in a crowded breeding colony can obstruct locally available orientation cues. Thus, navigation to specific locations can present a challenging problem. We investigated short-range orientation in King Penguin (Aptenodytes patagonicus) chicks that live in a large and densely populated colony. The two main objectives were to determine whether chicks displaced to a novel location away from the colony (i) can orient towards the colony and return to their crèche and (ii) rely on visual or non-visual cues for orientation. To address these questions, a circular arena was constructed 100 m away from the colony. Chicks were released in the arena during the day and at night. After the orientation experiment in the arena, chicks were allowed to return to their home crèche, if they could. Our results showed that, during day trials, chicks preferred the half of the arena closer to the colony, but not at night. However, at night, birds spent more time on ;the colony half' of the arena if the wind blew from the colony direction. When animals were allowed to leave the arena, 98% of chicks homed during the day but only 62% of chicks homed at night. Chicks that homed at night also took longer to find their crèche. The experiments suggest that King Penguin chicks can find their crèche from a novel location. Visual cues are important for homing but, when visual cues are not present, animals are able to make use of other information carried by the wind.

The sensory transduction pathways in bacterial chemotaxis

NASA Technical Reports Server (NTRS)

Taylor, Barry L.

1989-01-01

Bacterial chemotaxis is a useful model for investigating in molecular detail the behavioral response of cells to changes in their environment. Peritrichously flagellated bacteria such as coli and typhimurium swim by rotating helical flagella in a counterclockwise direction. If flagellar rotation is briefly reversed, the bacteria tumble and change the direction of swimming. The bacteria continuously sample the environment and use a temporal sensing mechanism to compare the present and immediate past environments. Bacteria respond to a broad range of stimuli including changes in temperature, oxygen concentration, pH and osmotic strength. Bacteria are attracted to potential sources of nutrition such as sugars and amino acids and are repelled by other chemicals. In the methylation-dependent pathways for sensory transduction and adaptation in E. coli and S. typhimurium, chemoeffectors bind to transducing proteins that span the plasma membrane. The transducing proteins are postulated to control the rate of autophosphorylation of the CheA protein, which in turn phosphorylates the CheY protein. The phospho-CheY protein binds to the switch on the flagellar motor and is the signal for clockwise rotation of the motor. Adaptation to an attractant is achieved by increasing methylation of the transducing protein until the attractant stimulus is cancelled. Responses to oxygen and certain sugars involve methylation-independent pathways in which adaption occurs without methylation of a transducing protein. Taxis toward oxygen is mediated by the electron transport system and changes in the proton motive force. Recent studies have shown that the methylation-independent pathway converges with the methylation-dependent pathway at or before the CheA protein.

Crew Health Care System (CHeCS) Design Research, Documentations, and Evaluations

NASA Technical Reports Server (NTRS)

CLement, Bethany M.

2011-01-01

The Crew Health Care System (CHeCS) is a group within the Space Life Science Directorate (SLSD) that focuses on the overall health of astronauts by reinforcing the three divisions - the Environmental Maintenance System (EMS), the Countermeasures System (CMS), and the Health Maintenance System (HMS). This internship provided opportunity to gain knowledge, experience, and skills in CHeCS engineering and operations tasks. Various and differing tasks allowed for occasions to work independently, network to get things done, and show leadership abilities. Specific exercises included reviewing hardware certification, operations, and documentation within the ongoing Med Kit Redesign (MKR) project, and learning, writing, and working various common pieces of paperwork used in the engineering and design process. Another project focused on the distribution of various pieces of hardware to off-site research facilities with an interest in space flight health care. The main focus of this internship, though, was on a broad and encompassing understanding of the engineering process as time was spent looking at each individual step in a variety of settings and tasks.

Evaluation of standardized Bacopa monniera extract in sodium fluoride-induced behavioural, biochemical, and histopathological alterations in mice.

PubMed

Balaji, Bhaskar; Kumar, Ekambaram Prem; Kumar, Anil

2015-01-01

Effect of standardized Bacopa monniera (BM; family: Scrophulariaceae) extract (100 and 300 mg/kg) against sodium fluoride (NaF; 100 and 200 ppm)-induced behavioural, biochemical, and neuropathological alterations in mice was evaluated. Akinesia, rotarod (motor coordination), forced swim test (depression), open field test (anxiety), transfer latency (memory), cholinesterase (ChE), and oxidative stress (superoxide dismutase, catalase, glutathione peroxidase, and lipid peroxidation) were determined in mice treated with NaF for 30 days alone and in combination with BM. NaF induced motor incoordination, depression, and memory impairment, and these were prevented by coadministration of BM in mice. However, NaF did not alter the weight gain, feed/water consumption, and anxiety profile. Suppression of ChE levels and increased oxidative stress were observed in mice treated with NaF. Coadministration of BM significantly improved the memory, ChE levels, and antioxidant enzymes but failed to alter the fluoride levels in NaF-treated mice. Histopathological studies revealed that BM protected the neuropathological alterations induced by NaF. © The Author(s) 2012.

CheS-Mapper - Chemical Space Mapping and Visualization in 3D.

PubMed

Gütlein, Martin; Karwath, Andreas; Kramer, Stefan

2012-03-17

Analyzing chemical datasets is a challenging task for scientific researchers in the field of chemoinformatics. It is important, yet difficult to understand the relationship between the structure of chemical compounds, their physico-chemical properties, and biological or toxic effects. To that respect, visualization tools can help to better comprehend the underlying correlations. Our recently developed 3D molecular viewer CheS-Mapper (Chemical Space Mapper) divides large datasets into clusters of similar compounds and consequently arranges them in 3D space, such that their spatial proximity reflects their similarity. The user can indirectly determine similarity, by selecting which features to employ in the process. The tool can use and calculate different kind of features, like structural fragments as well as quantitative chemical descriptors. These features can be highlighted within CheS-Mapper, which aids the chemist to better understand patterns and regularities and relate the observations to established scientific knowledge. As a final function, the tool can also be used to select and export specific subsets of a given dataset for further analysis.

CheS-Mapper - Chemical Space Mapping and Visualization in 3D

PubMed Central

2012-01-01

Analyzing chemical datasets is a challenging task for scientific researchers in the field of chemoinformatics. It is important, yet difficult to understand the relationship between the structure of chemical compounds, their physico-chemical properties, and biological or toxic effects. To that respect, visualization tools can help to better comprehend the underlying correlations. Our recently developed 3D molecular viewer CheS-Mapper (Chemical Space Mapper) divides large datasets into clusters of similar compounds and consequently arranges them in 3D space, such that their spatial proximity reflects their similarity. The user can indirectly determine similarity, by selecting which features to employ in the process. The tool can use and calculate different kind of features, like structural fragments as well as quantitative chemical descriptors. These features can be highlighted within CheS-Mapper, which aids the chemist to better understand patterns and regularities and relate the observations to established scientific knowledge. As a final function, the tool can also be used to select and export specific subsets of a given dataset for further analysis. PMID:22424447

[La diagnosi del disturbo da uso di alcol dal punto di vista psicologico].

PubMed

Coriale, Giovanna; Fiorentino, Daniela; Porrari, Raffaella; Battagliese, Gemma; Capriglione, Ida; Cereatti, Federica; Iannuzzi, Silvia; Mauri, Benilde; Galli, Domenica; Fiore, Marco; Attilia, Maria Luisa; Ceccanti, Mauro

2018-01-01

RIASSUNTO. Il disturbo da uso di alcol (DUA) è uno dei disturbi psichiatrici più comuni nella popolazione generale. Il DUA è caratterizzato da un pattern di bere eccessivo, che si mantiene nonostante gli effetti negativi che l'alcol ha sul funzionamento lavorativo, sulla salute, sulle problematiche legali, sull'educazione e sulla vita sociale. Attualmente, il modello bio-psico-sociale è quello che spiega meglio il DUA. Infatti, molte ricerche hanno fornito evidenze su come il DUA sia una patologia multidimensionale. Variabili biologiche, psicologiche e socio-culturali entrano in gioco nell'eziologia, nella natura, nel mantenimento e nel cambiamento nel tempo del disturbo. La fase diagnostica è un momento importante del processo di cura, perché il successo del trattamento dipende in larga misura dall'esattezza e dall'adeguatezza della diagnosi. La diagnosi clinica si basa su una valutazione globale del funzionamento del paziente e utilizza il colloquio e gli strumenti psicometrici come mezzo di raccolta di informazioni. Questo articolo fornirà una panoramica delle dimensioni psicologiche più importanti da valutare e sui migliori strumenti psicometrici da usare per una diagnosi adeguata.

Origin of the Giant Honeycomb Network of Quinones on Cu(111)

NASA Astrophysics Data System (ADS)

Einstein, T. L.; Kim, Kwangmoo; Wyrick, Jon; Cheng, Zhihai; Bartels, Ludwig; Berland, Kristian; Hyldgaard, Per

2011-03-01

We discuss the factors that lead to the amazing regular giant honeycomb network formed by quinones on Cu(111). Using a related lattice gas model with many characteristic energies, we can reproduce many experimental features. These models require a long-range attraction, which can be attributed to indirect interactions mediated by the Shockley surface state of Cu(111). However, Wyrick's preceding talk gave evidence that the network self-selects for the size of the pore rather than for the periodicity of the superstructure, suggesting that confined states are the key ingredient. We discuss this phenomenon in terms of the magic numbers of 2D quantum dots. We also report calculations of the effects of anthraquinones (AQ) in modifying the surface states by considering a superlattice of AQ chains with various separations. We discuss implications of these results for tuning the electronic states and, thence, superstructures. Supported by (TLE) NSF CHE 07-50334 & UMD MRSEC DMR 05-20471, (JW & LB) NSF CHE NSF CHE 07-49949, (KB & PH) Swedish Vetenskapsrådet VR 621-2008-4346.

Efficacy of fresh packed red blood transfusion in organophosphate poisoning.

PubMed

Bao, Hang-Xing; Tong, Pei-Jian; Li, Cai-Xia; Du, Jing; Chen, Bing-Yu; Huang, Zhi-Hui; Wang, Ying

2017-03-01

The mortality rate caused by organophosphate (OP) poisoning is still high, even the standard treatment such as atropine and oxime improves a lot. To search for alternative therapies, this study was aimed to investigate the effects of packed red blood cell (RBC) transfusion in acute OP poisoning, and compare the therapeutic effects of RBCs at different storage times.Patients diagnosed with OP poisoning were included in this prospective study. Fresh RBCs (packed RBCs stored less than 10 days) and longer-storage RBCs (stored more than 10 days but less than 35 days) were randomly transfused or not into OP poisoning patients. Cholinesterase (ChE) levels in blood, atropine usage and durations, pralidoxime durations were measured.We found that both fresh and longer-storage RBCs (200-400 mL) significantly increased blood ChE levels 6 hours after transfusion, shortened the duration for ChE recovery and length of hospital stay, and reduced the usage of atropine and pralidoxime. In addition, fresh RBCs demonstrated stronger therapeutic effects than longer-storage RBCs.Packed RBCs might be an alternative approach in patients with OP poisoning, especially during early stages.

Bioscavengers for the protection of humans against organophosphate toxicity.

PubMed

Doctor, Bhupendra P; Saxena, Ashima

2005-12-15

Current antidotes for organophosphorus compounds (OP) poisoning consist of a combination of pretreatment with carbamates (pyridostigmine bromide), to protect acetylcholinesterase (AChE) from irreversible inhibition by OP compounds, and post-exposure therapy with anti-cholinergic drugs (atropine sulfate) to counteract the effects of excess acetylcholine and oximes (e.g., 2-PAM chloride) to reactivate OP-inhibited AChE. These antidotes are effective in preventing lethality from OP poisoning, but they do not prevent post-exposure incapacitation, convulsions, seizures, performance decrements, or in many cases permanent brain damage. These symptoms are commonly observed in experimental animals and are likely to occur in humans. The problems intrinsic to these antidotes stimulated attempts to develop a single protective drug, itself devoid of pharmacological effects, which would provide protection against the lethality of OP compounds and prevent post-exposure incapacitation. One approach is the use of enzymes such as cholinesterases (ChEs), beta-esterases in general, as single pretreatment drugs to sequester highly toxic OP anti-ChEs before they reach their physiological targets. This approach turns the irreversible nature of the OP: ChE interaction from disadvantage to an advantage; instead of focusing on OP as an anti-ChE, one can use ChE as an anti-OP. Using this approach, it was shown that administration of fetal bovine serum AChE (FBSAChE) or equine serum butyrylcholinesterase (EqBChE) or human serum BChE (HuBChE) protected the animals from multiple LD50s of a variety of highly toxic OPs without any toxic effects or performance decrements. The bioscavengers that have been explored to date for the detoxification of OPs fall into three categories: (A) those that can catalytically hydrolyze OPs and thus render them non-toxic, such as OP hydrolase and OP anhydrase; (B) those that stoichiometrically bind to OPs, that is, 1 mol of enzyme neutralizes one or 2 mol of OP inactivating both, such as ChEs and related enzymes; and (C) and those generally termed as "pseudo catalytic", e.g., a combination of ChE and an oxime pre-treatment such that the catalytic activity of OP-inhibited ChE can rapidly and continuously be restored in the presence of an oxime. Since the biochemical mechanism underlying prophylaxis by exogenous esterases such as ChEs is established and tested in several animal species, including non-human primates, this concept should allow a reliable extrapolation of results from animal experiments to human application. Having being extensively investigated by several groups, plasma derived HuBChE is judged to be the most suitable bioscavenger for its advancement for human use. The program is being developed at the present time for conducting a safety clinical trial in human volunteers. Several other candidate bioscavengers will follow; e.g., recombinant HuBChE expressed in the milk of transgenic goats, pseudo catalytic scavenger(s), e.g., a combination of ChE and oxime, and possibly PON 1 as a catalytic scavenger in the future.

Optimal methylation noise for best chemotactic performance of E. coli

NASA Astrophysics Data System (ADS)

Dev, Subrata; Chatterjee, Sakuntala

2018-03-01

In response to a concentration gradient of chemoattractant, E. coli bacterium modulates the rotational bias of flagellar motors which control its run-and-tumble motion, to migrate towards regions of high chemoattractant concentration. Presence of stochastic noise in the biochemical pathway of the cell has important consequences on the switching mechanism of motor bias, which in turn affects the runs and tumbles of the cell in a significant way. We model the intracellular reaction network in terms of coupled time evolution of three stochastic variables—kinase activity, methylation level, and CheY-P protein level—and study the effect of methylation noise on the chemotactic performance of the cell. In presence of a spatially varying nutrient concentration profile, a good chemotactic performance allows the cell to climb up the concentration gradient quickly and localize in the nutrient-rich regions in the long time limit. Our simulations show that the best performance is obtained at an optimal noise strength. While it is expected that chemotaxis will be weaker for very large noise, it is counterintuitive that the performance worsens even when noise level falls below a certain value. We explain this striking result by detailed analysis of CheY-P protein level statistics for different noise strengths. We show that when the CheY-P level falls below a certain (noise-dependent) threshold the cell tends to move down the concentration gradient of the nutrient, which has a detrimental effect on its chemotactic response. This threshold value decreases as noise is increased, and this effect is responsible for noise-induced enhancement of chemotactic performance. In a harsh chemical environment, when the nutrient degrades with time, the amount of nutrient intercepted by the cell trajectory is an effective performance criterion. In this case also, depending on the nutrient lifetime, we find an optimum noise strength when the performance is at its best.

Development of a Physiologically Based Pharmacokinetic and Pharmacodynamic Model to Determine Dosimetry and Cholinesterase Inhibition for a Binary Mixture of Chlorpyrifos and Diazinon in the Rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Timchalk, Chuck; Poet, Torka S.

2008-05-01

Physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) models have been developed and validated for the organophosphorus (OP) insecticides chlorpyrifos (CPF) and diazinon (DZN). Based on similar pharmacokinetic and mode of action properties it is anticipated that these OPs could interact at a number of important metabolic steps including: CYP450 mediated activation/detoxification, and blood/tissue cholinesterase (ChE) binding/inhibition. We developed a binary PBPK/PD model for CPF, DZN and their metabolites based on previously published models for the individual insecticides. The metabolic interactions (CYP450) between CPF and DZN were evaluated in vitro and suggests that CPF is more substantially metabolized to its oxon metabolite than ismore » DZN. These data are consistent with their observed in vivo relative potency (CPF>DZN). Each insecticide inhibited the other’s in vitro metabolism in a concentration-dependent manner. The PBPK model code used to described the metabolism of CPF and DZN was modified to reflect the type of inhibition kinetics (i.e. competitive vs. non-competitive). The binary model was then evaluated against previously published rodent dosimetry and ChE inhibition data for the mixture. The PBPK/PD model simulations of the acute oral exposure to single- (15 mg/kg) vs. binary-mixtures (15+15 mg/kg) of CFP and DZN at this lower dose resulted in no differences in the predicted pharmacokinetics of either the parent OPs or their respective metabolites; whereas, a binary oral dose of CPF+DZN at 60+60 mg/kg did result in observable changes in the DZN pharmacokinetics. Cmax was more reasonably fit by modifying the absorption parameters. It is anticipated that at low environmentally relevant binary doses, most likely to be encountered in occupational or environmental related exposures, that the pharmacokinetics are expected to be linear, and ChE inhibition dose-additive.« less

Furoquinoline Alkaloids from the Leaves of Evodia lepta as Potential Cholinesterase Inhibitors and their Molecular Docking.

PubMed

Sichaem, Jirapast; Rojpitikul, Thanawan; Sawasdee, Pattara; Lugsannangarm, Kiattisak; Santi, Tip-pyang

2015-08-01

Nine furoquinoline alkaloids (1-9) were isolated from the leaves of Evodia lepta based on bioassay-guided fractionation and chromatographic techniques. All isolates were evaluated for their cholinesterase (ChEs) inhibitory activities, in which kokusaginine (7) and melineurine (5) exhibited the highest activity toward AChE and BChE, respectively. Lineweaver-Burk plots indicated that 5 and 7 were mixed mode inhibitors of both ChE enzymes. Molecular docking studies on the binding sites of AChE and BChE were performed in order to afford a molecular insight into the mode of action of these active compounds. From this study these compounds have emerged as promising molecules for Alzheimer's disease therapy.

Beryllofluoride mimics phosphorylation of NtrC and other bacterial response regulators

PubMed Central

Yan, Dalai; Cho, Ho S.; Hastings, Curtis A.; Igo, Michele M.; Lee, Seok-Yong; Pelton, Jeffrey G.; Stewart, Valley; Wemmer, David E.; Kustu, Sydney

1999-01-01

Two-component systems, sensor kinase-response regulator pairs, dominate bacterial signal transduction. Regulation is exerted by phosphorylation of an Asp in receiver domains of response regulators. Lability of the acyl phosphate linkage has limited structure determination for the active, phosphorylated forms of receiver domains. As assessed by both functional and structural criteria, beryllofluoride yields an excellent analogue of aspartyl phosphate in response regulator NtrC, a bacterial enhancer-binding protein. Beryllofluoride also appears to activate the chemotaxis, sporulation, osmosensing, and nitrate/nitrite response regulators CheY, Spo0F, OmpR, and NarL, respectively. NMR spectroscopic studies indicate that beryllofluoride will facilitate both biochemical and structural characterization of the active forms of receiver domains. PMID:10611291

DynaGuard: Armoring Canary-Based Protections against Brute-Force Attacks

DTIC Science & Technology

2015-12-11

public domain. Non-exclusive copying or redistribution is...sje ng 462 .lib qua ntu m 464 .h2 64r ef 471 .om net pp 473 .as tar 483 .xa lan cbm k Apa che Ng inx Pos tgre SQ L SQ Lite My SQ L Sl ow do w n (n...k 456 .hm me r 458 .sje ng 462 .lib qua ntu m 464 .h2 64r ef 471 .om net pp 473 .as tar 483 .xa lan cbm k Apa che Ng inx Pos tgre SQ L SQ Lite My

The Meteoritical Bulletin, No. 88, 2004 July

USGS Publications Warehouse

Russell, S.S.; Folco, L.; Grady, M.M.; Zolensky, M.E.; Jones, R.; Righter, K.; Zipfel, J.; Grossman, J.N.

2004-01-01

The Meteoritical Bulletin No. 88 lists information for 1610 newly classified meteorites, comprising 753 from Antarctica, 302 from Africa, 505 from Asia (495 of which are from Oman), 40 from North America, 5 from South America, 4 from Europe, and 1 of unknown origin. Information is provided for 9 falls (Alby sur Che??ran, Al Zarnkh, Devgaon, Kamioka, Kendrapara, Maromandia, New Orleans, Sivas, and Villalbeto de la Pen??a). Noteworthy specimens include a eucrite fall (Alby sur Che??ran), 6 martian meteorites, 13 lunar meteorites, and 12 irons including one weighing 3 metric ions (Dronino). ?? Meteoritical Society, 2004.

Efficacy of Recommended Pre-Hospital Human Equivalent Doses of Atropine and Pralidoxime against the Toxic Effects of Carbamate Poisoning in the Hartley Guinea Pig

PubMed Central

Brittain, Matthew K.; McGarry, Kevin G.; Moyer, Robert A.; Babin, Michael C.; Jett, David A.; Platoff, Gennady E.; Yeung, David T.

2016-01-01

Purpose Aldicarb and methomyl are carbamate pesticides commonly implicated in human poisonings. The primary toxic mechanism of action for carbamate poisoning is cholinesterase (ChE) inhibition. As such, it is logical to assume that the currently accepted therapies for organophosphate poisoning [muscarinic antagonist atropine and the oxime acetylcholinesterase reactivator pralidoxime chloride (2-PAM Cl),], could afford therapeutic protection. However, oximes have been shown to be contraindicated for poisoning by some carbamates. Methods A protective ratio study was conducted in guinea pigs to evaluate the efficacy of atropine and 2-PAM Cl. ChE activity was determined in both the blood and cerebral cortex.. Results Co-administration of atropine free base (0.4 mg/kg) and 2-PAM Cl (25.7 mg/kg) demonstrated protective ratios of 2 and 3 against aldicarb and methomyl, respectively, relative to saline. The data reported here show that this protection was primarily mediated by the action of atropine. The reactivator 2-PAM Cl had neither positive nor negative effects on survival. Both blood acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities were significantly reduced at 15 minutes post-challenge but gradually returned to normal within 24 h. Analysis of cerebral cortex showed that BChE, but not AChE, activity was reduced in animals that succumbed prior to 24 h after challenge. Conclusion The results suggest that co-administration of atropine and 2-PAM Cl at the currently recommended human equivalent doses for use in the pre-hospital setting to treat organophosphorus nerve agent and pesticide poisoning would likely also be effective against aldicarb or methomyl poisoning. PMID:27102179

Evaluation of liver and brain esterases in the spotted gar fish (Lepisosteus oculatus) as biomarkers of effect in the lower Mississippi River basin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, T.L.; Obih, P.O.; Jaiswal, R.

1997-05-01

The responses of various xenobiotic metabolizing enzymes in fish models are rapidly evolving as important biomarkers for monitoring unacceptable levels of environmental contaminants. Ethoxyresorufin O-deethylase, a specific cytochrome P450-dependent monooxygenase, is often used as an indicator of polycyclic aromatic hydrocarbon pollution. Another class of enzymes which are potential biomarkers are the B-type esterases. These enzymes are sensitive to inhibition by organophosphates, and include the cholinesterases (ChE) and carboxylesterases. ChEs are further subdivided into acetylcholinesterase and butyryl cholinesterase. Among fish, AChE is predominantly localized in the brain and muscle, whereas, BuChE activity is found mainly in liver and plasma. The precisemore » physiological role of BuChE is unknown, although it has been regarded as a marker enzyme for glial or supportive cells or other non-neuronal elements. Inhibition of ChE activity has often been associated with exposure to organophosphate and carbamate insecticides and other neurotoxic xenobiotics. Chemicals other than carbarnates and organophosphates that are environmental contaminants can also affect the activity of ChEs. Carboxylesterases represent a heterogenous group of isozymes that can catalyze the hydrolysis of a wide range of xenobiotic esters, amides and thioesters. For most CaE, their natural substrates are unknown, therefore, their physiological functions remain to be elucidated. These enzymes (CaE) occur widely in most tissues and are generally found in high levels in the liver. The purpose of this research was to evaluate the liver and brain esterases in the spotted gar fish as biomarkers of effect to multiple contaminants in the lower Mississippi River basin. 15 refs., 3 figs., 2 tabs.« less

Il ruolo svolto dall’attività lavorativa sull’ipertensione arteriosa

PubMed Central

Barbini, N.; Gorini, G.; Ferrucci, L.; Biggeri, A.

2009-01-01

RIASSUNTO Introduzione I parametri di pressione arteriosa, sistolica (PAS) o diastolica (PAD) hanno costituito I’oggetto di numerosi studi, alcuni dei quali stabiliscono un’associazione tra I’aumnto di tali parametri e la mortalità, in particolare alle età medie. I fattori di rischio di ipertensione più frequentemente studiati sono il consumo di alcol, il fumo e I’origine etnica in riferimento sia alle differenze genetiche che nella condotta alimentare, mentre i fattori di origine professionale sono stati presi in considerazione più raramente e in maniera poco approfondita, inoltre sono state riferite notevoli differenze nelle pressioni arteriose medie di individui che svolgono professioni diverse. Sembra infatti che i “colletti blu” siano più a rischio dei “colletti bianchi”. Obiettivi Il nostro scopo è valutare se determinati rischi o vincoli connessi con l’attività professionale o determinati stili di vita rappresentano un fattore di rischio per l’ipertensione arteriosa in considerazioni dell’aumentare dell’età. Elementi specifici che rendano conto di questa relazione non sono stati ancora completamente chiariti e soprattutto i dati sulla popolazione italiana sono molto limitati. Metodi La metodologia di ricerca utilizzata è stata quella dell’indagine francese ESTEV (Derriennic, Touranchet, Volkoff) - VISAT (Marquie, Janson), studio epidemiologico longitudinale su oltre 23000 lavoratori attivata in Francia nel 1990 al fine di indagare gli effetti a lungo termine delle condizioni di lavoro, riferite all’intera vita professionale, sia sull’invecchiamento sia sulla salute dei lavoratori. Analoga indagine è stata avviata in Italia, nel 2000, in 6 Regioni, prendendo in esame i lavoratori dipendenti di diversi settori produttivi appartenenti a 5 coorti di età: da 32 a 52 anni con intervallo di 5 anni. Le rilevazioni sono state effettuate dai medici del lavoro di azienda attraverso 3 questionari: 1. sulle condizioni professionali (esposizione a determinati rischi o vincoli); 2. sugli stili di vita e la salute percepita secondo il Nottingham Health Profile; 3. sulle condizioni oggettive di salute. Per il presente lavoro saranno considerati solo alcuni parametri utili all’approfondimento epidemiologico nel settore cardiocircolatorio. Essi riguarderanno: 1) le condizioni di lavoro, 2) la valutazione soggettiva del lavoro, 3) costrizioni specifiche del lavoro vissute come più gravose con l’avanzare dell’età. Relativamente all’ipertensione, sono stati considerati ipertesi i soggetti che presentavano una PAS ≥160 mm/Hg e/o una PAD ≥90 mm/Hg nonché coloro in cura antipertensiva. Risultati I risultati si riferiscono a 1104 lavoratori, di cui 76% uomini e 24% donne. La prevalenza di ipertensione si è dimostrata più elevata nei maschi (33% Vs 22%). Le stime del rischio hanno evidenziato una associazione statisticamente significativa con alcuni fattori lavorativi come mantenere posture difficili (O.R. 1.71), lavorare in presenza di calore (O.R. 1.43), a contatto con agenti chimici (O.R, 1.31). stare a lungo seduti (O.R. 1.48), fare più cose contemporaneamente (O.R. 1.41), essere interrotti nel proprio lavoro (O.R. 1,35). non poter distogilere gli occhi dal lavoro (O.R.1.61). Conclusioni Noi abbiamo osservato che alcune caratteristiche fisiche del lavoro, ma soprattutto quelle di tipo organizzativo sono fortemente associate all’ipertensione arteriosa. Un elemento importante è sembrata la valutazione soggettiva del valore che i lavoratori danno del proprio lavoro: tale elemento è fortemente connesso con I’organizzazione del lavoro, pertanto è un possibile target di prevenzione (fattore di rischio modificabile). PMID:17886759

Der Einfluss von Alitretinoin auf die Lebensqualität bei Patienten mit schwerem chronischen Handekzem: FUGETTA - Beobachtungsstudie unter Praxisbedingungen.

PubMed

Augustin, Matthias; Thaçi, Diamant; Kamps, Anja

2016-12-01

Alitretinoin ist die einzige zugelassene Behandlung für schweres chronisches Handekzem (CHE), das refraktär gegenüber potenten topischen Corticosteroiden ist. Bei dieser Studie (FUGETTA) wurde die Wirksamkeit von leitliniengerecht angewendetem oralem Alitretinoin sowie dessen Einfluss auf die Lebensqualität (LQ) bei Patienten mit schwerem refraktärem CHE beurteilt. Multizentrische, offene, nichtinterventionelle Beobachtungsstudie, durchgeführt in Deutschland. Die Patienten wurden nach Ermessen ihres behandelnden Arztes mit Alitretinoin 10 mg oder 30 mg einmal täglich über maximal 24 Wochen behandelt. Die Wirksamkeit wurde anhand des Physician Global Assessment (PGA) und des Dermatology Life Quality Index (DLQI) bewertet. Zudem wurden unerwünschte Ereignisse (UE) erfasst. Die Studienpopulation bestand aus 658 Patienten (30 mg: n = 581; 10 mg: n = 77). Bei Beobachtungsbeginn litten die meisten Patienten (83 %) gemäß PGA an einem schweren CHE. Bei Beobachtungsende war das Handekzem bei 48 % der Patienten gemäß PGA vollständig oder fast vollständig abgeheilt (30 mg: 49 %; 10 mg: 43 %). Die mittlere Verbesserung des DLQI-Scores in Woche 24 betrug 58 % (30 mg: mittlere [SD] Veränderung gegenüber dem Ausgangswert -10,4 [8,04]) und 70 % (10 mg: mittlere [SD] Veränderung gegenüber dem Ausgangswert -10,8 [7,29]). Die Gesamtinzidenz von NW war niedrig und in den beiden Gruppen ähnlich. Alitretinoin führte zu einer schnellen, deutlichen Verbesserung der LQ bei Patienten mit schwerem CHE. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Brain Training with Video Games in Covert Hepatic Encephalopathy.

PubMed

Bajaj, Jasmohan S; Ahluwalia, Vishwadeep; Thacker, Leroy R; Fagan, Andrew; Gavis, Edith A; Lennon, Michael; Heuman, Douglas M; Fuchs, Michael; Wade, James B

2017-02-01

Despite the associated adverse outcomes, pharmacologic intervention for covert hepatic encephalopathy (CHE) is not the standard of care. We hypothesized that a video game-based rehabilitation program would improve white matter integrity and brain connectivity in the visuospatial network on brain magnetic resonance imaging (MRI), resulting in improved cognitive function in CHE subjects on measures consistent with the cognitive skill set emphasized by the two video games (e.g., IQ Boost-visual working memory, and Aim and Fire Challenge-psychomotor speed), but also generalize to thinking skills beyond the focus of the cognitive training (Hopkins verbal learning test (HVLT)-verbal learning/memory) and improve their health-related quality of life (HRQOL). The trial included three phases over 8 weeks; during the learning phase (cognitive tests administered twice over 2 weeks without intervening intervention), training phase (daily video game training for 4 weeks), and post-training phase (testing 2 weeks after the video game training ended). Thirty CHE patients completed all visits with significant daily achievement on the video games. In a subset of 13 subjects that underwent brain MRI, there was a significant decrease in fractional anisotropy, and increased radial diffusivity (suggesting axonal sprouting or increased cross-fiber formation) involving similar brain regions (i.e., corpus callosum, internal capsule, and sections of the corticospinal tract) and improvement in the visuospatial resting-state connectivity corresponding to the video game training domains. No significant corresponding improvement in HRQOL or HVLT performance was noted, but cognitive performance did transiently improve on cognitive tests similar to the video games during training. Although multimodal brain imaging changes suggest reductions in tract edema and improved neural network connectivity, this trial of video game brain training did not improve the HRQOL or produce lasting improvement in cognitive function in patients with CHE.

Measurements of Oxychlorine species on Mars

NASA Astrophysics Data System (ADS)

Sutter, B.; Quinn, R. C.; Archer, P. D.; Glavin, D. P.; Glotch, T. D.; Kounaves, S. P.; Osterloo, M. M.; Rampe, E. B.; Ming, D. W.

2017-07-01

Mars landed and orbiter missions have instrumentation capable of detecting oxychlorine phases (e.g. perchlorate, chlorate) on the surface. Perchlorate (~0.6 wt%) was first detected by the Wet Chemistry Laboratory in the surface material at the Phoenix Mars Landing site. Subsequent analyses by the Thermal Evolved Gas Analyser aboard the same lander detected an oxygen release (~465°C) consistent with the thermal decomposition of perchlorate. Recent thermal analysis by the Mars Science Laboratory's Sample Analysis at Mars instrument has also indicated the presence of oxychlorine phases (up to 1.2 wt%) in Gale Crater materials. Despite being at detectable concentrations, the Chemistry and Mineralogy (CheMin) X-ray diffractometer has not detected oxychlorine phases. This suggests that Gale Crater oxychlorine may exist as poorly crystalline phases or that perchlorate/chlorate mixtures exist, so that individual oxychlorine concentrations are below CheMin detection limits (~1 wt%). Although not initially designed to detect oxychlorine phases, reinterpretation of Viking Gas Chromatography/Mass Spectrometer data also suggest that oxychlorine phases are present in the Viking surface materials. Remote near-infrared spectral analyses by the Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) instrument indicate that at least some martian recurring slope lineae (RSL) have spectral signatures consistent with the presence of hydrated perchlorates or chlorates during the seasons when RSL are most extensive. Despite the thermal emission spectrometer, Thermal Emission Imaging System, Observatoire pour la Minéralogie, l'Eau, les Glaces et l'Activité and CRISM detection of hundreds of anhydrous chloride (~10-25 vol%) deposits, expected associated oxychlorine phases (>5-10 vol%) have not been detected. Total Cl and oxychlorine data sets from the Phoenix Lander and the Mars Science Laboratory missions could be used to develop oxychlorine versus total Cl correlations, which may constrain oxychlorine concentrations at other locations on Mars by using total Cl determined by other missions (e.g. Viking, Pathfinder, MER and Odyssey). Development of microfluidic or `lab-on-a-chip' instrumentation has the potential to be the next generation analytical capability used to identify and quantify individual oxychlorine species on future landed robotic missions to Mars.

Behavioral dysfunctions correlate to altered physiology in rainbow trout (Oncorynchus mykiss) exposed to cholinesterase-inhibiting chemicals

USGS Publications Warehouse

Brewer, S.K.; Little, E.E.; DeLonay, A.J.; Beauvais, S.L.; Jones, S.B.; Ellersieck, Mark R.

2001-01-01

We selected four metrics of swimming behavior (distance swam, speed, rate of turning, and tortuosity of path) and the commonly used biochemical marker, brain cholinesterase (ChE) activity, to assess (1) the sensitivity and reliability of behavior as a potential biomarker in monitoring work, (2) the potential for these endpoints to be used in automated monitoring, and (3) the linkage between behavior and its underlying biochemistry. Malathion-exposed fish exhibited large decreases in distance and speed and swam in a more linear path than control fish after 24 h exposure. By 96 h exposure, fish still swam slower and traveled less distance; fish fully recovered after 48 h in clean water. Diazinon-exposed fish exhibited decreases in distance, speed, and turning rate compared to controls. After 48 h recovery in clean water, fish exposed to diazinon had not recovered to control levels. The behavioral responses provided measures of neurotoxicity that were easily quantifiable by automated means, implying that the inclusion of behavior in monitoring programs can be successful. Furthermore, correlations between behavior and biochemical endpoints, such as ChE inhibition, suggest that this approach can provide a meaningful link between biochemistry and behavior and can provide useful information on toxicant impacts.

Endothelium-Dependent Vasorelaxant Effect of Butanolic Fraction from Caryocar brasiliense Camb. Leaves in Rat Thoracic Aorta

PubMed Central

de Oliveira, Lais Moraes; Rodrigues, Aline Gabriela; da Silva, Elaine Fernanda; Cerqueira, Letícia Bonancio; Castro, Carlos Henrique; Pedrino, Gustavo Rodrigues; de Carvalho, Maria Helena Catelli; Pontarolo, Roberto; Costa, Elson Alves; Campos, Francinete Ramos; Filgueira, Fernando Paranaiba; Ghedini, Paulo César

2012-01-01

Caryocar brasiliense Camb. “pequi” is a native plant from the Cerrado region of Brazil that contains bioactive components reported to be antioxidant agents. Previous work has demonstrated that dietary supplementation with pequi decreased the arterial pressure of volunteer athletes. We found that the crude hydroalcoholic extract (CHE) of C. brasiliense leaves relaxed, in a concentration-dependent manner, rat aortic rings precontracted with phenylephrine, and that the butanolic fraction (BF) produced an effect similar to that of the CHE. Aortic relaxation induced by BF was abolished by endothelium removal, by incubation of the nitric oxide synthase inhibitor L-NAME, or the soluble guanylatecyclase inhibitor ODQ. However, incubation with atropine and pyrilamine had no effect on the BF-induced vasorelaxation. Moreover, this effect was not inhibited by indomethacin and tetraethylammonium. The concentration-response curve to calcium in denuded-endothelium rings was not modified after incubation with BF, and the vasorelaxation by BF in endothelium-intact rings precontracted with KCl was abolished after incubation with L-NAME. In addition, administration of BF in anesthetized rats resulted in a reversible hypotension. The results reveal that C. brasiliense possesses both in vivo and in vitro activities and that the vascular effect of BF involves stimulation of the nitric oxide/cyclic GMP pathway. PMID:22927883

Behavioral dysfunctions correlate to altered physiology in rainbow trout (Oncorynchus mykiss) exposed to cholinesterase-inhibiting chemicals.

PubMed

Brewer, S K; Little, E E; DeLonay, A J; Beauvais, S L; Jones, S B; Ellersieck, M R

2001-01-01

We selected four metrics of swimming behavior (distance swam, speed, rate of turning, and tortuosity of path) and the commonly used biochemical marker, brain cholinesterase (ChE) activity, to assess (1) the sensitivity and reliability of behavior as a potential biomarker in monitoring work, (2) the potential for these endpoints to be used in automated monitoring, and (3) the linkage between behavior and its underlying biochemistry. Malathion-exposed fish exhibited large decreases in distance and speed and swam in a more linear path than control fish after 24 h exposure. By 96 h exposure, fish still swam slower and traveled less distance; fish fully recovered after 48 h in clean water. Diazinon-exposed fish exhibited decreases in distance, speed, and turning rate compared to controls. After 48 h recovery in clean water, fish exposed to diazinon had not recovered to control levels. The behavioral responses provided measures of neurotoxicity that were easily quantifiable by automated means, implying that the inclusion of behavior in monitoring programs can be successful. Furthermore, correlations between behavior and biochemical endpoints, such as ChE inhibition, suggest that this approach can provide a meaningful link between biochemistry and behavior and can provide useful information on toxicant impacts.

Factors influencing poisoning symptoms: a case study of vegetable farmers exposed to mixed insecticides in Prek Balatchheng Village, Cambodia.

PubMed

Thetkathuek, Anamai; Suybros, Nhean; Daniell, William; Meepradit, Parvena; Jaidee, Wanlop

2014-01-01

This study aimed to identify factors influencing poisoning symptoms among 153 mixed insecticide-exposed vegetable farmers in one Cambodian village, where 153 factory workers were selected as a comparative nonexposed group. The research instruments were questionnaires and reactive-paper test kits. The majority of vegetable farmers were male, with approximately 87% of the total participants with an average age of 34 years. The personal hygiene scores of most vegetable farmers (108; 70.8%) were moderate, and knowledge scores were at poor level (131; 85.6%). Abnormally low cholinesterase (ChE) levels were detected among 119 (77.8%) farmers. Multiple logistic regression analysis was used to identify factors associated with possible poisoning symptoms. This study found that mixing an average of four to six types of insecticides (odds ratio [OR] = 4.6; P = .03) and abnormal ChE level (OR = 4.09; P = .004) was associated with central nervous system (CNS) symptoms. Age group >45 years (OR = 2.8; P = .04) and type of vegetable "other" (OR = 2.73; P = .02) were associated with gastrointestinal symptoms. Type of insecticide, organophosphates (OPs) and carbamates (CMs) (OR = 3.2; P = .04), was associated with respiratory symptoms. It is recommended that farmers should reduce insecticide spraying times, increase their use of personal protective equipment (PPE), and undergo training on insecticide use. These combined measures should improve the insecticide-related health status of vegetable farmers in this area.

Iran's Health Reform Plan: Measuring Changes in Equity Indices.

PubMed

Assari Arani, Abbas; Atashbar, Tohid; Antoun, Joseph; Bossert, Thomas

2018-03-01

Two years after the implementation of the Health Sector Evolution Plan (HSEP), this study evaluated the effects of the plan on health equity indices. The main indices assessed by the study were the Out-of-Pocket (OOP) health expenditures, the Fairness in Financial Contribution (FFC) to the health system index, the index of households' Catastrophic Health Expenditure (CHE) and the headcount ratio of Impoverishing Health Expenditure (IHE). The per capita share of costs for total health services has been decreased. The lowered costs have been more felt in rural areas, generally due to sharp decrease in inpatient costs. Per capita pay for outpatient services is almost constant or has slightly increased. The reform plan has managed to improve households' Catastrophic Health Expenditure (CHE) index from an average of 2.9% before the implementation of the plan to 2.3% after the plan. The Fairness in Financial Contribution (FFC) to the health system index has worsened from 0.79 to 0.76, and the headcount ratio of Impoverishing Health Expenditure (IHE) index deteriorated after the implementation of plan from 0.34 to 0.50. Considerable improvement, in decreasing the burden of catastrophic hospital costs in low income strata which is about 26% relative to the time before the implementation of the plan can be regarded as the main achievement of the plan, whereas the worsening in the headcount ratio of IHE and FFC are the equity bottlenecks of the plan.

A Gastric Pathogen Moves Chemotaxis in a New Direction

PubMed Central

Sweeney, Emily Goers; Guillemin, Karen

2011-01-01

Abstract For almost 50 years, Escherichia coli has been the model for understanding how bacteria orient their movement in response to chemical cues, but recent studies of chemotaxis in other bacteria have revealed interesting variations from prevailing paradigms. Investigating the human pathogen Helicobacter pylori, Amieva and colleagues [mBio 2(4):e00098-11, 2011] discovered a new chemotaxis regulator, ChePep, which modulates swimming behavior through the canonical histidine-aspartate phosphorelay system. Functionally conserved among the epsilonproteobacteria, ChePep is essential for H. pylori to navigate deep into the stomach’s gastric glands and may be an attractive target for novel antibiotics. PMID:21933915

Organisationsaspekte in der Umsetzung

NASA Astrophysics Data System (ADS)

Balck, Henning; Bungard, Walter; Hofmann, Karsten; Ganz, Walter; Schwenker, Burkhard; Hanßen, Dirk; Meindl, Rudolf; Schloske, Alexander; Thieme, Paul; Teufel, Peter

Strukturbrüche sind eine der Hauptursachen für die Schwierigkeiten vieler Unternehmen, ihre Organisationsform zu modernisieren und vor allem turbulenten Marktbedingungen anzupassen. Klassische Beispiele für Strukturbrüche finden sich in der Spaltung von Aufbau- und Ablauforganisation, der Spaltung von Produktion und Dienstleistung oder der Spaltung von Planung und Ausführung. Ein wirkungsvoller Ansatz zur Überwindung solcher Spaltungen ist eine Art Versöhnungsmuster: die Polare Organisation. Wesentliche Elemente dieser Organisationsform sind ihr Netzwerkcharakter, kooperatives Zusammenwirken, eine hohe Kommunikationsintensität und eine polare Koppelung der kommunizierenden Partner oder - in abstrahierter Form - die organisierte Balance erfolgskritischer Gegensätze, wie Kosten und Qualität.

May alcohol-induced increase of HDL be considered as atheroprotective?

PubMed

Králová Lesná, I; Suchánek, P; Stávek, P; Poledne, R

2010-01-01

It is well known that the consumption of moderate doses of alcohol leads to the increase of HDL-cholesterol (HDL-C). Atheroprotectivity of HDL particles is based primarily on their role in reverse cholesterol transport (RCT). In the study with a cross-over design 13 male volunteers were studied in two different regimens: i) drinking of 36 g alcohol daily and ii) drinking only non-alcoholic beverages, to test whether alcohol-induced increase of HDL cholesterol can affect cholesterol efflux (CHE) from cell culture of labeled human macrophages. Alcohol consumption induced significant (p < 0.05) increases of HDL cholesterol from 1.25 +/- 0.32 to 1.34 +/- 0.38 mmol/l and Apo A1 from 1.34 +/- 0.16 to 1.44 +/- 0.19 g/l. These changes were combined with a slight increase of cholesterol efflux from 13.8 +/- 2.15 to 14.9 +/- 1.85 % (p = 0.059). There were significant correlations between individual changes of HDL-C and Apo A1 concentrations and individual changes of CHE (0.51 and 0.60, respectively). In conclusion, moderate alcohol consumption changes the capacity of plasma to induce CHE only at a border line significance.

Noise effects in bacterial motor switch

NASA Astrophysics Data System (ADS)

Tu, Yuhai

2006-03-01

The clockwise (CW) or counter clockwise (CCW) spinning of bacterial flagellar motors is controlled by the concentration of a phosphorylated protein CheY-P. In this talk, we represent the stochastic switching behavior of a bacterial flagellar motor by a dynamical two-state (CW and CCW) model, with the energy levels of the two states fluctuating in time according to the variation of the CheY-P concentration in the cell. We show that with a generic normal distribution and a modest amplitude for CheY-P concentration fluctuations, the dynamical two-state model is capable of generating a power-law distribution (as opposed to an exponential Poisson-like distribution) for the durations of the CCW states, in agreement with recent experimental observations of Korobkova et al (Nature, 428, 574(2004)). In addition, we show that the power spectrum for the flagellar motor switching time series is not determined solely by the power-law duration distribution, but also by the temporal correlation between the duration times of different CCW intervals. We point out the intrinsic connection between anomalously large fluctuations of the motor output and the overall high gain of the bacterial chemotaxis system. Suggestions for experimental verification of the dynamical two-state model will also be discussed.

Lo Gnomone Clementino Astronomia Meridiana in Basilica

NASA Astrophysics Data System (ADS)

Sigismondi, Costantino

2014-05-01

Costruito per chiara volontà del papa 70 anni dopo il caso Galileo, lo Gnomone Clementino è un grande telescopio solare che non fa uso di lenti a 92 anni dall’invenzione del cannocchiale. Queste due caratteristiche basterebbero da sole a giustificare l’interesse verso questo strumento. L’astronomia meridiana è alla base dell’astrometria e dell’astrofisica moderna. Lo Gnomone Clementino sta oggi all’astronomia, come il veliero “Amerigo Vespucci” sta alla Marina Italiana. E’ possibile svolgere ogni genere di osservazione e studio su questo strumento, e dal 2002 vi tengo lezioni teorico-pratiche del corso di Storia dell’Astronomia e La Terra nel Sistema Solare della Sapienza, Università di Roma, Facoltà di Lettere e Filosofia. Questo testo aggiunge alcuni tasselli alla ricerca storica sulla meridiana, appoggiandosi, com’è naturale, sulle spalle di giganti che mi hanno preceduto in questi studi. In particolare la misura dell’azimut della meridiana, ed il suo inquadramento tra gli strumenti simili ed alcuni studi di astrometria sui dati del 1701-1703 di Bianchini, che sono apparsi fin’ora soltanto su riviste specializzate ed in Inglese vengono qui proposti in Italiano e semplificati, per valorizzare sempre più questa straordinaria opera d’arte e di scienza.

Modulators of heterogeneous protein surface water dynamics

NASA Astrophysics Data System (ADS)

Han, Songi

The hydration water that solvates proteins is a major factor in driving or enabling biological events, including protein-protein and protein-ligand interactions. We investigate the role of the protein surface in modulating the hydration water fluctuations on both the picosecond and nanosecond timescale with an emerging experimental NMR technique known as Overhauser Dynamic Nuclear Polarization (ODNP). We carry out site-specific ODNP measurements of the hydration water fluctuations along the surface of Chemotaxis Y (CheY), and correlate the measured fluctuations to hydropathic and topological properties of the CheY surface as derived from molecular dynamics (MD) simulation. Furthermore, we compare hydration water fluctuations measured on the CheY surface to that of other globular proteins, as well as intrinsically disordered proteins, peptides, and liposome surfaces to systematically test characteristic effects of the biomolecular surface on the hydration water dynamics. Our results suggest that the labile (ps) hydration water fluctuations are modulated by the chemical nature of the surface, while the bound (ns) water fluctuations are present on surfaces that feature a rough topology and chemical heterogeneity such as the surface of a folded and structured protein. In collaboration with: Ryan Barnes, Dept of Chemistry and Biochemistry, University of California Santa Barbara

Serum cholinesterase polymorphism (CHE1 and CHE2 loci) among several Indian groups from Amazon region of Brazil, and segregation of the C5 variant in families.

PubMed

Guerreiro, J F; Santos, S E; Aguiar, G F

1989-04-01

Eight Indian tribes from the Amazon region of Brazil (Araweté, Arara, Yamamadi, Kararaô, Karitiana, Waiampi, Surui and Cinta Larga) were studied for the distribution of the atypical and C5 variants of serum cholinesterase. None of them presented the CHE1*A allele, but the C5 variant was found in the Araweté (20.4%), Kararaô (15.6%), Karitiana (50.5%), Surui (12.3%) and Cinta Larga (19.6%) tribes. The frequency of the C5+ phenotype in the Karitiana is the highest reported thus far in human populations. Segregation studies considering the C5 variant were made among the Karitiana, and also among the Urubu-Kaapor and Munduruku tribes previously studied by Guerreiro et al [1987a, 1987b]. Most of the data were in agreement with the genetic hypothesis, but they also revealed a significant lack of the C5+ phenotype in offspring from C5+ X C5+ matings, as well as the occurrence of two C5+ children from C5- X C5- unions, in the Urubu-Kaapor tribe.

Insights into the Sulfur Mineralogy of Martian Soil at Rocknest, Gale Crater, Enabled by Evolved Gas Analyses

NASA Technical Reports Server (NTRS)

McAdam, A.; Franz, H.; Archer, P., Jr.; Freissinet, C.; Sutter, B.; Glavin, D.; Eigenbrode, J.; Bower, H.; Stern, J.; Mchaffy, P.;

Validation of EncephalApp, Smartphone-Based Stroop Test, for the Diagnosis of Covert Hepatic Encephalopathy.

PubMed

Bajaj, Jasmohan S; Heuman, Douglas M; Sterling, Richard K; Sanyal, Arun J; Siddiqui, Muhammad; Matherly, Scott; Luketic, Velimir; Stravitz, R Todd; Fuchs, Michael; Thacker, Leroy R; Gilles, HoChong; White, Melanie B; Unser, Ariel; Hovermale, James; Gavis, Edith; Noble, Nicole A; Wade, James B

2015-10-01

Detection of covert hepatic encephalopathy (CHE) is difficult, but point-of-care testing could increase rates of diagnosis. We aimed to validate the ability of the smartphone app EncephalApp, a streamlined version of Stroop App, to detect CHE. We evaluated face validity, test-retest reliability, and external validity. Patients with cirrhosis (n = 167; 38% with overt HE [OHE]; mean age, 55 years; mean Model for End-Stage Liver Disease score, 12) and controls (n = 114) were each given a paper and pencil cognitive battery (standard) along with EncephalApp. EncephalApp has Off and On states; results measured were OffTime, OnTime, OffTime+OnTime, and number of runs required to complete 5 off and on runs. Thirty-six patients with cirrhosis underwent driving simulation tests, and EncephalApp results were correlated with results. Test-retest reliability was analyzed in a subgroup of patients. The test was performed before and after transjugular intrahepatic portosystemic shunt placement, and before and after correction for hyponatremia, to determine external validity. All patients with cirrhosis performed worse on paper and pencil and EncephalApp tests than controls. Patients with cirrhosis and OHE performed worse than those without OHE. Age-dependent EncephalApp cutoffs (younger or older than 45 years) were set. An OffTime+OnTime value of >190 seconds identified all patients with CHE with an area under the receiver operator characteristic value of 0.91; the area under the receiver operator characteristic value was 0.88 for diagnosis of CHE in those without OHE. EncephalApp times correlated with crashes and illegal turns in driving simulation tests. Test-retest reliability was high (intraclass coefficient, 0.83) among 30 patients retested 1-3 months apart. OffTime+OnTime increased significantly (206 vs 255 seconds, P = .007) among 10 patients retested 33 ± 7 days after transjugular intrahepatic portosystemic shunt placement. OffTime+OnTime decreased significantly (242 vs 225 seconds, P = .03) in 7 patients tested before and after correction for hyponatremia (126 ± 3 to 132 ± 4 meq/L, P = .01) 10 ± 5 days apart. A smartphone app called EncephalApp has good face validity, test-retest reliability, and external validity for the diagnosis of CHE. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Validation of EncephalApp, Smartphone-based Stroop Test, for the Diagnosis of Covert Hepatic Encephalopathy

PubMed Central

Bajaj, Jasmohan S; Heuman, Douglas M; Sterling, Richard K; Sanyal, Arun J; Siddiqui, Muhammad; Matherly, Scott; Luketic, Velimir; Stravitz, R Todd; Fuchs, Michael; Thacker, Leroy R; Gilles, HoChong; White, Melanie B; Unser, Ariel; Hovermale, James; Gavis, Edith; Noble, Nicole A; Wade, James B

2014-01-01

Background & Aims Detection of covert hepatic encephalopathy (CHE) is difficult but point of care testing could increase rates of diagnosis. We aimed to validate the ability of the smartphone app EncephalApp, a streamlined version of Stroop App, to detect CHE. We evaluated face validity, test–retest reliability, and external validity. Methods Patients with cirrhosis (n=167; 38% with overt HE [OHE]; mean age, 55 years; mean model for end-stage liver disease score, 12) and controls (n=114) were each given a paper and pencil cognitive battery (standard) along with EncephalApp. EncephalApp has Off and On states; results measured were: OffTime, OnTime, OffTime+OnTime, and number of runs required to complete 5 off and on runs. Thirty-six patients with cirrhosis underwent driving simulation tests, and EncephalApp results were correlated with results. Test–retest reliability was analyzed in a subgroup of patients. The test was performed before and after transjugular intra-hepatic portosystemic shunt placement, before and after correction for hyponatremia, to determine external validity. Results All patients with cirrhosis performed worse on paper and pencil and EncephalApp tests than controls. Patients with cirrhosis and OHE performed worse than those without OHE. Age-dependent EncephalApp cut-offs (younger or older than 45 years) were set. An OffTime+OnTime value of >190 seconds identified all patients with CHE with an area under the receiver operator characteristic (AUROC) value of 0.91; the AUROC value was 0.88 for diagnosis of CHE in those without OHE. EncephalApp times correlated with crashes and illegal turns in driving simulation tests. Test–retest reliability was high (intra-class coefficient, 0.83) among 30 patients retested 1–3 months apart. OffTime+OnTime increased significantly (206 vs 255, P=.007) among 10 patients retested 33±7 days after transjugular intra-hepatic portosystemic shunt placement. OffTime+OnTime decreased significantly (242 vs 225, P=.03) in 7 patients tested before and after correction for hyponatremia (126±3 to 132±4 meq/L, P=.01), 10±5 days apart. Conclusions A smartphone app called EncephalApp has good face validity, test–retest reliability, and external validity for the diagnosis of CHE. PMID:24846278

Effects of repeated low-dose exposure of the nerve agent VX on monoamine levels in different brain structures in mice.

PubMed

Graziani, S; Christin, D; Daulon, S; Breton, P; Perrier, N; Taysse, L

2014-05-01

In a previous report, alterations of the serotonin metabolism were previously reported in mice intoxicated with repeated low doses of soman. In order to better understand the effects induced by repeated low-dose exposure to organophosphorus compounds on physiological and behavioural functions, the levels of endogenous monoamines (serotonin and dopamine) in different brain areas in mice intoxicated with sublethal dose of (O-ethyl-S-[2(di-isopropylamino) ethyl] methyl phosphonothioate) (VX) were analysed by HPLC method with electrochemical detection. Animals were injected once a day for three consecutive days with 0.10 LD50 of VX (5 μg/kg, i.p). Neither severe signs of cholinergic toxicity nor pathological changes in brain tissue of exposed animals were observed. Cholinesterase (ChE) activity was only inhibited in plasma (a maximum of 30% inhibition 24 h after the last injection of VX), but remained unchanged in the brain. Serotonin and dopamine (DA) metabolism appeared significantly modified. During the entire period of investigation, at least one of the three parameters investigated (i.e. DA and DOPAC levels and DOPAC/DA ratio) was modified. During the toxic challenge, an increase of the serotonin metabolism was noted in hippocampus (HPC), hypothalamus/thalamus, pons medulla and cerebellum (CER). This increase was maintained 4 weeks after exposure in HPC, pons medulla and CER whereas a decrease in cortex 3 weeks after the toxic challenge was observed. The lack of correlation between brain ChE activity and neurochemical outcomes points out to independent mechanisms. The involvement in possibly long-lasting behavioural disorders is discussed.

Intrahippocampal cholinesterase inhibition induces epileptogenesis in mice without evidence of neurodegenerative events.

PubMed

Pernot, F; Carpentier, P; Baille, V; Testylier, G; Beaup, C; Foquin, A; Filliat, P; Liscia, P; Coutan, M; Piérard, C; Béracochea, D; Dorandeu, F

2009-09-15

The mechanisms of epileptogenesis remain largely unknown and are probably diverse. The aim of this study was to investigate the role of focal cholinergic imbalance in epileptogenesis. To address this question, we monitored electroencephalogram (EEG) activity up to 12 weeks after the injection of a potent cholinesterase (ChE) inhibitor (soman) at different doses (0.53, 0.75, 1, 2, 2.8, 4 and 11 nmol) into the right dorsal hippocampus of C57BL/6 mice. Different parameters were used to choose the dose for a focal model of epileptogenesis (mainly electrographic patterns and peripheral ChE inhibition). The pattern of neuronal activation was studied by Fos immunohistochemistry (IHC). Brain damage was evaluated by hemalun-phloxin, neuronal nuclei antigen IHC and silver staining. Glial fibrillary acidic protein IHC was used to evaluate astroglial reaction. Finally, long-term behavioral consequences were characterized. At the highest dose (11 nmol), soman quickly evoked severe signs, including initial seizures and promoted epileptogenesis in the absence of tissue damage. With lower doses, late-onset seizures were evidenced, after 1-4 weeks depending on the dose, despite the absence of initial overt seizures and of brain damage. Only a weak astroglial reaction was observed. Following injection of 1 nmol, Fos changes were first evidenced in the ipsilateral hippocampus and then spread to extrahippocampal areas. A selective deficit in contextual fear conditioning was also evidenced two months after injection. Our data show that focal hypercholinergy may be a sufficient initial event to promote epilepsy and that major brain tissue changes (cellular damage, edema, neuroinflammation) are not necessary conditions.

Interaction between organophosphate compounds and cholinergic functions during development.

PubMed

Aluigi, M G; Angelini, C; Falugi, C; Fossa, R; Genever, P; Gallus, L; Layer, P G; Prestipino, G; Rakonczay, Z; Sgro, M; Thielecke, H; Trombino, S

2005-12-15

Organophosphate (OP) compounds exert inhibition on cholinesterase (ChE) activity by irreversibly binding to the catalytic site of the enzymes. For this reason, they are employed as insecticides for agricultural, gardening and indoor pest control. The biological function of the ChE enzymes is well known and has been studied since the beginning of the XXth century; in particular, acetylcholinesterase (AChE, E.C. 3.1.1.7) is an enzyme playing a key role in the modulation of neuromuscular impulse transmission. However, in the past decades, there has been increasing interest concerning its role in regulating non-neuromuscular cell-to-cell interactions mediated by electrical events, such as intracellular ion concentration changes, as the ones occurring during gamete interaction and embryonic development. An understanding of the mechanisms of the cholinergic regulation of these events can help us foresee the possible impact on environmental and human health, including gamete efficiency and possible teratogenic effects on different models, and help elucidate the extent to which OP exposure may affect human health. The chosen organophosphates were the ones mainly used in Europe: diazinon, chlorpyriphos, malathion, and phentoate, all of them belonging to the thionophosphate chemical class. This research has focused on the comparison between the effects of exposure on the developing embryos at different stages, identifying biomarkers and determining potential risk factors for sensitive subpopulations. The effects of OP oxonisation were not taken into account at this level, because embryonic responses were directly correlated to the changes of AChE activity, as determined by histochemical localisation and biochemical measurements. The identified biomarkers of effect for in vitro experiments were: cell proliferation/apoptosis as well as cell differentiation. For in vivo experiments, the endpoints were: developmental speed, size and shape of pre-gastrula embryos; developmental anomalies on neural tube, head, eye, heart. In all these events, we had evidence that the effects are mediated by ion channel activation, through the activation/inactivation of acetylcholine receptors (AChRs).

Lycopene modulates cholinergic dysfunction, Bcl-2/Bax balance, and antioxidant enzymes gene transcripts in monosodium glutamate (E621) induced neurotoxicity in a rat model.

PubMed

Sadek, Kadry; Abouzed, Tarek; Nasr, Sherif

2016-04-01

The effect of monosodium glutamate (MSG) on brain tissue and the relative ability of lycopene to avert these neurotoxic effects were investigated. Thirty-two male Wistar rats were distributed into 4 groups: group I, untreated (placebo); group II, injected with MSG (5 mg·kg(-1)) s.c.; group III, gastrogavaged with lycopene (10 mg·kg(-1)) p.o.; and group IV received MSG with lycopene with the same mentioned doses for 30 days. The results showed that MSG induced elevation in lipid peroxidation marker and perturbation in the antioxidant homeostasis and increased the levels of brain and serum cholinesterase (ChE), total creatine phosphokinase (CPK), creatine phosphokinase isoenzymes BB (CPK-BB), and lactate dehydrogenase (LDH). Glutathione S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities and gene expression were increased and glutathione content was reduced in the MSG-challenged rats, and these effects were ameliorated by lycopene. Furthermore, MSG induced apoptosis in brain tissues reflected in upregulation of pro-apoptotic Bax while lycopene upregulated the anti-apoptotic Bcl-2. Our results indicate that lycopene appears to be highly effective in relieving the toxic effects of MSG by inhibiting lipid peroxidation and inducing modifications in the activity of cholinesterase and antioxidant pathways. Interestingly, lycopene protects brain tissue by inhibiting apoptosis signaling induced by MSG.

Electrochemical vs X-ray Spectroscopic Measurements of NiFe(CN)6 Crystals

NASA Astrophysics Data System (ADS)

Peecher, Benjamin; Hampton, Jennifer

Pseudocapacitive materials like hexacyanoferrate have greater energy storage capabilities than standard capacitors while maintaining an ability to charge and discharge quickly. We modify the surface of an electrodeposited Ni thin film with a layer of hexacyanoferrate. Charging and discharging these modified films using cyclic voltammetry (CV) allows us to measure the electrochemically active Fe in the film. To determine how closely this resembles the full amount of Fe in the film, we measure the films' composition using particle-induced x-ray emission (PIXE). We also vary the amount of Ni deposited, both to compare the electrolysis value of charge deposited to the PIXE measurement of Ni in the film, and also to measure how varying the thickness of the Ni surface affects the presence of Fe in the film. Comparisons of the CV and PIXE measurements show agreement in Ni levels but disagreement in Fe levels. PIXE measurements of Fe in the film have positive correlation with Ni in the film. This correlation between PIXE measurements of Ni and Fe suggests that PIXE provides a reliable measure of Fe in the film. This implies that a variable proportion of total Fe in a given film is electrochemically active. This research was made possible by the Hope College Department of Physics Frissel Research Fund and the National Science Foundation under Grants RUI-DMR-1104725, MRI-CHE-0959282, and MRI/RUI-PHY-0319523.

[Application of Bayes Probability Model in Differentiation of Yin and Yang Jaundice Syndromes in Neonates].

PubMed

Mu, Chun-sun; Zhang, Ping; Kong, Chun-yan; Li, Yang-ning

2015-09-01

To study the application of Bayes probability model in differentiating yin and yang jaundice syndromes in neonates. Totally 107 jaundice neonates who admitted to hospital within 10 days after birth were assigned to two groups according to syndrome differentiation, 68 in the yang jaundice syndrome group and 39 in the yin jaundice syndrome group. Data collected for neonates were factors related to jaundice before, during and after birth. Blood routines, liver and renal functions, and myocardial enzymes were tested on the admission day or the next day. Logistic regression model and Bayes discriminating analysis were used to screen factors important for yin and yang jaundice syndrome differentiation. Finally, Bayes probability model for yin and yang jaundice syndromes was established and assessed. Factors important for yin and yang jaundice syndrome differentiation screened by Logistic regression model and Bayes discriminating analysis included mothers' age, mother with gestational diabetes mellitus (GDM), gestational age, asphyxia, or ABO hemolytic diseases, red blood cell distribution width (RDW-SD), platelet-large cell ratio (P-LCR), serum direct bilirubin (DBIL), alkaline phosphatase (ALP), cholinesterase (CHE). Bayes discriminating analysis was performed by SPSS to obtain Bayes discriminant function coefficient. Bayes discriminant function was established according to discriminant function coefficients. Yang jaundice syndrome: y1= -21. 701 +2. 589 x mother's age + 1. 037 x GDM-17. 175 x asphyxia + 13. 876 x gestational age + 6. 303 x ABO hemolytic disease + 2.116 x RDW-SD + 0. 831 x DBIL + 0. 012 x ALP + 1. 697 x LCR + 0. 001 x CHE; Yin jaundice syndrome: y2= -33. 511 + 2.991 x mother's age + 3.960 x GDM-12. 877 x asphyxia + 11. 848 x gestational age + 1. 820 x ABO hemolytic disease +2. 231 x RDW-SD +0. 999 x DBIL +0. 023 x ALP +1. 916 x LCR +0. 002 x CHE. Bayes discriminant function was hypothesis tested and got Wilks' λ =0. 393 (P =0. 000). So Bayes discriminant function was proved to be with statistical difference. To check Bayes probability model in discriminating yin and yang jaundice syndromes, coincidence rates for yin and yang jaundice syndromes were both 90% plus. Yin and yang jaundice syndromes in neonates could be accurately judged by Bayesian discriminating functions.

Indirect cannibalism by crèche-aged American White Pelican (Pelecanus erythrorhynchos) chicks

USGS Publications Warehouse

Bartos, Alisa J.; Sovada, Marsha A.; Igl, Lawrence D.; Pietz, Pamela J.

2013-01-01

At nesting colonies of American White Pelicans (Pelecanus erythrorhynchos), many chicks die from siblicide, severe weather, and disease; this results in carcasses available for scavenging by conspecifics (i.e., indirect cannibalism). Indirect cannibalism has not been reported previously for this species. We describe five cases of crèche-aged American White Pelican chicks consuming or attempting to consume dead younger chicks at two nesting colonies in the northern plains of North America. Cannibalism in the American White Pelican appears to be rare and likely plays no role in the species’ population ecology or dynamics; however, it might be an important survival strategy of individual chicks when food resources are limited.

VANET Clustering Based Routing Protocol Suitable for Deserts.

PubMed

Nasr, Mohammed Mohsen Mohammed; Abdelgader, Abdeldime Mohamed Salih; Wang, Zhi-Gong; Shen, Lian-Feng

2016-04-06

In recent years, there has emerged applications of vehicular ad hoc networks (VANETs) towards security, safety, rescue, exploration, military and communication redundancy systems in non-populated areas, besides its ordinary use in urban environments as an essential part of intelligent transportation systems (ITS). This paper proposes a novel algorithm for the process of organizing a cluster structure and cluster head election (CHE) suitable for VANETs. Moreover, it presents a robust clustering-based routing protocol, which is appropriate for deserts and can achieve high communication efficiency, ensuring reliable information delivery and optimal exploitation of the equipment on each vehicle. A comprehensive simulation is conducted to evaluate the performance of the proposed CHE and routing algorithms.

VANET Clustering Based Routing Protocol Suitable for Deserts

PubMed Central

Mohammed Nasr, Mohammed Mohsen; Abdelgader, Abdeldime Mohamed Salih; Wang, Zhi-Gong; Shen, Lian-Feng

2016-01-01

In recent years, there has emerged applications of vehicular ad hoc networks (VANETs) towards security, safety, rescue, exploration, military and communication redundancy systems in non-populated areas, besides its ordinary use in urban environments as an essential part of intelligent transportation systems (ITS). This paper proposes a novel algorithm for the process of organizing a cluster structure and cluster head election (CHE) suitable for VANETs. Moreover, it presents a robust clustering-based routing protocol, which is appropriate for deserts and can achieve high communication efficiency, ensuring reliable information delivery and optimal exploitation of the equipment on each vehicle. A comprehensive simulation is conducted to evaluate the performance of the proposed CHE and routing algorithms. PMID:27058539

CheD: chemical database compilation tool, Internet server, and client for SQL servers.

PubMed

Trepalin, S V; Yarkov, A V

2001-01-01

An efficient program, which runs on a personal computer, for the storage, retrieval, and processing of chemical information, is presented, The program can work both as a stand-alone application or in conjunction with a specifically written Web server application or with some standard SQL servers, e.g., Oracle, Interbase, and MS SQL. New types of data fields are introduced, e.g., arrays for spectral information storage, HTML and database links, and user-defined functions. CheD has an open architecture; thus, custom data types, controls, and services may be added. A WWW server application for chemical data retrieval features an easy and user-friendly installation on Windows NT or 95 platforms.

Calcium Sulfates at Gale Crater and Limitations on Gypsum Stability

NASA Technical Reports Server (NTRS)

Vantiman, D. T.; Martinez, G. M.; Rampe, E. B.; Bristow, T. F.; Blake, D. F.; Yen, A. H.; Ming, D. W.; Rapin, W.; Meslin, P. -Y.; Morookian, J. M.;

Color Histogram Diffusion for Image Enhancement

NASA Technical Reports Server (NTRS)

Kim, Taemin

2011-01-01

Various color histogram equalization (CHE) methods have been proposed to extend grayscale histogram equalization (GHE) for color images. In this paper a new method called histogram diffusion that extends the GHE method to arbitrary dimensions is proposed. Ranges in a histogram are specified as overlapping bars of uniform heights and variable widths which are proportional to their frequencies. This diagram is called the vistogram. As an alternative approach to GHE, the squared error of the vistogram from the uniform distribution is minimized. Each bar in the vistogram is approximated by a Gaussian function. Gaussian particles in the vistoram diffuse as a nonlinear autonomous system of ordinary differential equations. CHE results of color images showed that the approach is effective.

[Effect of altitude chronic hypoxia on liver enzymes and its correlation with ACE/ACE2 in yak and migrated cattle].

PubMed

Liu, Feng-yun; Hu, Lin; Li, Yu-xian; Liu, Shi-ming; Tang, Yong-ping; Qi, Sheng-gui; Yang, Lei; Wu, Tian-yi

2015-05-01

To investigate the difference of liver enzyme levels and its correlation with serum ACE/ACE2 among yak and cattle on Qinghai-Tibetan plateau, and to further explore the biochemical mechanism of their liver of altitude adaptation. The serum samples of yak were collected at 3,000 m, 3,500 m, 4,000 m and 4,300 m respectively, meanwhile the serum samples of migrated cattle on plateau (2,500 m) and lowland cattle (1,300 m) were also collected. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholinesterase (CHE), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), serum lipase (LPS), angiotensin converting enzyme(ACE), angiotensin converting enzyme-2 (ACE2) in serum were measured by using fully automatic blood biochemcal analyzer. We analysed the differences of the above enzymes and its correlation with ACE/ACE2. We used one way analysis of variance (ANOVA). The levels of ALT in 4,000 m group and 4,300 m group of yak increased significantly compared with other groups, there were no statistically significant differences in AST, CHE, GGT, ACE/ACE2 levels of yaks at different altitudes. As compared to lowland cattle, the serum levels of AST and CHE were increased, the level of LPS and ACE was decreased significantly, respectively, and especially, the ratio of ACE/ACE2 of migranted cattle reduced nearly two times. The levels of LPS were significantly correlated to the ratio of ACE/ACE2 in yak (r = 0.357, P < 0.01), and a high correlation between ALP and ACE/ACE2 in lowland cattle( r = 0.418, P < 0.05), But the biggest contribution rate of the ratio of ACE/ACE2 was only 17.5% for the changes of the levels of liver enzyme. The results indicated that with the altitude increased did not significantly influence the changes of liver enzymes' activities in mountainous yaks but not in cattle. However, all above these changes weren't actually correlated to the ratio of ACE/ACE2.

Pros and cons of the health transformation program in Iran: evidence from financial outcomes at the household level.

PubMed

Homaie Rad, Enayatollah; Yazdi-Feyzabad, Vahid; Yousefzadeh-Chabok, Shahrokh; Afkar, Abolhasan; Naghibzadeh, Ahmad

2017-01-01

The health transformation program was a recent reform in the health system of Iran that was implemented in early 2014. Some of the program's important goals were to improve the equity of payments and to reduce out-of-pocket (OOP) payments and catastrophic health expenditures (CHE). In this study, these goals were evaluated using a before-and-after analysis. Data on household income and expenditures in Guilan Province were gathered for the years 2013 and 2015. OOP payments for outpatient, inpatient, and drug services were calculated, and the results were compared using the propensity score matching technique after adjusting for confounding variables. Concentration indices and curves were added to quantify changes in inequity before and after the reform. The incidence of catastrophic expenditures was then calculated. Overall and outpatient service OOP payments increased by approximately 10 dollars, while for other types of services, no significant changes were found. Inequity and utilization of services did not change after the reform. However, a significant reduction was observed in CHE incidence (5.75 to 3.82%). The reform was successful in decreasing the incidence of CHE, but not in reducing the monetary amount of OOP payments or affecting the frequency of health service utilization.

Conjugates of magnetic nanoparticle-actinide specific chelator for radioactive waste separation.

PubMed

Kaur, Maninder; Zhang, Huijin; Martin, Leigh; Todd, Terry; Qiang, You

2013-01-01

A novel nanotechnology for the separation of radioactive waste that uses magnetic nanoparticles (MNPs) conjugated with actinide specific chelators (MNP-Che) is reviewed with a focus on design and process development. The MNP-Che separation process is an effective way of separating heat generating minor actinides (Np, Am, Cm) from spent nuclear fuel solution to reduce the radiological hazard. It utilizes coated MNPs to selectively adsorb the contaminants onto their surfaces, after which the loaded particles are collected using a magnetic field. The MNP-Che conjugates can be recycled by stripping contaminates into a separate, smaller volume of solution, and then become the final waste form for disposal after reusing number of times. Due to the highly selective chelators, this remediation method could be both simple and versatile while allowing the valuable actinides to be recovered and recycled. Key issues standing in the way of large-scale application are stability of the conjugates and their dispersion in solution to maintain their unique properties, especially large surface area, of MNPs. With substantial research progress made on MNPs and their surface functionalization, as well as development of environmentally benign chelators, this method could become very flexible and cost-effective for recycling used fuel. Finally, the development of this nanotechnology is summarized and its future direction is discussed.

Pros and cons of the health transformation program in Iran: evidence from financial outcomes at the household level

PubMed Central

2017-01-01

OBJECTIVES The health transformation program was a recent reform in the health system of Iran that was implemented in early 2014. Some of the program’s important goals were to improve the equity of payments and to reduce out-of-pocket (OOP) payments and catastrophic health expenditures (CHE). In this study, these goals were evaluated using a before-and-after analysis. METHODS Data on household income and expenditures in Guilan Province were gathered for the years 2013 and 2015. OOP payments for outpatient, inpatient, and drug services were calculated, and the results were compared using the propensity score matching technique after adjusting for confounding variables. Concentration indices and curves were added to quantify changes in inequity before and after the reform. The incidence of catastrophic expenditures was then calculated. RESULTS Overall and outpatient service OOP payments increased by approximately 10 dollars, while for other types of services, no significant changes were found. Inequity and utilization of services did not change after the reform. However, a significant reduction was observed in CHE incidence (5.75 to 3.82%). CONCLUSIONS The reform was successful in decreasing the incidence of CHE, but not in reducing the monetary amount of OOP payments or affecting the frequency of health service utilization. PMID:28728347

Isotopic Composition of Carbon Dioxide Released from Confidence Hills Sediment as Measured by the Sample Analysis at Mars (SAM) Quadrupole Mass Spectrometer

NASA Technical Reports Server (NTRS)

Franz, H. B.; Mahaffy, P. R.; Stern, J.; Archer, P., Jr.; Conrad, P.; Eigenbrode, J.; Freissinet, C.; Glavin, D.; Grotzinger, J. P.; Jones, J.;

Defining Specificity Determinants of cGMP Mediated Gustatory Sensory Transduction in Caenorhabditis elegans

PubMed Central

Smith, Heidi K.; Luo, Linjiao; O’Halloran, Damien; Guo, Dagang; Huang, Xin-Yun; Samuel, Aravinthan D. T.; Hobert, Oliver

2013-01-01

Cyclic guanosine monophosphate (cGMP) is a key secondary messenger used in signal transduction in various types of sensory neurons. The importance of cGMP in the ASE gustatory receptor neurons of the nematode Caenorhabditis elegans was deduced by the observation that multiple receptor-type guanylyl cyclases (rGCs), encoded by the gcy genes, and two presently known cyclic nucleotide-gated ion channel subunits, encoded by the tax-2 and tax-4 genes, are essential for ASE-mediated gustatory behavior. We describe here specific mechanistic features of cGMP-mediated signal transduction in the ASE neurons. First, we assess the specificity of the sensory functions of individual rGC proteins. We have previously shown that multiple rGC proteins are expressed in a left/right asymmetric manner in the functionally lateralized ASE neurons and are required to sense distinct salt cues. Through domain swap experiments among three different rGC proteins, we show here that the specificity of individual rGC proteins lies in their extracellular domains and not in their intracellular, signal-transducing domains. Furthermore, we find that rGC proteins are also sufficient to confer salt sensory responses to other neurons. Both findings support the hypothesis that rGC proteins are salt receptor proteins. Second, we identify a novel, likely downstream effector of the rGC proteins in gustatory signal transduction, a previously uncharacterized cyclic nucleotide-gated (CNG) ion channel, encoded by the che-6 locus. che-6 mutants show defects in gustatory sensory transduction that are similar to defects observed in animals lacking the tax-2 and tax-4 CNG channels. In contrast, thermosensory signal transduction, which also requires tax-2 and tax-4, does not require che-6, but requires another CNG, cng-3. We propose that CHE-6 may form together with two other CNG subunits, TAX-2 and TAX-4, a gustatory neuron-specific heteromeric CNG channel complex. PMID:23695300

Motility and Chemotaxis Mediate the Preferential Colonization of Gastric Injury Sites by Helicobacter pylori

PubMed Central

Aihara, Eitaro; Closson, Chet; Matthis, Andrea L.; Schumacher, Michael A.; Engevik, Amy C.; Zavros, Yana; Ottemann, Karen M.; Montrose, Marshall H.

2014-01-01

Helicobacter pylori (H. pylori) is a pathogen contributing to peptic inflammation, ulceration, and cancer. A crucial step in the pathogenic sequence is when the bacterium first interacts with gastric tissue, an event that is poorly understood in vivo. We have shown that the luminal space adjacent to gastric epithelial damage is a microenvironment, and we hypothesized that this microenvironment might enhance H. pylori colonization. Inoculation with 106 H. pylori (wild-type Sydney Strain 1, SS1) significantly delayed healing of acetic-acid induced ulcers at Day 1, 7 and 30 post-inoculation, and wild-type SS1 preferentially colonized the ulcerated area compared to uninjured gastric tissue in the same animal at all time points. Gastric resident Lactobacillus spp. did not preferentially colonize ulcerated tissue. To determine whether bacterial motility and chemotaxis are important to ulcer healing and colonization, we analyzed isogenic H. pylori mutants defective in motility (ΔmotB) or chemotaxis (ΔcheY). ΔmotB (106) failed to colonize ulcerated or healthy stomach tissue. ΔcheY (106) colonized both tissues, but without preferential colonization of ulcerated tissue. However, ΔcheY did modestly delay ulcer healing, suggesting that chemotaxis is not required for this process. We used two-photon microscopy to induce microscopic epithelial lesions in vivo, and evaluated accumulation of fluorescently labeled H. pylori at gastric damage sites in the time frame of minutes instead of days. By 5 min after inducing damage, H. pylori SS1 preferentially accumulated at the site of damage and inhibited gastric epithelial restitution. H. pylori ΔcheY modestly accumulated at the gastric surface and inhibited restitution, but did not preferentially accumulate at the injury site. H. pylori ΔmotB neither accumulated at the surface nor inhibited restitution. We conclude that bacterial chemosensing and motility rapidly promote H. pylori colonization of injury sites, and thereby biases the injured tissue towards sustained gastric damage. PMID:25033386

Motility and chemotaxis mediate the preferential colonization of gastric injury sites by Helicobacter pylori.

PubMed

Aihara, Eitaro; Closson, Chet; Matthis, Andrea L; Schumacher, Michael A; Engevik, Amy C; Zavros, Yana; Ottemann, Karen M; Montrose, Marshall H

2014-07-01

Helicobacter pylori (H. pylori) is a pathogen contributing to peptic inflammation, ulceration, and cancer. A crucial step in the pathogenic sequence is when the bacterium first interacts with gastric tissue, an event that is poorly understood in vivo. We have shown that the luminal space adjacent to gastric epithelial damage is a microenvironment, and we hypothesized that this microenvironment might enhance H. pylori colonization. Inoculation with 106 H. pylori (wild-type Sydney Strain 1, SS1) significantly delayed healing of acetic-acid induced ulcers at Day 1, 7 and 30 post-inoculation, and wild-type SS1 preferentially colonized the ulcerated area compared to uninjured gastric tissue in the same animal at all time points. Gastric resident Lactobacillus spp. did not preferentially colonize ulcerated tissue. To determine whether bacterial motility and chemotaxis are important to ulcer healing and colonization, we analyzed isogenic H. pylori mutants defective in motility (ΔmotB) or chemotaxis (ΔcheY). ΔmotB (10(6)) failed to colonize ulcerated or healthy stomach tissue. ΔcheY (10(6)) colonized both tissues, but without preferential colonization of ulcerated tissue. However, ΔcheY did modestly delay ulcer healing, suggesting that chemotaxis is not required for this process. We used two-photon microscopy to induce microscopic epithelial lesions in vivo, and evaluated accumulation of fluorescently labeled H. pylori at gastric damage sites in the time frame of minutes instead of days. By 5 min after inducing damage, H. pylori SS1 preferentially accumulated at the site of damage and inhibited gastric epithelial restitution. H. pylori ΔcheY modestly accumulated at the gastric surface and inhibited restitution, but did not preferentially accumulate at the injury site. H. pylori ΔmotB neither accumulated at the surface nor inhibited restitution. We conclude that bacterial chemosensing and motility rapidly promote H. pylori colonization of injury sites, and thereby biases the injured tissue towards sustained gastric damage.

Detecting Nanophase Weathering Products with CheMin: Reference Intensity Ratios of Allophane, Aluminosilicate Gel, and Ferrihydrite

NASA Technical Reports Server (NTRS)

Rampe, E. B.; Bish, D. L.; Chipera, S. J.; Morris, R. V.; Achilles, C. N.; Ming, D W.; Blake, D. F.; Anderson, R. C.; Bristow, T. F.; Crisp, A.;