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Sample records for activity tests showed

  1. 4. VIEW SOUTHWEST COMPONENTS TEST LAB TEST BAY DETAIL SHOWING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. VIEW SOUTHWEST COMPONENTS TEST LAB TEST BAY DETAIL SHOWING EMERGENCY SHOWER, AND EYEWASH, AND OBSERVATION WINDOW. STORAGE TANKS ON ROOF. - Marshall Space Flight Center, East Test Area, Components Test Laboratory, Huntsville, Madison County, AL

  2. 1. VIEW EAST, COMPONENTS TEST LABORATORY SHOWING CATCH BASINS, TURBINE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. VIEW EAST, COMPONENTS TEST LABORATORY SHOWING CATCH BASINS, TURBINE TESTING AREA, AND PUMP TESTING TOWER. - Marshall Space Flight Center, East Test Area, Components Test Laboratory, Huntsville, Madison County, AL

  3. Tetrahydrobiopterin shows chaperone activity for tyrosine hydroxylase.

    PubMed

    Thöny, Beat; Calvo, Ana C; Scherer, Tanja; Svebak, Randi M; Haavik, Jan; Blau, Nenad; Martinez, Aurora

    2008-07-01

    Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the synthesis of catecholamine neurotransmitters. Primary inherited defects in TH have been associated with l-DOPA responsive and non-responsive dystonia and infantile parkinsonism. In this study, we show that both the cofactor (6R)-l-erythro-5,6,7,8-tetrahydrobiopterin (BH(4)) and the feedback inhibitor and catecholamine product dopamine increase the kinetic stability of human TH isoform 1 in vitro. Activity measurements and synthesis of the enzyme by in vitro transcription-translation revealed a complex regulation by the cofactor including both enzyme inactivation and conformational stabilization. Oral BH(4) supplementation to mice increased TH activity and protein levels in brain extracts, while the Th-mRNA level was not affected. All together our results indicate that the molecular mechanisms for the stabilization are a primary folding-aid effect of BH(4) and a secondary effect by increased synthesis and binding of catecholamine ligands. Our results also establish that orally administered BH(4) crosses the blood-brain barrier and therapeutic regimes based on BH(4) supplementation should thus consider the effect on TH. Furthermore, BH(4) supplementation arises as a putative therapeutic agent in the treatment of brain disorders associated with TH misfolding, such as for the human TH isoform 1 mutation L205P.

  4. Serving Up Activities for TV Cooking Shows.

    ERIC Educational Resources Information Center

    Katchen, Johanna E.

    This paper documents a presentation given on the use of English-language television cooking shows in English-as-a-Second-Language (ESL) and English-as-a-Foreign-Language (EFL) classrooms in Taiwan. Such shows can be ideal for classroom use, since they have a predictable structure consisting of short segments, are of interest to most students,…

  5. Surveys show support for green 'activities'.

    PubMed

    Baillie, Jonathan

    2012-03-01

    Two independently conducted surveys on sustainability - one into the 'views and values' of NHS 'leaders', and the other questioning the public about the importance of the 'green agenda' in the NHS, and their opinions on how the service might most effectively reduce its carbon footprint, form the basis of Sustainability in the NHS: Health Check 2012, a new NHS Sustainable Development Unit (NHS SDU) publication. As HEJ editor Jonathan Baillie reports, the new document also presents updated data on the 'size' of the carbon footprint of the NHS in England, showing that, although good work by a number of Trusts in the past two years has seen healthcare-generated carbon emissions start to 'level off', the biggest contributors have been the current health service spending review, and the increased national availability of renewable energy.

  6. Detail of east side of Test Sand 'A' base, showing ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail of east side of Test Sand 'A' base, showing flame deflector at bottom of stand. Stairs and handrails were added after test stand was converted to test propellant flow in components as opposed to firing rocket engines. - Jet Propulsion Laboratory Edwards Facility, Test Stand A, Edwards Air Force Base, Boron, Kern County, CA

  7. 17. Building 202, observation room for test cell, showing panel, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    17. Building 202, observation room for test cell, showing panel, abort button, phones, and observation window. View looking northwest. - Rocket Engine Testing Facility, GRC Building No. 202, NASA Glenn Research Center, Cleveland, Cuyahoga County, OH

  8. Coagulation tests show significant differences in patients with breast cancer.

    PubMed

    Tas, Faruk; Kilic, Leyla; Duranyildiz, Derya

    2014-06-01

    Activated coagulation and fibrinolytic system in cancer patients is associated with tumor stroma formation and metastasis in different cancer types. The aim of this study is to explore the correlation of blood coagulation assays for various clinicopathologic factors in breast cancer patients. A total of 123 female breast cancer patients were enrolled into the study. All the patients were treatment naïve. Pretreatment blood coagulation tests including PT, APTT, PTA, INR, D-dimer, fibrinogen levels, and platelet counts were evaluated. Median age of diagnosis was 51 years old (range 26-82). Twenty-two percent of the group consisted of metastatic breast cancer patients. The plasma level of all coagulation tests revealed statistically significant difference between patient and control group except for PT (p<0.001 for all variables except for PT; p=0.08). Elderly age (>50 years) was associated with higher D-dimer levels (p=0.003). Metastatic patients exhibited significantly higher D-dimer values when compared with early breast cancer patients (p=0.049). Advanced tumor stage (T3 and T4) was associated with higher INR (p=0.05) and lower PTA (p=0.025). In conclusion, coagulation tests show significant differences in patients with breast cancer.

  9. Detail of north side of Test Stand 'A' base, showing ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail of north side of Test Stand 'A' base, showing tanks for distilled water (left), fuel (center), and gaseous nitrogen (right). Other tanks present for tests were removed before this image was taken. - Jet Propulsion Laboratory Edwards Facility, Test Stand A, Edwards Air Force Base, Boron, Kern County, CA

  10. 2. ROCKET ENGINE TEST STAND, SHOWING TANK (BUILDING 1929) AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. ROCKET ENGINE TEST STAND, SHOWING TANK (BUILDING 1929) AND GARAGE (BUILDING 1930) AT LEFT REAR. Looking to west. - Edwards Air Force Base, X-15 Engine Test Complex, Rocket Engine & Complete X-15 Vehicle Test Stands, Rogers Dry Lake, east of runway between North Base & South Base, Boron, Kern County, CA

  11. 3. EAST SIDE, ALSO SHOWING COVERED TANKS AND TEST STAND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. EAST SIDE, ALSO SHOWING COVERED TANKS AND TEST STAND 1-5 AT RIGHT. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Test Stand 1-4, Test Area 1-115, northwest end of Saturn Boulevard, Boron, Kern County, CA

  12. 39. Historic photo of Building 202 test cell exterior, showing ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    39. Historic photo of Building 202 test cell exterior, showing fiberglass cladding blown out by hydrogen fire during rocket engine testing, April 27, 1959. On file at NASA Plumbrook Research Center, Sandusky, Ohio. NASA photo number C-50472. - Rocket Engine Testing Facility, GRC Building No. 202, NASA Glenn Research Center, Cleveland, Cuyahoga County, OH

  13. 38. Historic photo of Building 202 test cell interior, showing ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    38. Historic photo of Building 202 test cell interior, showing damage to test stand A and rocket engine after failure and explosion of engine, December 12, 1958. On file at NASA Plumbrook Research Center, Sandusky, Ohio. NASA photo number C-49376. - Rocket Engine Testing Facility, GRC Building No. 202, NASA Glenn Research Center, Cleveland, Cuyahoga County, OH

  14. 1. Photographic copy of engineering drawing showing structure of Test ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Photographic copy of engineering drawing showing structure of Test Stand 'B' (4215/E-16), also known as the 'Short Snorter.' California Institute of Technology, Jet Propulsion Laboratory, Plant Engineering 'Structural Addition - Bldg. E-12, Edwards Test Station,' drawing no. E12/1-1, 8 August 1957. - Jet Propulsion Laboratory Edwards Facility, Test Stand B, Edwards Air Force Base, Boron, Kern County, CA

  15. 8. LOW OBLIQUE AERIAL VIEW OF TEST AREA 1115, SHOWING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. LOW OBLIQUE AERIAL VIEW OF TEST AREA 1-115, SHOWING TEST STANDS 1-5, 1-4, AND 1-3 (LEFT TO RIGHT). - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Leuhman Ridge near Highways 58 & 395, Boron, Kern County, CA

  16. 18. INTERIOR VIEW INSIDE BUNKER DURING PREPARATIONS FOR TEST. SHOWS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    18. INTERIOR VIEW INSIDE BUNKER DURING PREPARATIONS FOR TEST. SHOWS TWO OPERATORS, INCLUDING ONE AIR FORCE MAN, INSTRUMENT PANEL, EQUIPMENT, MONITORING SCREENS, AND OTHER EQUIPMENT, SOME OF IT NAMED (IE, 'GALVANOMETER,' 'HONEYWELL,' 'KODAC.' INEL PHOTO NUMBER 65-6180, TAKEN NOVEMBER 10, 1965. - Idaho National Engineering Laboratory, Advanced Reentry Vehicle Fusing System, Scoville, Butte County, ID

  17. 12. Exterior view, showing tank and piping associated with Test ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    12. Exterior view, showing tank and piping associated with Test Cell 7, Systems Integration Laboratory Building (T-28), looking west. - Air Force Plant PJKS, Systems Integration Laboratory, Systems Integration Laboratory Building, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

  18. Detail, Face C (rear), showing Interference Analysis System Linear Test ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail, Face C (rear), showing Interference Analysis System Linear Test Array mounted at Level 4A - Beale Air Force Base, Perimeter Acquisition Vehicle Entry Phased-Array Warning System, Techinical Equipment Building, End of Spencer Paul Road, north of Warren Shingle Road (14th Street), Marysville, Yuba County, CA

  19. Could Acoustic Emission Testing Show a Pipe Failure in Advance?

    NASA Astrophysics Data System (ADS)

    Soares, S. D.; Teixeira, J. C. G.

    2004-02-01

    During the last 20 years PETROBRAS has been attempting to use Acoustic Emission (AE) as an inspection tool. In this period the AE concept has changed from a revolutionary method to a way of finding areas to make a complete inspection. PETROBRAS has a lot of pressure vessels inspected by AE and with other NDTs techniques to establish their relationship. In other hand, PETROBRAS R&D Center has conducted destructive hydrostatic tests in pipelines samples with artificial defects made by milling. Those tests were monitored by acoustic emission and manual ultrasonic until the complete failure of pipe sample. This article shows the results obtained and a brief proposal of analysis criteria for this environment of test.

  20. Croton grewioides Baill. (Euphorbiaceae) Shows Antidiarrheal Activity in Mice

    PubMed Central

    da Silva, Anne Dayse Soares; de Melo e Silva, Karoline; Neto, José Clementino; Costa, Vicente Carlos de Oliveira; Pessôa, Hilzeth de Luna F.; Tavares, Josean Fechine; da Silva, Marcelo Sobral; Cavalcante, Fabiana de Andrade

    2016-01-01

    Based on chemotaxonomy, we decided to investigate the possible antidiarrheal activity in mice of a crude ethanolic extract obtained from aerial parts of Croton grewioides (CG-EtOH). We tested for any possible toxicity in rat erythrocytes and acute toxicity in mice. Antidiarrheal activity was assessed by determining the effect of CG-EtOH on defecation frequency, liquid stool, intestinal motility and intestinal fluid accumulation. CG-EtOH showed no in vitro cytotoxicity and was not orally lethal. In contrast, the extract given intraperitoneally (at 2000 mg/kg) was lethal, but only in females. CG-EtOH produced a significant and equipotent antidiarrheal activity, both in defecation frequency (ED50 = 106.0 ± 8.1 mg/kg) and liquid stools (ED50 = 105.0 ± 9.2 mg/kg). However, CG-EtOH (125 mg/kg) decreased intestinal motility by only 22.7% ± 4.4%. Moreover, extract markedly inhibited the castor oil-induced intestinal contents (ED50 = 34.6 ± 5.4 mg/kg). We thus conclude that CG-EtOH is not orally lethal and contains active principles with antidiarrheal activity, and this effect seems to involve mostly changes in intestinal secretion. SUMMARY CG-EtOH showed no in vitro cytotoxicity and was not orally lethal. In contrast, the extract given intraperitoneally (at 2000 mg/kg) was lethal, but only in females.CG-EtOH probably contains active metabolites with antidiarrheal activity.CG-EtOH reduced the frequency and number of liquid stools.Metabolites presents in the CG-EtOH act mainly by reducing intestinal fluid and, to a lesser extent, reducing intestinal motility. Abbreviations Used: CG-EtOH: crude ethanolic extract obtained from the aerial parts of C. grewioides; WHO: World Health Organization; ED50: dose of a drug that produces 50% of its maximum effect; Emax: maximum effect PMID:27365990

  1. Ovalbumin with Glycated Carboxyl Groups Shows Membrane-Damaging Activity

    PubMed Central

    Tang, Ching-Chia; Shi, Yi-Jun; Chen, Ying-Jung; Chang, Long-Sen

    2017-01-01

    The aim of the present study was to investigate whether glycated ovalbumin (OVA) showed novel activity at the lipid-water interface. Mannosylated OVA (Man-OVA) was prepared by modification of the carboxyl groups with p-aminophenyl α-dextro (d)-mannopyranoside. An increase in the number of modified carboxyl groups increased the membrane-damaging activity of Man-OVA on cell membrane-mimicking vesicles, whereas OVA did not induce membrane permeability in the tested phospholipid vesicles. The glycation of carboxyl groups caused a notable change in the gross conformation of OVA. Moreover, owing to their spatial positions, the Trp residues in Man-OVA were more exposed, unlike those in OVA. Fluorescence quenching studies suggested that the Trp residues in Man-OVA were located on the interface binds with the lipid vesicles, and their microenvironment was abundant in positively charged residues. Although OVA and Man-OVA showed a similar binding affinity for lipid vesicles, the lipid-interacting feature of Man-OVA was distinct from that of OVA. Chemical modification studies revealed that Lys and Arg residues, but not Trp residues, played a crucial role in the membrane-damaging activity of Man-OVA. Taken together, our data suggest that glycation of carboxyl groups causes changes in the structural properties and membrane-interacting features of OVA, generating OVA with membrane-perturbing activities at the lipid-water interface. PMID:28264493

  2. Fluvoxamine, a new antidepressant drug, fails to show antiserotonin activity.

    PubMed

    Maj, J; Rogóz, Z; Skuza, G

    1982-07-09

    Fluvoxamine, (E)-5-methoxy-4'-(trifluoromethyl)valerophenone O-2(2-aminoethyl)oxime, a new antidepressant drug inhibiting serotonin (5-HT) uptake, was studied in rats and mice in order to check whether it has any central anti-5-HT activity, as do some tricyclic antidepressants, e.g. amitriptyline and doxepin. Fluvoxamine did not influence either the 5-hydroxytryptophan-induced head twitch response in mice or the tryptamine convulsions in rats. In the hind limb flexor reflex of the spinal rat the stimulation induced by fenfluramine was inhibited, that induced by LSD was not changed. Fluvoxamine also antagonized the hyperthermia (at ambient temperature of 28 degrees C), induced in rats by fenfluramine or p-chloroamphetamine. The hyperthermia caused by m-chlorophenylpiperazine was not inhibited. Fluvoxamine did not antagonize the 5-HT pressor effect in pithed rats. It has no effect on the immobility time in the behavioural despair test in rats. The results indicate that fluvoxamine fails to show anti-5-HT activity.

  3. Tests show that aluminum welds are improved by bead removal

    NASA Technical Reports Server (NTRS)

    Hood, D. W.

    1967-01-01

    Tests with 2218-T87 aluminum alloy plate indicate improvements in strength, ductility, fatigue properties, and burst pressure result when one or both of the top and bottom weld beads are removed. There is, however, a drop in yield strength. The consistency of test data is considerably improved by weld bead removal.

  4. 1. TEST STAND 1A ENVIRONS, SHOWING WEST SIDE OF TEST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. TEST STAND 1-A ENVIRONS, SHOWING WEST SIDE OF TEST STAND 1-A, RP1 COMBINED FUEL STORAGE TANK FARM BELOW WATER TANKS ON HILLSIDE TO LEFT, AND TEST STAND 1-B IN DISTANCE AT RIGHT. Looking east. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Test Stand 1-A, Test Area 1-120, north end of Jupiter Boulevard, Boron, Kern County, CA

  5. Tests show production logging problems in horizontal gas wells

    SciTech Connect

    Branagan, P. ); Knight, B.L. ); Aslakson, J. ); Middlebrook, M.L. )

    1994-01-10

    A study has concluded that production logging tools employed to evaluate multiphase horizontal well production behavior should be carefully screened as to their response characteristics in fully-segregated, two-phase flow. The study, performed at Marathon Oil Co.'s petroleum technology center in Littleton, Colo., indicated that gas in highly deviated well bores segregates rapidly in the presence of water, creating a downhole environment that produces sporadic responses from full bore and diverter spinners as well as density and holdup tools. Gas Research Institute (GRI), as part of its horizontal gas well completion technology program, initiated the full-scale laboratory study to determine the severity and consequences of multiphase flow on tool response from horizontal well production. The paper discusses background of the problem, the test objectives, test facility, experimental procedures, single-phase flow, two-phase flow, and recommendations.

  6. Liquefaction tests show promise, but DOE budget promises cuts

    SciTech Connect

    Kaplan, D.

    1993-06-02

    Low-rank Western coal, abundant in supply but stingy in heating value, could suddenly become a vital ingredient in the nation's energy mix if an Energy Department clean coal project can build on its initial success. TEL-KOL Partnership's ENCOAL Corp. of Gillette, Wy., reported that after 16-days of tests in April, 5,000 tons of low-grade coal were successfully converted into a fuel oil substitute and a low-moisture coal. The Liquids from Coal Process, developed by SGI International Corp., takes the principle behind oil refining-extracting different fuels from one energy source - and applies it to coal. Using high-moisture, low-sulfur coal, the process is designed to produce three fuels: A low-sulfur, high-energy coal; a low-sulfur No. 6 feedstock oil for boiler fuel or refinery feedstock; and a gas byproduct to power the plant. Using computer and sensory systems, the technology determines the coal's physical characteristics, and then simultaneously adjusts temperatures and gas flows throughout the coal bed during processing to create desired co-product combinations. Because of its unique ability to control how much of each fuel is produced, the system can be adjusted to yield more of one particular fuel when market conditions are favorable.

  7. Your Library--Greatest Show of All! Activity Manual.

    ERIC Educational Resources Information Center

    Jackson, Mary, Ed.

    Intended as a companion volume for librarians planning a children's summer reading program, this activity manual provides ideas for games, puzzles, puppet shows, story reading, and more, all based on the theme of "Circus Summer." The manual suggests ways to promote the program, such as visits to schools, and provides directions for…

  8. Flight Tests of an Airplane Showing Dependence of the Maximum Lift Coefficient on the Test Conditions

    NASA Technical Reports Server (NTRS)

    Soule, H A; Hootman, James A

    1937-01-01

    Data are presented to show the extent to which the maximum lift coefficient and consequently the minimum speed of an airplane, determined by flight tests, may vary with test conditions. The data show that cl-max may vary as much as 14 percent, depending on the altitude and wing loading at which the tests were made, the position or motion of the propeller, and the rate at which the angle of attack is changing when the maximum lift coefficient is obtained. The variation of the maximum lift coefficient with these factors, which are under the control of the test engineer, shows the need of standardizing the test procedure. A further variation is shown with wing conditions as affected by weathering and vibration, factors that cannot be completely controlled.

  9. Tetrahdroxysqualene from Rhus taitensis Shows Antimycobacterial Activity Against Mycobacterium tuberculosis

    PubMed Central

    Noro, Jeffrey C.; Barrows, Louis R.; Gideon, Osia G.; Ireland, Chris M.; Koch, Michael; Matainaho, Teatulohi; Piskaut, Pius; Pond, Christopher D.; Bugni, Tim S.

    2010-01-01

    Tuberculosis has become a major health problem, in particular with the emergence of extremely drug resistant tuberculosis (XDRTB). In our search for new therapeutic leads against TB, we isolated a new triterpene (1) from the plant Rhus taitensis collected in Papua New Guinea. Tetrahydroxysqualene (1) was isolated using bioassay-guided fractionation of the methanolic extract of R. taitensis leaves and twigs. The structure of tetrahydroxysqualene (1) was elucidated on the basis of HRESIMS and 1D and 2D NMR spectra. Tetrahydroxysqualene (1) exhibited anti–tuberculosis activity with an MIC of 10.0 μg/mL while showing only modest cytotoxicity. PMID:18710283

  10. Extracts of marine algae show inhibitory activity against osteoclast differentiation.

    PubMed

    Koyama, Tomoyuki

    2011-01-01

    Osteoclasts are multinucleated cells that play a crucial role in bone resorption. The imbalance between bone resorption and bone formation results in osteoporosis. Therefore, substances that can suppress osteoclast formation are potential candidate materials for drug development or functional foods. There have been reports that extracts or purified compounds from marine micro- and macroalgae can suppress osteoclast differentiation. Symbioimine, isolated from the cultured dinoflagellate Symbiodinium sp., had suppressive effects against osteoclast differentiation in osteoclast-like cells. Norzoanthamine, isolated from the colonial zoanthid Zoanthas sp., has been shown to have antiosteoporosis activity in ovariectomized mice. With regard to marine extracts, the fucoxanthin-rich component from brown algae has been shown to have suppressive effects against osteoclast differentiation. An extract of Sargassum fusiforme has recently been shown to have antiosteoporosis activity. This extract suppressed both osteoclast differentiation and accelerated osteoblast formation in separate in vitro experiments. It also showed antiosteoporosis activity in ovariectomized mice by regulating the balance between bone resorption and bone formation. These marine algae and their extracts may be sources of marine medicinal foods for the prevention of osteoporosis.

  11. The Oral Antimalarial Drug Tafenoquine Shows Activity against Trypanosoma brucei

    PubMed Central

    Carvalho, Luis; Martínez-García, Marta; Pérez-Victoria, Ignacio; Manzano, José Ignacio; Yardley, Vanessa

    2015-01-01

    The protozoan parasite Trypanosoma brucei causes human African trypanosomiasis, or sleeping sickness, a neglected tropical disease that requires new, safer, and more effective treatments. Repurposing oral drugs could reduce both the time and cost involved in sleeping sickness drug discovery. Tafenoquine (TFQ) is an oral antimalarial drug belonging to the 8-aminoquinoline family which is currently in clinical phase III. We show here that TFQ efficiently kills different T. brucei spp. in the submicromolar concentration range. Our results suggest that TFQ accumulates into acidic compartments and induces a necrotic process involving cell membrane disintegration and loss of cytoplasmic content, leading to parasite death. Cell lysis is preceded by a wide and multitarget drug action, affecting the lysosome, mitochondria, and acidocalcisomes and inducing a depolarization of the mitochondrial membrane potential, elevation of intracellular Ca2+, and production of reactive oxygen species. This is the first report of an 8-aminoquinoline demonstrating significant in vitro activity against T. brucei. PMID:26195527

  12. A novel nucleic acid analogue shows strong angiogenic activity

    SciTech Connect

    Tsukamoto, Ikuko; Sakakibara, Norikazu; Maruyama, Tokumi; Igarashi, Junsuke; Kosaka, Hiroaki; Kubota, Yasuo; Tokuda, Masaaki; Ashino, Hiromi; Hattori, Kenichi; Tanaka, Shinji; Kawata, Mitsuhiro; Konishi, Ryoji

    2010-09-03

    Research highlights: {yields} A novel nucleic acid analogue (2Cl-C.OXT-A, m.w. 284) showed angiogenic potency. {yields} It stimulated the tube formation, proliferation and migration of HUVEC in vitro. {yields} 2Cl-C.OXT-A induced the activation of ERK1/2 and MEK in HUVEC. {yields} Angiogenic potency in vivo was confirmed in CAM assay and rabbit cornea assay. {yields} A synthesized small angiogenic agent would have great clinical therapeutic value. -- Abstract: A novel nucleic acid analogue (2Cl-C.OXT-A) significantly stimulated tube formation of human umbilical endothelial cells (HUVEC). Its maximum potency at 100 {mu}M was stronger than that of vascular endothelial growth factor (VEGF), a positive control. At this concentration, 2Cl-C.OXT-A moderately stimulated proliferation as well as migration of HUVEC. To gain mechanistic insights how 2Cl-C.OXT-A promotes angiogenic responses in HUVEC, we performed immunoblot analyses using phospho-specific antibodies as probes. 2Cl-C.OXT-A induced robust phosphorylation/activation of MAP kinase ERK1/2 and an upstream MAP kinase kinase MEK. Conversely, a MEK inhibitor PD98059 abolished ERK1/2 activation and tube formation both enhanced by 2Cl-C.OXT-A. In contrast, MAP kinase responses elicited by 2Cl-C.OXT-A were not inhibited by SU5416, a specific inhibitor of VEGF receptor tyrosine kinase. Collectively these results suggest that 2Cl-C.OXT-A-induces angiogenic responses in HUVEC mediated by a MAP kinase cascade comprising MEK and ERK1/2, but independently of VEGF receptor tyrosine kinase. In vivo assay using chicken chorioallantoic membrane (CAM) and rabbit cornea also suggested the angiogenic potency of 2Cl-C.OXT-A.

  13. High-Resolution Observations of a Filament showing Activated Barb

    NASA Astrophysics Data System (ADS)

    Joshi, Anand; Martin, Sara F.; Mathew, Shibu; Srivastava, Nandita

    2012-07-01

    Analysis of a filament showing an activated barb using observations from the Dutch Open Telescope (DOT) on 2010 August 20 are presented. The DOT takes Doppler images in Hα, among other wavelengths, in a region about 110 × 110 arcsec^{2} in area, at a cadence of 30~seconds. The offline image restoration technique of speckle reconstruction is applied to obtain diffraction limited images. The filament developed a new barb in 10~minutes, which disappeared within the next 35~minutes. Such a rapid formation and disappearance of a filament barb is unusual, and has not been reported earlier. Line-of-sight velocity maps were constructed from the Doppler images of the target filament. We observe flows in the filament spine towards the barb location prior to its formation, and flows in the barb towards the spine during its disappearance. Photospheric magnetograms from Heliospheric Magnetic Imager on board the Solar Dynamics Observatory, at a cadence of 45~seconds, were used to determine the changes in magnetic flux in the region surrounding the barb location. The variation of magnetic flux in this duration supports the view that barbs are rooted in minor magnetic polarity. Our analysis shows that barbs can be short-lived and formation and disappearance of the barb was associated with cancellation of magnetic flux.

  14. Silver nanoparticles synthesised using plant extracts show strong antibacterial activity.

    PubMed

    Kumari, Avnesh; Guliani, Anika; Singla, Rubbel; Yadav, Ramdhan; Yadav, Sudesh Kumar

    2015-06-01

    In this study, three plants Populus alba, Hibiscus arboreus and Lantana camara were explored for the synthesis of silver nanoparticles (SNPs). The effect of reaction temperature and leaf extract (LE) concentration of P. alba, H. arboreus and L. camara was evaluated on the synthesis and size of SNPs. The SNPs were characterised by ultra-violet-visible spectroscopy, scanning electron microscopy and atomic force microscopy. The synthesis rate of SNPs was highest with LE of L. camara followed by H. arboreus and P. alba under similar conditions. L. camara LE showed maximum potential of smaller size SNPs synthesis, whereas bigger particles were formed by H. arboreous LE. The size and shape of L. camara LE synthesised SNPs were analysed by transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDX). TEM analysis revealed the formation of SNPs of average size 17±9.5 nm with 5% LE of L. camara. The SNPs synthesised by LE of L. camara showed strong antibacterial activity against Escherichia coli. The results document that desired size SNPs can be synthesised using these plant LEs at a particular temperature for applications in the biomedical field.

  15. Computationally designed variants of Escherichia coli chorismate mutase show altered catalytic activity.

    PubMed

    Lassila, Jonathan Kyle; Keeffe, Jennifer R; Oelschlaeger, Peter; Mayo, Stephen L

    2005-04-01

    Computational protein design methods were used to predict five variants of monofunctional Escherichia coli chorismate mutase expected to maintain catalytic activity. The variants were tested experimentally and three active site mutants exhibited catalytic activity similar to or greater than the wild-type enzyme. One mutant, Ala32Ser, showed increased catalytic efficiency.

  16. NASA's Fermi Shows How Active Galaxies Can Be

    NASA Video Gallery

    Active galaxies called blazars make up the largest class of objects detected by Fermi's Large Area Telescope (LAT). Massive black holes in the hearts of these galaxies fire particle jets in our dir...

  17. An active principle of Nigella sativa L., thymoquinone, showing significant antimicrobial activity against anaerobic bacteria

    PubMed Central

    Randhawa, Mohammad Akram; Alenazy, Awwad Khalaf; Alrowaili, Majed Gorayan; Basha, Jamith

    2017-01-01

    Aim/Background: Thymoquinone (TQ) is the major active principle of Nigella sativa seed (black seed) and is known to control many fungi, bacteria, and some viruses. However, the activity of TQ against anaerobic bacteria is not well demonstrated. Anaerobic bacteria can cause severe infections, including diarrhea, aspiration pneumonia, and brain abscess, particularly in immunodeficient individuals. The present study aimed to investigate the in vitro antimicrobial activity of TQ against some anaerobic pathogens in comparison to metronidazole. Methods: Standard, ATCC, strains of four anaerobic bacteria (Clostridium difficile, Clostridium perfringens, Bacteroides fragilis, and Bacteroides thetaiotaomicron), were initially isolated on special Brucella agar base (with hemin and vitamin K). Then, minimum inhibitory concentrations (MICs) of TQ and metronidazole were determined against these anaerobes when grown in Brucella agar, using serial agar dilution method according to the recommended guidelines for anaerobic organisms instructed by the Clinical and Laboratory Standards Institute. Results: TQ showed a significant antimicrobial activity against anaerobic bacteria although much weaker than metronidazole. MICs of TQ and metronidazole against various anaerobic human pathogens tested were found to be between 10-160 mg/L and 0.19-6.25 mg/L, respectively. Conclusions: TQ controlled the anaerobic human pathogenic bacteria, which supports the use of N. sativa in the treatment of diarrhea in folk medicine. Further investigations are in need for determination of the synergistic effect of TQ in combination with metronidazole and the activity of derivatives of TQ against anaerobic infections. PMID:28163966

  18. Psychopaths Show Enhanced Amygdala Activation during Fear Conditioning.

    PubMed

    Schultz, Douglas H; Balderston, Nicholas L; Baskin-Sommers, Arielle R; Larson, Christine L; Helmstetter, Fred J

    2016-01-01

    Psychopathy is a personality disorder characterized by emotional deficits and a failure to inhibit impulsive behavior and is often subdivided into "primary" and "secondary" psychopathic subtypes. The maladaptive behavior related to primary psychopathy is thought to reflect constitutional "fearlessness," while the problematic behavior related to secondary psychopathy is motivated by other factors. The fearlessness observed in psychopathy has often been interpreted as reflecting a fundamental deficit in amygdala function, and previous studies have provided support for a low-fear model of psychopathy. However, many of these studies fail to use appropriate screening procedures, use liberal inclusion criteria, or have used unconventional approaches to assay amygdala function. We measured brain activity with BOLD imaging in primary and secondary psychopaths and non-psychopathic control subjects during Pavlovian fear conditioning. In contrast to the low-fear model, we observed normal fear expression in primary psychopaths. Psychopaths also displayed greater differential BOLD activity in the amygdala relative to matched controls. Inverse patterns of activity were observed in the anterior cingulate cortex (ACC) for primary versus secondary psychopaths. Primary psychopaths exhibited a pattern of activity in the dorsal and ventral ACC consistent with enhanced fear expression, while secondary psychopaths exhibited a pattern of activity in these regions consistent with fear inhibition. These results contradict the low-fear model of psychopathy and suggest that the low fear observed for psychopaths in previous studies may be specific to secondary psychopaths.

  19. Psychopaths Show Enhanced Amygdala Activation during Fear Conditioning

    PubMed Central

    Schultz, Douglas H.; Balderston, Nicholas L.; Baskin-Sommers, Arielle R.; Larson, Christine L.; Helmstetter, Fred J.

    2016-01-01

    Psychopathy is a personality disorder characterized by emotional deficits and a failure to inhibit impulsive behavior and is often subdivided into “primary” and “secondary” psychopathic subtypes. The maladaptive behavior related to primary psychopathy is thought to reflect constitutional “fearlessness,” while the problematic behavior related to secondary psychopathy is motivated by other factors. The fearlessness observed in psychopathy has often been interpreted as reflecting a fundamental deficit in amygdala function, and previous studies have provided support for a low-fear model of psychopathy. However, many of these studies fail to use appropriate screening procedures, use liberal inclusion criteria, or have used unconventional approaches to assay amygdala function. We measured brain activity with BOLD imaging in primary and secondary psychopaths and non-psychopathic control subjects during Pavlovian fear conditioning. In contrast to the low-fear model, we observed normal fear expression in primary psychopaths. Psychopaths also displayed greater differential BOLD activity in the amygdala relative to matched controls. Inverse patterns of activity were observed in the anterior cingulate cortex (ACC) for primary versus secondary psychopaths. Primary psychopaths exhibited a pattern of activity in the dorsal and ventral ACC consistent with enhanced fear expression, while secondary psychopaths exhibited a pattern of activity in these regions consistent with fear inhibition. These results contradict the low-fear model of psychopathy and suggest that the low fear observed for psychopaths in previous studies may be specific to secondary psychopaths. PMID:27014154

  20. Show and Tell: An Appreciation of "Making" Activities.

    ERIC Educational Resources Information Center

    Kozolanka, Karne

    This paper describes the incorporation of a "making" activity as part of a course for education majors at Queen's Faculty of Education of the University of Regina (Saskatchewan, Canada). The course was an introductory one in which students explored the methods and merits of outdoor and experiential education. Each student was given a…

  1. Conjugation of ovotransferrin with catechin shows improved antioxidant activity.

    PubMed

    You, Juan; Luo, Yongkang; Wu, Jianping

    2014-03-26

    Ovotransferrin (OTF), representing 12-13% of the total egg white, is a member of transferrin family with antimicrobial and antioxidant activities. Catechin is a polyphenolic antioxidant found in green tea. The objective of the study was to conjugate ovotransferrin with catechin to improve the antioxidant activity of OTF. Conjugates were prepared either by the free radical method using hydrogen peroxide-ascorbic acid as the initiator or by the alkaline method at pH of 9.0. The oxygen-radical-scavenging effect was increased from 3.95 mol trolox equivalent (TE)/mol of ovotransferrin to 22.80 and 17.14 mol TE/mol sample, respectively, in radical and alkaline prepared conjugates, which indicated that conjugation with catechin is an effective way to improve antioxidant activity of the protein. Conjugation between ovotransferrin and catechin was analyzed by fluorescence analyses, ultra performance liquid chromatography, matrix-assisted laser desorption ionization time-of-flight mass spectrometry and liquid chromatography coupled online to a tandem mass spectrometer. Catechin was covalently bound to lysine (residues 327) and glutamic acid (residues 186) in ovotransferrin. The ovotransferrin-catechin conjugate may have a potential application as a functional food and nutraceutical ingredient.

  2. Insurance Applications of Active Fault Maps Showing Epistemic Uncertainty

    NASA Astrophysics Data System (ADS)

    Woo, G.

    2005-12-01

    Insurance loss modeling for earthquakes utilizes available maps of active faulting produced by geoscientists. All such maps are subject to uncertainty, arising from lack of knowledge of fault geometry and rupture history. Field work to undertake geological fault investigations drains human and monetary resources, and this inevitably limits the resolution of fault parameters. Some areas are more accessible than others; some may be of greater social or economic importance than others; some areas may be investigated more rapidly or diligently than others; or funding restrictions may have curtailed the extent of the fault mapping program. In contrast with the aleatory uncertainty associated with the inherent variability in the dynamics of earthquake fault rupture, uncertainty associated with lack of knowledge of fault geometry and rupture history is epistemic. The extent of this epistemic uncertainty may vary substantially from one regional or national fault map to another. However aware the local cartographer may be, this uncertainty is generally not conveyed in detail to the international map user. For example, an area may be left blank for a variety of reasons, ranging from lack of sufficient investigation of a fault to lack of convincing evidence of activity. Epistemic uncertainty in fault parameters is of concern in any probabilistic assessment of seismic hazard, not least in insurance earthquake risk applications. A logic-tree framework is appropriate for incorporating epistemic uncertainty. Some insurance contracts cover specific high-value properties or transport infrastructure, and therefore are extremely sensitive to the geometry of active faulting. Alternative Risk Transfer (ART) to the capital markets may also be considered. In order for such insurance or ART contracts to be properly priced, uncertainty should be taken into account. Accordingly, an estimate is needed for the likelihood of surface rupture capable of causing severe damage. Especially where a

  3. Trajectory Hunting: Analysis of UARS Measurements showing Rapid Chlorine Activation

    NASA Technical Reports Server (NTRS)

    Danilin, M.Y.; Santee, M. L.; Rodriquez, J. M.; Ko, M. K. W.; Mergenthaler, J. M.; Kumer, J. B.; Tabazadeh, A.

    1998-01-01

    Trajectory hunting (i.e., a technique to find air parcels sampled at least twice over the course of a few days) is applied to analyze Upper Atmosphere Research Satellite (UARS) measurements in conjunction with the AER photochemical box model. In this study, we investigate rapid chlorine activation in the Arctic lower stratosphere on 29 Dec 1992 associated with a polar stratospheric cloud (PSC) event. Six air parcels that have been sampled twice were followed along 5-day trajectories at the 465 K (approximately 46 mb) and 585 K (approximately 22 mb) levels. A detailed sensitivity study with the AER. photochemical box model along these trajectories leads to the following conclusions for the episode considered: (1) model results are in better agreement with UARS measurements at these levels if the UKMO temperature is decreased by at least 1-2 K; (2) the NAT (nitric acid trihydrate) PSC formation scheme produces results in better agreement with observations than the STS (supercooled ternary solution) scheme; (3) the model can explain the UARS measurements at 585 K, but under-estimates the ClO abundance at 465 K, suggesting some inconsistency between the UARS measurements at this level.

  4. Trajectory Hunting: Analysis of UARS Measurements Showing Rapid Chlorine Activation

    NASA Technical Reports Server (NTRS)

    Danilin, M. Y.; Santee, M. L.; Rodriquez, J. M.; Ko, M. K. W.; Mergenthaler, J. M.; Kumer, J. B.; Tabazadeh, A.

    1998-01-01

    Trajectory hunting (i.e., a technique to find air parcels sampled at least twice over the course of a few days) is applied to analyze Upper Atmosphere Research Satellite (UARS) measurements in conjunction with the AER photochemical box model. In this study, we investigate rapid chlorine activation in the Arctic lower stratosphere on 29 Dec. 1992 associated with a polar stratospheric cloud (PSC) event. Six air parcels that have been sampled twice were followed along 5-day trajectories at the 465 K (approx. 46 mb) and 585 K (approxi. 22 mb) levels. A detailed sensitivity study with the AER photochemical box model along these trajectories leads to the following conclusions for the episode considered: 1) model results are in better agreement with UARS measurements at these levels if the U.K. Meteorological Office (UKMO) temperature is decreased by at least 1-2 K; 2) the NAT (nitric acid trihydrate) PSC formation scheme produces results in better agreement with observations than the STS (supercooled ternary solution) scheme; 3) the model can explain the UARS measurements at 585 K, but under-estimates the ClO abundance at 465 K, suggesting some inconsistency between the UARS measurements at this level.

  5. Sulfur dioxide - Episodic injection shows evidence for active Venus volcanism

    NASA Astrophysics Data System (ADS)

    Esposito, L. W.

    1984-03-01

    Pioneer Venus ultraviolet spectra from the first 5 years of operation show a decline (by more than a factor of 10) in sulfur dioxide abundance at the cloud tops and in the amount of submicron haze above the clouds. At the time of the Pioneer Venus encounter, the values for both parameters greatly exceeded earlier upper limits. However, Venus had a similar appearance in the late 1950's, implying the episodic injection of sulfur dioxide possibly caused by episodic volcanism. The amount of haze in the Venus middle atmosphere is about ten times that found in earth's stratosphere after the most recent major volcanic eruptions, and the thermal energy required for this injection on Venus is greater by about an order of magnitude than the largest of these recent earth eruptions and about as large as the Krakatoa eruption of 1883. The episodic behavior of sulfur dioxide implies that steady-state models of the chemistry and dynamics of cloud-top regions may be of limited use.

  6. Sulfur dioxide - Episodic injection shows evidence for active Venus volcanism

    NASA Technical Reports Server (NTRS)

    Esposito, L. W.

    1984-01-01

    Pioneer Venus ultraviolet spectra from the first 5 years of operation show a decline (by more than a factor of 10) in sulfur dioxide abundance at the cloud tops and in the amount of submicron haze above the clouds. At the time of the Pioneer Venus encounter, the values for both parameters greatly exceeded earlier upper limits. However, Venus had a similar appearance in the late 1950's, implying the episodic injection of sulfur dioxide possibly caused by episodic volcanism. The amount of haze in the Venus middle atmosphere is about ten times that found in earth's stratosphere after the most recent major volcanic eruptions, and the thermal energy required for this injection on Venus is greater by about an order of magnitude than the largest of these recent earth eruptions and about as large as the Krakatoa eruption of 1883. The episodic behavior of sulfur dioxide implies that steady-state models of the chemistry and dynamics of cloud-top regions may be of limited use.

  7. 8. X15 ENGINE TESTING. A color print showing the engine ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. X-15 ENGINE TESTING. A color print showing the engine during test firing. View from the rear of the test stand looking northwest. - Edwards Air Force Base, X-15 Engine Test Complex, Rocket Engine & Complete X-15 Vehicle Test Stands, Rogers Dry Lake, east of runway between North Base & South Base, Boron, Kern County, CA

  8. 7. BUILDING 604F, INTERIOR OF BULL PEN SHOWING TESTING STAND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. BUILDING 604-F, INTERIOR OF BULL PEN SHOWING TESTING STAND AND HEAVY WOOD LINING ON CONCRETE WALLS. STEEL PLATE ABOVE TEST STAND DEFLECTS SHRAPNEL, SCREEN FURTHER HELPS TO CONTAIN PARTICLES. ONLY SMALL EXPLOSIVES WERE TESTED HERE (GRENADES, MINES, BOMB FUZES, ETC.). - Picatinny Arsenal, 600 Area, Test Areas District, State Route 15 near I-80, Dover, Morris County, NJ

  9. Testing Tests on Active Galactic Nucleus Microvariability

    NASA Astrophysics Data System (ADS)

    de Diego, José A.

    2010-03-01

    Literature on optical and infrared microvariability in active galactic nuclei (AGNs) reflects a diversity of statistical tests and strategies to detect tiny variations in the light curves of these sources. Comparison between the results obtained using different methodologies is difficult, and the pros and cons of each statistical method are often badly understood or even ignored. Even worse, improperly tested methodologies are becoming more and more common, and biased results may be misleading with regard to the origin of the AGN microvariability. This paper intends to point future research on AGN microvariability toward the use of powerful and well-tested statistical methodologies, providing a reference for choosing the best strategy to obtain unbiased results. Light curves monitoring has been simulated for quasars and for reference and comparison stars. Changes for the quasar light curves include both Gaussian fluctuations and linear variations. Simulated light curves have been analyzed using χ2 tests, F tests for variances, one-way analyses of variance and C-statistics. Statistical Type I and Type II errors, which indicate the robustness and the power of the tests, have been obtained in each case. One-way analyses of variance and χ2 prove to be powerful and robust estimators for microvariations, while the C-statistic is not a reliable methodology and its use should be avoided.

  10. TESTING TESTS ON ACTIVE GALACTIC NUCLEI MICROVARIABILITY

    SciTech Connect

    De Diego, Jose A.

    2010-03-15

    Literature on optical and infrared microvariability in active galactic nuclei (AGNs) reflects a diversity of statistical tests and strategies to detect tiny variations in the light curves of these sources. Comparison between the results obtained using different methodologies is difficult, and the pros and cons of each statistical method are often badly understood or even ignored. Even worse, improperly tested methodologies are becoming more and more common, and biased results may be misleading with regard to the origin of the AGN microvariability. This paper intends to point future research on AGN microvariability toward the use of powerful and well-tested statistical methodologies, providing a reference for choosing the best strategy to obtain unbiased results. Light curves monitoring has been simulated for quasars and for reference and comparison stars. Changes for the quasar light curves include both Gaussian fluctuations and linear variations. Simulated light curves have been analyzed using {chi}{sup 2} tests, F tests for variances, one-way analyses of variance and C-statistics. Statistical Type I and Type II errors, which indicate the robustness and the power of the tests, have been obtained in each case. One-way analyses of variance and {chi}{sup 2} prove to be powerful and robust estimators for microvariations, while the C-statistic is not a reliable methodology and its use should be avoided.

  11. Antibodies to meningococcal H.8 (Lip) antigen fail to show bactericidal activity.

    PubMed

    Bhattacharjee, A K; Moran, E E; Zollinger, W D

    1990-02-01

    Purified H.8 (Lip) antigen was coupled to tresyl-activated Sepharose 4B and used in affinity columns to purify anti-Lip antibodies from convalescent patient sera and from immune rabbit sera. Affinity-purified anti-Lip antibodies isolated from two convalescent patient sera contained 1000 and 1280 ELISA units of antibody and included antibodies of IgG, IgA, and IgM isotypes. An anti-Lip mouse monoclonal ascites (2-1-CA2) had 28,400 ELISA units of antibody. Bactericidal assays were performed using three different case strains of Neisseria meningitidis group B, namely 44/76, 8532, and 8047. Neither preparation of purified human anti-Lip antibodies had detectable bactericidal activity against strains 44/76 and 8532, but one of the two had a titer of 1:4 against strain 8047. Anti-Lip antibodies that were purified from immune rabbit serum and contained 1600 ELISA units of anti-Lip antibodies also failed to show detectable bactericidal activity. The rabbits were immunized with purified Lip antigen and showed specific antibody levels of 2000-2200 units by ELISA, but even the unfractionated sera had little or no bactericidal activity against the test strains. The high titer mouse monoclonal ascites had no bactericidal activity against the test strains. The poor bactericidal activity associated with monoclonal and polyclonal antibodies to the Lip antigen suggest that in spite of other attractive properties it may not be useful as a meningococcal vaccine.

  12. 3. INTERIOR VIEW, SHOWING JET ENGINE TEST STAND. WrightPatterson ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. INTERIOR VIEW, SHOWING JET ENGINE TEST STAND. - Wright-Patterson Air Force Base, Area B, Building 71A, Propulsion Research Laboratory, Seventh Street between D & G Streets, Dayton, Montgomery County, OH

  13. 95. ARAIV. Aerial view of ML1. Shows test and control ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    95. ARA-IV. Aerial view of ML-1. Shows test and control buildings, berms, fencing. March 14, 1963. Ineel photo no. 63-1666. - Idaho National Engineering Laboratory, Army Reactors Experimental Area, Scoville, Butte County, ID

  14. Investigating CSI: portrayals of DNA testing on a forensic crime show and their potential effects.

    PubMed

    Ley, Barbara L; Jankowski, Natalie; Brewer, Paul R

    2012-01-01

    The popularity of forensic crime shows such as CSI has fueled debate about their potential social impact. This study considers CSI's potential effects on public understandings regarding DNA testing in the context of judicial processes, the policy debates surrounding crime laboratory procedures, and the forensic science profession, as well as an effect not discussed in previous accounts: namely, the show's potential impact on public understandings of DNA and genetics more generally. To develop a theoretical foundation for research on the "CSI effect," it draws on cultivation theory, social cognitive theory, and audience reception studies. It then uses content analysis and textual analysis to illuminate how the show depicts DNA testing. The results demonstrate that CSI tends to depict DNA testing as routine, swift, useful, and reliable and that it echoes broader discourses about genetics. At times, however, the show suggests more complex ways of thinking about DNA testing and genetics.

  15. LPT. Shield test facility (TAN645) interior. Boiler room shows one ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    LPT. Shield test facility (TAN-645) interior. Boiler room shows one boiler, diesel electric stand unit, and related equipment. Pumice block walls. Photographer: Jack L. Anderson. Date: January 19, 1959. INEEL negative no. 59-286 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

  16. New Eugenol Glucoside-based Derivative Shows Fungistatic and Fungicidal Activity against Opportunistic Candida glabrata.

    PubMed

    de Souza, Thiago Belarmino; Brito, Keila Mercês de Oliveira; Silva, Naiara Chaves; Rocha, Raissa Prado; de Sousa, Grasiely Faria; Duarte, Lucienir Pains; Coelho, Luiz Felipe Leomil; Dias, Amanda Latércia Tranches; Veloso, Marcia Paranho; Carvalho, Diogo Teixeira; Dias, Danielle Ferreira

    2016-01-01

    A new series of glucosides modified in their saccharide units were synthesized, evaluated against Candida sp., and compared to prototype 1, an eugenol tetracetyl glucoside previously synthesized and shown to be active against Candida glabrata. Among the new glucosides, benzyl derivative 5 was the most promising, showing fungistatic activity at IC50 18.1 μm against Candida glabrata (threefold higher than fluconazole) and fungicidal activity with a low IC90 value of 36.2 μm. Moreover, the cytotoxic activity of compound 5 (CC50 : 580.9 μm), tested in peripheral blood mononuclear cells, suggests its potential as an agent to treat Candida glabrata infections, with a selectivity index of 32. The new eugenol glucoside 5 may be considered as a novel structural pattern in the development of new anti-Candida drugs.

  17. Satellite microglia show spontaneous electrical activity that is uncorrelated with activity of the attached neuron.

    PubMed

    Wogram, Emile; Wendt, Stefan; Matyash, Marina; Pivneva, Tatyana; Draguhn, Andreas; Kettenmann, Helmut

    2016-06-01

    Microglia are innate immune cells of the brain. We have studied a subpopulation of microglia, called satellite microglia. This cell type is defined by a close morphological soma-to-soma association with a neuron, indicative of a direct functional interaction. Indeed, ultrastructural analysis revealed closely attached plasma membranes of satellite microglia and neurons. However, we found no apparent morphological specializations of the contact, and biocytin injection into satellite microglia showed no dye-coupling with the apposed neurons or any other cell. Likewise, evoked local field potentials or action potentials and postsynaptic potentials of the associated neuron did not lead to any transmembrane currents or non-capacitive changes in the membrane potential of the satellite microglia in the cortex and hippocampus. Both satellite and non-satellite microglia, however, showed spontaneous transient membrane depolarizations that were not correlated with neuronal activity. These events could be divided into fast-rising and slow-rising depolarizations, which showed different characteristics in satellite and non-satellite microglia. Fast-rising and slow-rising potentials differed with regard to voltage dependence. The frequency of these events was not affected by the application of tetrodotoxin, but the fast-rising event frequency decreased after application of GABA. We conclude that microglia show spontaneous electrical activity that is uncorrelated with the activity of adjacent neurons.

  18. LPT. Shield test facility (TAN645 and 646). Elevations show three ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    LPT. Shield test facility (TAN-645 and -646). Elevations show three types of siding: Asbestos cement, pumice block, concrete. Ralph M. Parsons 1229-17 ANP/GE-6-6445-A-3. April 1957. Approved by INEEL Classification Office for public release. INEEL index code no. 037-06445/0646-00-693-107349 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

  19. LPT. Shield test facility (TAN645 and 646). Sections show relationships ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    LPT. Shield test facility (TAN-645 and -646). Sections show relationships among control rooms, coupling station, counting rooms, pools, equipment rooms, data room and other areas. Ralph M. Parsons 1229-17 ANP/GE-6-645-A-4. April 1957. Approved by INEEL Classification Office for public release. INEEL index code no. 037-0645/0646-00-693-107350 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

  20. Plant crude extracts could be the solution: extracts showing in vivo antitumorigenic activity.

    PubMed

    Amara, A A; El-Masry, M H; Bogdady, H H

    2008-04-01

    Screening active compounds from plants lead to discover new medicinal drugs which have efficient protection and treatment roles against various diseases including cancer. In our study, extracts from different plants represent seeds of: Gossypium barbadense, Ricinus communis, Sesamum indicum, Nigella sativa, Vinca rosea and Melia azedarah; fruits of: Xanthium occidental; flowers of: Atriplex nummularia; barks of: Cinnamomum zeylanicum; latex of: Ficus carica and rhizomes of: Curcuma longa and Zingiber officinale were tested in vivo using three subsequent bioassays: the BST (Brine Shrimp Toxicity bioassay), AWD (Agar well diffusion antimicrobial bioassay) and AtPDT (Agrobacterium tumefaciens Potato Disc Tumor bioassay). AWD technique omitted any extracts have antimicrobial activities while BST omitted any extract did not has physiological activity and determined the various LC(50) of each plant extract. For the first time, using a range of concentrations in the AtPDT modified protocol allowed the detection of tumor promotion caused by extract represented by A. nummularia. Using cluster analysis leads to classifying the different plant extracts activities to six groups regarding to their toxicity, antitumor activities and both of them. The extracts from edible plants represent 50% of the first and the second group which have the highest antitumor activities represented in F. caraica (group 1) and C. longa (group 2) as well as the non-edible plant extracts of Gossypium barbadense and Ricinus communis. A comparison study between the edible and herbaceous plants different extracts for their antitumor activities was performed. We recommended using the modified protocols used in this study for investigating more plants and using crude plant extracts which have antitumor activities in cancer treatment. Edible plants, which show in vivo antitumor activities, are recommended as save sources for antitumor compounds.

  1. A Paradox of Syntactic Priming: Why Response Tendencies Show Priming for Passives, and Response Latencies Show Priming for Actives

    PubMed Central

    Segaert, Katrien; Menenti, Laura; Weber, Kirsten; Hagoort, Peter

    2011-01-01

    Speakers tend to repeat syntactic structures across sentences, a phenomenon called syntactic priming. Although it has been suggested that repeating syntactic structures should result in speeded responses, previous research has focused on effects in response tendencies. We investigated syntactic priming effects simultaneously in response tendencies and response latencies for active and passive transitive sentences in a picture description task. In Experiment 1, there were priming effects in response tendencies for passives and in response latencies for actives. However, when participants' pre-existing preference for actives was altered in Experiment 2, syntactic priming occurred for both actives and passives in response tendencies as well as in response latencies. This is the first investigation of the effects of structure frequency on both response tendencies and latencies in syntactic priming. We discuss the implications of these data for current theories of syntactic processing. PMID:22022352

  2. Sterols from Mytilidae show anti-aging and neuroprotective effects via anti-oxidative activity.

    PubMed

    Sun, Yujuan; Lin, Yanfei; Cao, Xueli; Xiang, Lan; Qi, Jianhua

    2014-11-25

    For screening anti-aging samples from marine natural products, K6001 yeast strain was employed as a bioassay system. The active mussel extract was separated to give an active sterol fraction (SF). SF was further purified, and four sterol compounds were obtained. Their structures were determined to be cholesterol (CHOL), brassicasterol, crinosterol, and 24-methylenecholesterol. All compounds showed similar anti-aging activity. To understand the action mechanism involved, anti-oxidative experiments, reactive oxygen species (ROS) assays, and malondialdehyde (MDA) tests were performed on the most abundant compound, CHOL. Results indicated that treatment with CHOL increases the survival rate of yeast under oxidative stress and decreases ROS and MDA levels. In addition, mutations of uth1, skn7, sod1, and sod2, which feature a K6001 background, were employed and the lifespans of the mutations were not affected by CHOL. These results demonstrate that CHOL exerts anti-aging effects via anti-oxidative stress. Based on the connection between neuroprotection and anti-aging, neuroprotective experiments were performed in PC12 cells. Paraquat was used to induce oxidative stress and the results showed that the CHOL and SF protect the PC12 cells from the injury induced by paraquat. In addition, these substance exhibited nerve growth factor (NGF) mimic activities again confirmed their neuroprotective function.

  3. Guppies Show Behavioural but Not Cognitive Sex Differences in a Novel Object Recognition Test

    PubMed Central

    Lucon-Xiccato, Tyrone; Dadda, Marco

    2016-01-01

    The novel object recognition (NOR) test is a widely-used paradigm to study learning and memory in rodents. NOR performance is typically measured as the preference to interact with a novel object over a familiar object based on spontaneous exploratory behaviour. In rats and mice, females usually have greater NOR ability than males. The NOR test is now available for a large number of species, including fish, but sex differences have not been properly tested outside of rodents. We compared male and female guppies (Poecilia reticulata) in a NOR test to study whether sex differences exist also for fish. We focused on sex differences in both performance and behaviour of guppies during the test. In our experiment, adult guppies expressed a preference for the novel object as most rodents and other species do. When we looked at sex differences, we found the two sexes showed a similar preference for the novel object over the familiar object, suggesting that male and female guppies have similar NOR performances. Analysis of behaviour revealed that males were more inclined to swim in the proximity of the two objects than females. Further, males explored the novel object at the beginning of the experiment while females did so afterwards. These two behavioural differences are possibly due to sex differences in exploration. Even though NOR performance is not different between male and female guppies, the behavioural sex differences we found could affect the results of the experiments and should be carefully considered when assessing fish memory with the NOR test. PMID:27305102

  4. Task Control Signals in Pediatric Tourette Syndrome Show Evidence of Immature and Anomalous Functional Activity

    PubMed Central

    Church, Jessica A.; Wenger, Kristin K.; Dosenbach, Nico U. F.; Miezin, Francis M.; Petersen, Steven E.; Schlaggar, Bradley L.

    2009-01-01

    Tourette Syndrome (TS) is a pediatric movement disorder that may affect control signaling in the brain. Previous work has proposed a dual-networks architecture of control processing involving a task-maintenance network and an adaptive control network (Dosenbach et al., 2008). A prior resting-state functional connectivity MRI (rs-fcMRI) analysis in TS has revealed functional immaturity in both putative control networks, with “anomalous” correlations (i.e., correlations outside the typical developmental range) limited to the adaptive control network (Church et al., 2009). The present study used functional MRI (fMRI) to study brain activity related to adaptive control (by studying start-cues signals), and to task-maintenance (by studying signals sustained across a task set). Two hypotheses from the previous rs-fcMRI results were tested. First, adaptive control (i.e., start-cue) activity will be altered in TS, including activity inconsistent with typical development (“anomalous”). Second, group differences found in task-maintenance (i.e., sustained) activity will be consistent with functional immaturity in TS. We examined regions found through a direct comparison of adolescents with and without TS, as well as regions derived from a previous investigation that showed differences between unaffected children and adults. The TS group showed decreased start-cue signal magnitude in regions where start-cue activity is unchanged over typical development, consistent with anomalous adaptive control. The TS group also had higher magnitude sustained signals in frontal cortex regions that overlapped with regions showing differences over typical development, consistent with immature task-maintenance in TS. The results demonstrate task-related fMRI signal differences anticipated by the atypical functional connectivity found previously in adolescents with TS, strengthening the evidence for functional immaturity and anomalous signaling in control networks in adolescents with TS

  5. First laboratory perforating tests in coal show lower-than-expected penetration

    SciTech Connect

    Snider, P.M.; Walton, I.C.; Skinner, T.K.; Atwood, D.C.; Grove, B.M.; Graham, C.

    2008-06-15

    Worldwide Coal Bed Methane (CBM) resources are huge, estimated at 3,000 to 9,000 Tcf. The production rate from CBM reservoirs is low, perhaps 50-100 mcf/day. Various completion methods are being evaluated and new technologies are being developed with the aim of increasing production rates. Considering this interest and activity level, little attention has been paid to the CBM completion fundamentals. Perforating is a critical part of this process, especially considering the PRB development migration from single-coal, open-hole completions into multi-zone, cased-hole completions. This paper describes the first known laboratory-testing program to investigate shaped charge penetration in coal targets. We describe mechanical properties of the coals tested, and penetration results for different shaped charges (of different designs), shot at various stress conditions. CT scan and cutaway imaging of the perforation tunnels are also discussed. Tests were conducted under dry and saturated conditions. The preliminary experiments reported here indicate that shaped charge penetration in coal is significantly less than expected, considering the target's density and strength. The authors provide insight into what may be the reasons for these unexpected results and recommend a path forward for shaped charge testing, designs, predictive tools, and how to optimize CBM completions.

  6. Children who stutter show reduced action-related activity in the rostral cingulate zone.

    PubMed

    Harrewijn, A; Schel, M A; Boelens, H; Nater, C M; Haggard, P; Crone, E A

    2017-02-01

    Previous studies have indicated that children who stutter show not only speech-related problems, but also wider difficulties in self-control. In this study we test the novel hypothesis that children who stutter may experience difficulties with inhibitory control over voluntary actions. We used functional MRI to compare brain activity between children who stutter and children who do not stutter in a task that captures key cognitive aspects of voluntary action control. Participants performed a rolling marble task, in which they were instructed to press a key to stop a rolling marble from crashing on some of the trials (instructed action condition). They were also asked to choose voluntarily whether to execute or inhibit this prepotent response in other trials (volition condition). Children who stutter reported less motor and cognitive impulsivity and had shorter stop-signal reaction times when controlled for IQ, consistent with greater inhibition, compared to children who do not stutter. At the neural level, children who stutter showed decreased activation in the rostral cingulate zone during voluntary action selection compared to children who do not stutter. This effect was more pronounced for children who were rated as showing more stuttered syllables in the stutter screening, and was furthermore correlated with stop-signal reaction times and impulsivity ratings. These findings suggest that stuttering in childhood could reflect wider difficulties in self-control, also in the non-verbal domain. Understanding these neural mechanisms could potentially lead to more focused treatments of stuttering.

  7. Vv-AMP1, a ripening induced peptide from Vitis vinifera shows strong antifungal activity

    PubMed Central

    de Beer, Abré; Vivier, Melané A

    2008-01-01

    Background Latest research shows that small antimicrobial peptides play a role in the innate defense system of plants. These peptides typically contribute to preformed defense by developing protective barriers around germinating seeds or between different tissue layers within plant organs. The encoding genes could also be upregulated by abiotic and biotic stimuli during active defense processes. The peptides display a broad spectrum of antimicrobial activities. Their potent anti-pathogenic characteristics have ensured that they are promising targets in the medical and agricultural biotechnology sectors. Results A berry specific cDNA sequence designated Vv-AMP1, Vitis vinifera antimicrobial peptide 1, was isolated from Vitis vinifera. Vv-AMP1 encodes for a 77 amino acid peptide that shows sequence homology to the family of plant defensins. Vv-AMP1 is expressed in a tissue specific, developmentally regulated manner, being only expressed in berry tissue at the onset of berry ripening and onwards. Treatment of leaf and berry tissue with biotic or abiotic factors did not lead to increased expression of Vv-AMP1 under the conditions tested. The predicted signal peptide of Vv-AMP1, fused to the green fluorescent protein (GFP), showed that the signal peptide allowed accumulation of its product in the apoplast. Vv-AMP1 peptide, produced in Escherichia coli, had a molecular mass of 5.495 kDa as determined by mass spectrometry. Recombinant Vv-AMP1 was extremely heat-stable and showed strong antifungal activity against a broad spectrum of plant pathogenic fungi, with very high levels of activity against the wilting disease causing pathogens Fusarium oxysporum and Verticillium dahliae. The Vv-AMP1 peptide did not induce morphological changes on the treated fungal hyphae, but instead strongly inhibited hyphal elongation. A propidium iodide uptake assay suggested that the inhibitory activity of Vv-AMP1 might be associated with altering the membrane permeability of the fungal

  8. Astronomy Diagnostic Test Results Reflect Course Goals and Show Room for Improvement

    NASA Astrophysics Data System (ADS)

    Lopresto, Michael C.

    The results of administering the Astronomy Diagnostic Test (ADT) to introductory astronomy students at Henry Ford Community College over three years have shown gains comparable with national averages. Results have also accurately corresponded to course goals, showing greater gains in topics covered in more detail, and lower gains in topics covered in less detail. Also evident in the results were topics for which improvement of instruction is needed. These factors and the ease with which the ADT can be administered constitute evidence of the usefulness of the ADT as an assessment instrument for introductory astronomy.

  9. Tannic acid modified silver nanoparticles show antiviral activity in herpes simplex virus type 2 infection.

    PubMed

    Orlowski, Piotr; Tomaszewska, Emilia; Gniadek, Marianna; Baska, Piotr; Nowakowska, Julita; Sokolowska, Justyna; Nowak, Zuzanna; Donten, Mikolaj; Celichowski, Grzegorz; Grobelny, Jaroslaw; Krzyzowska, Malgorzata

    2014-01-01

    The interaction between silver nanoparticles and herpesviruses is attracting great interest due to their antiviral activity and possibility to use as microbicides for oral and anogenital herpes. In this work, we demonstrate that tannic acid modified silver nanoparticles sized 13 nm, 33 nm and 46 nm are capable of reducing HSV-2 infectivity both in vitro and in vivo. The antiviral activity of tannic acid modified silver nanoparticles was size-related, required direct interaction and blocked virus attachment, penetration and further spread. All tested tannic acid modified silver nanoparticles reduced both infection and inflammatory reaction in the mouse model of HSV-2 infection when used at infection or for a post-infection treatment. Smaller-sized nanoparticles induced production of cytokines and chemokines important for anti-viral response. The corresponding control buffers with tannic acid showed inferior antiviral effects in vitro and were ineffective in blocking in vivo infection. Our results show that tannic acid modified silver nanoparticles are good candidates for microbicides used in treatment of herpesvirus infections.

  10. CpG oligodeoxynucleotides with double stem-loops show strong immunostimulatory activity.

    PubMed

    Yang, Liang; Wu, Xiuli; Wan, Min; Yu, Yue; Yu, Yongli; Wang, Liying

    2013-01-01

    Based on the current understanding of TLR9 recognition of CpG ODN, we have tried to design a series of CpG ODNs that display double stem-loops when being analyzed for their secondary structures using 'mfold web server'. Proliferation of human PBMC and bioassay for IFN production were used as technical platforms in primary screening. Interestingly, two of them, designated as DSL01 and D-SL03, belonging to B class CpG ODN and C class CpG ODN respectively, showed vigorous immunostimulatory activity and were chosen for further tests. Flow cytometry analysis showed that both of them could activate human B cells, NK cells, mononuclear cells and T cells and up-regulate expression of CD80, CD86 and HLA-DR on the surface of subsets in human PBMCs. Furthermore, we demonstrated that those two ODNs potently stimulated proliferation of PBMC/splenocytes obtained from diverse vertebrate species. Noticeably, both of them displayed anti-breast cancer effect in mice when administered by peritumoral injection.

  11. Tannic Acid Modified Silver Nanoparticles Show Antiviral Activity in Herpes Simplex Virus Type 2 Infection

    PubMed Central

    Orlowski, Piotr; Tomaszewska, Emilia; Gniadek, Marianna; Baska, Piotr; Nowakowska, Julita; Sokolowska, Justyna; Nowak, Zuzanna; Donten, Mikolaj; Celichowski, Grzegorz; Grobelny, Jaroslaw; Krzyzowska, Malgorzata

    2014-01-01

    The interaction between silver nanoparticles and herpesviruses is attracting great interest due to their antiviral activity and possibility to use as microbicides for oral and anogenital herpes. In this work, we demonstrate that tannic acid modified silver nanoparticles sized 13 nm, 33 nm and 46 nm are capable of reducing HSV-2 infectivity both in vitro and in vivo. The antiviral activity of tannic acid modified silver nanoparticles was size-related, required direct interaction and blocked virus attachment, penetration and further spread. All tested tannic acid modified silver nanoparticles reduced both infection and inflammatory reaction in the mouse model of HSV-2 infection when used at infection or for a post-infection treatment. Smaller-sized nanoparticles induced production of cytokines and chemokines important for anti-viral response. The corresponding control buffers with tannic acid showed inferior antiviral effects in vitro and were ineffective in blocking in vivo infection. Our results show that tannic acid modified silver nanoparticles are good candidates for microbicides used in treatment of herpesvirus infections. PMID:25117537

  12. Active Matrix OLED Test Report

    NASA Technical Reports Server (NTRS)

    Salazar, George

    2013-01-01

    This report focuses on the limited environmental testing of the AMOLED display performed as an engineering evaluation by The NASA Johnson Space Center (JSC)-specifically. EMI. Thermal Vac, and radiation tests. The AMOLED display is an active-matrix Organic Light Emitting Diode (OLED) technology. The testing provided an initial understanding of the technology and its suitability for space applications. Relative to light emitting diode (LED) displays or liquid crystal displays (LCDs), AMOLED displays provide a superior viewing experience even though they are much lighter and smaller, produce higher contrast ratio and richer colors, and require less power to operate than LCDs. However, AMOLED technology has not been demonstrated in a space environment. Therefore, some risks with the technology must be addressed before they can be seriously considered for human spaceflight. The environmental tests provided preliminary performance data on the ability of the display technology to handle some of the simulated induced space/spacecraft environments that an AMOLED display will see during a spacecraft certification test program. This engineering evaluation is part of a Space Act Agreement (SM) between The NASA/JSC and Honeywell International (HI) as a collaborative effort to evaluate the potential use of AMOLED technology for future human spaceflight missions- both government-led and commercial. Under this SM, HI is responsible for doing optical performance evaluation, as well as temperature and touch screen studies. The NASA/JSC is responsible for performing environmental testing comprised of EMI, Thermal Vac, and radiation tests. Additionally, as part of the testing, limited optical data was acquired to assess performance as the display was subjected to the induced environments. The NASA will benefit from this engineering evaluation by understanding AMOLED suitability for future use in space as well as becoming a smarter buyer (or developer) of the technology. HI benefits

  13. Particulate Titanium Matrix Composites Tested--Show Promise for Space Propulsion Applications

    NASA Technical Reports Server (NTRS)

    Lerch, Bradley A.; Ellis, J. Rodney; Arnold. Steven M.

    2004-01-01

    Uniformly distributed particle-strengthened titanium matrix composites (TMCs) can be manufactured at lower cost than many types of continuous-fiber composites. The innovative manufacturing technology combines cold and hot isostatic pressing procedures to produce near-final-shape components. Material stiffness is increased up to 26-percent greater than that of components made with conventional titanium materials at no significant increase in the weight. The improved mechanical performance and low-cost manufacturing capability motivated an independent review to assess the improved properties of ceramic titanium carbide (TiC) particulate-reinforced titanium at elevated temperature. Researchers at the NASA Glenn Research Center creatively designed and executed deformation and durability tests to reveal operating regimes where these materials could lower the cost and weight of space propulsion systems. The program compares the elevated-temperature performance of titanium alloy Ti-6Al-4V matrix material to an alloy containing 10 wt% of TiC particles. Initial experiments showed that at these relatively low particle concentrations the material stiffness of the TMC was improved 20 percent over that of the plain Ti-6Al-4V alloy when tested at 427 C. The proportional limit and ultimate strength of the composite in tension are 21- and 14-percent greater than those of the plain alloy. Compression tests showed that the proportional limit is about 30 percent greater for TMC than for the plain alloy. The enhanced deformation resistance of the TMC was also evident in a series of tensile and compressive stress relaxation tests that were made. Specimens were subjected to tensile or compressive strain amplitudes of 0.75 percent for 24 hr followed by a return to zero strain imposed for 24 hr. The stress relaxation data were normalized with respect to the maximum stress for each case and plotted as a function of time in the following graph. Tensile stresses relaxed 19 percent for the

  14. The metastasis-promoting phosphatase PRL-3 shows activity toward phosphoinositides.

    PubMed

    McParland, Victoria; Varsano, Giulia; Li, Xun; Thornton, Janet; Baby, Jancy; Aravind, Ajay; Meyer, Christoph; Pavic, Karolina; Rios, Pablo; Köhn, Maja

    2011-09-06

    Phosphatase of regenerating liver 3 (PRL-3) is suggested as a biomarker and therapeutic target in several cancers. It has a well-established causative role in cancer metastasis. However, little is known about its natural substrates, pathways, and biological functions, and only a few protein substrates have been suggested so far. To improve our understanding of the substrate specificity and molecular determinants of PRL-3 activity, the wild-type (WT) protein, two supposedly catalytically inactive mutants D72A and C104S, and the reported hyperactive mutant A111S were tested in vitro for substrate specificity and activity toward phosphopeptides and phosphoinositides (PIPs), their structural stability, and their ability to promote cell migration using stable HEK293 cell lines. We discovered that WT PRL-3 does not dephosphorylate the tested phosphopeptides in vitro. However, as shown by two complementary biochemical assays, PRL-3 is active toward the phosphoinositide PI(4,5)P(2). Our experimental results substantiated by molecular docking studies suggest that PRL-3 is a phosphatidylinositol 5-phosphatase. The C104S variant was shown to be not only catalytically inactive but also structurally destabilized and unable to promote cell migration, whereas WT PRL-3 promotes cell migration. The D72A mutant is structurally stable and does not dephosphorylate the unnatural substrate 3-O-methylfluorescein phosphate (OMFP). However, we observed residual in vitro activity of D72A against PI(4,5)P(2), and in accordance with this, it exhibits the same cellular phenotype as WT PRL-3. Our analysis of the A111S variant shows that the hyperactivity toward the unnatural OMFP substrate is not apparent in dephosphorylation assays with phosphoinositides: the mutant is completely inactive against PIPs. We observed significant structural destabilization of this variant. The cellular phenotype of this mutant equals that of the catalytically inactive C104S mutant. These results provide a possible

  15. Alkaloids from the seeds of Peganum harmala showing antiplasmodial and vasorelaxant activities.

    PubMed

    Astulla, Adil; Zaima, Kazumasa; Matsuno, Yosuke; Hirasawa, Yusuke; Ekasari, Wiwied; Widyawaruyanti, Aty; Zaini, Noor Cholies; Morita, Hiroshi

    2008-10-01

    Bioassay-guided purification from the seeds of Peganum harmala led to the isolation of harmine (1), harmaline (2), vasicinone (3), and deoxyvasicinone (4). Harmine (1) and harmaline (2) showed a moderate in vitro antiplasmodial activity against Plasmodium falciparum. Quinazoline alkaloid, vasicinone (3), showed a vasorelaxant activity against phenylephrine-induced contraction of isolated rat aorta.

  16. Acidophilic actinobacteria synthesised silver nanoparticles showed remarkable activity against fungi-causing superficial mycoses in humans.

    PubMed

    Anasane, N; Golińska, P; Wypij, M; Rathod, D; Dahm, H; Rai, M

    2016-03-01

    Superficial mycoses are limited to the most external part of the skin and hair and caused by Malassezia sp., Trichophyton sp. and Candida sp. We report extracellular biosynthesis of silver nanoparticles (AgNPs) by acidophilic actinobacteria (SF23, C9) and its in vitro antifungal activity against fungi-causing superficial mycoses. The phylogenetic analysis based on the 16S rRNA gene sequence of strains SF23 and C9 showed that they are most closely related to Pilimelia columellifera subsp. pallida GU269552(T). The detection of AgNPs was confirmed by visual observation of colour changes from colourless to brown, and UV-vis spectrophotometer analysis, which showed peaks at 432 and 427 nm, respectively. These AgNPs were further characterised by nanoparticle tracking analysis (NTA), Zeta potential, Fourier-transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM). The FTIR analysis exhibited the presence of proteins as capping agents. The TEM analysis revealed the formation of spherical and polydispersed nanoparticles in the size range of 4-36 nm and 8-60 nm, respectively. The biosynthesised AgNPs were screened against fungi-causing superficial mycoses viz., Malassezia furfur, Trichophyton rubrum, Candida albicans and C. tropicalis. The highest antifungal activity of AgNPs from SF23 and C9 against T. rubrum and the least against M. furfur and C. albicans was observed as compared to other tested fungi. The biosynthesised AgNPs were found to be potential anti-antifungal agent against fungi-causing superficial mycoses.

  17. Physically active men show better semen parameters and hormone values than sedentary men.

    PubMed

    Vaamonde, Diana; Da Silva-Grigoletto, Marzo Edir; García-Manso, Juan Manuel; Barrera, Natalibeth; Vaamonde-Lemos, Ricardo

    2012-09-01

    Physical exercise promotes many health benefits. The present study was undertaken to assess possible semen and hormone differences among physically active (PA) subjects and sedentary subjects (SE). The analyzed qualitative sperm parameters were: volume, sperm count, motility, and morphology; where needed, additional testing was performed. The measured hormones were: follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), cortisol (C), and the ratio between T and C (T/C). Maximum oxygen consumption was also assessed to check for differences in fitness level. Statistically significant differences were found for several semen parameters such as total progressive motility (PA: 60.94 ± 5.03; SE: 56.07 ± 4.55) and morphology (PA: 15.54 ± 1.38, SE: 14.40 ± 1.15). The seminological values observed were supported by differences in hormones, with FSH, LH, and T being higher in PA than in SE (5.68 ± 2.51 vs. 3.14 ± 1.84; 5.95 ± 1.11 vs. 5.08 ± 0.98; 7.68 ± 0.77 vs. 6.49 ± 0.80, respectively). Likewise, the T/C ratio, index of anabolic versus catabolic status, was also higher in PA (0.46 ± 0.11 vs. 0.32 ± 0.07), which further supports the possibility of an improved hormonal environment. The present study shows that there are differences in semen and hormone values of physically active subjects and sedentary subjects. Physically active subjects seem to have a more anabolic hormonal environment and a healthier semen production.

  18. How action selection can be embodied: intracranial gamma band recording shows response competition during the Eriksen flankers test

    PubMed Central

    Caruana, Fausto; Uithol, Sebo; Cantalupo, Gaetano; Sartori, Ivana; Lo Russo, Giorgio; Avanzini, Pietro

    2014-01-01

    Recent findings in monkeys suggest that action selection is based on a competition between various action options that are automatically planned by the motor system. Here we discuss data from intracranial EEG recordings in human premotor cortex (PMC) during a bimanual version of the Eriksen flankers test that suggest that the same principles apply to human action decisions. Recording sites in the dorsal PMC show an early but undifferentiated activation, a delayed response that depends on the experimental conditions and, finally, a movement related activation during action execution. Additionally, we found that the medial part of the PMC show a significant increase in response for ipsilateral trials, suggesting a role in inhibiting the wrong response. The ventral PMC seems to be involved in action execution, rather than action selection. Together these findings suggest that the human PMC is part of a network that specifies, selects, and executes actions. PMID:25206328

  19. Boron-10 ABUNCL Active Testing

    SciTech Connect

    Kouzes, Richard T.; Ely, James H.; Lintereur, Azaree T.; Siciliano, Edward R.

    2013-07-09

    The Department of Energy Office of Nuclear Safeguards and Security (NA-241) is supporting the project Coincidence Counting With Boron-Based Alternative Neutron Detection Technology at Pacific Northwest National Laboratory (PNNL) for the development of a 3He proportional counter alternative neutron coincidence counter. The goal of this project is to design, build and demonstrate a system based upon 10B-lined proportional tubes in a configuration typical for 3He-based coincidence counter applications. This report provides results from testing of the active mode of the General Electric Reuter-Stokes Alternative Boron-Based Uranium Neutron Coincidence Collar (ABUNCL) at Los Alamos National Laboratory using sources and fuel pins.

  20. Geothermal reservoir characterization through active thermal testing

    NASA Astrophysics Data System (ADS)

    Jung, Martin; Klepikova, Maria; Jalali, Mohammadreza; Fisch, Hansruedi; Loew, Simon; Amann, Florian

    2016-04-01

    Development and deployment of Enhanced Geothermal Systems (EGS) as renewable energy resources are part of the Swiss Energy Strategy 2050. To pioneer further EGS projects in Switzerland, a decameter-scale in-situ hydraulic stimulation and circulation (ISC) experiment has been launched at the Grimsel Test Site (GTS). The experiments are hosted in a low fracture density volume of the Grimsel granodiorite, similar to those expected at the potential enhanced geothermal system sites in the deep basement rocks of Northern Switzerland. One of the key goals of this multi-disciplinary experiment is to provide a pre- and post-stimulation characterization of the hydraulic and thermal properties of the stimulated fracture network with high resolution and to determine natural structures controlling the fluid flow and heat transport. Active thermal tests including thermal dilution tests and heat tracer tests allow for investigation of groundwater fluid flow and heat transport. Moreover, the spatial and temporal integrity of distributed temperature sensing (DTS) monitoring upgrades the potential and applicability of thermal tests in boreholes (e.g. Read et al., 2013). Here, we present active thermal test results and discuss the advantages and limitations of this method compared to classical approaches (hydraulic packer tests, solute tracer tests, flowing fluid electrical conductivity logging). The experimental tests were conducted in two boreholes intersected by a few low to moderately transmissive fault zones (fracture transmissivity of about 1E-9 m2/s - 1E-7 m2/s). Our preliminary results show that even in low-permeable environments active thermal testing may provide valuable insights into groundwater and heat transport pathways. Read T., O. Bour, V. Bense, T. Le Borgne, P. Goderniaux, M.V. Klepikova, R. Hochreutener, N. Lavenant, and V. Boschero (2013), Characterizing groundwater flow and heat transport in fractured rock using Fiber-Optic Distributed Temperature Sensing

  1. SYNTHESIS AND BIOLOGICAL ACTIVITY OF SULFUR COMPOUNDS SHOWING STRUCTURAL ANALOGY WITH COMBRETASTATIN A-4

    PubMed Central

    dos Santos, Edson dos A.; Prado, Paulo C.; de Carvalho, Wanderley R.; de Lima, Ricardo V.; Beatriz e, Adilson; de Lima, Dênis P.; Hamel, Ernest; Dyba, Marzena A.; Albuquerque, Sergio

    2013-01-01

    We extended our previous exploration of sulfur bridges as bioisosteric replacements for atoms forming the bridge between the aromatic rings of combretastatin A-4. Employing coupling reactions between 5-iodo-1,2,3-trimethoxybenzene and substituted thiols, followed by oxidation to sulfones with m-CPBA, different locations for attaching the sulfur atom to ring A through the synthesis of nine compounds were examined. Antitubulin activity was performed with electrophoretically homogenous bovine brain tubulin, and activity occurred with the 1,2,3-trimethoxy-4-[(4-methoxyphenyl)thio]benzene (12), while the other compounds were inactive. The compounds were also tested for leishmanicidal activity using promastigote forms of Leishmania braziliensis (MHOM/BR175/M2904), and the greatest activity was observed with 1,2,3-trimethoxy-4-(phenylthio)benzene (10) and 1,2,3-trimethoxy-4-[(4-methoxyphenyl) sulfinyl]benzene (15). PMID:23766547

  2. SYNTHESIS AND BIOLOGICAL ACTIVITY OF SULFUR COMPOUNDS SHOWING STRUCTURAL ANALOGY WITH COMBRETASTATIN A-4.

    PubMed

    Dos Santos, Edson Dos A; Prado, Paulo C; de Carvalho, Wanderley R; de Lima, Ricardo V; Beatriz E, Adilson; de Lima, Dênis P; Hamel, Ernest; Dyba, Marzena A; Albuquerque, Sergio

    2013-02-01

    We extended our previous exploration of sulfur bridges as bioisosteric replacements for atoms forming the bridge between the aromatic rings of combretastatin A-4. Employing coupling reactions between 5-iodo-1,2,3-trimethoxybenzene and substituted thiols, followed by oxidation to sulfones with m-CPBA, different locations for attaching the sulfur atom to ring A through the synthesis of nine compounds were examined. Antitubulin activity was performed with electrophoretically homogenous bovine brain tubulin, and activity occurred with the 1,2,3-trimethoxy-4-[(4-methoxyphenyl)thio]benzene (12), while the other compounds were inactive. The compounds were also tested for leishmanicidal activity using promastigote forms of Leishmania braziliensis (MHOM/BR175/M2904), and the greatest activity was observed with 1,2,3-trimethoxy-4-(phenylthio)benzene (10) and 1,2,3-trimethoxy-4-[(4-methoxyphenyl) sulfinyl]benzene (15).

  3. Mice lacking brain-type creatine kinase activity show defective thermoregulation

    PubMed Central

    Streijger, Femke; Pluk, Helma; Oerlemans, Frank; Beckers, Gaby; Bianco, Antonio C.; Ribeiro, Miriam O.; Wieringa, Bé; Van der Zee, Catharina E.E.M.

    2010-01-01

    The cytosolic brain-type creatine kinase and mitochondrial ubiquitous creatine kinase (CK-B and UbCKmit) are expressed during the prepubescent and adult period of mammalian life. These creatine kinase (CK) isoforms are present in neural cell types throughout the central and peripheral nervous system and in smooth muscle containing tissues, where they have an important role in cellular energy homeostasis. Here, we report on the coupling of CK activity to body temperature rhythm and adaptive thermoregulation in mice. With both brain-type CK isoforms being absent, the body temperature reproducibly drops ~1.0°C below normal during every morning (inactive) period in the daily cycle. Facultative non-shivering thermogenesis is also impaired, since CK−−/−− mice develop severe hypothermia during 24 h cold exposure. A relationship with fat metabolism was suggested because comparison of CK−−/−− mice with wildtype controls revealed decreased weight gain associated with less white and brown fat accumulation and smaller brown adipocytes. Also, circulating levels of glucose, triglycerides and leptin are reduced. Extensive physiological testing and uncoupling protein1 analysis showed, however, that the thermogenic problems are not due to abnormal responsiveness of brown adipocytes, since noradrenaline infusion produced a normal increase of body temperature. Moreover, we demonstrate that the cyclic drop in morning temperature is also not related to altered rhythmicity with reduced locomotion, diminished food intake or increased torpor sensitivity. Although several integral functions appear altered when CK is absent in the brain, combined findings point into the direction of inefficient neuronal transmission as the dominant factor in the thermoregulatory defect. PMID:19419668

  4. Florida Defeats the Skeptics: Test Scores Show Genuine Progress in the Sunshine State

    ERIC Educational Resources Information Center

    Winters, Marcus

    2012-01-01

    Among the 50 states, Florida's gains on the National Assessment of Educational Progress (NAEP) between 1992 and 2011 ranked second only to Maryland's. Florida's progress has been particularly impressive in the early grades. In 1998, Florida scored about one grade level below the national average on the 4th-grade NAEP reading test, but it was…

  5. D.C. Student Test Scores Show Uneven Progress. Data Snapshot

    ERIC Educational Resources Information Center

    DuPre, Mary

    2011-01-01

    Over the past five years, both DC Public Schools (DCPS) and public charter schools (PCS) have seen significant growth in secondary reading and math scores on the state test known as the District of Columbia Comprehensive Assessment System (DC CAS). However, scores have not improved as much at the elementary level. Reading and math scores for DCPS…

  6. A humanized anti-M2 scFv shows protective in vitro activity against influenza

    SciTech Connect

    Bradbury, Andrew M; Velappan, Nileena; Schmidt, Jurgen G

    2008-01-01

    M2 is one of the most conserved influenza proteins, and has been widely prospected as a potential universal vaccine target, with protection predominantly mediated by antibodies. In this paper we describe the creation of a humanized single chain Fv from 14C2, a potent monoclonal antibody against M2. We show that the humanized scFv demonstrates similar activity to the parental mAb: it is able to recognize M2 in its native context on cell surfaces and is able to show protective in vitro activity against influenza, and so represents a potential lead antibody candidate for universal prophylactic or therapeutic intervention in influenza.

  7. Distributive Education--Fashion Show. Kit No. 88. Instructor's Manual [and] Student Learning Activity Guide.

    ERIC Educational Resources Information Center

    Walters, Brenda B.

    An instructor's manual and student activity guide on fashion shows are provided in this set of prevocational education materials which focuses on the vocational area of distributive education. (This set of materials is one of ninety-two prevocational education sets arranged around a cluster of seven vocational offerings: agriculture, home…

  8. 26 CFR 1.513-3 - Qualified convention and trade show activity.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... purpose of the sponsoring organization in conducting the show is the education of its members, or the promotion and stimulation of interest in, and demand for, the products or services of the industry (or... interest in, and demand for such products or services; (ii) Activities designed to educate persons in...

  9. 26 CFR 1.513-3 - Qualified convention and trade show activity.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... purpose of the sponsoring organization in conducting the show is the education of its members, or the promotion and stimulation of interest in, and demand for, the products or services of the industry (or... interest in, and demand for such products or services; (ii) Activities designed to educate persons in...

  10. 26 CFR 1.513-3 - Qualified convention and trade show activity.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... purpose of the sponsoring organization in conducting the show is the education of its members, or the promotion and stimulation of interest in, and demand for, the products or services of the industry (or... interest in, and demand for such products or services; (ii) Activities designed to educate persons in...

  11. 26 CFR 1.513-3 - Qualified convention and trade show activity.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... purpose of the sponsoring organization in conducting the show is the education of its members, or the promotion and stimulation of interest in, and demand for, the products or services of the industry (or... interest in, and demand for such products or services; (ii) Activities designed to educate persons in...

  12. 26 CFR 1.513-3 - Qualified convention and trade show activity.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... purpose of the sponsoring organization in conducting the show is the education of its members, or the promotion and stimulation of interest in, and demand for, the products or services of the industry (or... interest in, and demand for such products or services; (ii) Activities designed to educate persons in...

  13. Standardization Activities in TMF Test Methodologies

    NASA Technical Reports Server (NTRS)

    Verrilli, M. J.; Castelli, M. G.; Bressers, J.; Oehmke, R. L. T.

    1996-01-01

    No standard test practice currently exists for strain-controlled thermomechanical fatigue (TMF) testing. This paper discusses recent activities which lay the foundation for standardization of TMF test methods. Specifically, the paper documents the results of two interlaboratory TMF test programs, identifies key TMF symposia and workshops, and discusses efforts toward drafting a TMF standard test practice.

  14. High-throughput olfactory conditioning and memory retention test show variation in Nasonia parasitic wasps.

    PubMed

    Hoedjes, K M; Steidle, J L M; Werren, J H; Vet, L E M; Smid, H M

    2012-10-01

    Most of our knowledge on learning and memory formation results from extensive studies on a small number of animal species. Although features and cellular pathways of learning and memory are highly similar in this diverse group of species, there are also subtle differences. Closely related species of parasitic wasps display substantial variation in memory dynamics and can be instrumental to understanding both the adaptive benefit of and mechanisms underlying this variation. Parasitic wasps of the genus Nasonia offer excellent opportunities for multidisciplinary research on this topic. Genetic and genomic resources available for Nasonia are unrivaled among parasitic wasps, providing tools for genetic dissection of mechanisms that cause differences in learning. This study presents a robust, high-throughput method for olfactory conditioning of Nasonia using a host encounter as reward. A T-maze olfactometer facilitates high-throughput memory retention testing and employs standardized odors of equal detectability, as quantified by electroantennogram recordings. Using this setup, differences in memory retention between Nasonia species were shown. In both Nasonia vitripennis and Nasonia longicornis, memory was observed up to at least 5 days after a single conditioning trial, whereas Nasonia giraulti lost its memory after 2 days. This difference in learning may be an adaptation to species-specific differences in ecological factors, for example, host preference. The high-throughput methods for conditioning and memory retention testing are essential tools to study both ultimate and proximate factors that cause variation in learning and memory formation in Nasonia and other parasitic wasp species.

  15. Physical Stress Echocardiography: Prediction of Mortality and Cardiac Events in Patients with Exercise Test showing Ischemia.

    PubMed

    Araujo, Ana Carla Pereira de; Santos, Bruno F de Oliveira; Calasans, Flavia Ricci; Pinto, Ibraim M Francisco; Oliveira, Daniel Pio de; Melo, Luiza Dantas; Andrade, Stephanie Macedo; Tavares, Irlaneide da Silva; Sousa, Antonio Carlos Sobral; Oliveira, Joselina Luzia Menezes

    2014-11-01

    Background: Studies have demonstrated the diagnostic accuracy and prognostic value of physical stress echocardiography in coronary artery disease. However, the prediction of mortality and major cardiac events in patients with exercise test positive for myocardial ischemia is limited. Objective: To evaluate the effectiveness of physical stress echocardiography in the prediction of mortality and major cardiac events in patients with exercise test positive for myocardial ischemia. Methods: This is a retrospective cohort in which 866 consecutive patients with exercise test positive for myocardial ischemia, and who underwent physical stress echocardiography were studied. Patients were divided into two groups: with physical stress echocardiography negative (G1) or positive (G2) for myocardial ischemia. The endpoints analyzed were all-cause mortality and major cardiac events, defined as cardiac death and non-fatal acute myocardial infarction. Results: G2 comprised 205 patients (23.7%). During the mean 85.6 ± 15.0-month follow-up, there were 26 deaths, of which six were cardiac deaths, and 25 non-fatal myocardial infarction cases. The independent predictors of mortality were: age, diabetes mellitus, and positive physical stress echocardiography (hazard ratio: 2.69; 95% confidence interval: 1.20 - 6.01; p = 0.016). The independent predictors of major cardiac events were: age, previous coronary artery disease, positive physical stress echocardiography (hazard ratio: 2.75; 95% confidence interval: 1.15 - 6.53; p = 0.022) and absence of a 10% increase in ejection fraction. All-cause mortality and the incidence of major cardiac events were significantly higher in G2 (p < 0. 001 and p = 0.001, respectively). Conclusion: Physical stress echocardiography provides additional prognostic information in patients with exercise test positive for myocardial ischemia.Fundamento: Estudos têm demonstrado a acurácia diagnóstica e o valor prognóstico da ecocardiografia com estresse f

  16. Isolation of Lactic Acid Bacteria Showing Antioxidative and Probiotic Activities from Kimchi and Infant Feces.

    PubMed

    Ji, Keunho; Jang, Na Young; Kim, Young Tae

    2015-09-01

    The purpose of this study was to investigate lactic acid bacteria with antioxidative and probiotic activities isolated from Korean healthy infant feces and kimchi. Isolates A1, A2, S1, S2, and S3 were assigned to Lactobacillus sp. and isolates A3, A4, E1, E2, E3, and E4 were assigned to Leuconostoc sp. on the basis of their physiological properties and 16S ribosomal DNA sequence analysis. Most strains were confirmed as safe bioresources through nonhemolytic activities and non-production of harmful enzymes such as β-glucosidase, β- glucuronidase and tryptophanase. The 11 isolates showed different resistance to acid and bile acids. In addition, they exhibited antibacterial activity against foodborne bacteria, especially Bacillus cereus, Listeria monocytogenes, and Escherichia coli. Furthermore, all strains showed significantly high levels of hydrophobicity. The antioxidant effects of culture filtrates of the 11 strains included 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging capacity, 2.2'- azino-bis (2-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical cation scavenging activity, and superoxide dismutase activity. The results revealed that most of the culture filtrates have effective scavenging activity for DPPH and ABTS radicals. All strains appeared to have effective superoxide dismutase activity. In conclusion, the isolated strains A1, A3, S1, and S3 have significant probiotic activities applicable to the development of functional foods and health-related products. These strains might also contribute to preventing and controlling several diseases associated with oxidative stress, when used as probiotics.

  17. Blood tests showing nonpaternity-conclusive or rebuttable evidence? The Chaplin case revisited.

    PubMed

    Benson, F

    1981-09-01

    A defendant accused of being the father of an illegitimate child denies responsibility. Blood samples from the child, mother, and alleged father are studied and the results reveal that the alleged father is excluded. What weight, if any, should the court (if a trial is held) or the jury give to the evidence of nonpaternity? Should the evidence be treated as conclusive proof of nonpaternity or should other evidence be admitted in the trial to overcome the nonpaternity evidence? A medical expert might conclude that a controversy exists because of the court's questioned trustworthiness of the paternity blood testing, while a legal expert might conclude that the controversy arises because of burdens of proof. Both conclusions are valid. The Berry v. Chaplin case held in California in 1946 illustrates this circumstance. In refreshing our memories on this case, we can review the problem in light of today's knowledge.

  18. Residue organic mixtures from drinking water show in vitro mutagenic and transforming activity.

    PubMed

    Loper, J C; Lang, D R; Schoeny, R S; Richmond, B B; Gallagher, P M; Smith, C C

    1978-01-01

    Indications of possible health effects of residue organics in drinking water have been sought using short-term tests of mutagenic and transforming activity. Ten percent or less of the total organic material in drinking water has been identified; the remainder is believed to include thousands of unknown nonvolatile compounds. Residual organics were concentrated from drinking water from representative U.S. cities by reverse osmosis followed by liquid-liquid extraction [yielding the reverse osmosis concentrate-organic extract (ROC-OE) fraction] and sorption-desorption on XAD-2 resin. Samples of these residue organics were provided by the Environmental Protection Agency for bioassay. They were examined for mutagenic activity by using Salmonella tester strains (primarily TA98 and TA100) and for transforming activity by using mouse fibroblasts (BALB/3T3 clone 1-13). City-specific patterns of dose-dependent bacterial mutagenesis and of bacterial toxicity were observed for these samples and for subfractions generated by sequential extractions with hexane, ethyl ether, and acetone. Mutagenic effects were essentially independent of a microsome activation system prepared from liver of Aroclor 1254-induced rats. On the basis of strain-specific effects in mutagenesis and differential distributions of mutagenic activity during liquid-liquid extraction, at least some of the active compounds are thought to be acidic, frameshift mutagens. The ROC-OE fraction of a New Orleans sample transformed BALB/3T3 cells in replicate experiments. By comparison with the bacterial mutagenesis data, cell transformation is a relatively sensitive method for detecting possible mutagenic and carcinogenic activity in this sample. The appropriateness of these systems for the assay of complex mixtures and the degree to which reverse osmosis concentrates contain the unaltered organic compounds in the original samples are discussed.

  19. Testing an Emerging Paradigm in Migration Ecology Shows Surprising Differences in Efficiency between Flight Modes

    PubMed Central

    Duerr, Adam E.; Miller, Tricia A.; Lanzone, Michael; Brandes, Dave; Cooper, Jeff; O'Malley, Kieran; Maisonneuve, Charles; Tremblay, Junior; Katzner, Todd

    2012-01-01

    To maximize fitness, flying animals should maximize flight speed while minimizing energetic expenditure. Soaring speeds of large-bodied birds are determined by flight routes and tradeoffs between minimizing time and energetic costs. Large raptors migrating in eastern North America predominantly glide between thermals that provide lift or soar along slopes or ridgelines using orographic lift (slope soaring). It is usually assumed that slope soaring is faster than thermal gliding because forward progress is constant compared to interrupted progress when birds pause to regain altitude in thermals. We tested this slope-soaring hypothesis using high-frequency GPS-GSM telemetry devices to track golden eagles during northbound migration. In contrast to expectations, flight speed was slower when slope soaring and eagles also were diverted from their migratory path, incurring possible energetic costs and reducing speed of progress towards a migratory endpoint. When gliding between thermals, eagles stayed on track and fast gliding speeds compensated for lack of progress during thermal soaring. When thermals were not available, eagles minimized migration time, not energy, by choosing energetically expensive slope soaring instead of waiting for thermals to develop. Sites suited to slope soaring include ridges preferred for wind-energy generation, thus avian risk of collision with wind turbines is associated with evolutionary trade-offs required to maximize fitness of time-minimizing migratory raptors. PMID:22558166

  20. Testing an emerging paradigm in migration ecology shows surprising differences in efficiency between flight modes.

    PubMed

    Duerr, Adam E; Miller, Tricia A; Lanzone, Michael; Brandes, Dave; Cooper, Jeff; O'Malley, Kieran; Maisonneuve, Charles; Tremblay, Junior; Katzner, Todd

    2012-01-01

    To maximize fitness, flying animals should maximize flight speed while minimizing energetic expenditure. Soaring speeds of large-bodied birds are determined by flight routes and tradeoffs between minimizing time and energetic costs. Large raptors migrating in eastern North America predominantly glide between thermals that provide lift or soar along slopes or ridgelines using orographic lift (slope soaring). It is usually assumed that slope soaring is faster than thermal gliding because forward progress is constant compared to interrupted progress when birds pause to regain altitude in thermals. We tested this slope-soaring hypothesis using high-frequency GPS-GSM telemetry devices to track golden eagles during northbound migration. In contrast to expectations, flight speed was slower when slope soaring and eagles also were diverted from their migratory path, incurring possible energetic costs and reducing speed of progress towards a migratory endpoint. When gliding between thermals, eagles stayed on track and fast gliding speeds compensated for lack of progress during thermal soaring. When thermals were not available, eagles minimized migration time, not energy, by choosing energetically expensive slope soaring instead of waiting for thermals to develop. Sites suited to slope soaring include ridges preferred for wind-energy generation, thus avian risk of collision with wind turbines is associated with evolutionary trade-offs required to maximize fitness of time-minimizing migratory raptors.

  1. Comparative ergoespirometric adaptations to a treadmill exercise test in untrained show Andalusian and Arabian horses.

    PubMed

    Castejón-Riber, Cristina; Muñoz, Ana; Trigo, Pablo; Riber, Cristina; Santisteban, Rafael; Castejón, Francisco

    2012-03-01

    Significant differences exist in the respiratory adaptation to exercise in different equine breeds. This research describes the ergoespirometric response to exercise of Andalusian (AN) and Arabian (A) horses, both selected according to morphological criteria. Thirteen untrained male horses (6 AN and 7 A) performed a treadmill exercise test (TET) with a slope of 6%, with workloads starting from 5 m/s and increasing 1 m/s every 3 min until the horses were not able to keep the required velocity. Tidal volume (TV), respiratory rate, minute ventilation (VE), oxygen uptake (VO2), carbon dioxide production, peak oxygen uptake (VO2peak), respiratory exchange ratio (RER), exercise time to fatigue (ETF) and respiratory aerobic threshold (RAT) were determined. AN horses presented higher TV and VE, whereas respiratory rate, VO2 and VCO2 were lower at the same velocities. RER was similar between breeds. ETF was longer in A horses (556.7 ± 66.5 in AN vs. 607.1 ± 71.1 s in A) and no significant differences were found in RAT (5.50 ± 0.50 in AN vs. 5.86 ± 1.07 m/s in A). In summary, despite the more intense ventilatory response to exercise at the same velocity, AN horses had lower VO2. The AN horse develops a more intense ventilatory response to fixed velocities than the A horse and it could be interesting to clarify the role of the locomotion characteristics in this response.

  2. Bovine chromaffin cells in culture show carboxylesterase activities sensitive to organophosphorus compounds.

    PubMed

    Sogorb, M A; Vilanova, E; Quintanar, J L; Viniegra, S

    1996-09-01

    Carboxylesterase activities are widely distributed in a great variety of tissues; however, the biological function of these enzymes remains unclear. Some organophosphorus compounds induce a neurodegenarative syndrome related to the covalent modification of a carboxylesterase known as neuropathy target esterase. We investigated the expression of neuropathy target esterase and related carboxylesterase in bovine chromaffin cells with the aim of developing a potential in vitro model for studying the cellular function of carboxylesterase enzymes and toxic effects of organophosphorus compounds. Total phenyl valerate esterase exhibited an activity of 1.27 +/- 0.19 mU/10(5) cells (SD, n = 15). From the phenyl valerate esterase paraoxon and mipafox inhibition curves the following activities have been determined: B-activity (resistant to 40 microM paraoxon), 1.05 +/- 0.08 mU/10(5) cells (n = 8); C-activity (resistant to 40 microM paraoxon plus 250 microM mipafox), 0.12 +/- 0.05 mU/10(5) cells (n = 8); and neuropathy target esterase, calculated by the difference between B- and C-activities, 0.93 +/- 0.08 mU/10(5) cells (n = 8). All of these activities increased linearly with the number of cells and time of incubation with the substrate. Most of the phenol product of the reaction was released and detected in the extracellular medium. None of the components of the reaction were shown to affect cell viability when assessed by trypan blue exclusion. The study shows that bovine chromaffin cells possess carboxylesterase activities and respond to inhibition by paraoxon and mipafox, thus facilitating the discrimination of neuropathy target esterase. In conclusion, bovine chromaffin cells are appropriate as an in vitro cell model for studying toxic effects of organophosphorus compounds.

  3. Antiparkinson drug--Mucuna pruriens shows antioxidant and metal chelating activity.

    PubMed

    Dhanasekaran, Muralikrishnan; Tharakan, Binu; Manyam, Bala V

    2008-01-01

    Parkinson's disease is a neurodegenerative disorder for which no neurorestorative therapeutic treatment is currently available. Oxidative stress plays an important role in the pathophysiology of Parkinson's disease. The ancient Indian medical system, Ayurveda, traditionally uses Mucuna pruriens to treat Parkinson's disease. In our earlier studies, Mucuna pruriens has been shown to possess antiparkinson and neuroprotective effects in animal models of Parkinson's disease. The antioxidant activity of Mucuna pruriens was demonstrated by its ability to scavenge DPPH radicals, ABTS radicals and reactive oxygen species. Mucuna pruriens significantly inhibited the oxidation of lipids and deoxyribose sugar. Mucuna pruriens exhibited divalent iron chelating activity and did not show any genotoxic/mutagenic effect on the plasmid DNA. These results suggest that the neuroprotective and neurorestorative effect of Mucuna pruriens may be related to its antioxidant activity independent of the symptomatic effect. In addition, the drug appears to be therapeutically safe in the treatment of patients with Parkinson's disease.

  4. Cytorhabdovirus phosphoprotein shows RNA silencing suppressor activity in plants, but not in insect cells.

    PubMed

    Mann, Krin S; Johnson, Karyn N; Dietzgen, Ralf G

    2015-02-01

    RNA silencing in plants and insects provides an antiviral defense and as a countermeasure most viruses encode RNA silencing suppressors (RSS). For the family Rhabdoviridae, no detailed functional RSS studies have been reported in plant hosts and insect vectors. In agroinfiltrated Nicotiana benthamiana leaves we show for the first time for a cytorhabdovirus, lettuce necrotic yellows virus (LNYV), that one of the nucleocapsid core proteins, phosphoprotein (P) has relatively weak local RSS activity and delays systemic silencing of a GFP reporter. Analysis of GFP small RNAs indicated that the P protein did not prevent siRNA accumulation. To explore RSS activity in insects, we used a Flock House virus replicon system in Drosophila S2 cells. In contrast to the plant host, LNYV P protein did not exhibit RSS activity in the insect cells. Taken together our results suggest that P protein may target plant-specific components of RNA silencing post siRNA biogenesis.

  5. Collagen-Immobilized Lipases Show Good Activity and Reusability for Butyl Butyrate Synthesis.

    PubMed

    Dewei, Song; Min, Chen; Haiming, Cheng

    2016-11-01

    Candida rugosa lipases were immobilized onto collagen fibers through glutaraldehyde cross-linking method. The immobilization process has been optimized. Under the optimal immobilization conditions, the activity of the collagen-immobilized lipase reached 340 U/g. The activity was recovered of 28.3 % by immobilization. The operational stability of the obtained collagen-immobilized lipase for hydrolysis of olive oil emulsion was determined. The collagen-immobilized lipase showed good tolerance to temperature and pH variations in comparison to free lipase. The collagen-immobilized lipase was also applied as biocatalyst for synthesis of butyl butyrate from butyric acid and 1-butanol in n-hexane. The conversion yield was 94 % at the optimal conditions. Of its initial activity, 64 % was retained after 5 cycles for synthesizing butyl butyrate in n-hexane.

  6. Functional characterization of a Plagiochasma appendiculatum flavone synthase I showing flavanone 2-hydroxylase activity.

    PubMed

    Han, Xiao-Juan; Wu, Yi-Feng; Gao, Shuai; Yu, Hai-Na; Xu, Rui-Xue; Lou, Hong-Xiang; Cheng, Ai-Xia

    2014-06-27

    FNS I is a 2-oxoglutarate dependent dioxygenase (2-ODD) found mainly in species of the Apiaceae family. Here, an FNS I cDNA sequence was isolated from the liverwort Plagiochasma appendiculatum (Aytoniaceae) and characterized. The recombinant protein exhibited high FNS I activity catalyzing the conversion of naringenin to apigenin and 2-hydroxynaringenin. The critical residue for flavanone-2-hydroxylation activity was Tyr240, as identified from homology modeling and site-directed mutagenesis. The recombinant protein also showed some flavonol synthase activity, as it can convert dihydrokaempferol to kaempferol. When the Leu311 residue was mutated to Phe, the enzyme's capacity to convert dihydrokaempferol to kaempferol was substantially increased. PaFNS I represents a 2-ODD in which a hydrophobic π-stacking interaction between the key residue and the naringenin A-ring determines 2-hydroxyflavanone formation.

  7. Antibodies to Meningococcal H.8 (Lip) Antigen Fail to Show Bactericidal Activity

    DTIC Science & Technology

    1990-01-01

    monoclonaux n’avaient pas non plus d’activit6 bactericide contre ces souches. La faible activitt bactdricide associee aux anticorps monoclonaux et...MENINGOCOCCAL H.8 (Lip) ANTIGEN FAILTO SHOW BACTERICIDAL ACTIVITY. 12. PERSONAL. DUTHOR(S AK BHATTACHARJEE, EE MORAN, & WD ZOLLINGER. lb. TMP OP REPORT DATE...isotypes. An anti-Lip mouse monoclonal ascites (2-1-CA2) had 28 400 ELISA units of antibody. Bactericidal assays were performed using three different

  8. The three catalases in Deinococcus radiodurans: Only two show catalase activity.

    PubMed

    Jeong, Sun-Wook; Jung, Jong-Hyun; Kim, Min-Kyu; Seo, Ho Seong; Lim, Heon-Man; Lim, Sangyong

    2016-01-15

    Deinococcus radiodurans, which is extremely resistant to ionizing radiation and oxidative stress, is known to have three catalases (DR1998, DRA0146, and DRA0259). In this study, to investigate the role of each catalase, we constructed catalase mutants (Δdr1998, ΔdrA0146, and ΔdrA0259) of D. radiodurans. Of the three mutants, Δdr1998 exhibited the greatest decrease in hydrogen peroxide (H2O2) resistance and the highest increase in intracellular reactive oxygen species (ROS) levels following H2O2 treatments, whereas ΔdrA0146 showed no change in its H2O2 resistance or ROS level. Catalase activity was not attenuated in ΔdrA0146, and none of the three bands detected in an in-gel catalase activity assay disappeared in ΔdrA0146. The purified His-tagged recombinant DRA0146 did not show catalase activity. In addition, the phylogenetic analysis of the deinococcal catalases revealed that the DR1998-type catalase is common in the genus Deinococcus, but the DRA0146-type catalase was found in only 4 of 23 Deinococcus species. Taken together, these results indicate that DR1998 plays a critical role in the anti-oxidative system of D. radiodurans by detoxifying H2O2, but DRA0146 does not have catalase activity and is not involved in the resistance to H2O2 stress.

  9. Water-soluble extracts from defatted sesame seed flour show antioxidant activity in vitro.

    PubMed

    Ben Othman, Sana; Katsuno, Nakako; Kanamaru, Yoshihiro; Yabe, Tomio

    2015-05-15

    Defatted white and gold sesame seed flour, recovered as a byproduct after sesame oil extraction, was extracted with 70% ethanol to obtain polar-soluble crude extracts. The in vitro antioxidant activity of the extract was evaluated by DPPH free radical scavenging activity and oxygen radical absorbing capacity (ORAC). The polar-soluble crude extracts of both sesame seed types exhibited good antioxidant capacity, especially by the ORAC method with 34,720 and 21,700 μmol Trolox equivalent/100g of white and gold sesame seed extract, respectively. HPLC, butanol extraction, and UPLC-MS analyses showed that different compounds contributed to the antioxidant activity of the polar-soluble crude extracts. Sesaminol glycosides were identified in the butanol-soluble fractions; whereas, purified water-soluble fraction contained ferulic and vanillic acids. This study shows that hydrophilic antioxidants in the purified water-soluble fraction contributed to the antioxidant activity of white and gold sesame seed polar-soluble crude extracts.

  10. Bovine serum albumin with glycated carboxyl groups shows membrane-perturbing activities.

    PubMed

    Yang, Shin-Yi; Chen, Ying-Jung; Kao, Pei-Hsiu; Chang, Long-Sen

    2014-12-15

    The aim of the present study aimed to investigate whether glycated bovine serum albumin (BSA) showed novel activities on the lipid-water interface. Mannosylated BSA (Man-BSA) was prepared by modification of the carboxyl groups with p-aminophenyl α-d-mannopyranoside. In contrast to BSA, Man-BSA notably induced membrane permeability of egg yolk phosphatidylcholine (EYPC)/egg yolk sphingomyelin (EYSM)/cholesterol (Chol) and EYPC/EYSM vesicles. Noticeably, Man-BSA induced the fusion of EYPC/EYSM/Chol vesicles, but not of EYPC/EYSM vesicles. Although BSA and Man-BSA showed similar binding affinity for lipid vesicles, the lipid-bound conformation of Man-BSA was distinct from that of BSA. Moreover, Man-BSA adopted distinct structure upon binding with the EYPC/EYSM/Chol and EYPC/EYSM vesicles. Man-BSA could induce the fusion of EYPC/EYSM/Chol vesicles with K562 and MCF-7 cells, while Man-BSA greatly induced the leakage of Chol-depleted K562 and MCF-7 cells. The modified BSA prepared by conjugating carboxyl groups with p-aminophenyl α-d-glucopyranoside also showed membrane-perturbing activities. Collectively, our data indicate that conjugation of carboxyl groups with monosaccharide generates functional BSA with membrane-perturbing activities on the lipid-water interface.

  11. Multiple regression methods show great potential for rare variant association tests.

    PubMed

    Xu, ChangJiang; Ladouceur, Martin; Dastani, Zari; Richards, J Brent; Ciampi, Antonio; Greenwood, Celia M T

    2012-01-01

    The investigation of associations between rare genetic variants and diseases or phenotypes has two goals. Firstly, the identification of which genes or genomic regions are associated, and secondly, discrimination of associated variants from background noise within each region. Over the last few years, many new methods have been developed which associate genomic regions with phenotypes. However, classical methods for high-dimensional data have received little attention. Here we investigate whether several classical statistical methods for high-dimensional data: ridge regression (RR), principal components regression (PCR), partial least squares regression (PLS), a sparse version of PLS (SPLS), and the LASSO are able to detect associations with rare genetic variants. These approaches have been extensively used in statistics to identify the true associations in data sets containing many predictor variables. Using genetic variants identified in three genes that were Sanger sequenced in 1998 individuals, we simulated continuous phenotypes under several different models, and we show that these feature selection and feature extraction methods can substantially outperform several popular methods for rare variant analysis. Furthermore, these approaches can identify which variants are contributing most to the model fit, and therefore both goals of rare variant analysis can be achieved simultaneously with the use of regression regularization methods. These methods are briefly illustrated with an analysis of adiponectin levels and variants in the ADIPOQ gene.

  12. Performic acid (PFA): tests on an advanced primary effluent show promising disinfection performance.

    PubMed

    Gehr, R; Chen, D; Moreau, M

    2009-01-01

    Performic acid, or PFA (CH(2)O(3)), is a well-known oxidizing agent and disinfectant in the medical field and food industry. It has recently become available on a commercial scale for potential use in wastewater disinfection. This study investigated its application to an advanced primary effluent which is recalcitrant to disinfection by UV and peracetic acid (PAA). Methods were developed for determining PFA concentrations in stock solutions as well as in residual concentrations in the wastewater. Batch and continuous-flow pilot studies showed a correlation between log fecal coliform removals and PFA doses. A PFA dose of approximately 3.4 mg/L and a contact time of 45 minutes could achieve 3-logs removal, and almost total disinfection could be achieved using a dose of 6 mg/L. The by-products of PFA addition are hydrogen peroxide and formic acid (CHOOH), neither of which is considered to be toxic to aquatic fauna at the doses required for disinfection.

  13. Subunits of the Snf1 kinase heterotrimer show interdependence for association and activity.

    PubMed

    Elbing, Karin; Rubenstein, Eric M; McCartney, Rhonda R; Schmidt, Martin C

    2006-09-08

    The Snf1 kinase and its mammalian orthologue, the AMP-activated protein kinase (AMPK), function as heterotrimers composed of a catalytic alpha-subunit and two non-catalytic subunits, beta and gamma. The beta-subunit is thought to hold the complex together and control subcellular localization whereas the gamma-subunit plays a regulatory role by binding to and blocking the function of an auto-inhibitory domain (AID) present in the alpha-subunit. In addition, catalytic activity requires phosphorylation by a distinct upstream kinase. In yeast, any one of three Snf1-activating kinases, Sak1, Tos3, or Elm1, can fulfill this role. We have previously shown that Sak1 is the only Snf1-activating kinase that forms a stable complex with Snf1. Here we show that the formation of the Sak1.Snf1 complex requires the beta- and gamma-subunits in vivo. However, formation of the Sak1.Snf1 complex is not necessary for glucose-regulated phosphorylation of the Snf1 activation loop. Snf1 kinase purified from cells lacking the beta-subunits do not contain any gamma-subunit, indicating that the Snf1 kinase does not form a stable alphagamma dimer in vivo. In vitro kinase assays using purified full-length and truncated Snf1 proteins demonstrate that the kinase domain, which lacks the AID, is significantly more active than the full-length Snf1 protein. Addition of purified beta- and gamma-subunits could stimulate the kinase activity of the full-length alpha-subunit but only when all three subunits were present, suggesting an interdependence of all three subunits for assembly of a functional complex.

  14. Negatively charged liposomes show potent adjuvant activity when simply admixed with protein antigens

    PubMed Central

    Yanasarn, Nijaporn; Sloat, Brian R.; Cui, Zhengrong

    2011-01-01

    Liposomes have been investigated extensively as a vaccine delivery system. Herein the adjuvant activities of liposomes with different net surface charges (neutral, positive, or negative) were evaluated when admixed with protein antigens, ovalbumin (OVA, pI = 4.7), Bacillus anthracis protective antigen protein (PA, pI = 5.6), or cationized OVA (cOVA). Mice immunized subcutaneously with OVA admixed with different liposomes generated different antibody responses. Interestingly, OVA admixed with net negatively charged liposomes prepared with DOPA was as immunogenic as OVA admixed with positively charged liposomes prepared with DOTAP. Immunization of mice with the anthrax PA protein admixed with the net negatively charged DOPA liposomes also induced a strong and functional anti-PA antibody response. When the cationized OVA was used as a model antigen, liposomes with net neutral, negative, or positive charges showed comparable adjuvant activities. Immunization of mice with the OVA admixed with DOPA liposomes also induced OVA-specific CD8+ cytotoxic T lymphocyte responses and significantly delayed the growth of OVA-expressing B16-OVA tumors in mice. However, not all net negatively charged liposomes showed a strong adjuvant activity. The adjuvant activity of the negatively charged liposomes may be related to the liposome’s ability (i) to up-regulate the expression of molecules related to the activation and maturation of antigen-presenting cells and (ii) to slightly facilitate the uptake of the antigens by antigen-presenting cells. Simply admixing certain negatively charged liposomes with certain protein antigens of interest may represent a novel platform for vaccine development. PMID:21615153

  15. A novel cathelicidin from Bufo bufo gargarizans Cantor showed specific activity to its habitat bacteria.

    PubMed

    Sun, Tongyi; Zhan, Bo; Gao, Yuanyuan

    2015-10-25

    Toad Bufo bufo gargarizans Cantor is still used in China as traditional Chinese medicine. However, present investigations on its skin secretions were mainly focused on the bufadienolides, the proteins/peptides contained in the secretions are largely unknown. A cDNA encoding a novel cathelicidin termed BG-CATH was identified by analysis of the toad skin transcriptome. The BG-CATH precursor was predicted to have 2 possible cleavage sites following dibasic cleavage signals at its C-terminal, which will generate two mature peptides, BG-CATH37 and BG-CATH(5-37). Phylogenetic analysis suggests that amphibian cathelicidins might evolve from common ancestors. The two predicted mature cathelicidins from B. bufo gargarizans were synthesized and both of them showed weak antimicrobial activities against human pathogenic bacteria Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus (MIC ≥ 200 μg/mL). However, BG-CATH37 and BG-CATH(5-37) had strong antimicrobial activities against aquatic bacteria of Vibrio splendidus, Streptococcus iniae and Aeromorus hydrophila, which were common microorganisms in the habitat of B. bufo gargarizans (MIC 3.125-40 μg/mL). BG-CATH37 and BG-CATH(5-37) showed no hemolytic activity even at high concentrations (400 μg/mL). CD spectra analysis suggested that structure rigidity of BG-CATH37 and BG-CATH(5-37) might play an important role to regulate their biological activities. Selective antimicrobial activity against habitat microorganisms might reflect the adaptation of amphibians to their living environments.

  16. Newly derived GH43 gene from compost metagenome showing dual xylanase and cellulase activities.

    PubMed

    Sae-Lee, Ritthironk; Boonmee, Atcha

    2014-09-01

    A metagenomic fosmid library was constructed from compost microbial communities that were collected from various farms throughout the Khon Kaen province, Thailand. The library was enriched in carboxymethylcellulose (CM-cellulose)--containing media prior to the screening of clones capable of degrading cellulosic materials. Two clones were selected for further subcloning and sequencing based on different patterns from restriction analysis. Deduced amino acid analysis of possible ORFs revealed one novel gene encoding an enzyme belonging to glycosyl hydrolase family 43 (GH43), which is a GH family rarely found in metagenomic studies. The most notable finding is that this enzyme, designated as Biof1_09, shows dual activities, namely endocellulase and endoxylanase activities. Biof1_09 showed greater than 50% of its activity under acidic conditions ranging from pH 3.5 to 5.5 with a pH optimum of 4.5. The optimum temperature of this enzyme was between 45 and 55 °C with an optimum of 50 °C. The properties of Biof1_09 make this enzyme an attractive candidate for large-scale expression for use in lignocellulose degradation for various bioprocess applications, including bioethanol fermentation.

  17. Brain potentials show rapid activation of implicit attitudes towards young and old people.

    PubMed

    van der Lugt, Arie H; Banfield, Jane F; Osinsky, Roman; Münte, Thomas F

    2012-01-06

    While previous behavioural research suggests that attitudes, for example towards elderly people, may be activated automatically, this type of research does not provide information about the detailed time-course of such processing in the brain. We investigated the impact of age related attitude information in a Go/NoGo association task that paired photographs of elderly or young faces with positive or negative words. Event related brain potentials showed an N200 (NoGo) component, which appeared earlier in runs which required similar responses for congruent stimulus pairings (e.g. respond to pictures of elderly faces or negative words) than for incongruent pairings (e.g. respond to elderly faces or positive words). As information processing leading to a certain attitude must precede differential brain activity according to the congruence of the paired words and faces, we show that this type of information is activated almost immediately following the structural encoding of the face, between 170 and 230 ms after onset of the face.

  18. Variegation of comet 67P/Churyumov-Gerasimenko in regions showing activity

    NASA Astrophysics Data System (ADS)

    Oklay, N.; Vincent, J.-B.; Fornasier, S.; Pajola, M.; Besse, S.; Davidsson, B. J. R.; Lara, L. M.; Mottola, S.; Naletto, G.; Sierks, H.; Barucci, A. M.; Scholten, F.; Preusker, F.; Pommerol, A.; Masoumzadeh, N.; Lazzarin, M.; Barbieri, C.; Lamy, P. L.; Rodrigo, R.; Koschny, D.; Rickman, H.; A'Hearn, M. F.; Bertaux, J.-L.; Bertini, I.; Bodewits, D.; Cremonese, G.; Da Deppo, V.; Debei, S.; De Cecco, M.; Fulle, M.; Groussin, O.; Gutiérrez, P. J.; Güttler, C.; Hall, I.; Hofmann, M.; Hviid, S. F.; Ip, W.-H.; Jorda, L.; Keller, H. U.; Knollenberg, J.; Kovacs, G.; Kramm, J.-R.; Kührt, E.; Küppers, M.; Lin, Z.-Y.; Lopez Moreno, J. J.; Marzari, F.; Moreno, F.; Shi, X.; Thomas, N.; Toth, I.; Tubiana, C.

    2016-02-01

    Aims.We carried out an investigation of the surface variegation of comet 67P/Churyumov-Gerasimenko, the detection of regions showing activity, the determination of active and inactive surface regions of the comet with spectral methods, and the detection of fallback material. Methods: We analyzed multispectral data generated with Optical, Spectroscopic, and Infrared Remote Imaging System (OSIRIS) narrow angle camera (NAC) observations via spectral techniques, reflectance ratios, and spectral slopes in order to study active regions. We applied clustering analysis to the results of the reflectance ratios, and introduced the new technique of activity thresholds to detect areas potentially enriched in volatiles. Results: Local color inhomogeneities are detected over the investigated surface regions. Active regions, such as Hapi, the active pits of Seth and Ma'at, the clustered and isolated bright features in Imhotep, the alcoves in Seth and Ma'at, and the large alcove in Anuket, have bluer spectra than the overall surface. The spectra generated with OSIRIS NAC observations are dominated by cometary emissions of around 700 nm to 750 nm as a result of the coma between the comet's surface and the camera. One of the two isolated bright features in the Imhotep region displays an absorption band of around 700 nm, which probably indicates the existence of hydrated silicates. An absorption band with a center between 800-900 nm is tentatively observed in some regions of the nucleus surface. This absorption band can be explained by the crystal field absorption of Fe2+, which is a common spectral feature seen in silicates.

  19. Active thermal testing of moisture in bricks

    NASA Astrophysics Data System (ADS)

    Bison, Paolo G.; Bressan, Chiara; Grinzato, Ermanno G.; Marinetti, Sergio; Vavilov, Vladimir P.

    1993-04-01

    Measurement by active thermal testing of effusivity on porous moistened material is analyzed. Moistened bricks show that thermal properties of this porous solid depend on water content. Various solutions of the heat transfer problem are taken into account and approximations introduced to simplify the data reduction are discussed. Error analysis is also considered to justify the adoption of relative technique. Errors analysis speaks strongly in favor of reference method which allows to avoid the measurement of incident energy and optical properties of a specimen. This procedure allows to introduce a rather simple expression to extract moisture values from one-side thermal test. Diffusivity measurement trough flash method is proposed to determine the influence of moisture on the variation of thermal conductivity.

  20. Active testing search for point cloud matching.

    PubMed

    Pinheiro, Miguel Amável; Sznitman, Raphael; Serradell, Eduard; Kybic, Jan; Moreno-Noguer, Francesc; Fua, Pascal

    2013-01-01

    We present a general approach for solving the point-cloud matching problem for the case of mildly nonlinear transformations. Our method quickly finds a coarse approximation of the solution by exploring a reduced set of partial matches using an approach to which we refer to as Active Testing Search (ATS). We apply the method to registration of graph structures by branching point matching. It is based solely on the geometric position of the points, no additional information is used nor the knowledge of an initial alignment. In the second stage, we use dynamic programming to refine the solution. We tested our algorithm on angiography, retinal fundus, and neuronal data gathered using electron and light microscopy. We show that our method solves cases not solved by most approaches, and is faster than the remaining ones.

  1. Two chitinase-like proteins abundantly accumulated in latex of mulberry show insecticidal activity

    PubMed Central

    2010-01-01

    Background Plant latex is the cytoplasm of highly specialized cells known as laticifers, and is thought to have a critical role in defense against herbivorous insects. Proteins abundantly accumulated in latex might therefore be involved in the defense system. Results We purified latex abundant protein a and b (LA-a and LA-b) from mulberry (Morus sp.) and analyzed their properties. LA-a and LA-b have molecular masses of approximately 50 and 46 kDa, respectively, and are abundant in the soluble fraction of latex. Western blotting analysis suggested that they share sequence similarity with each other. The sequences of LA-a and LA-b, as determined by Edman degradation, showed chitin-binding domains of plant chitinases at the N termini. These proteins showed small but significant chitinase and chitosanase activities. Lectin RCA120 indicated that, unlike common plant chitinases, LA-a and LA-b are glycosylated. LA-a and LA-b showed insecticidal activities when fed to larvae of the model insect Drosophila melanogaster. Conclusions Our results suggest that the two LA proteins have a crucial role in defense against herbivorous insects, possibly by hydrolyzing their chitin. PMID:20109180

  2. Two Analogues of Fenarimol Show Curative Activity in an Experimental Model of Chagas Disease

    PubMed Central

    2013-01-01

    Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is an increasing threat to global health. Available medicines were introduced over 40 years ago, have undesirable side effects, and give equivocal results of cure in the chronic stage of the disease. We report the development of two compounds, 6 and (S)-7, with PCR-confirmed curative activity in a mouse model of established T. cruzi infection after once daily oral dosing for 20 days at 20 mg/kg 6 and 10 mg/kg (S)-7. Compounds 6 and (S)-7 have potent in vitro activity, are noncytotoxic, show no adverse effects in vivo following repeat dosing, are prepared by a short synthetic route, and have druglike properties suitable for preclinical development. PMID:24304150

  3. Endolymphatic Sac Tumor Showing Increased Activity on 68Ga DOTATATE PET/CT.

    PubMed

    Papadakis, Georgios Z; Millo, Corina; Sadowski, Samira M; Bagci, Ulas; Patronas, Nicholas J

    2016-10-01

    Endolymphatic sac tumors (ELSTs) are rare tumors arising from the epithelium of the endolymphatic sac and duct that can be either sporadic or associated with von Hippel-Lindau (VHL) disease. We report a case of a VHL patient with histologically proven residual ELST who underwent Ga DOTATATE PET/CT showing increased activity (SUVmax, 6.29) by the ELST. The presented case of a VHL-associated ELST with increased Ga DOTATATE uptake indicates cell-surface expression of somatostatin receptors by this tumor, suggesting the potential application of somatostatin receptor imaging using Ga DOTA-conjugated peptides in the workup and management of these patients.

  4. Heterocyclic aromatic hydrocarbons show estrogenic activity upon metabolization in a recombinant transactivation assay.

    PubMed

    Brinkmann, Markus; Maletz, Sibylle; Krauss, Martin; Bluhm, Kerstin; Schiwy, Sabrina; Kuckelkorn, Jochen; Tiehm, Andreas; Brack, Werner; Hollert, Henner

    2014-05-20

    Heterocyclic aromatic hydrocarbons (hetero-PAHs) are increasingly studied at contaminated sites; especially at former industrial facilities where coal tar-oil was handled, e.g., wood treatment plants, high concentrations of hetero-PAHs are frequently detected in groundwater plumes. In previous studies, fractions of groundwater with high estrogenic activity contained hetero-PAHs and their hydroxylated metabolites. To evaluate this preliminary evidence, selected hetero-PAHs were screened for their estrogenic activity in lyticase yeast estrogen screen (LYES) and ER CALUX. All tested substances were inactive in the LYES. Hetero-PAHs such as acridine, xanthene, indole, 2-methylbenzofuran, 2,3-dimethylbenzofuran, dibenzofuran, dibenzothiophene, quinoline, and 6-methylquinoline were positive in the ER CALUX, with estradiol equivalence factors (EEFs) from 2.85 × 10(-7) to 3.18 × 10(-5). The EEF values of these substances were comparable to those of other xenoestrogens (e.g., alkylphenols or bisphenol A) that are sometimes found in surface water. Chemical analyses revealed that T47Dluc cells could metabolize most of the substances. Among the metabolites (tentatively) identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) were hydroxides and their keto tautomers, sulfates, sulfoxides, and N-oxides. Because of their high concentrations measured in groundwater, we conclude that hetero-PAHs and metabolites may be a potential risk and should be the subject of further research.

  5. Minimized natural versions of fungal ribotoxins show improved active site plasticity.

    PubMed

    Maestro-López, Moisés; Olombrada, Miriam; García-Ortega, Lucía; Serrano-González, Daniel; Lacadena, Javier; Oñaderra, Mercedes; Gavilanes, José G; Martínez-Del-Pozo, Álvaro

    2017-04-01

    Fungal ribotoxins are highly specific extracellular RNases which cleave a single phosphodiester bond at the ribosomal sarcin-ricin loop, inhibiting protein biosynthesis by interfering with elongation factors. Most ribotoxins show high degree of conservation, with similar sizes and amino acid sequence identities above 85%. Only two exceptions are known: hirsutellin A and anisoplin, produced by the entomopathogenic fungi Hirsutella thompsonii and Metarhizium anisopliae, respectively. Both proteins are similar but smaller than the other known ribotoxins (130 vs 150 amino acids), displaying only about 25% sequence identity with them. They can be considered minimized natural versions of their larger counterparts, best represented by α-sarcin. The conserved α-sarcin active site residue Tyr48 has been replaced by the geometrically equivalent Asp, present in the minimized ribotoxins, to produce and characterize the corresponding mutant. As a control, the inverse anisoplin mutant (D43Y) has been also studied. The results show how the smaller versions of ribotoxins represent an optimum compromise among conformational freedom, stability, specificity, and active-site plasticity which allow these toxic proteins to accommodate the characteristic abilities of ribotoxins into a shorter amino acid sequence and more stable structure of intermediate size between that of other nontoxic fungal RNases and previously known larger ribotoxins.

  6. Children with High Functioning Autism show increased prefrontal and temporal cortex activity during error monitoring

    PubMed Central

    Goldberg, Melissa C.; Spinelli, Simona; Joel, Suresh; Pekar, James J.; Denckla, Martha B.; Mostofsky, Stewart H.

    2010-01-01

    Evidence exists for deficits in error monitoring in autism. These deficits may be particularly important because they may contribute to excessive perseveration and repetitive behavior in autism. We examined the neural correlates of error monitoring using fMRI in 8–12-year-old children with high-functioning autism (HFA, n=11) and typically developing children (TD, n=15) during performance of a Go/No-Go task by comparing the neural correlates of commission errors versus correct response inhibition trials. Compared to TD children, children with HFA showed increased BOLD fMRI signal in the anterior medial prefrontal cortex (amPFC) and the left superior temporal gyrus (STempG) during commission error (versus correct inhibition) trials. A follow-up region-of-interest analysis also showed increased BOLD signal in the right insula in HFA compared to TD controls. Our findings of increased amPFC and STempG activity in HFA, together with the increased activity in the insula, suggest a greater attention towards the internally-driven emotional state associated with making an error in children with HFA. Since error monitoring occurs across different cognitive tasks throughout daily life, an increased emotional reaction to errors may have important consequences for early learning processes. PMID:21151713

  7. Staurosporine shows insecticidal activity against Mythimna separata Walker (Lepidoptera: Noctuidae) potentially via induction of apoptosis.

    PubMed

    Zhang, Yang; Liu, Songlin; Yang, Xing; Yang, Mingjun; Xu, Wenping; Li, Yaxiao; Tao, Liming

    2016-03-01

    Staurosporine (STS), a wide-spectrum kinase inhibitor, is widely used in studies of apoptosis in mammalian cells. However, its physiological and mechanistic effects have never been clearly defined in insect cells, and other applications of STS have rarely been reported. The present study reveals the insecticidal activity of STS on larvae of Mythimna separata Walker, and the apoptotic mechanism induced by STS on lepidopteran Sf9 cell lines. We demonstrate that the viability of Sf9 cells is inhibited by STS in a time- and concentration-dependent manner. Intracellular biochemical assays show that STS-induced apoptosis of Sf9 cells coincides with a decrease in the mitochondrial membrane potential, the release of cytochrome c into the cytosol, a significant increase of the Bax/Bcl-2 ratio, and a marked activation of caspase-9 and caspase-3. These results indicate that a mitochondrial-dependent intrinsic pathway contributes to STS induced caspase-3 activation and apoptosis in Sf9 cells which is homologous to the mechanisms in mammalian cells. This study contributes to our understanding of the mechanism of insect cell apoptosis and suggests a possible new application of STS as a potential insecticide against Lepidopteran insect pests in agriculture.

  8. Adolescent earthquake survivors' show increased prefrontal cortex activation to masked earthquake images as adults.

    PubMed

    Du, Xue; Wei, Dongtao; Ganzel, Barbara L; Kim, Pilyoung; Zhang, Qinglin; Qiu, Jiang

    2015-03-01

    The great Sichuan earthquake in China on May 12, 2008 was a traumatic event to many who live near the earthquake area. However, at present, there are few studies that explore the long-term impact of the adolescent trauma exposure on adults' brain function. In the present study, we used functional magnetic resonance imaging (fMRI) to investigate the brain activation evoked by masked trauma-related stimuli (earthquake versus neutral images) in 14 adults who lived near the epicenter of the great Sichuan earthquake when they were adolescents (trauma-exposed group) and 14 adults who lived farther from the epicenter of the earthquake when they were adolescents (control group). Compared with the control group, the trauma-exposed group showed significant elevation of activation in the right anterior cingulate cortex (ACC) and the medial prefrontal cortex (MPFC) in response to masked earthquake-related images. In the trauma-exposed group, the right ACC activation was negatively correlated with the frequency of symptoms of post-traumatic stress disorder (PTSD). These findings differ markedly from the long-term effects of trauma exposure in adults. This suggests that trauma exposure during adolescence may have a unique long-term impact on ACC/MPFC function, top-down modulation of trauma-related information, and subsequent symptoms of PTSD.

  9. Men and women show distinct brain activations during imagery of sexual and emotional infidelity.

    PubMed

    Takahashi, Hidehiko; Matsuura, Masato; Yahata, Noriaki; Koeda, Michihiko; Suhara, Tetsuya; Okubo, Yoshiro

    2006-09-01

    Jealousy-related behaviors such as intimate partner violence and morbid jealousy are more common in males. Principal questionnaire studies suggest that men and women have different modules to process cues of sexual and emotional infidelity. We aimed to elucidate the neural response to sentences depicting sexual and emotional infidelity in men and women using functional magnetic resonance imaging. Although there was no sex difference in the self-rating score of jealousy for sexual and emotional infidelity, men and women showed different brain activation patterns in response to the two types of infidelity. During jealous conditions, men demonstrated greater activation than women in the brain regions involved in sexual/aggressive behaviors such as the amygdala and hypothalamus. In contrast, women demonstrated greater activation in the posterior superior temporal sulcus. Our fMRI results are in favor of the notion that men and women have different neuropsychological modules to process sexual and emotional infidelity. Our findings might contribute to a better understanding of the neural basis of the jealousy-related behaviors predominantly observed in males.

  10. An inhibitory RNA aptamer against the lambda cI repressor shows transcriptional activator activity in vivo.

    PubMed

    Ohuchi, Shoji; Suess, Beatrix

    2017-04-13

    An RNA aptamer is one of the promising components for constructing artificial genetic circuits. In this study, we developed a transcriptional activator based on an RNA aptamer against one of the most frequently applied repressor proteins, lambda phage cI. In vitro selection (SELEX), followed by in vivo screening identified an RNA aptamer with the intended transcriptional activator activity from an RNA pool containing a 40-nucleotide long random region. Quantitative analysis showed 35-fold elevation of reporter expression upon aptamer expression. These results suggest that the diversity of artificial transcriptional activators can be extended by employing RNA aptamers against repressor proteins to broaden the tools available for constructing genetic circuits. This article is protected by copyright. All rights reserved.

  11. Etoposide incorporated into camel milk phospholipids liposomes shows increased activity against fibrosarcoma in a mouse model.

    PubMed

    Maswadeh, Hamzah M; Aljarbou, Ahmad N; Alorainy, Mohammed S; Alsharidah, Mansour S; Khan, Masood A

    2015-01-01

    Phospholipids were isolated from camel milk and identified by using high performance liquid chromatography and gas chromatography-mass spectrometry (GC/MS). Anticancer drug etoposide (ETP) was entrapped in liposomes, prepared from camel milk phospholipids, to determine its activity against fibrosarcoma in a murine model. Fibrosarcoma was induced in mice by injecting benzopyrene (BAP) and tumor-bearing mice were treated with various formulations of etoposide, including etoposide entrapped camel milk phospholipids liposomes (ETP-Cam-liposomes) and etoposide-loaded DPPC-liposomes (ETP-DPPC-liposomes). The tumor-bearing mice treated with ETP-Cam-liposomes showed slow progression of tumors and increased survival compared to free ETP or ETP-DPPC-liposomes. These results suggest that ETP-Cam-liposomes may prove to be a better drug delivery system for anticancer drugs.

  12. Cysteamine, the natural metabolite of pantetheinase, shows specific activity against Plasmodium.

    PubMed

    Min-Oo, Gundula; Ayi, Kodjo; Bongfen, Silayuv E; Tam, Mifong; Radovanovic, Irena; Gauthier, Susan; Santiago, Helton; Rothfuchs, Antonio Gigliotti; Roffê, Ester; Sher, Alan; Mullick, Alaka; Fortin, Anny; Stevenson, Mary M; Kain, Kevin C; Gros, Philippe

    2010-08-01

    In mice, loss of pantetheinase activity causes susceptibility to infection with Plasmodium chabaudi AS. Treatment of mice with the pantetheinase metabolite cysteamine reduces blood-stage replication of P. chabaudi and significantly increases survival. Similarly, a short exposure of Plasmodium to cysteamine ex vivo is sufficient to suppress parasite infectivity in vivo. This effect of cysteamine is specific and not observed with a related thiol (dimercaptosuccinic acid) or with the pantethine precursor of cysteamine. Also, cysteamine does not protect against infection with the parasite Trypanosoma cruzi or the fungal pathogen Candida albicans, suggesting cysteamine acts directly against the parasite and does not modulate host inflammatory response. Cysteamine exposure also blocks replication of P. falciparum in vitro; moreover, these treated parasites show higher levels of intact hemoglobin. This study highlights the in vivo action of cysteamine against Plasmodium and provides further evidence for the involvement of pantetheinase in host response to this infection.

  13. Montmorillonite enhanced ciprofloxacin transport in saturated porous media with sorbed ciprofloxacin showing antibiotic activity

    NASA Astrophysics Data System (ADS)

    Chen, Hao; Gao, Bin; Yang, Liu-Yan; Ma, Lena Q.

    2015-02-01

    Antibiotic ciprofloxacin (CIP) is immobile in the subsurface but it has been frequently detected in the aquatic system. Therefore it is important to investigate the factors impacting CIP's mobilization in aquifer. Laboratory columns packed with sand were used to test colloid-facilitated CIP transport by 1) using kaolinite or montmorillonite to mobilize presorbed-CIP in a column or 2) co-transporting with CIP by pre-mixing them before transport. The Langmuir model showed that CIP sorption by montmorillonite (23 g kg- 1) was 100 times more effective than sand or kaolinite. Even with strong CIP complexation ability to Fe/Al coating on sand surface, montmorillonite promoted CIP transport, but not kaolinite. All presorbed-CIP by sand was mobilized by montmorillonite after 3 pore volumes through co-transporting of CIP with montmorillonite. The majority of CIP was fixed onto the montmorillonite interlayer but still showed inhibition of bacteria growth. Our results suggested that montmorillonite with high CIP sorption ability can act as a carrier to enhance CIP's mobility in aquifer.

  14. DC-159a Shows Inhibitory Activity against DNA Gyrases of Mycobacterium leprae

    PubMed Central

    Yamaguchi, Tomoyuki; Yokoyama, Kazumasa; Nakajima, Chie

    2016-01-01

    Background Fluoroquinolones are a class of antibacterial agents used for leprosy treatment. Some new fluoroquinolones have been attracting interest due to their remarkable potency that is reportedly better than that of ofloxacin, the fluoroquinolone currently recommended for treatment of leprosy. For example, DC-159a, a recently developed 8-methoxy fluoroquinolone, has been found to be highly potent against various bacterial species. Nonetheless, the efficacy of DC-159a against Mycobacterium leprae is yet to be examined. Methodology/Principal Findings To gather data that can support highly effective fluoroquinolones as candidates for new remedies for leprosy treatment, we conducted in vitro assays to assess and compare the inhibitory activities of DC-159a and two fluoroquinolones that are already known to be more effective against M. leprae than ofloxacin. The fluoroquinolone-inhibited DNA supercoiling assay using recombinant DNA gyrases of wild type and ofloxacin-resistant M. leprae revealed that inhibitory activities of DC-159a and sitafloxacin were at most 9.8- and 11.9-fold higher than moxifloxacin. Also the fluoroquinolone–mediated cleavage assay showed that potencies of those drugs were at most 13.5- and 9.8-fold higher than moxifloxacin. In addition, these two drugs retained their inhibitory activities even against DNA gyrases of ofloxacin-resistant M. leprae. Conclusions/Significance The results indicated that DC-159a and sitafloxacin are more effective against wild type and mutant M. leprae DNA gyrases than moxifloxacin, suggesting that these antibacterial drugs can be good candidates that may supersede current fluoroquinolone remedies. DC-159a in particular is very promising because it is classified in a subgroup of fluoroquinolones that is known to be less likely to cause adverse effects. Our results implied that DC-159a is well worth further investigation to ascertain its in vivo effectiveness and clinical safety for humans. PMID:27681932

  15. Sphaeropsidin A shows promising activity against drug-resistant cancer cells by targeting regulatory volume increase

    PubMed Central

    Mathieu, Véronique; Chantôme, Aurélie; Lefranc, Florence; Cimmino, Alessio; Miklos, Walter; Paulitschke, Verena; Mohr, Thomas; Maddau, Lucia; Kornienko, Alexander; Berger, Walter; Vandier, Christophe; Evidente, Antonio; Delpire, Eric; Kiss, Robert

    2016-01-01

    Despite the recent advances in the treatment of tumors with intrinsic chemotherapy resistance, such as melanoma and renal cancers, their prognosis remains poor and new chemical agents with promising activity against these cancers are urgently needed. Sphaeropsidin A, a fungal metabolite whose anticancer potential had previously received little attention, was isolated from Diplodia cupressi and found to display specific anticancer activity in vitro against melanoma and kidney cancer subpanels in the National Cancer Institute (NCI) 60-cell line screen. The NCI data revealed a mean LC50 of ca. 10 μM and a cellular sensitivity profile that did not match that of any other agent in the 765,000 compound database. Subsequent mechanistic studies in melanoma and other multidrug-resistant in vitro cancer models showed that sphaeropsidin A can overcome apoptosis as well as multidrug resistance by inducing a marked and rapid cellular shrinkage related to the loss of intracellular Cl− and the decreased HCO3− concentration in the culture supernatant. These changes in ion homeostasis and the absence of effects on the plasma membrane potential were attributed to the sphaeropsidin A-induced impairment of regulatory volume increase (RVI). Preliminary results also indicate that depending on the type of cancer, the sphaeropsidin A effects on RVI could be related to Na–K–2Cl electroneutral cotransporter or Cl−/HCO3− anion exchanger(s) targeting. This study underscores the modulation of ion-transporter activity as a promising therapeutic strategy to combat drug-resistant cancers and identifies the fungal metabolite, sphaeropsidin A, as a lead to develop anticancer agents targeting RVI in cancer cells. PMID:25868554

  16. Novel, potent and selective inhibitors of protein kinase C show oral anti-inflammatory activity.

    PubMed

    Nixon, J S; Bishop, J; Bradshaw, D; Davis, P D; Hill, C H; Elliott, L H; Kumar, H; Lawton, G; Lewis, E J; Mulqueen, M

    1991-01-01

    Clarification of the precise role of protein kinase C (PKC) in cellular functional responses has been hampered by a lack of potent, selective inhibitors. The structural lead provided by staurosporine, a potent but non-selective protein kinase (PK) inhibitor, was used to derive a series of bis(indolyl)maleimides of which the most potent, Ro 31-8425 (I50: PKC = 8 nM) showed 350-fold selectivity for PKC over cAMP-dependent protein kinase. Ro 31-8425 antagonised cellular processes triggered by phorbol esters (potent, specific PKC activators) and inhibited the allogeneic mixed lymphocyte reaction, suggesting a role for PKC in T-cell activation. Methylation of the primary amine in Ro 31-8425 produced an analogue. Ro 31-8830 which, when administered orally, produced a dose-dependent inhibition of a phorbol ester-induced paw oedema in mice (minimum effective dose = 15 mg/kg). Ro 31-8830 also selectively inhibited the secondary inflammation in a developing adjuvant arthritis model in the rat. The results presented here suggest that these selective inhibitors of PKC may have therapeutic value in the treatment of T-cell-mediated autoimmune diseases.

  17. Aluminum hydroxide nanoparticles show a stronger vaccine adjuvant activity than traditional aluminum hydroxide microparticles.

    PubMed

    Li, Xinran; Aldayel, Abdulaziz M; Cui, Zhengrong

    2014-01-10

    Aluminum hydroxide is used as a vaccine adjuvant in various human vaccines. Unfortunately, despite its favorable safety profile, aluminum hydroxide can only weakly or moderately potentiate antigen-specific antibody responses. When dispersed in an aqueous solution, aluminum hydroxide forms particulates of 1-20μm. There is increasing evidence that nanoparticles around or less than 200nm as vaccine or antigen carriers have a more potent adjuvant activity than large microparticles. In the present study, we synthesized aluminum hydroxide nanoparticles of 112nm. Using ovalbumin and Bacillus anthracis protective antigen protein as model antigens, we showed that protein antigens adsorbed on the aluminum hydroxide nanoparticles induced a stronger antigen-specific antibody response than the same protein antigens adsorbed on the traditional aluminum hydroxide microparticles of around 9.3μm. The potent adjuvant activity of the aluminum hydroxide nanoparticles was likely related to their ability to more effectively facilitate the uptake of the antigens adsorbed on them by antigen-presenting cells. Finally, the local inflammation induced by aluminum hydroxide nanoparticles in the injection sites was milder than that induced by microparticles. Simply reducing the particle size of the traditional aluminum hydroxide adjuvant into nanometers represents a novel and effective approach to improve its adjuvanticity.

  18. Boehmenan, a lignan from Hibiscus ficulneus, showed Wnt signal inhibitory activity.

    PubMed

    Shono, Takumi; Ishikawa, Naoki; Toume, Kazufumi; Arai, Midori A; Ahmed, Firoj; Sadhu, Samir K; Ishibashi, Masami

    2015-07-15

    The Wnt signal pathway modulates numerous biological processes, and its aberrant activation is related to various diseases. Therefore, inhibition of the Wnt signal may provide an effective (or efficient) strategy for these diseases. Cell-based luciferase assay targeting the Wnt signal (TOP assay) revealed that Hibiscus ficulneus extract inhibited the Wnt signal. The activity-guided isolation of the MeOH extract of H. ficulneus stems yielded four known (1-4) lignans along with myriceric acid (5). Compounds 1-4 potently inhibited the Wnt signal with TOPflash IC50 values of 1.0, 4.5, 6.3, and 1.9 μM, respectively. Compound 1 exhibited cytotoxicity against both Wnt-dependent (HCT116) and Wnt-independent (RKO) cells. Western blot analysis showed that 1 decreased the expression of full, cytosolic and nuclear β-catenin along with c-myc in STF/293 cells. Our results suggested that 1 may have inhibited the Wnt signal by decreasing β-catenin levels.

  19. The left occipitotemporal cortex does not show preferential activity for words.

    PubMed

    Vogel, Alecia C; Petersen, Steven E; Schlaggar, Bradley L

    2012-12-01

    Regions in left occipitotemporal (OT) cortex, including the putative visual word form area, are among the most commonly activated in imaging studies of single-word reading. It remains unclear whether this part of the brain is more precisely characterized as specialized for words and/or letters or contains more general-use visual regions having properties useful for processing word stimuli, among others. In Analysis 1, we found no evidence of greater activity in left OT regions for words or letter strings relative to other high-spatial frequency high-contrast stimuli, including line drawings and Amharic strings (which constitute the Ethiopian writing system). In Analysis 2, we further investigated processing characteristics of OT cortex potentially useful in reading. Analysis 2 showed that a specific part of OT cortex 1) is responsive to visual feature complexity, measured by the number of strokes forming groups of letters or Amharic strings and 2) processes learned combinations of characters, such as those in words and pseudowords, as groups but does not do so in consonant and Amharic strings. Together, these results indicate that while regions of left OT cortex are not specialized for words, at least part of OT cortex has properties particularly useful for processing words and letters.

  20. Water Extract of Fructus Hordei Germinatus Shows Antihyperprolactinemia Activity via Dopamine D2 Receptor

    PubMed Central

    Wang, Xiong; Ma, Li; Zhang, En-jing; Zou, Ji-li; Guo, Hao; Peng, Si-wei; Wu, Jin-hu

    2014-01-01

    Objective. Fructus Hordei Germinatus is widely used in treating hyperprolactinemia (hyperPRL) as a kind of Chinese traditional herb in China. In this study, we investigated the anti-hyperPRL activity of water extract of Fructus Hordei Germinatus (WEFHG) and mechanism of action. Methods. Effect of WEFHG on serum prolactin (PRL), estradiol (E2), progesterone (P), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and hypothalamus protein kinase A (PKA) and cyclic adenosine monophosphate (cAMP) levels of hyperPRL rats were investigated. And effect of WEFHG on PRL secretion, D2 receptors, and dopamine transporters (DAT) was studied in MMQ, GH3, and PC12 cells, respectively. Results. WEFHG reduced the secretion of PRL in hyperPRL rats effectively. In MMQ cell, treatment with WEFHG at 1–5 mg/mL significantly suppressed PRL secretion and synthesis. Consistent with a D2-action, WEFHG did not affect PRL in rat pituitary lactotropic tumor-derived GH3 cells that lack the D2 receptor expression but significantly increased the expression of D2 receptors and DAT in PC12 cells. In addition, WEFHG reduced the cAMP and PKA levels of hypothalamus in hyperPRL rats significantly. Conclusions. WEFHG showed anti-hyperPRL activity via dopamine D2 receptor, which was related to the second messenger cAMP and PKA. PMID:25254056

  1. Neural activation in the "reward circuit" shows a nonlinear response to facial attractiveness.

    PubMed

    Liang, Xiaoyun; Zebrowitz, Leslie A; Zhang, Yi

    2010-01-01

    Positive behavioral responses to attractive faces have led neuroscientists to investigate underlying neural mechanisms in a "reward circuit" that includes brain regions innervated by dopamine pathways. Using male faces ranging from attractive to extremely unattractive, disfigured ones, this study is the first to demonstrate heightened responses to both rewarding and aversive faces in numerous areas of this putative reward circuit. Parametric analyses employing orthogonal linear and nonlinear regressors revealed positive nonlinear effects in anterior cingulate cortex, lateral orbital frontal cortex (LOFC), striatum (nucleus accumbens, caudate, putamen), and ventral tegmental area, in addition to replicating previously documented linear effects in medial orbital frontal cortex (MOFC) and LOFC and nonlinear effects in amygdala and MOFC. The widespread nonlinear responses are consistent with single cell recordings in animals showing responses to both rewarding and aversive stimuli, and with some human fMRI investigations of non-face stimuli. They indicate that the reward circuit does not process face valence with any simple dissociation of function across structures. Perceiver gender modulated some responses to our male faces: Women showed stronger linear effects, and men showed stronger nonlinear effects, which may have functional implications. Our discovery of nonlinear responses to attractiveness throughout the reward circuit echoes the history of amygdala research: Early work indicated a linear response to threatening stimuli, including faces; later work also revealed a nonlinear response with heightened activation to affectively salient stimuli regardless of valence. The challenge remains to determine how such dual coding influences feelings, such as pleasure and pain, and guides goal-related behavioral responses, such as approach and avoidance.

  2. Chlorpheniramine-induced anaphylaxis diagnosed by basophil activation test.

    PubMed

    Lee, Hyun-Seung; Song, Woo-Jung; Lee, Ji-Won; Cho, Young-Yoon; Park, Han-Ki; Kang, Min-Gyu; Cho, Sang-Heon; Sohn, Seong-Wook

    2015-07-01

    Chlorpheniramine is a widely prescribed H1-antihistamine for relieving urticaria or histamine-mediated allergic reactions. However, although rare, it may cause immediate hypersensitivity reactions. The diagnosis is usually made by provocation test, but its application is often limited due to comorbidities or potential risk of severe reactions. In those cases, skin tests and basophil activation tests can be considered as additional diagnostic tests for the drug allergy. Here, we report a 33-year-old female with underlying chronic urticaria, who recurrently developed anaphylaxis after chlorpheniramine administration. Intradermal test showed positive responses in the patient at 0.02 mg/mL of chlorpheniramine, but not in healthy controls. Basophil activation test showed significant up-regulation of CD63 and CD203c by chlorpheniramine. The present case reminds the rare but potential allergic risk of chlorpheniramine, and also suggests the potential utility of basophil activation test in making the diagnosis.

  3. HATS-2b: A transiting extrasolar planet orbiting a K-type star showing starspot activity

    NASA Astrophysics Data System (ADS)

    Mohler-Fischer, M.; Mancini, L.; Hartman, J. D.; Bakos, G. Á.; Penev, K.; Bayliss, D.; Jordán, A.; Csubry, Z.; Zhou, G.; Rabus, M.; Nikolov, N.; Brahm, R.; Espinoza, N.; Buchhave, L. A.; Béky, B.; Suc, V.; Csák, B.; Henning, T.; Wright, D. J.; Tinney, C. G.; Addison, B. C.; Schmidt, B.; Noyes, R. W.; Papp, I.; Lázár, J.; Sári, P.; Conroy, P.

    2013-10-01

    We report the discovery of HATS-2b, the second transiting extrasolar planet detected by the HATSouth survey. HATS-2b is moving on a circular orbit around a V = 13.6 mag, K-type dwarf star (GSC 6665-00236), at a separation of 0.0230 ± 0.0003 AU and with a period of 1.3541 days. The planetary parameters have been robustly determined using a simultaneous fit of the HATSouth, MPG/ESO 2.2 m/GROND, Faulkes Telescope South/Spectral transit photometry, and MPG/ESO 2.2 m/FEROS, Euler 1.2 m/CORALIE, AAT 3.9 m/CYCLOPS radial-velocity measurements. HATS-2b has a mass of 1.37 ± 0.16 MJ, a radius of 1.14 ± 0.03 RJ, and an equilibrium temperature of 1567 ± 30 K. The host star has a mass of 0.88 ± 0.04 M⊙ and a radius of 0.89 ± 0.02 R⊙, and it shows starspot activity. We characterized the stellar activity by analyzing two photometric follow-up transit light curves taken with the GROND instrument, both obtained simultaneously in four optical bands (covering the wavelength range of 3860-9520 Å). The two light curves contain anomalies compatible with starspots on the photosphere of the host star along the same transit chord. Tables of the individual photometric measurements are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/558/A55

  4. Total alkaloids of Rubus alceifolius Poir shows anti-angiogenic activity in vivo and in vitro.

    PubMed

    Zhao, Jinyan; Lin, Wei; Zhuang, Qunchuan; Zhong, Xiaoyong; Cao, Zhiyun; Hong, Zhenfeng; Peng, Jun

    2014-11-01

    Total alkaloids is an active ingredient of the natural plant Rubus alceifolius Poir, commonly used for the treatment of various cancers. Antitumor effects may be mediated through anti-angiogenic mechanisms. As such, the goal of the present study was to investigate and evaluate the effect of total alkaloids in Rubus alceifolius Poir (TARAP) on tumor angiogenesis and investigate the underlying molecular mechanisms of TARAP action in vivo and in vitro. A chick embryo chorioallantoic membrane (CAM) assay was used to assess angiogenesis in vivo. An MTT assay was performed to determine the viability of human umbilical vein endothelial cells (HUVECs) with and without treatment. Cell cycle progression of HUVECs was examined by FACS analysis with propidium iodide staining. HUVEC migration was determined using a scratch wound method. Tube formation of HUVECs was assessed with an ECMatrix gel system, and mRNA and protein expression of VEGF-A in both HUVECs and HepG2 human hepatocellular carcinoma cells were examined by RT-PCR and ELISA, respectively. Our results showed that TARAP inhibited angiogenesis in the CAM model in vivo and inhibited HUVEC proliferation via blocking cell cycle G1 to S progression in a dose- and time-dependent manners in vitro. Moreover, TARAP inhibited HUVEC migration and tube formation and downregulated mRNA and protein expression of VEGF-A in both HepG2 cells and HUVECs. Our findings suggest that the anti-angiogenic activity of TARAP may partly contribute to its antitumor properties and may be valuable for the treatment of diseases involving pathologic angiogenesis such as cancer.

  5. Using analogy role-play activity in an undergraduate biology classroom to show central dogma revision.

    PubMed

    Takemura, Masaharu; Kurabayashi, Mario

    2014-01-01

    For the study of biology in an undergraduate classroom, a classroom exercise was developed: an analogy role-play to learn mechanisms of gene transcription and protein translation (central dogma). To develop the central dogma role-play exercise, we made DNA and mRNA using paper sheets, tRNA using a wire dress hanger, and amino acids using Lego® blocks (Lego System A/S, Denmark). Students were studying in the course of mathematics, physics, or chemistry, so biology was not among their usual studies. In this exercise, students perform the central dogma role-play and respectively act out nuclear matrix proteins, a transcription factor, an RNA polymerase II, an mRNA transport protein, nuclear pore proteins, a large ribosomal subunit, a small ribosomal subunit, and several amino-acyl tRNA synthetases. Questionnaire results obtained after the activity show that this central dogma role-play analogy holds student interest in the practical molecular biological processes of transcription and translation.

  6. Novel Peptides from Skins of Amphibians Showed Broad-Spectrum Antimicrobial Activities.

    PubMed

    Wang, Ying; Zhang, Yue; Lee, Wen-Hui; Yang, Xinwang; Zhang, Yun

    2016-03-01

    Peptide agents are often considered as potential biomaterials for developing new drugs that can overcome the rising resistance of pathogenic micro-organisms to classic antibiotic treatments. One key source of peptide agents is amphibian skin, as they provide a great deal of naturally occurring antimicrobial peptide (AMP) templates awaiting further exploitation and utilization. In this study, 12 novel AMPs from the skins of 3 ranid frogs, Rana limnocharis, R. exilispinosa, and Amolops afghanus, were identified using a 5' PCR primer. A total of 11 AMPs exhibited similarities with currently known AMP families, including brevinin-1, brevinin-2, esculentin-1, and nigrocin, besides, one AMP, named as Limnochariin, represented a novel AMP family. All 12 AMPs contain a C-terminus cyclic motif and most of them show obvious antimicrobial activities against 18 standard and clinically isolated strains of bacteria, including 4 Gram-positive bacteria, 11 Gram-negative bacteria, and 3 fungus. These findings provide helpful insight that will be useful in the design of anti-infective peptide agents.

  7. Biofunctional constituent isolated from Citrullus colocynthis fruits and structure-activity relationships of its analogues show acaricidal and insecticidal efficacy.

    PubMed

    Jeon, Ju-Hyun; Lee, Hoi-Seon

    2014-08-27

    The acaricidal and insecticidal potential of the active constituent isolated from Citrullus colocynthis fruits and its structurally related analogues was evaluated by performing leaf disk, contact toxicity, and fumigant toxicity bioassays against Tetranychus urticae, Sitophilus oryzae, and Sitophilus zeamais adults. The active constituent of C. colocynthis fruits was isolated by chromatographic techniques and was identified as 4-methylquinoline on the basis of spectroscopic analyses. To investigate the structure-activity relationships, 4-methylquinoline and its structural analogues were tested against mites and two insect pests. On the basis of the LC50 values, 7,8-benzoquinoline was the most effective against T. urticae. Quinoline, 8-hydroxyquinoline, 2-methylquinoline, 4-methylquinoline, 6-methylquinoline, 8-methylquinoline, and 7,8-benzoquinoline showed high insecticidal activities against S. oryzae and S. zeamais regardless of the application method. These results indicate that introduction of a functional group into the quinoline skeleton and changing the position of the group have an important influence on the acaricidal and insecticidal activities. Furthermore, 4-methylquinoline isolated from C. colocynthis fruits, along with its structural analogues, could be effective natural pesticides for managing spider mites and stored grain weevils.

  8. Syzyguim guineense Extracts Show Antioxidant Activities and Beneficial Activities on Oxidative Stress Induced by Ferric Chloride in the Liver Homogenate.

    PubMed

    Pieme, Constant Anatole; Ngoupayo, Joseph; Nkoulou, Claude Herve Khou-Kouz; Moukette, Bruno Moukette; Nono, Borgia Legrand Njinkio; Moor, Vicky Jocelyne Ama; Minkande, Jacqueline Ze; Ngogang, Jeanne Yonkeu

    2014-09-19

    The aim of this study was to determine the in vitro antioxidant activity, free radical scavenging property and the beneficial effects of extracts of various parts of Syzygium guineense in reducing oxidative stress damage in the liver. The effects of extracts on free radicals were determined on radicals DPPH, ABTS, NO and OH followed by the antioxidant properties using Ferric Reducing Antioxidant Power assay (FRAP) and hosphomolybdenum (PPMB). The phytochemical screening of these extracts was performed by determination of the phenolic content. The oxidative damage inhibition in the liver was determined by measuring malondialdehyde (MDA) as well as the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and peroxidase. Overall, the bark extract of the ethanol/water or methanol showed the highest radical scavenging activities against DPPH, ABTS and OH radicals compared to the other extracts. This extract also contained the highest phenolic content implying the potential contribution of phenolic compounds towards the antioxidant activities. However, the methanol extract of the root demonstrated the highest protective effects of SOD and CAT against ferric chloride while the hydro-ethanol extract of the leaves exhibited the highest inhibitory effects on lipid peroxidation. These findings suggest that antioxidant properties of S. guineense extracts could be attributed to phenolic compounds revealed by phytochemical studies. Thus, the present results indicate clearly that the extracts of S. guineense possess antioxidant properties and could serve as free radical inhibitors or scavengers, acting possibly as primary antioxidants. The antioxidant properties of the bark extract may thus sustain its various biological activities.

  9. Syzyguim guineense Extracts Show Antioxidant Activities and Beneficial Activities on Oxidative Stress Induced by Ferric Chloride in the Liver Homogenate

    PubMed Central

    Pieme, Constant Anatole; Ngoupayo, Joseph; Khou-Kouz Nkoulou, Claude Herve; Moukette Moukette, Bruno; Njinkio Nono, Borgia Legrand; Ama Moor, Vicky Jocelyne; Ze Minkande, Jacqueline; Yonkeu Ngogang, Jeanne

    2014-01-01

    The aim of this study was to determine the in vitro antioxidant activity, free radical scavenging property and the beneficial effects of extracts of various parts of Syzygium guineense in reducing oxidative stress damage in the liver. The effects of extracts on free radicals were determined on radicals DPPH, ABTS, NO and OH followed by the antioxidant properties using Ferric Reducing Antioxidant Power assay (FRAP) and hosphomolybdenum (PPMB). The phytochemical screening of these extracts was performed by determination of the phenolic content. The oxidative damage inhibition in the liver was determined by measuring malondialdehyde (MDA) as well as the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and peroxidase. Overall, the bark extract of the ethanol/water or methanol showed the highest radical scavenging activities against DPPH, ABTS and OH radicals compared to the other extracts. This extract also contained the highest phenolic content implying the potential contribution of phenolic compounds towards the antioxidant activities. However, the methanol extract of the root demonstrated the highest protective effects of SOD and CAT against ferric chloride while the hydro-ethanol extract of the leaves exhibited the highest inhibitory effects on lipid peroxidation. These findings suggest that antioxidant properties of S. guineense extracts could be attributed to phenolic compounds revealed by phytochemical studies. Thus, the present results indicate clearly that the extracts of S. guineense possess antioxidant properties and could serve as free radical inhibitors or scavengers, acting possibly as primary antioxidants. The antioxidant properties of the bark extract may thus sustain its various biological activities. PMID:26785075

  10. Quercetin and quercetin 3-O-glycosides from Bauhinia longifolia (Bong.) Steud. show anti-Mayaro virus activity

    PubMed Central

    2014-01-01

    Background The arthropod-borne Mayaro virus (MAYV) causes ‘Mayaro fever’, a disease of medical significance, primarily affecting individuals in permanent contact with forested areas in tropical South America. Recently, MAYV has attracted attention due to its likely urbanization. Currently, there are no licensed drugs against most mosquito-transmitted viruses. Here, we investigated the in vitro anti-MAYV activity of the flavonoids quercetin and its derivatives from the Brazilian shrub Bauhinia longifolia (Bong.) Steud. Methods Flavonoids were purified by chromatographic fractionation from leaf extracts of B. longifolia and chemically identified as quercetin and quercetin glycosides using spectroscopic techniques. Cytotoxicity of purified flavonoids and of EtOAc- and n-BuOH-containing flavonoid mixtures was measured by the dye-uptake assay while their antiviral activity was evaluated by a virus yield inhibition assay. Results The following flavonoids were purified from B. longifolia leaves: non-glycosylated quercetin and its glycosides guaijaverin, quercitrin, isoquercitrin, and hyperin. EtOAc and n-BuOH fractions containing these flavonoids demonstrated the highest antiviral activity of all tested substances, while quercetin had the highest antiviral activity amongst purified flavonoids. Quercetin, EtOAc, or n-BuOH fractions inhibited MAYV production by more than 90% at 25 μg/mL, displaying a stronger antiviral effect than the licensed antiviral ribavirin. A mixture of the isomers isoquercitrin and hyperin had a modest antiviral effect (IC90 = 104.9), while guaijaverin and quercitrin did not show significant antiviral activity. Conclusions B. longifolia is a good source of flavonoids with anti-Mayaro virus activity. This is the first report of the activity of quercetin and its derivatives against an alphavirus. PMID:24678592

  11. Single concentration tests show synergism among Bacillus thuringiensis subsp. israelensis toxins against the malaria vector mosquito Anopheles albimanus.

    PubMed

    Fernández-Luna, María Teresa; Tabashnik, Bruce E; Lanz-Mendoza, Humberto; Bravo, Alejandra; Soberón, Mario; Miranda-Ríos, Juan

    2010-07-01

    Bioassays of insecticidal proteins from Bacillus thuringiensis subsp. israelensis with larvae of the malaria vector mosquito Anopheles albimanus showed that the cytolytic protein Cyt1Aa was not toxic alone, but it increased the toxicity of the crystalline proteins Cry4Ba and Cry11Aa. Synergism also occurred between Cry4Ba and Cry11Aa toxins. Whereas many previous analyses of synergism have been based on a series of toxin concentrations leading to comparisons between expected and observed values for the concentration killing 50% of insects tested (LC(50)), we describe and apply a method here that enables testing for synergism based on single concentrations of toxins.

  12. T cells conditioned with MDSC show an increased anti-tumor activity after adoptive T cell based immunotherapy.

    PubMed

    Raber, Patrick L; Sierra, Rosa A; Thevenot, Paul T; Shuzhong, Zhang; Wyczechowska, Dorota D; Kumai, Takumi; Celis, Esteban; Rodriguez, Paulo C

    2016-04-05

    The success of adoptive T cell-based immunotherapy (ACT) in cancer is limited in part by the accumulation of myeloid-derived suppressor cells (MDSC), which block several T cell functions, including T cell proliferation and the expression of various cytotoxic mediators. Paradoxically, the inhibition of CD8+ T cell differentiation into cytotoxic populations increased their efficacy after ACT into tumor-bearing hosts. Therefore, we aimed to test the impact of conditioning CD8+ T cells with MDSC on their differentiation potential and ACT efficacy. Our results indicate that MDSC impaired the progression of CD8+ T cells into effector populations, without altering their activation status, production of IL-2, or signaling through the T cell receptor. In addition, culture of CD8+ T cells with MDSC resulted in an increased ACT anti-tumor efficacy, which correlated with a higher frequency of the transferred T cells and elevated IFNγ production. Interestingly, activated CD62L+ CD8+ T cells were responsible for the enhanced anti-tumor activity showed by MDSC-exposed T cells. Additional results showed a decreased protein synthesis rate and lower activity of the mammalian/mechanistic target of rapamycin (mTOR) in T cells conditioned with MDSC. Silencing of the negative mTOR regulator tuberous sclerosis complex-2 in T cells co-cultured with MDSC restored mTOR activity, but resulted in T cell apoptosis. These results indicate that conditioning of T cells with MDSC induces stress survival pathways mediated by a blunted mTOR signaling, which regulated T cell differentiation and ACT efficacy. Continuation of this research will enable the development of better strategies to increase ACT responses in cancer.

  13. Platinum-based complexes of bioactive 3-(5-nitrofuryl)acroleine thiosemicarbazones showing anti-Trypanosoma cruzi activity.

    PubMed

    Vieites, Marisol; Otero, Lucía; Santos, Diego; Olea-Azar, Claudio; Norambuena, Ester; Aguirre, Gabriela; Cerecetto, Hugo; González, Mercedes; Kemmerling, Ulrike; Morello, Antonio; Diego Maya, Juan; Gambino, Dinorah

    2009-03-01

    Eight new platinum(II) complexes with 3-(5-nitrofuryl)acroleine thiosemicarbazones showing anti-trypanosomal activity were synthesized, characterized and in vitro evaluated. Most of the complexes showed IC(50) values in the micromolar range against two different strains of Trypanosoma cruzi, causative agent of Chagas disease (American Trypanosomiasis). In addition, most of the newly developed complexes, together with the analogous platinum 5-nitrofuraldehyde containing thiosemicarbazones previously reported, resulted more active than the reference trypanocidal drug nifurtimox on the infective trypomastigote form of the parasite. Their capacity to produce free radicals that could lead to parasite death was evaluated by ESR experiments in the parasite and by respiration measurements. Compounds were tested for their DNA interaction ability. Results showed that some of the compounds could act as dual inhibitors in the parasite, through production of toxic free radicals and interaction with DNA. All the results were compared with those previously reported for the free ligands, the analogous palladium(II) compounds and the previously reported series of platinum(II) compounds.

  14. A Boronic Acid Conjugate of Angiogenin that Shows ROS-Responsive Neuroprotective Activity.

    PubMed

    Hoang, Trish T; Smith, Thomas P; Raines, Ronald T

    2017-03-01

    Angiogenin (ANG) is a human ribonuclease that is compromised in patients with amyotrophic lateral sclerosis (ALS). ANG also promotes neovascularization, and can induce hemorrhage and encourage tumor growth. The causal neurodegeneration of ALS is associated with reactive oxygen species, which are also known to elicit the oxidative cleavage of carbon-boron bonds. We have developed a synthetic boronic acid mask that restrains the ribonucleolytic activity of ANG. The masked ANG does not stimulate endothelial cell proliferation but protects astrocytes from oxidative stress. By differentiating between the two dichotomous biological activities of ANG, this strategy could provide a viable pharmacological approach for the treatment of ALS.

  15. Basophil Activation Test identifies the patients with Chronic Spontaneous Urticaria suffering the most active disease

    PubMed Central

    Curto‐Barredo, Laia; Yelamos, Jose; Gimeno, Ramon; Mojal, Sergi; Pujol, Ramon M.

    2016-01-01

    Abstract Introduction The basophil activation test showing CD63 up regulation could be a specific and sensitive in vitro complementary text to the in vivo autologous serum skin test for the activity assessment of the patients suffering autoimmune chronic spontaneous urticaria. The aim of this study is to define the basophil activation test as a useful tool in clinical practice in order to identify those patients with more active disease. Methods We screened 139 patients (96 women) diagnosed of chronic spontaneous urticaria using simultaneously autologous serum skin test and basophil activation test and their relationship with disease activity. Results Positive autologous serum skin test was found in 56.8%; from them, 31.6% were basophil activation test positive. Negative autologous serum skin test result was found in the 43.2% of the sample that showed negative CD63 expression results in all cases, except one. Patients with positive autologous serum skin test and positive CD63 by basophil activation test showed significant higher Urticaria Activity Score of 7 days (P = 0.004) and of 3 weeks (P = 0.001) than patients with positive autologous serum skin test and negative CD63 (mean ± standard deviation [SD] 26.57 ± 10.56 versus 18.40 ± 12.05 for the Urticaria Activity Score of 7 days and 56.47 ± 23.78 versus 39.88 ± 25.44 for the Urticaria Activity Score of 3 weeks). Conclusions The CD63 expression on basophils appears as a reliable in vitro marker, useful in clinical practice in combination with autologous serum skin test to define chronic spontaneous urticaria patients with the highest urticaria activity that impairs a normal life. PMID:27980778

  16. DNA sequence-selective C8-linked pyrrolobenzodiazepine-heterocyclic polyamide conjugates show anti-tubercular-specific activities.

    PubMed

    Brucoli, Federico; Guzman, Juan D; Basher, Mohammad A; Evangelopoulos, Dimitrios; McMahon, Eleanor; Munshi, Tulika; McHugh, Timothy D; Fox, Keith R; Bhakta, Sanjib

    2016-12-01

    New chemotherapeutic agents with novel mechanisms of action are in urgent need to combat the tuberculosis pandemic. A library of 12 C8-linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD)-heterocyclic polyamide conjugates (1-12) was evaluated for anti-tubercular activity and DNA sequence selectivity. The PBD conjugates were screened against slow-growing Mycobacterium bovis Bacillus Calmette-Guérin and M. tuberculosis H37Rv, and fast-growing Escherichia coli, Pseudomonas putida and Rhodococcus sp. RHA1 bacteria. DNase I footprinting and DNA thermal denaturation experiments were used to determine the molecules' DNA recognition properties. The PBD conjugates were highly selective for the mycobacterial strains and exhibited significant growth inhibitory activity against the pathogenic M. tuberculosis H37Rv, with compound 4 showing MIC values (MIC=0.08 mg l(-1)) similar to those of rifampin and isoniazid. DNase I footprinting results showed that the PBD conjugates with three heterocyclic moieties had enhanced sequence selectivity and produced larger footprints, with distinct cleavage patterns compared with the two-heterocyclic chain PBD conjugates. DNA melting experiments indicated a covalent binding of the PBD conjugates to two AT-rich DNA-duplexes containing either a central GGATCC or GTATAC sequence, and showed that the polyamide chains affect the interactions of the molecules with DNA. The PBD-C8 conjugates tested in this study have a remarkable anti-mycobacterial activity and can be further developed as DNA-targeted anti-tubercular drugs.

  17. Water Works: A Great Show on Earth. Classroom Activities for Third and Fourth Grades.

    ERIC Educational Resources Information Center

    McClure, Judy; Clark, Neil

    This curriculum guide is divided into five lessons, each containing several activities that reflect the natural path of inquiry that third or fourth grade students might take in considering the water that arrives in their bathroom sinks each morning. Starting from the familiar faucet, the students are encouraged to reflect on their own habits and…

  18. Systematic Review Shows Only Few Reliable Studies of Physical Activity Intervention in Adolescents

    PubMed Central

    Soares, Nara Michelle Moura; Leão, Arley Santos; Santos, Josivan Rosa; Monteiro, Glauber Rocha; dos Santos, Jorge Rollemberg; Thomazzi, Sara Maria; Silva, Roberto Jerônimo dos Santos

    2014-01-01

    Introduction. Several studies have pointed to the high prevalence of low levels of physical activity in adolescents, suggesting the need for more effective interventions for this group. The aim of this study was to present evidence of intervention programs for efficacy of physical activity for adolescents. Methods. Surveys in PubMed, SportDiscus, LiLacs, and SciELO databases were conducted using keywords to identify population, intervention, and outcome, as well as DeCS and MeSH terms in English, Portuguese, and Spanish, whenever appropriate. The review included observational studies with minimal intervention of six months, minimum sample size of 100 adolescents, written in any language, and those who have reached STROBE score greater than 70%. Results. Only seven studies met all inclusion criteria. Of these, five were pre- and postintervention and two had n > 2000 participants. Interventions were of several types, durations, and strategies for physical activity implementation. Behavior change was assessed in 43% of studies and three reported success in some way. Conclusion. Due to heterogeneity in their contents and methodologies, as well as the lack of jobs that accompany adolescents after the intervention period, one cannot draw conclusions about the actual effects of the intervention programs of physical activity on the behavior of young people. PMID:25152903

  19. C(5) modified uracil derivatives showing antiproliferative and erythroid differentiation inducing activities on human chronic myelogenous leukemia K562 cells

    PubMed Central

    Brognara, Eleonora; Lampronti, Ilaria; Breveglieri, Giulia; Accetta, Alessandro; Corradini, Roberto; Manicardi, Alex; Borgatti, Monica; Canella, Alessandro; Multineddu, Chiara; Marchelli, Rosangela; Gambari, Roberto

    2011-01-01

    The K562 cell line has been proposed as a useful experimental system to identify anti-tumor compounds acting by inducing terminal erythroid differentiation. K562 cells exhibit a low proportion of hemoglobin-synthesizing cells under standard cell growth conditions, but are able to undergo terminal erythroid differentiation when treated with a variety of anti-tumor compounds. In this paper we report a screening study on a set of different modified C(5) uracil derivatives for the evaluation of their antiproliferative effect in connection with erythroid differentiation pathways, and for defining a new class of drug candidates for the treatment of chronic myelogenous leukemia. Activity of the derivatives tested can be classified in two effect: an antiproliferative effect linked to a high level of erythroid differentiation activity and an antiproliferative effect without activation of gamma globin genes The highest antiproliferative effect and erythroid induction was shown by compound 9, a thymine derivative bearing a n-octyl chain on nitrogen N(1), whereas thymine did not show any effect, suggesting the importance of the linear alkyl chain in position N(1). To our knowledge this compound should be considered among the most efficient inducers of erythroid differentiation of K562 cells. This work is the starting point for the quest of more effective and specific drugs for the induction of terminal erythroid differentiation, for leading new insights in the treatment of neoplastic diseases with molecules acting by inducing differentiation rather than by simply exerting cytotoxic effects. PMID:21958870

  20. A novel solubility-enhanced curcumin formulation showing stability and maintenance of anticancer activity.

    PubMed

    Zhang, Fang; Koh, Gar Yee; Jeansonne, Duane P; Hollingsworth, Javoris; Russo, Paul S; Vicente, Graca; Stout, Rhett W; Liu, Zhijun

    2011-07-01

    Curcumin (CUR) is an active food compound, but its insolubility and instability in water contributes to low bioavailability. In this study, the solubility of CUR was enhanced by utilizing the solubilizing properties of rubusoside (RUB). The solubility of CUR in water increased linearly from 61 μg/mL to 2.318 mg/mL in the presence of RUB ranging from 1% to 10% (w/v). Dynamic light scattering and transmission electron microscopy studies found that CUR and RUB formed CUR-RUB nanoparticle (∼8 nm) complexes. The RUB-solubilized CUR was stable in physiological conditions and did not precipitate when diluted or degrade when spray-dried to a completely reconstitutable powder. Furthermore, cell viability assays demonstrated the efficacy of RUB-solubilized CUR against human colon, breast, and pancreatic cancer cell lines. The development of this new solubilized, stable, and biologically active CUR formulation lays the foundation for future bioavailability improvement.

  1. Arginine kinase shows nucleoside diphosphate kinase-like activity toward deoxythymidine diphosphate.

    PubMed

    Lopez-Zavala, Alonso A; Sotelo-Mundo, Rogerio R; Hernandez-Flores, Jose M; Lugo-Sanchez, Maria E; Sugich-Miranda, Rocio; Garcia-Orozco, Karina D

    2016-06-01

    Arginine kinase (AK) (ATP: L-arginine phosphotransferase, E.C. 2.7.3.3) catalyzes the reversible transfer of ATP γ-phosphate group to L-arginine to synthetize phospho-arginine as a high-energy storage. Previous studies suggest additional roles for AK in cellular processes. Since AK is found only in invertebrates and it is homologous to creatine kinase from vertebrates, the objective of this work was to demonstrate nucleoside diphosphate kinase-like activity for shrimp AK. For this, AK from marine shrimp Litopenaeus vannamei (LvAK) was purified and its activity was assayed for phosphorylation of TDP using ATP as phosphate donor. Moreover, by using high-pressure liquid chromatography (HPLC) the phosphate transfer reaction was followed. Also, LvAK tryptophan fluorescence emission changes were detected by dTDP titration, suggesting that the hydrophobic environment of Trp 221, which is located in the top of the active site, is perturbed upon dTDP binding. The kinetic constants for both substrates Arg and dTDP were calculated by isothermal titration calorimetry (ITC). Besides, docking calculations suggested that dTDP could bind LvAK in the same cavity where ATP bind, and LvAK basic residues (Arg124, 126 and 309) stabilize the dTDP phosphate groups and the pyrimidine base interact with His284 and Ser122. These results suggest that LvAK bind and phosphorylate dTDP being ATP the phosphate donor, thus describing a novel alternate nucleoside diphosphate kinase-like activity for this enzyme.

  2. Identification of MET and SRC Activation in Melanoma Cell Lines Showing Primary Resistance to PLX403212

    PubMed Central

    Vergani, Elisabetta; Vallacchi, Viviana; Frigerio, Simona; Deho, Paola; Mondellini, Piera; Perego, Paola; Cassinelli, Giuliana; Lanzi, Cinzia; Testi, Maria Adele; Rivoltini, Licia; Bongarzone, Italia; Rodolfo, Monica

    2011-01-01

    PLX4032/vemurafenib is a first-in-class small-molecule BRAFV600E inhibitor with clinical activity in patients with BRAF mutant melanoma. Nevertheless, drug resistance develops in treated patients, and strategies to overcome primary and acquired resistance are required. To explore the molecular mechanisms involved in primary resistance to PLX4032, we investigated its effects on cell proliferation and signaling in a panel of 27 genetically characterized patient-derived melanoma cell lines. Cell sensitivity to PLX4032 was dependent on BRAFV600E and independent from other gene alterations that commonly occur in melanoma such as PTEN loss, BRAF, and MITF gene amplification. Two cell lines lacking sensitivity to PLX4032 and harboring a different set of genetic alterations were studied as models of primary resistance. Treatment with the MEK inhibitor UO126 but not with PLX4032 inhibited cell growth and ERK activation. Resistance to PLX4032 was maintained after CRAF down-regulation by siRNA indicating alternative activation of MEK-ERK signaling. Genetic characterization by multiplex ligation-dependent probe amplification and analysis of phosphotyrosine signaling by MALDI-TOF mass spectrometry analysis revealed the activation of MET and SRC signaling, associated with the amplification of MET and of CTNNB1 and CCND1 genes, respectively. The combination of PLX4032 with drugs or siRNA targeting MET was effective in inhibiting cell growth and reducing cell invasion and migration in melanoma cells with MET amplification; similar effects were observed after targeting SRC in the other cell line, indicating a role for MET and SRC signaling in primary resistance to PLX4032. Our results support the development of classification of melanoma in molecular subtypes for more effective therapies. PMID:22241959

  3. NF-κB dynamics show digital activation and analog information processing in cells

    NASA Astrophysics Data System (ADS)

    Tay, Savas; Hughey, Jake; Lee, Timothy; Lipniacki, Tomasz; Covert, Markus; Quake, Stephen

    2010-03-01

    Cells operate in ever changing environments using extraordinary communication capabilities. Cell-to-cell communication is mediated by signaling molecules that form spatiotemporal concentration gradients, which requires cells to respond to a wide range of signal intensities. We used high-throughput microfluidic cell culture, quantitative gene expression analysis and mathematical modeling to investigate how single mammalian cells respond to different concentrations of the signaling molecule TNF-α via the transcription factor NF-κB. We measured NF-κB activity in thousands of live cells under TNF-α doses covering four orders of magnitude. In contrast to population studies, the activation is a stochastic, switch-like process at the single cell level with fewer cells responding at lower doses. The activated cells respond fully and express early genes independent of the TNF-α concentration, while only high dose stimulation results in the expression of late genes. Cells also encode a set of analog parameters such as the NF-κB peak intensity, response time and number of oscillations to modulate the outcome. We developed a stochastic model that reproduces both the digital and analog dynamics as well as the gene expression profiles at all measured conditions, constituting a broadly applicable model for TNF-α induced NF-κB signaling in various types of cells.

  4. [The enzyme activity of bacilli showing promise for incorporation into biopreparations].

    PubMed

    Slabospitskaia, A T; Krymovskaia, S S; Reznik, S R

    1990-01-01

    The enzymic activity (amalyse, protease, lipase, pectolytic and cellulase) has been studied in 5 strains of aerobic spore-forming bacteria (Bacillus subtilis, B. licheniformis, B. coagulans, B. pumilis, B. badius) being of interest for creation of medical and prophylactic biopreparations. The above-mentioned enzymes were found in some studied strains. This may provide participation of bacilli in the degradation processes of a number of substrates in the digestive tract of a human being and animals and is an advantage of preparations from the genus Bacillus bacteria as compared with the available biopreparations of other microbial cultures for prophylaxis and treatment of gastrointestinal diseases.

  5. Alcoholic Extract of Eclipta alba Shows In Vitro Antioxidant and Anticancer Activity without Exhibiting Toxicological Effects

    PubMed Central

    Arya, Rakesh Kumar; Dev, Kapil; Sharma, Chetan; Hossain, Zakir; Meena, Sanjeev; Arya, K. R.; Gayen, J. R.

    2017-01-01

    As per WHO estimates, 80% of people around the world use medicinal plants for the cure and prevention of various diseases including cancer owing to their easy availability and cost effectiveness. Eclipta alba has long been used in Ayurveda to treat liver diseases, eye ailments, and hair related disorders. The promising medicinal value of E. alba prompted us to study the antioxidant, nontoxic, and anticancer potential of its alcoholic extract. In the current study, we evaluated the in vitro cytotoxic and antioxidant effect of the alcoholic extract of Eclipta alba (AEEA) in multiple cancer cell lines along with control. We have also evaluated its effect on different in vivo toxicity parameters. Here, we found that AEEA was found to be most active in most of the cancer cell lines but it significantly induced apoptosis in human breast cancer cell lines by disrupting mitochondrial membrane potential and DNA damage. Moreover, AEEA treatment inhibited migration in both MCF 7 and MDA-MB-231 cells in a dose dependent manner. Further, AEEA possesses robust in vitro antioxidant activity along with high total phenolic and flavonoid contents. In summary, our results indicate that Eclipta alba has enormous potential in complementary and alternative medicine for the treatment of cancer. PMID:28250894

  6. X-ray microtomography shows pore structure and tortuosity in alkali-activated binders

    SciTech Connect

    Provis, John L.; Myers, Rupert J.; White, Claire E.; Rose, Volker; Deventer, Jannie S.J. van

    2012-06-15

    Durability of alkali-activated binders is of vital importance in their commercial application, and depends strongly on microstructure and pore network characteristics. X-ray microtomography ({mu}CT) offers, for the first time, direct insight into microstructural and pore structure characteristics in three dimensions. Here, {mu}CT is performed on a set of sodium metasilicate-activated fly ash/slag blends, using a synchrotron beamline instrument. Segmentation of the samples into pore and solid regions is then conducted, and pore tortuosity is calculated by a random walker method. Segmented porosity and diffusion tortuosity are correlated, and vary as a function of slag content (slag addition reduces porosity and increases tortuosity), and sample age (extended curing gives lower porosity and higher tortuosity). This is particularly notable for samples with {>=} 50% slag content, where a space-filling calcium (alumino)silicate hydrate gel provides porosity reductions which are not observed for the sodium aluminosilicate ('geopolymer') gels which do not chemically bind water of hydration.

  7. Medicinal plants and their isolated compounds showing anti-Trichomonas vaginalis- activity.

    PubMed

    Mehriardestani, Mozhgan; Aliahmadi, Atousa; Toliat, Tayebeh; Rahimi, Roja

    2017-04-01

    Trichomonas vaginalis is a major of non-viral sexually-transmitted infection and an important cause of serious obstetrical and gynecological complications. Treatment options for trichomoniasis are limited to nitroimidazole compounds. The increasing resistance and allergic reactions to nitroimidazole and recurrent trichomoniasis make it essential to identify and develop new drugs against trichomoniasis. Medicinal plants are an important source for discovery of new medications. This review discusses the anti-trichomonas effects of medicinal plants and their chemical constituents to find better options against this pathogenic protozoon. Electronic databases were searched to collect all data from the year 2000 through September 2015 for in vitro, in vivo and clinical studies on the effect of medicinal plants on T. vaginalis. A total of 95 in vitro and clinical studies were identified. Only four human studies were found in this review. The Asteracea, Lamiaceae and Myrtaceae families contained the greatest number of plants with anti-trichomonas activity. Persea americana, Ocimum basilicum and Verbascum thapsus were the most efficacious against T. vaginalis. Plant metabolites containing alkaloids, isoflavonoid glucosides, essential oils, lipids, saponins and sesquiterpene lactones were found to possess anti-trichomonas properties. Assessing the structure-activity of highly-potent anti-trichomonas phytochemicals is suggested for finding natural, semisynthetic and synthetic anti-trichomonas compounds. Further clinical studies are necessary for confirmation of natural anti-trichomonas substances and completion of their safety profiles.

  8. Bacillus cereus strain S2 shows high nematicidal activity against Meloidogyne incognita by producing sphingosine

    PubMed Central

    Gao, Huijuan; Qi, Gaofu; Yin, Rong; Zhang, Hongchun; Li, Chenggang; Zhao, Xiuyun

    2016-01-01

    Plant-parasitic nematodes cause serious crop losses worldwidely. This study intended to discover the antagonistic mechanism of Bacillus cereus strain S2 against Meloidogyne incognita. Treatment with B. cereus strain S2 resulted in a mortality of 77.89% to Caenorhabditis elegans (a model organism) and 90.96% to M. incognita. In pot experiment, control efficiency of B. cereus S2 culture or supernatants were 81.36% and 67.42% towards M. incognita, respectively. In field experiment, control efficiency was 58.97% towards M. incognita. Nematicidal substances were isolated from culture supernatant of B. cereus S2 by polarity gradient extraction, silica gel column chromatography and HPLC. Two nematicidal compounds were identified as C16 sphingosine and phytosphingosine by LC-MS. The median lethal concentration of sphingosine was determined as 0.64 μg/ml. Sphingosine could obviously inhibit reproduction of C. elegans, with an inhibition rate of 42.72% for 24 h. After treatment with sphingosine, ROS was induced in intestinal tract, and genital area disappeared in nematode. Furthermore, B. cereus S2 could induce systemic resistance in tomato, and enhance activity of defense-related enzymes for biocontrol of M. incognita. This study demonstrates the nematicidal activity of B. cereus and its product sphingosine, as well provides a possibility for biocontrol of M. incognita. PMID:27338781

  9. Rhesus macaques (Macaca mulatta) with self-injurious behavior show less behavioral anxiety during the human intruder test.

    PubMed

    Peterson, Emily J; Worlein, Julie M; Lee, Grace H; Dettmer, Amanda M; Varner, Elana K; Novak, Melinda A

    2017-01-01

    Self-injurious behavior (SIB) has been linked to anxiety in the human literature, but relatively few studies have explored this link in rhesus macaques. A widely used behavioral assessment of anxiety, the human intruder test (HIT), employs the mildly stressful stimulus of an unfamiliar experimenter to assess anxious behavior in macaques. The HIT was conducted on 59 (20 male) laboratory housed rhesus macaques, 30 with a record of SIB (10 male). If monkeys with SIB have a more anxious phenotype, they should show stronger reactions to the HIT. However, contrary to our predictions, monkeys with SIB did not show higher levels of anxious behavior compared to controls. They spent significantly less time showing anxious behavior and displayed little aggression in response to the stare of the intruder. SIB and control monkeys did not differ in a range score (number of unique behaviors expressed per phase); however, SIB monkeys had a lower change score (total number of behaviors expressed including repetitions) than controls. In general, monkeys that paced regardless of SIB status, showed a reduction in pacing when the intruder entered the room. Possible explanations for the failure of SIB monkeys to show increased anxiety in the HIT include greater exposure of SIB monkeys to unfamiliar humans because of their condition, evidence for a subtype of SIB which is not anxiety related, and/or the presence of comorbid depressive-like symptoms. Am. J. Primatol. 79:e22569, 2017. © 2016 Wiley Periodicals, Inc.

  10. Arabidopsis profilin isoforms, PRF1 and PRF2 show distinctive binding activities and subcellular distributions.

    PubMed

    Wang, Feng; Jing, Yanping; Wang, Zhen; Mao, Tonglin; Samaj, Jozef; Yuan, Ming; Ren, Haiyun

    2009-02-01

    Profilin is an actin-binding protein that shows complex effects on the dynamics of the actin cytoskeleton. There are five profilin isoforms in Arabidopsis thaliana L. However, it is still an open question whether these isoforms are functionally different. In the present study, two profilin isoforms from Arabidopsis, PRF1 and PRF2 were fused with green fluorescent protein (GFP) tag and expressed in Escherichia coli and A. thaliana in order to compare their biochemical properties in vitro and their cellular distributions in vivo. Biochemical analysis revealed that fusion proteins of GFP-PRF1 and GFP-PRF2 can bind to poly-L-proline and G-actin showing remarkable differences. GFP-PRF1 has much higher affinities for both poly-L-proline and G-actin compared with GFP-PRF2. Observations of living cells in stable transgenic A. thaliana lines revealed that 35S::GFP-PRF1 formed a filamentous network, while 35S::GFP-PRF2 formed polygonal meshes. Results from the treatment with latrunculin A and a subsequent recovery experiment indicated that filamentous alignment of GFP-PRF1 was likely associated with actin filaments. However, GFP-PRF2 localized to polygonal meshes resembling the endoplasmic reticulum. Our results provide evidence that Arabidopsis profilin isoforms PRF1 and PRF2 have different biochemical affinities for poly-L-proline and G-actin, and show distinctive localizations in living cells. These data suggest that PRF1 and PRF2 are functionally different isoforms.

  11. Cell-penetrating peptide TP10 shows broad-spectrum activity against both Plasmodium falciparum and Trypanosoma brucei brucei.

    PubMed

    Arrighi, Romanico B G; Ebikeme, Charles; Jiang, Yang; Ranford-Cartwright, Lisa; Barrett, Michael P; Langel, Ulo; Faye, Ingrid

    2008-09-01

    Malaria and trypanosomiasis are diseases which afflict millions and for which novel therapies are urgently required. We have tested two well-characterized cell-penetrating peptides (CPPs) for antiparasitic activity. One CPP, designated TP10, has broad-spectrum antiparasitic activity against Plasmodium falciparum, both blood and mosquito stages, and against blood-stage Trypanosoma brucei brucei.

  12. γ Sulphate PNA (PNA S): highly selective DNA binding molecule showing promising antigene activity.

    PubMed

    Avitabile, Concetta; Moggio, Loredana; Malgieri, Gaetano; Capasso, Domenica; Di Gaetano, Sonia; Saviano, Michele; Pedone, Carlo; Romanelli, Alessandra

    2012-01-01

    Peptide Nucleic Acids (PNAs), nucleic acid analogues showing high stability to enzyme degradation and strong affinity and specificity of binding toward DNA and RNA are widely investigated as tools to interfere in gene expression. Several studies have been focused on PNA analogues with modifications on the backbone and bases in the attempt to overcome solubility, uptake and aggregation issues. γ PNAs, PNA derivatives having a substituent in the γ position of the backbone show interesting properties in terms of secondary structure and affinity of binding toward complementary nucleic acids. In this paper we illustrate our results obtained on new analogues, bearing a sulphate in the γ position of the backbone, developed to be more DNA-like in terms of polarity and charge. The synthesis of monomers and oligomers is described. NMR studies on the conformational properties of monomers and studies on the secondary structure of single strands and triplexes are reported. Furthermore the hybrid stability and the effect of mismatches on the stability have also been investigated. Finally, the ability of the new analogue to work as antigene, interfering with the transcription of the ErbB2 gene on a human cell line overexpressing ErbB2 (SKBR3), assessed by FACS and qPCR, is described.

  13. A nanoporous metallic mat showing excellent and stable surface enhanced Raman spectroscopy activities.

    PubMed

    Kim, Nam-Jung; Lin, Mengshi

    2010-08-01

    A novel nanoporous mat structure was made of gold nanoparticles through a simple, inexpensive self-assembly process as a bottom-up approach to produce an affordable and high-quality SERS substrate. This nanostructure mat shows an excellent SERS reproducibility, physical stability, and strong Raman enhancement, which may satisfy all the criteria as a universal-type SERS substrate. The limit of detection for crystal violet dye on the nanostructured substrates is estimated to reach ppb levels and the SERS enhancement factor is found to be two orders of magnitude higher than that from conventional de-alloy nanoporous films. Mechanical strength of the nano-cluster network can be increased by a post-assembly annealing process. The nanoparticle-based SERS substrate holds promise in practical sensing applications toward a rapid determination of harmful substances or contaminants in food and environment.

  14. Antioxidant, Antimicrobial Activity and Toxicity Test of Pilea microphylla

    PubMed Central

    Modarresi Chahardehi, Amir; Ibrahim, Darah; Fariza Sulaiman, Shaida

    2010-01-01

    A total of 9 plant extracts were tested, using two different kinds of extracting methods to evaluate the antioxidant and antimicrobial activities from Pilea microphylla (Urticaceae family) and including toxicity test. Antioxidant activity were tested by using DPPH free radical scavenging, also total phenolic contents and total flavonoid contents were determined. Toxicity assay carried out by using brine shrimps. Methanol extract of method I (ME I) showed the highest antioxidant activity at 69.51 ± 1.03. Chloroform extract of method I (CE I) showed the highest total phenolic contents at 72.10 ± 0.71 and chloroform extract of method II (CE II) showed the highest total flavonoid contents at 60.14 ± 0.33. The antimicrobial activity of Pilea microphylla extract was tested in vitro by using disc diffusion method and minimum inhibitory concentration (MIC). The Pilea microphylla extract showed antibacterial activity against some Gram negative and positive bacteria. The extracts did not exhibit antifungal and antiyeast activity. The hexane extract of method I (HE I) was not toxic against brine shrimp (LC50 value was 3880 μg/ml). Therefore, the extracts could be suitable as antimicrobial and antioxidative agents in food industry. PMID:20652052

  15. Quantitative and Qualitative Responses to Topical Cold in Healthy Caucasians Show Variance between Individuals but High Test-Retest Reliability

    PubMed Central

    Moss, Penny; Whitnell, Jasmine; Wright, Anthony

    2016-01-01

    Increased sensitivity to cold may be a predictor of persistent pain, but cold pain threshold is often viewed as unreliable. This study aimed to determine the within-subject reliability and between-subject variance of cold response, measured comprehensively as cold pain threshold plus pain intensity and sensation quality at threshold. A test-retest design was used over three sessions, one day apart. Response to cold was assessed at four sites (thenar eminence, volar forearm, tibialis anterior, plantar foot). Cold pain threshold was measured using a Medoc thermode and standard method of limits. Intensity of pain at threshold was rated using a 10cm visual analogue scale. Quality of sensation at threshold was quantified with indices calculated from subjects' selection of descriptors from a standard McGill Pain Questionnaire. Within-subject reliability for each measure was calculated with intra-class correlation coefficients and between-subject variance was evaluated as group coefficient of variation percentage (CV%). Gender and site comparisons were also made. Forty-five healthy adults participated: 20 male, 25 female; mean age 29 (range 18–56) years. All measures at all four test sites showed high within-subject reliability: cold pain thresholds r = 0.92–0.95; pain rating r = 0.93–0.97; McGill pain quality indices r = 0.87–0.85. In contrast, all measures showed wide between-subject variance (CV% between 51.4% and 92.5%). Upper limb sites were consistently more sensitive than lower limb sites, but equally reliable. Females showed elevated cold pain thresholds, although similar pain intensity and quality to males. Females were also more reliable and showed lower variance for all measures. Thus, although there was clear population variation, response to cold for healthy individuals was found to be highly reliable, whether measured as pain threshold, pain intensity or sensation quality. A comprehensive approach to cold response testing therefore may add validity

  16. Active diffraction gratings: Development and tests

    NASA Astrophysics Data System (ADS)

    Bonora, S.; Frassetto, F.; Zanchetta, E.; Della Giustina, G.; Brusatin, G.; Poletto, L.

    2012-12-01

    We present the realization and characterization of an active spherical diffraction grating with variable radius of curvature to be used in grazing-incidence monochromators. The device consists of a bimorph deformable mirror on the top of which a diffraction grating with laminar profile is realized by UV lithography. The experimental results show that the active grating can optimize the beam focalization of visible wavelengths through its rotation and focus accommodation.

  17. Estradiol shows anti-skin cancer activities through decreasing MDM2 expression.

    PubMed

    Li, Li; Feng, Jianguo; Chen, Ying; Li, Shun; Ou, Mengting; Sun, Weichao; Tang, Liling

    2017-01-31

    Estradiol plays important roles in many biological responses inducing tumor genesis and cancer treatment. However, the effects of estradiol on tumors were inconsistent among a lot of researches and the mechanism is not fully understood. Our previous study indicated that splicing factor hnRNPA1 could bind to the human homologue of mouse double minute (MDM2), an oncogene which has been observed to be over-expressed in numerous types of cancers. In this research, we investigated whether and how estradiol correlate to cancer cell behaviors through heterogeneous nuclear ribonucleoprotein (hnRNPA1) and MDM2. Results showed that 10×10-13Mestradiol elevated the expression of hnRNPA1 regardless ER expression in cells, and then down-regulated the expression of MDM2. At the same time, estradiol inhibited cell proliferation, migration and epithelial-mesenchymal transition progression of A375 and GLL19 cells. While, knocking down hnRNPA1 through the transfection of hnRNPA1 siRNA led to the increase of MDM2 at both protein level and gene level In vivo experiment, subcutaneous injection with estradiol every two days near the tumor at doses of 2.5mg/kg/d suppressed tumor growth and reduced MDM2 expression. In a word, via increasing hnRNPA1 level and then reducing the expression of MDM2, estradiol prevented carcinogenesis in melanomas. We confirmed therapeutic effect of estradiol, as well as a new way for estradiol to resist skin cancer.

  18. KefF, the regulatory subunit of the potassium efflux system KefC, shows quinone oxidoreductase activity.

    PubMed

    Lyngberg, Lisbeth; Healy, Jessica; Bartlett, Wendy; Miller, Samantha; Conway, Stuart J; Booth, Ian R; Rasmussen, Tim

    2011-09-01

    Escherichia coli and many other Gram-negative pathogenic bacteria protect themselves from the toxic effects of electrophilic compounds by using a potassium efflux system (Kef). Potassium efflux is coupled to the influx of protons, which lowers the internal pH and results in immediate protection. The activity of the Kef system is subject to complex regulation by glutathione and its S conjugates. Full activation of KefC requires a soluble ancillary protein, KefF. This protein has structural similarities to oxidoreductases, including human quinone reductases 1 and 2. Here, we show that KefF has enzymatic activity as an oxidoreductase, in addition to its role as the KefC activator. It accepts NADH and NADPH as electron donors and quinones and ferricyanide (in addition to other compounds) as acceptors. However, typical electrophilic activators of the Kef system, e.g., N-ethyl maleimide, are not substrates. If the enzymatic activity is disrupted by site-directed mutagenesis while retaining structural integrity, KefF is still able to activate the Kef system, showing that the role as an activator is independent of the enzyme activity. Potassium efflux assays show that electrophilic quinones are able to activate the Kef system by forming S conjugates with glutathione. Therefore, it appears that the enzymatic activity of KefF diminishes the redox toxicity of quinones, in parallel with the protection afforded by activation of the Kef system.

  19. Basophil activation tests: time for a reconsideration.

    PubMed

    Uyttebroek, Astrid P; Sabato, Vito; Faber, Margaretha A; Cop, Nathalie; Bridts, Chris H; Lapeere, Hilde; De Clerck, Luc S; Ebo, Didier G

    2014-10-01

    Challenges in in vitro allergy diagnostics lie in the development of accessible and reliable assays allowing identification of all offending allergens and cross-reactive structures. Flow-assisted analysis and quantification of in vitro activated basophils serves as a diagnostic instrument with increasing applications developed over the years. From the earliest days it was clear that the test could constitute a diagnostic asset in basophil-mediated hypersensitivity. However, utility of the basophil activation test should be reassessed regarding difficulties with preparation, characterization and validation of allergen extracts; availability and the potential of more accessible diagnostics. Today, the added value mainly lies in diagnosis of immediate drug hypersensitivity. Other potential indications are monitoring venom-immunotherapy and follow-up of natural history of food allergies. However, results in these nondiagnostic applications are preliminary. We review the most relevant clinical applications of the basophil activation test. Some personal comments and views about perspectives and challenges about flow-assisted allergy diagnosis are made.

  20. Frontal theta activity during working memory in test anxiety.

    PubMed

    Shi, Zhan; Gao, Xin; Zhou, Renlai

    2015-03-04

    Previous studies have shown that working memory (WM) processes are related to frontal-midline theta (FM-theta) activity (4-8 Hz) and test anxiety impairs WM performance. However, the effect of test anxiety on FM-theta activity during WM has not been investigated as yet. To examine this question, 37 undergraduates were asked to complete a modified reading span task involving neutral working memory capacity (WMC) and emotional WMC while their electroencephalography was measured. The results showed that relative to neutral WMC performance (the ability to remember the letter lists in the context of valence-neutral sentences), emotional WMC performance (the ability to remember the letter lists in the context of test-related sentences) was poorer for highly test anxious participants compared with lowly test anxious participants. Relative to FM-theta activity during remembering the letter lists in the valence-neutral context, FM-theta activity was weaker during remembering the letter lists in the test-related context for highly test anxious participants compared with lowly test anxious participants. These findings indicate that FM-theta is an index not only for successful WM manipulation but also for efficient prefrontal cortex functioning during WM.

  1. Standardization activities for harmonization of test results.

    PubMed

    Dati, F; Brand, B

    2000-07-01

    In the last years the search for sensitive and specific markers of renal damage and/or renal function has conducted to the development of laboratory assays for measurement of urinary proteins such as albumin, beta(2)-microglobulin, alpha(1)-microglobulin, cystatin C, etc. Furthermore, there have been new applications of already known markers based on different, reformulated methods which often rely on more advanced technologies. It is evident that such developments are connected with analytical and interpretative problems for laboratory managers and clinicians. In this situation, it is essential that international societies develop comprehensive measures for the quality management of these assays and issue uniform and carefully elaborated guidelines to ensure optimal test utilization. International activities are also directed to the development of optimized and standardized methods as well as to the production and evaluation of appropriate reference materials and, finally, to the establishment of appropriate reference ranges and cut-off values for specific analytes. The main use of reference materials is in the transfer of their accurately assigned values to the calibrators of diagnostic companies for calibration of commercially available test systems. These international standardization activities and strategies will allow a harmonized approach to disease management using a more reliable laboratory testing based on quality and value.

  2. Patients with idiopathic recurrent miscarriage show higher levels of DR+ activated T-cells that are less responsive to mitogens.

    PubMed

    Kuon, R J; Schaumann, J; Goeggl, T; Strowitzki, T; Sadeghi, M; Opelz, G; Daniel, V; Toth, B

    2015-11-01

    In 50% of recurrent miscarriages (RM) the cause remains unknown and standardized immunological diagnosis and treatment of idiopathic RM (iRM) is yet not established. In this prospective case-control study, out of 220 RM patients screened, 97 iRM patients were identified and compared to 26 healthy controls without a previous pregnancy or blood transfusion in order to identify deregulated immunological parameters. Blood levels of lymphocyte subpopulations, cytokines and neopterin were determined by FACS, ELISA, and Luminex technique. Lymphocyte function was studied by in-vitro lympocyte proliferation tests. As compared to controls, patients had significantly higher proportions of activated CD3+DR+, CD4+DR+ and CD8+DR+ lymphocytes, elevated levels of neopterin and a lower in-vitro proliferation of lymphocytes (all p<0.05). Within the iRM patients higher proportions of CD3+DR+ T-lymphocytes correlated with higher proportions and absolute numbers of CD4+DR+ and CD8+DR+ T-lymphocytes and lower CD16+CD56+ NK-cells. Further, it was associated with lower absolute numbers of CD19+ B-lymphocytes, CD3+CD25+ T-lymphocytes and CD45+ total lymphocytes (all p<0.05). In addition we found decreased in-vitro lymphocyte proliferation in iRM patients with high CD3+DR+ T-lymphocytes (p<0.05). In summary patients with iRM showed increased activated T-cells that are less responsive to mitogens in-vitro. The inverse relationship of increased DR but decreased CD25 expression on CD3+ T-cells and the decreased in-vitro proliferation characterize an immunological disorder with similarities to T-cell exhaustion in patients with HIV and cancer. These abnormalities potentially contribute to the pathogenesis of iRM and might be a target for future immunomodulatory therapies.

  3. The Isothiocyanate Isolated from Moringa oleifera Shows Potent Anti-Inflammatory Activity in the Treatment of Murine Subacute Parkinson's Disease.

    PubMed

    Giacoppo, Sabrina; Rajan, Thangavelu Soundara; De Nicola, Gina Rosalinda; Iori, Renato; Rollin, Patrick; Bramanti, Placido; Mazzon, Emanuela

    2017-02-01

    The present study was aimed at estimating a possible neuroprotective effect of glucomoringin (GMG) [4-(α-L-rhamnopyranosyloxy)benzyl glucosinolate] bioactivated with the enzyme myrosinase to form the corresponding isothiocyanate [4-(α-L-rhamnopyranosyloxy)benzyl C; moringin] in the treatment or prevention of Parkinson's disease (PD). In this study, the beneficial effects of moringin were compared with those of pure GMG, not enzymatically activated, in an in vivo experimental mouse model of subacute PD. Subacute PD was induced in C57BL/6 mice by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice were pretreated daily for 1 week with moringin (10 mg/kg +5 μL myrosinase/mouse) and with GMG (10 mg/kg). Behavioral evaluations were also performed to assess motor deficits and bradykinesia in MPTP mice. Besides, assuming that pretreatment with moringin could modulate the triggering of inflammatory cascade with a correlated response, we tested its in vitro anti-inflammatory activity by using a model of RAW 264.7 macrophages stimulated with lipopolysaccharide. Achieved results in vivo showed a higher efficacy of moringin compared with GMG not only to modulate the inflammatory pathway but also oxidative stress and apoptotic pathways. In addition, the greater effectiveness of moringin in countering mainly the inflammatory pathway has been corroborated by the results obtained in vitro. The relevance and innovation of the present study lie in the possible use of a safe formulation of a bioactive compound, resulting from exogenous myrosinase hydrolysis of the natural phytochemical GMG, which can be used in clinical practice as a useful drug for the treatment or prevention of PD.

  4. Dynamic Docking Test System (DDTS) active table frequency response test results. [Apollo Soyuz Test Project

    NASA Technical Reports Server (NTRS)

    Gates, R. M.

    1974-01-01

    Results are presented of the frequency response test performed on the dynamic docking test system (DDTS) active table. Sinusoidal displacement commands were applied to the table and the dynamic response determined from measured actuator responses and accelerometers mounted to the table and one actuator.

  5. Rats maintained chronically on buprenorphine show reduced heroin and cocaine seeking in tests of extinction and drug-induced reinstatement.

    PubMed

    Sorge, Robert E; Rajabi, Heshmat; Stewart, Jane

    2005-09-01

    Buprenorphine is being introduced as a maintenance therapy in opioid addiction, but it is not clear how buprenorphine will affect co-use of cocaine in opioid users. We examined the effects of chronic buprenorphine (BUP0: 0.0 mg/kg/day; BUP1.5: 1.5 mg/kg/day; BUP3: 3.0 mg/kg/day) on the locomotor activity effects of acute heroin (0.25 mg/kg, subcutaneously (s.c.)) and cocaine (20 mg/kg, intraperitoneally (i.p.)). Buprenorphine had no effect on the stimulatory effect of heroin, but potentiated the locomotor response to cocaine. To investigate further the interactions between buprenorphine (BUP1.5 and BUP3), heroin (0.125, 0.25 and 0.375 mg/kg, s.c.), and cocaine (10, 20 and 30 mg/kg, i.p.), we used in vivo microdialysis and high-performance liquid chromatography to analyze extracellular levels of dopamine (DA) in the nucleus accumbens (NAc). Buprenorphine attenuated the heroin-induced rise in NAc DA, but greatly potentiated the cocaine-induced rise. Finally, we examined the potential of the highest dose of buprenorphine (BUP3) to reduce heroin and cocaine seeking in the presence of drug-associated cues under extinction conditions and in tests for reinstatement induced by heroin (0.25 mg/kg, s.c.), cocaine (20 mg/kg, i.p.), and 15-min footshock stress (0.8 mA, 0.5 s/shock, 40 s mean OFF time) in rats trained to self-administer both drugs. Buprenorphine reduced heroin and cocaine seeking during extinction and following acute heroin and cocaine priming injections, but had no effect on stress-induced reinstatement. These results indicate that the suppression of responding following priming injections of drugs did not result from reduced motor activity, but possibly from a reduction in the salience of drug-associated cues induced by chronic buprenorphine treatment.

  6. A novel inhibitor of fatty acid synthase shows activity against HER2+ breast cancer xenografts and is active in anti-HER2 drug-resistant cell lines

    PubMed Central

    2011-01-01

    Introduction Inhibiting the enzyme Fatty Acid Synthase (FASN) leads to apoptosis of breast carcinoma cells, and this is linked to human epidermal growth factor receptor 2 (HER2) signaling pathways in models of simultaneous expression of FASN and HER2. Methods In a xenograft model of breast carcinoma cells that are FASN+ and HER2+, we have characterised the anticancer activity and the toxicity profile of G28UCM, the lead compound of a novel family of synthetic FASN inhibitors. In vitro, we analysed the cellular and molecular interactions of combining G28UCM with anti-HER drugs. Finally, we tested the cytotoxic ability of G28UCM on breast cancer cells resistant to trastuzumab or lapatinib, that we developed in our laboratory. Results In vivo, G28UCM reduced the size of 5 out of 14 established xenografts. In the responding tumours, we observed inhibition of FASN activity, cleavage of poly-ADPribose polymerase (PARP) and a decrease of p-HER2, p- protein kinase B (AKT) and p-ERK1/2, which were not observed in the nonresponding tumours. In the G28UCM-treated animals, no significant toxicities occurred, and weight loss was not observed. In vitro, G28UCM showed marked synergistic interactions with trastuzumab, lapatinib, erlotinib or gefitinib (but not with cetuximab), which correlated with increases in apoptosis and with decreases in the activation of HER2, extracellular signal-regulated kinase (ERK)1/2 and AKT. In trastuzumab-resistant and in lapatinib-resistant breast cancer cells, in which trastuzumab and lapatinib were not effective, G28UCM retained the anticancer activity observed in the parental cells. Conclusions G28UCM inhibits fatty acid synthase (FASN) activity and the growth of breast carcinoma xenografts in vivo, and is active in cells with acquired resistance to anti-HER2 drugs, which make it a candidate for further pre-clinical development. PMID:22177475

  7. The benzimidazole based drugs show good activity against T. gondii but poor activity against its proposed enoyl reductase enzyme target.

    PubMed

    Wilkinson, Craig; McPhillie, Martin J; Zhou, Ying; Woods, Stuart; Afanador, Gustavo A; Rawson, Shaun; Khaliq, Farzana; Prigge, Sean T; Roberts, Craig W; Rice, David W; McLeod, Rima; Fishwick, Colin W; Muench, Stephen P

    2014-02-01

    The enoyl acyl-carrier protein reductase (ENR) enzyme of the apicomplexan parasite family has been intensely studied for antiparasitic drug design for over a decade, with the most potent inhibitors targeting the NAD(+) bound form of the enzyme. However, the higher affinity for the NADH co-factor over NAD(+) and its availability in the natural environment makes the NADH complex form of ENR an attractive target. Herein, we have examined a benzimidazole family of inhibitors which target the NADH form of Francisella ENR, but despite good efficacy against Toxoplasma gondii, the IC50 for T. gondii ENR is poor, with no inhibitory activity at 1 μM. Moreover similar benzimidazole scaffolds are potent against fungi which lack the ENR enzyme and as such we believe that there may be significant off target effects for this family of inhibitors.

  8. Altered DNA-binding specificity mutants of EKLF and Sp1 show that EKLF is an activator of the β-globin locus control region in vivo

    PubMed Central

    Gillemans, Nynke; Tewari, Rita; Lindeboom, Fokke; Rottier, Robbert; de Wit, Ton; Wijgerde, Mark; Grosveld, Frank; Philipsen, Sjaak

    1998-01-01

    The locus control region of the β-globin cluster contains five DNase I hypersensitive sites (5′HS1–5) required for locus activation. 5′HS3 contains six G-rich motifs that are essential for its activity. Members of a protein family, characterized by three zinc fingers highly homologous to those found in transcription factor Sp1, interact with these motifs. Because point mutagenesis cannot distinguish between family members, it is not known which protein activates 5′HS3. We show that the function of such closely related proteins can be distinguished in vivo by matching point mutations in 5′HS3 with amino acid changes in the zinc fingers of Sp1 and EKLF. Testing their activity in transgenic mice shows that EKLF is a direct activator of 5′HS3. PMID:9744863

  9. The temperate Burkholderia phage AP3 of the Peduovirinae shows efficient antimicrobial activity against B. cenocepacia of the IIIA lineage.

    PubMed

    Roszniowski, Bartosz; Latka, Agnieszka; Maciejewska, Barbara; Vandenheuvel, Dieter; Olszak, Tomasz; Briers, Yves; Holt, Giles S; Valvano, Miguel A; Lavigne, Rob; Smith, Darren L; Drulis-Kawa, Zuzanna

    2017-02-01

    Burkholderia phage AP3 (vB_BceM_AP3) is a temperate virus of the Myoviridae and the Peduovirinae subfamily (P2likevirus genus). This phage specifically infects multidrug-resistant clinical Burkholderia cenocepacia lineage IIIA strains commonly isolated from cystic fibrosis patients. AP3 exhibits high pairwise nucleotide identity (61.7 %) to Burkholderia phage KS5, specific to the same B. cenocepacia host, and has 46.7-49.5 % identity to phages infecting other species of Burkholderia. The lysis cassette of these related phages has a similar organization (putative antiholin, putative holin, endolysin, and spanins) and shows 29-98 % homology between specific lysis genes, in contrast to Enterobacteria phage P2, the hallmark phage of this genus. The AP3 and KS5 lysis genes have conserved locations and high amino acid sequence similarity. The AP3 bacteriophage particles remain infective up to 5 h at pH 4-10 and are stable at 60 °C for 30 min, but are sensitive to chloroform, with no remaining infective particles after 24 h of treatment. AP3 lysogeny can occur by stable genomic integration and by pseudo-lysogeny. The lysogenic bacterial mutants did not exhibit any significant changes in virulence compared to wild-type host strain when tested in the Galleria mellonella moth wax model. Moreover, AP3 treatment of larvae infected with B. cenocepacia revealed a significant increase (P < 0.0001) in larvae survival in comparison to AP3-untreated infected larvae. AP3 showed robust lytic activity, as evidenced by its broad host range, the absence of increased virulence in lysogenic isolates, the lack of bacterial gene disruption conditioned by bacterial tRNA downstream integration site, and the absence of detected toxin sequences. These data suggest that the AP3 phage is a promising potent agent against bacteria belonging to the most common B. cenocepacia IIIA lineage strains.

  10. Genome Sequence of Lactobacillus salivarius SMXD51, a Potential Probiotic Strain Isolated from Chicken Cecum, Showing Anti-Campylobacter Activity

    PubMed Central

    Kergourlay, Gilles; Messaoudi, Soumaya; Dousset, Xavier

    2012-01-01

    We report the draft genome sequence of Lactobacillus salivarius SMXD51, isolated from the cecum of healthy chickens showing an activity against Campylobacter—the food-borne pathogen that is the most common cause of gastroenteritis in the European Union (EU)—and potentially interesting features for a probiotic strain, explaining our interest in it. PMID:22582370

  11. Magnetosomes extracted from Magnetospirillum magneticum strain AMB-1 showed enhanced peroxidase-like activity under visible-light irradiation.

    PubMed

    Li, Kefeng; Chen, Chuanfang; Chen, Changyou; Wang, Yuzhan; Wei, Zhao; Pan, Weidong; Song, Tao

    2015-05-01

    Magnetosomes are intracellular structures produced by magnetotactic bacteria and are magnetic nanoparticles surrounded by a lipid bilayer membrane. Magnetosomes reportedly possess intrinsic enzyme mimetic activity similar to that found in horseradish peroxidase (HRP) and can scavenge reactive oxygen species depending on peroxidase activity. Our previous study has demonstrated the phototaxis characteristics of Magnetospirillum magneticum strain AMB-1 cells, but the mechanism is not well understood. Therefore, we studied the relationship between visible-light irradiation and peroxidase-like activity of magnetosomes extracted from M. magneticum strain AMB-1. We then compared this characteristic with that of HRP, iron ions, and naked magnetosomes using 3,3',5,5'-tetramethylbenzidine as a peroxidase substrate in the presence of H2O2. Results showed that HRP and iron ions had different activities from those of magnetosomes and naked magnetosomes when exposed to visible-light irradiation. Magnetosomes and naked magnetosomes had enhanced peroxidase-like activities under visible-light irradiation, but magnetosomes showed less affinity toward substrates than naked magnetosomes under visible-light irradiation. These results suggested that the peroxidase-like activity of magnetosomes may follow an ordered ternary mechanism rather than a ping-pong mechanism. This finding may provide new insight into the function of magnetosomes in the phototaxis in magnetotactic bacteria.

  12. Something That Test Scores Do Not Show: Engaging in Community Diversity as a Local Response to Global Education Trends

    ERIC Educational Resources Information Center

    Valdiviezo, Laura A.

    2014-01-01

    At Smith Street Elementary School, the globalizing education trends that English language learner (ELL) teachers face focus on measuring student achievement through testing and the English mainstreaming of non-dominant students as opposed to the cultivation of the students' linguistic and cultural diversity. The ELL teachers at Smith Street…

  13. Simulations Show Diagnostic Testing For Malaria In Young African Children Can Be Cost-Saving Or Cost-Effective

    PubMed Central

    Phillips, Victoria; Njau, Joseph; Li, Shang; Kachur, Patrick

    2015-01-01

    Malaria imposes a substantial global disease burden. It disproportionately affects sub-Saharan Africans, particularly young children. In an effort to improve disease management, the World Health Organization (WHO) recommended in 2010 that countries test children younger than age five who present with suspected malaria fever to confirm the diagnosis instead of treating them presumptively with antimalarial drugs. Costs and concerns about the overall health impact of such diagnostic testing for malaria in children remain barriers to full implementation. Using data from national Malaria Indicator Surveys, we estimated two-stage microsimulation models for Angola, Tanzania, and Uganda to assess the policy’s cost-effectiveness. We found that diagnostic testing for malaria in children younger than five is cost-saving in Angola. In Tanzania and Uganda the cost per life-year gained is $5.54 and $94.28, respectively. The costs projected for Tanzania and Uganda are less than the WHO standard of $150 per life-year gained. Our results were robust under varying assumptions about cost, prevalence of malaria, and behavior, and they strongly suggest the pursuit of policies that facilitate full implementation of testing for malaria in children younger than five. PMID:26153315

  14. Virome analysis of antiretroviral-treated HIV patients shows no correlation between T-cell activation and anelloviruses levels

    PubMed Central

    Li, Linlin; Deng, Xutao; Da Costa, Antonio Charlys; Bruhn, Roberta; Deeks, Steven G.; Delwart, Eric

    2015-01-01

    Background Abnormally high levels of T-cell activation can persist in HIV-infected subjects despite effective anti-retroviral therapy (ART) and has been associated with negative health outcomes. The nature of the antigenic drivers or other causes of this residual T-cell activation remain uncertain. Anelloviruses are universally acquired soon after birth, resulting in persistent viremia, and considered part of the commensal human virome. Reduced immunocompetence results in increased anellovirus levels. Objectives To test whether increased levels of anelloviruses or other viruses in plasma are associated with higher levels of persistent T-cell activation during ART. Study design Two amplification methods combined with next generation sequencing were used to detect all viruses and estimate relative anellovirus levels in plasma from 19 adults on effective ART who exhibited a wide range of T-cell activation levels. Results Nucleic acids from HBV and HCV were detected in one patient each while pegivirus A (GBV-C) was found in three patients. Anellovirus DNA was detected in all patients with some individuals carrying up to eight different genotypes. Specific anellovirus genotypes or higher level of co-infections were not detected in subjects with higher levels of T-cell activation. No association was detected between relative plasma anellovirus DNA levels and the percentage of activated CD4 or CD8 T cells. Conclusions Human anelloviruses were detected in all HIV suppressed subjects, exhibited a wide range of viremia levels, and were genetically highly diverse. The level of persistent T-cell activation was not correlated with the level of viremia or genotypes present indicating that anellovirus antigens are unlikely to be a dominant source of antigens driving chronic T-cell activation. PMID:26479202

  15. Testing a Theoretical Model of Immigration Transition and Physical Activity.

    PubMed

    Chang, Sun Ju; Im, Eun-Ok

    2015-01-01

    The purposes of the study were to develop a theoretical model to explain the relationships between immigration transition and midlife women's physical activity and test the relationships among the major variables of the model. A theoretical model, which was developed based on transitions theory and the midlife women's attitudes toward physical activity theory, consists of 4 major variables, including length of stay in the United States, country of birth, level of acculturation, and midlife women's physical activity. To test the theoretical model, a secondary analysis with data from 127 Hispanic women and 123 non-Hispanic (NH) Asian women in a national Internet study was used. Among the major variables of the model, length of stay in the United States was negatively associated with physical activity in Hispanic women. Level of acculturation in NH Asian women was positively correlated with women's physical activity. Country of birth and level of acculturation were significant factors that influenced physical activity in both Hispanic and NH Asian women. The findings support the theoretical model that was developed to examine relationships between immigration transition and physical activity; it shows that immigration transition can play an essential role in influencing health behaviors of immigrant populations in the United States. The NH theoretical model can be widely used in nursing practice and research that focus on immigrant women and their health behaviors. Health care providers need to consider the influences of immigration transition to promote immigrant women's physical activity.

  16. Sex and stress: Men and women show different cortisol responses to psychological stress induced by the Trier social stress test and the Iowa singing social stress test.

    PubMed

    Reschke-Hernández, Alaine E; Okerstrom, Katrina L; Bowles Edwards, Angela; Tranel, Daniel

    2017-01-02

    Acute psychological stress affects each of us in our daily lives and is increasingly a topic of discussion for its role in mental illness, aging, cognition, and overall health. A better understanding of how such stress affects the body and mind could contribute to the development of more effective clinical interventions and prevention practices. Over the past 3 decades, the Trier Social Stress Test (TSST) has been widely used to induce acute stress in a laboratory setting based on the principles of social evaluative threat, namely, a judged speech-making task. A comparable alternative task may expand options for examining acute stress in a controlled laboratory setting. This study uses a within-subjects design to examine healthy adult participants' (n = 20 men, n = 20 women) subjective stress and salivary cortisol responses to the standard TSST (involving public speaking and math) and the newly created Iowa Singing Social Stress Test (I-SSST). The I-SSST is similar to the TSST but with a new twist: public singing. Results indicated that men and women reported similarly high levels of subjective stress in response to both tasks. However, men and women demonstrated different cortisol responses; men showed a robust response to both tasks, and women displayed a lesser response. These findings are in line with previous literature and further underscore the importance of examining possible sex differences throughout various phases of research, including design, analysis, and interpretation of results. Furthermore, this nascent examination of the I-SSST suggests a possible alternative for inducing stress in the laboratory. © 2016 Wiley Periodicals, Inc.

  17. Fluorescence-based measurement of cystine uptake through xCT shows requirement for ROS detoxification in activated lymphocytes.

    PubMed

    Siska, Peter J; Kim, Bumki; Ji, Xiangming; Hoeksema, Megan D; Massion, Pierre P; Beckermann, Kathryn E; Wu, Jianli; Chi, Jen-Tsan; Hong, Jiyong; Rathmell, Jeffrey C

    2016-11-01

    T and B lymphocytes undergo metabolic re-programming upon activation that is essential to allow bioenergetics, cell survival, and intermediates for cell proliferation and function. To support changes in the activity of signaling pathways and to provide sufficient and necessary intracellular metabolites, uptake of extracellular nutrients increases sharply with metabolic re-programming. One result of increased metabolic activity can be reactive oxygen species (ROS), which can be toxic when accumulated in excess. Uptake of cystine allows accumulation of cysteine that is necessary for glutathione synthesis and ROS detoxification. Cystine uptake is required for T cell activation and function but measurements based on radioactive labeling do not allow analysis on single cell level. Here we show the critical role for cystine uptake in T cells using a method for measurement of cystine uptake using a novel CystineFITC probe. T cell receptor stimulation lead to upregulation of the cystine transporter xCT (SLC7a11) and increased cystine uptake in CD4+ and CD8+ human T cells. Similarly, lipopolysaccharide stimulation increased cystine uptake in human B cells. The CystineFITC probe was not toxic and could be metabolized to prevent cystine starvation induced cell death. Furthermore, blockade of xCT or competition with natural cystine decreased uptake of CystineFITC. CystineFITC is thus a versatile tool that allows measurement of cystine uptake on single cell level and shows the critical role for cystine uptake for T cell ROS regulation and activation.

  18. Malten, a new synthetic molecule showing in vitro antiproliferative activity against tumour cells and induction of complex DNA structural alterations

    PubMed Central

    Amatori, S; Bagaloni, I; Macedi, E; Formica, M; Giorgi, L; Fusi, V; Fanelli, M

    2010-01-01

    Background: Hydroxypyrones represent several classes of molecules known for their high synthetic versatility. This family of molecules shows several interesting pharmaceutical activities and is considered as a promising source of new antineoplastic compounds. Methods: In the quest to identify new potential anticancer agents, a new maltol (3-hydroxy-2-methyl-4-pyrone)-derived molecule, named malten (N,N′-bis((3-hydroxy-4-pyron-2-yl)methyl)-N,N′-dimethylethylendiamine), has been synthesised and analysed at both biological and molecular levels for its antiproliferative activity in eight tumour cell lines. Results: Malten exposure led to a dose-dependent reduction in cell survival in all the neoplastic models studied. Sublethal concentrations of malten induce profound cell cycle changes, particularly affecting the S and/or G2-M phases, whereas exposure to lethal doses causes the induction of programmed cell death. The molecular response to malten was also investigated in JURKAT and U937 cells. It showed the modulation of genes having key roles in cell cycle progression and apoptosis. Finally, as part of the effort to clarify the action mechanism, we showed that malten is able to impair DNA electrophoretic mobility and drastically reduce both PCR amplificability and fragmentation susceptibility of DNA. Conclusion: Taken together, these results show that malten may exert its antiproliferative activity through the induction of complex DNA structural modifications. This evidence, together with the high synthetic versatility of maltol-derived compounds, makes malten an interesting molecular scaffold for the future design of new potential anticancer agents. PMID:20571494

  19. Pomalidomide shows significant therapeutic activity against CNS lymphoma with a major impact on the tumor microenvironment in murine models.

    PubMed

    Li, Zhimin; Qiu, Yushi; Personett, David; Huang, Peng; Edenfield, Brandy; Katz, Jason; Babusis, Darius; Tang, Yang; Shirely, Michael A; Moghaddam, Mehran F; Copland, John A; Tun, Han W

    2013-01-01

    Primary CNS lymphoma carries a poor prognosis. Novel therapeutic agents are urgently needed. Pomalidomide (POM) is a novel immunomodulatory drug with anti-lymphoma activity. CNS pharmacokinetic analysis was performed in rats to assess the CNS penetration of POM. Preclinical evaluation of POM was performed in two murine models to assess its therapeutic activity against CNS lymphoma. The impact of POM on the CNS lymphoma immune microenvironment was evaluated by immunohistochemistry and immunofluorescence. In vitro cell culture experiments were carried out to further investigate the impact of POM on the biology of macrophages. POM crosses the blood brain barrier with CNS penetration of ~ 39%. Preclinical evaluations showed that it had significant therapeutic activity against CNS lymphoma with significant reduction in tumor growth rate and prolongation of survival, that it had a major impact on the tumor microenvironment with an increase in macrophages and natural killer cells, and that it decreased M2-polarized tumor-associated macrophages and increased M1-polarized macrophages when macrophages were evaluated based on polarization status. In vitro studies using various macrophage models showed that POM converted the polarization status of IL4-stimulated macrophages from M2 to M1, that M2 to M1 conversion by POM in the polarization status of lymphoma-associated macrophages is dependent on the presence of NK cells, that POM induced M2 to M1 conversion in the polarization of macrophages by inactivating STAT6 signaling and activating STAT1 signaling, and that POM functionally increased the phagocytic activity of macrophages. Based on our findings, POM is a promising therapeutic agent for CNS lymphoma with excellent CNS penetration, significant preclinical therapeutic activity, and a major impact on the tumor microenvironment. It can induce significant biological changes in tumor-associated macrophages, which likely play a major role in its therapeutic activity against CNS

  20. Prolonged ELS test with the marine flatfish sole (Solea solea) shows delayed toxic effects of previous exposure to PCB 126.

    PubMed

    Foekema, Edwin M; Deerenberg, Charlotte M; Murk, Albertinka J

    2008-11-21

    The effect of the dioxin-like PCB 126 (3,3',4,4',5-pentachlorobiphenyl) on the early development of the marine flatfish sole (Solea solea) was tested in a newly developed early life stage (ELS) test that includes the metamorphosis of the symmetric larvae into an asymmetrical flatfish. Early life stages of sole were exposed to a concentration series of PCB 126 in seawater until 4, 8, 10 and 15 days post fertilisation (dpf). Subsequently the development of the larvae was registered under further unexposed conditions. The LC50s at the start of the free-feeding stage (12 dpf) ranged between 39 and 83 ng PCB 126/l depending on exposure duration. After the fish had completed the metamorphosis, the LC50 values ranged between 1.7 and 3.7 ng PCB 126/l for the groups exposed for 4, 8 and 10 dpf, respectively. Thus exposure for only 4 days, covering only the egg stage, was sufficient to cause adverse effects during a critical developmental phase two weeks later. The internal dosages of these larvae, determined by means of an in vitro gene reporter assay as dioxin-equivalent values (TEQ), revealed a LD50 of 1ng TEQ/g lipid, which is within the same order of magnitude as TEQ levels found in fish from highly polluted areas. This study indicates that ELS fish tests that are terminated shortly after the fish becomes free-feeding, underestimate the toxic potential of compounds with low acute toxicity such as PCBs. Our prolonged ELS with this native marine flatfish suggests that reproductive success of fish populations at contaminated sites can be affected by persistent compounds that are accumulated by the female fish and passed on to the eggs.

  1. Backbone cyclised peptides from plants show molluscicidal activity against the rice pest Pomacea canaliculata (golden apple snail).

    PubMed

    Plan, Manuel Rey R; Saska, Ivana; Cagauan, Arsenia G; Craik, David J

    2008-07-09

    Golden apple snails ( Pomacea canaliculata) are serious pests of rice in South East Asia. Cyclotides are backbone cyclized peptides produced by plants from Rubiaceae and Violaceae. In this study, we investigated the molluscicidal activity of cyclotides against golden apple snails. Crude cyclotide extracts from both Oldenlandia affinis and Viola odorata plants showed molluscicidal activity comparable to the synthetic molluscicide metaldehyde. Individual cyclotides from each extract demonstrated a range of molluscicidal activities. The cyclotides cycloviolacin O1, kalata B1, and kalata B2 were more toxic to golden apple snails than metaldehyde, while kalata B7 and kalata B8 did not cause significant mortality. The toxicity of the cyclotide kalata B2 on a nontarget species, the Nile tilapia ( Oreochromis niloticus), was three times lower than the common piscicide rotenone. Our findings suggest that the existing diversity of cyclotides in plants could be used to develop natural molluscicides.

  2. Actinobacteria from Termite Mounds Show Antiviral Activity against Bovine Viral Diarrhea Virus, a Surrogate Model for Hepatitis C Virus

    PubMed Central

    Padilla, Marina Aiello; Rodrigues, Rodney Alexandre Ferreira; Bastos, Juliana Cristina Santiago; Martini, Matheus Cavalheiro; Barnabé, Ana Caroline de Souza; Kohn, Luciana Konecny; Uetanabaro, Ana Paula Trovatti; Bomfim, Getúlio Freitas; Afonso, Rafael Sanches; Fantinatti-Garboggini, Fabiana; Arns, Clarice Weis

    2015-01-01

    Extracts from termite-associated bacteria were evaluated for in vitro antiviral activity against bovine viral diarrhea virus (BVDV). Two bacterial strains were identified as active, with percentages of inhibition (IP) equal to 98%. Both strains were subjected to functional analysis via the addition of virus and extract at different time points in cell culture; the results showed that they were effective as posttreatments. Moreover, we performed MTT colorimetric assays to identify the CC50, IC50, and SI values of these strains, and strain CDPA27 was considered the most promising. In parallel, the isolates were identified as Streptomyces through 16S rRNA gene sequencing analysis. Specifically, CDPA27 was identified as S. chartreusis. The CDPA27 extract was fractionated on a C18-E SPE cartridge, and the fractions were reevaluated. A 100% methanol fraction was identified to contain the compound(s) responsible for antiviral activity, which had an SI of 262.41. GC-MS analysis showed that this activity was likely associated with the compound(s) that had a peak retention time of 5 min. Taken together, the results of the present study provide new information for antiviral research using natural sources, demonstrate the antiviral potential of Streptomyces chartreusis compounds isolated from termite mounds against BVDV, and lay the foundation for further studies on the treatment of HCV infection. PMID:26579205

  3. Actinobacteria from Termite Mounds Show Antiviral Activity against Bovine Viral Diarrhea Virus, a Surrogate Model for Hepatitis C Virus.

    PubMed

    Padilla, Marina Aiello; Rodrigues, Rodney Alexandre Ferreira; Bastos, Juliana Cristina Santiago; Martini, Matheus Cavalheiro; Barnabé, Ana Caroline de Souza; Kohn, Luciana Konecny; Uetanabaro, Ana Paula Trovatti; Bomfim, Getúlio Freitas; Afonso, Rafael Sanches; Fantinatti-Garboggini, Fabiana; Arns, Clarice Weis

    2015-01-01

    Extracts from termite-associated bacteria were evaluated for in vitro antiviral activity against bovine viral diarrhea virus (BVDV). Two bacterial strains were identified as active, with percentages of inhibition (IP) equal to 98%. Both strains were subjected to functional analysis via the addition of virus and extract at different time points in cell culture; the results showed that they were effective as posttreatments. Moreover, we performed MTT colorimetric assays to identify the CC50, IC50, and SI values of these strains, and strain CDPA27 was considered the most promising. In parallel, the isolates were identified as Streptomyces through 16S rRNA gene sequencing analysis. Specifically, CDPA27 was identified as S. chartreusis. The CDPA27 extract was fractionated on a C18-E SPE cartridge, and the fractions were reevaluated. A 100% methanol fraction was identified to contain the compound(s) responsible for antiviral activity, which had an SI of 262.41. GC-MS analysis showed that this activity was likely associated with the compound(s) that had a peak retention time of 5 min. Taken together, the results of the present study provide new information for antiviral research using natural sources, demonstrate the antiviral potential of Streptomyces chartreusis compounds isolated from termite mounds against BVDV, and lay the foundation for further studies on the treatment of HCV infection.

  4. The novel HSP90 inhibitor NVP-AUY922 shows synergistic anti-leukemic activity with cytarabine in vivo.

    PubMed

    Wendel, Torunn; Zhen, Yan; Suo, Zenhe; Bruheim, Skjalg; Wiedlocha, Antoni

    2016-01-15

    HSP90 is a molecular chaperone essential for stability, activity and intracellular sorting of many proteins, including oncoproteins, such as tyrosine kinases, transcription factors and cell cycle regulatory proteins. Therefore, inhibitors of HSP90 are being investigated for their potential as anti-cancer drugs. Here we show that the HSP90 inhibitor NVP-AUY922 induced degradation of the fusion oncoprotein FOP2-FGFR1 in a human acute myeloid leukemia (AML) cell line, KG-1a. Concordantly, downstream signaling cascades, such as STAT1, STAT3 and PLCγ were abrogated. At concentrations that caused FOP2-FGFR1 degradation and signaling abrogation, NVP-AUY922 treatment caused significant cell death and inhibition of proliferation of KG-1a cells in vitro. In an animal model for AML, NVP-AUY922 administrated alone showed no anti-leukemic activity. However, when NVP-AUY922 was administered in combination with cytarabine, the two compounds showed significant synergistic anti-leukemic activity in vivo. Thus NVP-AUY922 and cytarabine combination therapy might be a prospective strategy for AML treatment.

  5. Pazopanib, a novel multi-kinase inhibitor, shows potent antitumor activity in colon cancer through PUMA-mediated apoptosis.

    PubMed

    Zhang, Lingling; Wang, Huanan; Li, Wei; Zhong, Juchang; Yu, Rongcheng; Huang, Xinfeng; Wang, Honghui; Tan, Zhikai; Wang, Jiangang; Zhang, Yingjie

    2017-01-10

    Colon cancer is still the third most common cancer which has a high mortality but low five-year survival rate. Novel tyrosine kinase inhibitors (TKI) such as pazopanib become effective antineoplastic agents that show promising clinical activity in a variety of carcinoma, including colon cancer. However, the precise underlying mechanism against tumor is unclear. Here, we demonstrated that pazopanib promoted colon cancer cell apoptosis through inducing PUMA expression. Pazopanib induced p53-independent PUMA activation by inhibiting PI3K/Akt signaling pathway, thereby activating Foxo3a, which subsequently bound to the promoter of PUMA to activate its transcription. After induction, PUMA activated Bax and triggered the intrinsic mitochondrial apoptosis pathway. Furthermore, administration of pazopanib highly suppressed tumor growth in a xenograft model. PUMA deletion in cells and tumors led to resistance of pazopanib, indicating PUMA-mediated pro-apoptotic and anti-tumor effects in vitro and in vivo. Combing pazopanib with some conventional or novel drugs, produced heightened and synergistic antitumor effects that were associated with potentiated PUMA induction via different pathways. Taken together, these results establish a critical role of PUMA in mediating the anticancer effects of pazopanib in colon cancer cells and provide the rationale for clinical evaluation.

  6. Activity/inactivity circadian rhythm shows high similarities between young obesity-induced rats and old rats.

    PubMed

    Bravo Santos, R; Delgado, J; Cubero, J; Franco, L; Ruiz-Moyano, S; Mesa, M; Rodríguez, A B; Uguz, C; Barriga, C

    2016-03-01

    The objective of the present study was to compare differences between elderly rats and young obesity-induced rats in their activity/inactivity circadian rhythm. The investigation was motivated by the differences reported previously for the circadian rhythms of both obese and elderly humans (and other animals), and those of healthy, young or mature individuals. Three groups of rats were formed: a young control group which was fed a standard chow for rodents; a young obesity-induced group which was fed a high-fat diet for four months; and an elderly control group with rats aged 2.5 years that was fed a standard chow for rodents. Activity/inactivity data were registered through actimetry using infrared actimeter systems in each cage to detect activity. Data were logged on a computer and chronobiological analysis were performed. The results showed diurnal activity (sleep time), nocturnal activity (awake time), amplitude, acrophase, and interdaily stability to be similar between the young obesity-induced group and the elderly control group, but different in the young control group. We have concluded that obesity leads to a chronodisruption status in the body similar to the circadian rhythm degradation observed in the elderly.

  7. A test of the intergenerational conflict model in Indonesia shows no evidence of earlier menopause in female-dispersing groups

    PubMed Central

    Snopkowski, Kristin; Moya, Cristina; Sear, Rebecca

    2014-01-01

    Menopause remains an evolutionary puzzle, as humans are unique among primates in having a long post-fertile lifespan. One model proposes that intergenerational conflict in patrilocal populations favours female reproductive cessation. This model predicts that women should experience menopause earlier in groups with an evolutionary history of patrilocality compared with matrilocal groups. Using data from the Indonesia Family Life Survey, we test this model at multiple timescales: deep historical time, comparing age at menopause in ancestrally patrilocal Chinese Indonesians with ancestrally matrilocal Austronesian Indonesians; more recent historical time, comparing age at menopause in ethnic groups with differing postmarital residence within Indonesia and finally, analysing age at menopause at an individual-level, assuming a woman facultatively adjusts her age at menopause based on her postmarital residence. We find a significant effect only at the intermediate timescale where, contrary to predictions, ethnic groups with a history of multilocal postnuptial residence (where couples choose where to live) have the slowest progression to menopause, whereas matrilocal and patrilocal ethnic groups have similar progression rates. Multilocal residence may reduce intergenerational conflicts between women, thus influencing reproductive behaviour, but our results provide no support for the female-dispersal model of intergenerational conflict as an explanation of menopause. PMID:24966311

  8. A test of the intergenerational conflict model in Indonesia shows no evidence of earlier menopause in female-dispersing groups.

    PubMed

    Snopkowski, Kristin; Moya, Cristina; Sear, Rebecca

    2014-08-07

    Menopause remains an evolutionary puzzle, as humans are unique among primates in having a long post-fertile lifespan. One model proposes that intergenerational conflict in patrilocal populations favours female reproductive cessation. This model predicts that women should experience menopause earlier in groups with an evolutionary history of patrilocality compared with matrilocal groups. Using data from the Indonesia Family Life Survey, we test this model at multiple timescales: deep historical time, comparing age at menopause in ancestrally patrilocal Chinese Indonesians with ancestrally matrilocal Austronesian Indonesians; more recent historical time, comparing age at menopause in ethnic groups with differing postmarital residence within Indonesia and finally, analysing age at menopause at an individual-level, assuming a woman facultatively adjusts her age at menopause based on her postmarital residence. We find a significant effect only at the intermediate timescale where, contrary to predictions, ethnic groups with a history of multilocal postnuptial residence (where couples choose where to live) have the slowest progression to menopause, whereas matrilocal and patrilocal ethnic groups have similar progression rates. Multilocal residence may reduce intergenerational conflicts between women, thus influencing reproductive behaviour, but our results provide no support for the female-dispersal model of intergenerational conflict as an explanation of menopause.

  9. Tank Tests to Show the Effect Rivet Heads on the Water Performance of a Seaplane-Float

    NASA Technical Reports Server (NTRS)

    Parkinson, J B

    1938-01-01

    A 1/3.5 full-sized model of a seaplane float constructed from lines supplied by the Bureau of Aeronautics, Navy Department, was tested first with smooth painted bottom surfaces and then with round-head rivets, plate laps, and keel plates fitted to simulate the actual bottom of a metal float. A percentage increase in water resistance caused by the added roughness was found to be from 5 to 20 percent at the hump speed and from 15 to 40 percent at high speeds. The effect of the roughness of the afterbody was found to be negligible except at high trims. The model data were extrapolated to full size by the usual method that assumes the forces to vary according to Froude's law and, in the case of the smooth model, by a method of separation that takes into account the effect of scale on the frictional resistance. It was concluded that the effect of rivet heads on the take-off performance of a relatively high-powered float seaplane is of little consequence, but it may be of greater importance in the case of more moderately powered flying boats.

  10. Repressible extracellular phosphodiesterases showing cyclic 2',3'- and cyclic 3',5'-nucleotide phosphodiesterase activities in Neurospora crassa.

    PubMed Central

    Hasunuma, K

    1983-01-01

    Two molecular species of repressible extracellular phosphodiesterases showing cyclic 2',3'- and cyclic 3',5'-nucleotide phosphodiesterase activities were detected in mycelial culture media of wild-type Neurospora crassa and purified. The two molecular species were found to be monomeric and polymeric forms of an enzyme constituted of identical subunits having molecular weights of 50,000. This enzyme had the same electrophoretic mobility as repressible acid phosphatase. The enzyme designated repressible cyclic phosphodiesterase showed pH optima of 3.2 to 4.0 with a cyclic 3',5'-AMP substrate and 5.0 to 5.6 with a cyclic 2',3'-AMP substrate. Repressible cyclic phosphodiesterase was activated by MnCl2 and CoCl2 with cyclic 2',3'-AMP as substrate and was slightly activated by MnCl2 with cyclic 3',5'-AMP. The enzyme hydrolyzed cyclic 3',5'- and cyclic 2',3'-nucleotides, in addition to bis-rho-nitrophenyl phosphate, but not certain 5' -and 3'-nucleotides. 3'-GMP and 3'-CMP were hydrolyzed less efficiently. Mutant strains A1 (nuc-1) and B1 (nuc-2), which cannot utilize RNA or DNA as a sole source of phosphorus, were unable to produce repressible cyclic phosphodiesterase. The wild type (74A) and a heterocaryon between strains A1 and B1 produced the enzyme and showed growth on orthophosphate-free media containing cyclic 2',3'-AMP or cyclic 3',5'-AMP, whereas both mutants showed little or no growth on these media. Images PMID:6311798

  11. BO-1055, a novel DNA cross-linking agent with remarkable low myelotoxicity shows potent activity in sarcoma models

    PubMed Central

    Ambati, Srikanth R.; Shieh, Jae-Hung; Pera, Benet; Lopes, Eloisi Caldas; Chaudhry, Anisha; Wong, Elissa W.P.; Saxena, Ashish; Su, Tsann-Long; Moore, Malcolm A.S.

    2016-01-01

    DNA damaging agents cause rapid shrinkage of tumors and form the basis of chemotherapy for sarcomas despite significant toxicities. Drugs having superior efficacy and wider therapeutic windows are needed to improve patient outcomes. We used cell proliferation and apoptosis assays in sarcoma cell lines and benign cells; γ-H2AX expression, comet assay, immunoblot analyses and drug combination studies in vitro and in patient derived xenograft (PDX) models. BO-1055 caused apoptosis and cell death in a concentration and time dependent manner in sarcoma cell lines. BO-1055 had potent activity (submicromolar IC50) against Ewing sarcoma and rhabdomyosarcoma, intermediate activity in DSRCT (IC50 = 2-3μM) and very weak activity in osteosarcoma (IC50 >10μM) cell lines. BO-1055 exhibited a wide therapeutic window compared to other DNA damaging drugs. BO-1055 induced more DNA double strand breaks and γH2AX expression in cancer cells compared to benign cells. BO-1055 showed inhibition of tumor growth in A673 xenografts and caused tumor regression in cyclophosphamide resistant patient-derived Ewing sarcoma xenografts and A204 xenografts. Combination of BO-1055 and irinotecan demonstrated synergism in Ewing sarcoma PDX models. Potent activity on sarcoma cells and its relative lack of toxicity presents a strong rationale for further development of BO-1055 as a therapeutic agent. PMID:27248664

  12. In Vitro Assays of BciC Showing C132-Demethoxycarbonylase Activity Requisite for Biosynthesis of Chlorosomal Chlorophyll Pigments.

    PubMed

    Teramura, Misato; Harada, Jiro; Mizoguchi, Tadashi; Yamamoto, Ken; Tamiaki, Hitoshi

    2016-05-01

    A BciC enzyme is related to the removal of the C13(2)-methoxycarbonyl group in biosynthesis of bacteriochlorophylls (BChls) c, d and e functioning in green sulfur bacteria, filamentous anoxygenic phototrophs and phototrophic acidobacteria. These photosynthetic bacteria have the largest and the most efficient light-harvesting antenna systems, called chlorosomes, containing unique self-aggregates of BChl c, d or e pigments, that lack the C13(2)-methoxycarbonyl group which disturbs chlorosomal self-aggregation. In this study, we characterized the BciC derived from the green sulfur bacterium Chlorobaculum tepidum, and examined the in vitro enzymatic activities of its recombinant protein. The BciC-catalyzing reactions of various substrates showed that the enzyme recognized chlorophyllide (Chlide) a and 3,8-divinyl(DV)-Chlide a as chlorin substrates to give 3-vinyl-bacteriochlorophyllide (3V-BChlide) d and DV-BChlide d, respectively. Since the BciC afforded a higher activity with Chlide a than that with DV-Chlide a and no activity with (DV-)protoChlides a (porphyrin substrates) and 3V-BChlide a (a bacteriochlorin substrate), this enzyme was effective for diverting the chlorosomal pigment biosynthetic pathway at the stage of Chlide a away from syntheses of other pigments such as BChl a and Chl a The addition of methanol to the reaction mixture did not prevent the BciC activity, and we identified this enzyme as Chlide a demethoxycarbonylase, not methylesterase.

  13. Map showing recently active breaks along the San Andreas Fault between Pt. Delgada and Bolinas Bay, California

    USGS Publications Warehouse

    Brown, Robert D.; Wolfe, Edward W.

    1970-01-01

    This strip map is one of a series of maps showing recently active fault breaks along the San Andreas and other active faults in California. It is designed to inform persons who are concerned with land use near the fault of the location of those fault breaks that have moved recently. The lines on the map are lines of rupture and creep that can be identified by field evidence and that clearly affect the present surface of the land. Map users should keep in mind that these lines are intended primarily as guides to help locate the fault; the mapped lines are not necessarily shown with the precision demanded by some engineering or land utilization needs.

  14. Silk gland-specific proteinase inhibitor serpin16 from the Bombyx mori shows cysteine proteinase inhibitory activity.

    PubMed

    Guo, Peng-Chao; Dong, Zhaoming; Xiao, Li; Li, Tao; Zhang, Yan; He, Huawei; Xia, Qingyou; Zhao, Ping

    2015-01-30

    Serpins (serine proteinase inhibitors) are widely distributed in different species and are well known for their inhibitory activities towards serine proteinases. Here, we report the functional characterization of Bombyx mori serpin16. Expression analysis showed that serpin16 was specifically expressed at high levels in the silk gland at both the transcriptional and translational levels. Moreover, homology modeling and multi-sequence alignment suggested that serpin16 had a canonical serpin fold, but it contained a unique reactive center loop, which was obviously shorter than that of typical serpins. Inhibitory activity analyses revealed that the target proteinase of serpin18 is a cysteine proteinase, rather than a serine proteinase. Furthermore, a Michaelis complex model of serpin16 with its target proteinase was constructed to explain the structural basis of how serpin16 recognizes the cysteine proteinase and its target specificity.

  15. Coadministration of doxorubicin and etoposide loaded in camel milk phospholipids liposomes showed increased antitumor activity in a murine model.

    PubMed

    Maswadeh, Hamzah M; Aljarbou, Ahmed N; Alorainy, Mohammed S; Rahmani, Arshad H; Khan, Masood A

    2015-01-01

    Small unilamellar vesicles from camel milk phospholipids (CML) mixture or from 1,2 dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) were prepared, and anticancer drugs doxorubicin (Dox) or etoposide (ETP) were loaded. Liposomal formulations were used against fibrosarcoma in a murine model. Results showed a very high percentage of Dox encapsulation (~98%) in liposomes (Lip) prepared from CML-Lip or DPPC-Lip, whereas the percentage of encapsulations of ETP was on the lower side, 22% of CML-Lip and 18% for DPPC-Lip. Differential scanning calorimetry curves show that Dox enhances the lamellar formation in CML-Lip, whereas ETP enhances the nonlamellar formation. Differential scanning calorimetry curves also showed that the presence of Dox and ETP together into DPPC-Lip produced the interdigitation effect. The in vivo anticancer activity of liposomal formulations of Dox or ETP or a combination of both was assessed against benzopyrene (BAP)-induced fibrosarcoma in a murine model. Tumor-bearing mice treated with a combination of Dox and ETP loaded into CML-Lip showed increased survival and reduced tumor growth compared to other groups, including the combination of Dox and ETP in DPPC-Lip. Fibrosarcoma-bearing mice treated with a combination of free (Dox + ETP) showed much higher tumor growth compared to those groups treated with CML-Lip-(Dox + ETP) or DPPC-Lip-(Dox + ETP). Immunohistochemical study was also performed to show the expression of tumor-suppressor PTEN, and it was found that the tumor tissues from the group of mice treated with a combination of free (Dox + ETP) showed greater loss of cytoplasmic PTEN than tumor tissues obtained from the groups of mice treated with CML-Lip-(Dox + ETP) or DPPC-Lip-(Dox + ETP).

  16. Epididymal Cystadenomas in von Hippel-Lindau Disease Showing Increased Activity on 68Ga DOTATATE PET/CT.

    PubMed

    Papadakis, Georgios Z; Millo, Corina; Sadowski, Samira M; Bagci, Ulas; Patronas, Nicholas J

    2016-10-01

    von Hippel-Lindau (VHL) disease is a familial cancer syndrome characterized by the development of a variety of malignant and benign tumors, including epididymal cystadenomas. We report a case of a VHL patient with bilateral epididymal cystadenomas who was evaluated with Ga DOTATATE PET/CT, showing intensely increased activity (SUVmax, 21.6) associated with the epididymal cystadenomas, indicating cell-surface overexpression of somatostatin receptors. The presented case supports the usefulness of somatostatin receptor imaging using Ga DOTA-conjugated peptides for detection and follow-up of VHL manifestations, as well as surveillance of asymptomatic gene carriers.

  17. Dyslexic Children Show Atypical Cerebellar Activation and Cerebro-Cerebellar Functional Connectivity in Orthographic and Phonological Processing.

    PubMed

    Feng, Xiaoxia; Li, Le; Zhang, Manli; Yang, Xiujie; Tian, Mengyu; Xie, Weiyi; Lu, Yao; Liu, Li; Bélanger, Nathalie N; Meng, Xiangzhi; Ding, Guosheng

    2017-04-01

    Previous neuroimaging studies have found atypical cerebellar activation in individuals with dyslexia in either motor-related tasks or language tasks. However, studies investigating atypical cerebellar activation in individuals with dyslexia have mostly used tasks tapping phonological processing. A question that is yet unanswered is whether the cerebellum in individuals with dyslexia functions properly during orthographic processing of words, as growing evidence shows that the cerebellum is also involved in visual and spatial processing. Here, we investigated cerebellar activation and cerebro-cerebellar functional connectivity during word processing in dyslexic readers and typically developing readers using tasks that tap orthographic and phonological codes. In children with dyslexia, we observed an abnormally higher engagement of the bilateral cerebellum for the orthographic task, which was negatively correlated with literacy measures. The greater the reading impairment was for young dyslexic readers, the stronger the cerebellar activation was. This suggests a compensatory role of the cerebellum in reading for children with dyslexia. In addition, a tendency for higher cerebellar activation in dyslexic readers was found in the phonological task. Moreover, the functional connectivity was stronger for dyslexic readers relative to typically developing readers between the lobule VI of the right cerebellum and the left fusiform gyrus during the orthographic task and between the lobule VI of the left cerebellum and the left supramarginal gyrus during the phonological task. This pattern of results suggests that the cerebellum compensates for reading impairment through the connections with specific brain regions responsible for the ongoing reading task. These findings enhance our understanding of the cerebellum's involvement in reading and reading impairment.

  18. Brain Correlates of Cognitive Remediation in Schizophrenia: Activation Likelihood Analysis Shows Preliminary Evidence of Neural Target Engagement

    PubMed Central

    Ramsay, Ian S.; MacDonald, Angus W.

    2015-01-01

    Cognitive remediation training (CRT) for schizophrenia has been found to improve cognitive functioning and influence neural plasticity. However, with various training approaches and mixed findings, the mechanisms driving generalization of cognitive skills from CRT are unclear. In this meta-analysis of extant imaging studies examining CRT’s effects, we sought to clarify whether varying approaches to CRT suggest common neural changes and whether such mechanisms are restorative or compensatory. We conducted a literature search to identify studies appropriate for inclusion in an activation likelihood estimation (ALE) meta-analysis. Our criteria required studies to consist of training-based interventions designed to improve patients’ cognitive or social functioning, including generalization to untrained circumstances. Studies were also required to examine changes in pre- vs posttraining functional activation using functional magnetic resonance imaging or positron emission tomography. The literature search identified 162 articles, 9 of which were appropriate for inclusion. ALE analyses comparing pre- and posttraining brain activation showed increased activity in the lateral and medial prefrontal cortex (PFC), parietal cortex, insula, and the caudate and thalamus. Notably, activation associated with CRT in the left PFC and thalamus partially overlapped with previous meta-analytically identified areas associated with deficits in working memory, executive control, and facial emotion processing in schizophrenia. We conclude that CRT interventions from varying theoretic modalities elicit plasticity in areas that support cognitive and socioemotional processes in this early set of studies. While preliminary, these changes appear to be both restorative and compensatory, though thalamocortical areas previously associated with dysfunction may be common sources of plasticity for cognitive remediation in schizophrenia. PMID:25800249

  19. Antimicrobial peptides expressed in medicinal maggots of the blow fly Lucilia sericata show combinatorial activity against bacteria.

    PubMed

    Pöppel, Anne-Kathrin; Vogel, Heiko; Wiesner, Jochen; Vilcinskas, Andreas

    2015-05-01

    The larvae of the common green bottle fly (Lucilia sericata) produce antibacterial secretions that have a therapeutic effect on chronic and nonhealing wounds. Recent developments in insect biotechnology have made it possible to use these larvae as a source of novel anti-infectives. Here, we report the application of next-generation RNA sequencing (RNA-Seq) to characterize the transcriptomes of the larval glands, crop, and gut, which contribute to the synthesis of antimicrobial peptides (AMPs) and proteins secreted into wounds. Our data confirm that L. sericata larvae have adapted in order to colonize microbially contaminated habitats, such as carrion and necrotic wounds, and are protected against infection by a diverse spectrum of AMPs. L. sericata AMPs include not only lucifensin and lucimycin but also novel attacins, cecropins, diptericins, proline-rich peptides, and sarcotoxins. We identified 47 genes encoding putative AMPs and produced 23 as synthetic analogs, among which some displayed activities against a broad spectrum of microbial pathogens, including Pseudomonas aeruginosa, Proteus vulgaris, and Enterococcus faecalis. Against Escherichia coli (Gram negative) and Micrococcus luteus (Gram positive), we found mostly additive effects but also synergistic activity when selected AMPs were tested in combination. The AMPs that are easy to synthesize are currently being produced in bulk to allow their evaluation as novel anti-infectives that can be formulated in hydrogels to produce therapeutic wound dressings and adhesive bandages.

  20. Antimicrobial Peptides Expressed in Medicinal Maggots of the Blow Fly Lucilia sericata Show Combinatorial Activity against Bacteria

    PubMed Central

    Pöppel, Anne-Kathrin; Vogel, Heiko; Wiesner, Jochen

    2015-01-01

    The larvae of the common green bottle fly (Lucilia sericata) produce antibacterial secretions that have a therapeutic effect on chronic and nonhealing wounds. Recent developments in insect biotechnology have made it possible to use these larvae as a source of novel anti-infectives. Here, we report the application of next-generation RNA sequencing (RNA-Seq) to characterize the transcriptomes of the larval glands, crop, and gut, which contribute to the synthesis of antimicrobial peptides (AMPs) and proteins secreted into wounds. Our data confirm that L. sericata larvae have adapted in order to colonize microbially contaminated habitats, such as carrion and necrotic wounds, and are protected against infection by a diverse spectrum of AMPs. L. sericata AMPs include not only lucifensin and lucimycin but also novel attacins, cecropins, diptericins, proline-rich peptides, and sarcotoxins. We identified 47 genes encoding putative AMPs and produced 23 as synthetic analogs, among which some displayed activities against a broad spectrum of microbial pathogens, including Pseudomonas aeruginosa, Proteus vulgaris, and Enterococcus faecalis. Against Escherichia coli (Gram negative) and Micrococcus luteus (Gram positive), we found mostly additive effects but also synergistic activity when selected AMPs were tested in combination. The AMPs that are easy to synthesize are currently being produced in bulk to allow their evaluation as novel anti-infectives that can be formulated in hydrogels to produce therapeutic wound dressings and adhesive bandages. PMID:25666157

  1. Epigallocatechin-3-gallate shows anti-proliferative activity in HeLa cells targeting tubulin-microtubule equilibrium.

    PubMed

    Chakrabarty, Subhendu; Ganguli, Arnab; Das, Amlan; Nag, Debasish; Chakrabarti, Gopal

    2015-12-05

    In this study our main objective was to find out a novel target of the major bioactive green tea polyphenol, Epigallocatechin-3-gallate (EGCG), in cervical carcinoma HeLa cells. We found that EGCG showed antiproliferative activity against HeLa cells through depolymerization of cellular microtubule. EGCG also prevented the reformation of the cellular microtubule network distorted by cold treatment and inhibited polymerization of tubulin in cell-free system with IC50 of 39.6 ± 0.63 μM. Fluorescence spectroscopic analysis showed that EGCG prevented colchicine binding to tubulin and in silico study revealed that EGCG bound to the α-subunit of tubulin at the interphase of the α-and β-heterodimers and very close to colchicine binding site. The binding is entropy driven (ΔS(0) was 18.75 ± 1.48 cal K(-1) mol(-1)) with Kd value of 3.50 ± 0.40 μM. This is a novel mechanism of antipriliferative activity of EGCG.

  2. Polyphenol-rich strawberry extract (PRSE) shows in vitro and in vivo biological activity against invasive breast cancer cells.

    PubMed

    Amatori, Stefano; Mazzoni, Luca; Alvarez-Suarez, Josè Miguel; Giampieri, Francesca; Gasparrini, Massimiliano; Forbes-Hernandez, Tamara Yuliett; Afrin, Sadia; Errico Provenzano, Alfredo; Persico, Giuseppe; Mezzetti, Bruno; Amici, Augusto; Fanelli, Mirco; Battino, Maurizio

    2016-08-08

    We describe the biological effects of a polyphenol-rich strawberry extract (PRSE), obtained from the "Alba" variety, on the highly aggressive and invasive basal-like breast cancer cell line A17. Dose-response and time-course experiments showed that PRSE is able to decrease the cellular viability of A17 cells in a time- and dose-dependent manner. PRSE effect on cell survival was investigated in other tumor and normal cell lines of both mouse and human origin, demonstrating that PRSE is more active against breast cancer cells. Cytofluorimetric analysis of A17 cells demonstrated that sub-lethal doses of PRSE reduce the number of cells in S phase, inducing the accumulation of cells in G1 phase of cell cycle. In addition, the migration of A17 cells was studied monitoring the ability of PRSE to inhibit cellular mobility. Gene expression analysis revealed the modulation of 12 genes playing different roles in the cellular migration, adhesion and invasion processes. Finally, in vivo experiments showed the growth inhibition of A17 cells orthotopically transplanted into FVB syngeneic mice fed with PRSE. Overall, we demonstrated that PRSE exerts important biological activities against a highly invasive breast cancer cell line both in vitro and in vivo suggesting the strawberry extracts as preventive/curative food strategy.

  3. Polyphenol-rich strawberry extract (PRSE) shows in vitro and in vivo biological activity against invasive breast cancer cells

    PubMed Central

    Amatori, Stefano; Mazzoni, Luca; Alvarez-Suarez, Josè Miguel; Giampieri, Francesca; Gasparrini, Massimiliano; Forbes-Hernandez, Tamara Yuliett; Afrin, Sadia; Errico Provenzano, Alfredo; Persico, Giuseppe; Mezzetti, Bruno; Amici, Augusto; Fanelli, Mirco; Battino, Maurizio

    2016-01-01

    We describe the biological effects of a polyphenol-rich strawberry extract (PRSE), obtained from the “Alba” variety, on the highly aggressive and invasive basal-like breast cancer cell line A17. Dose-response and time-course experiments showed that PRSE is able to decrease the cellular viability of A17 cells in a time- and dose-dependent manner. PRSE effect on cell survival was investigated in other tumor and normal cell lines of both mouse and human origin, demonstrating that PRSE is more active against breast cancer cells. Cytofluorimetric analysis of A17 cells demonstrated that sub-lethal doses of PRSE reduce the number of cells in S phase, inducing the accumulation of cells in G1 phase of cell cycle. In addition, the migration of A17 cells was studied monitoring the ability of PRSE to inhibit cellular mobility. Gene expression analysis revealed the modulation of 12 genes playing different roles in the cellular migration, adhesion and invasion processes. Finally, in vivo experiments showed the growth inhibition of A17 cells orthotopically transplanted into FVB syngeneic mice fed with PRSE. Overall, we demonstrated that PRSE exerts important biological activities against a highly invasive breast cancer cell line both in vitro and in vivo suggesting the strawberry extracts as preventive/curative food strategy. PMID:27498973

  4. Simple dialkyl pyrazole-3,5-dicarboxylates show in vitro and in vivo activity against disease-causing trypanosomatids.

    PubMed

    Reviriego, Felipe; Olmo, Francisco; Navarro, Pilar; Marín, Clotilde; Ramírez-Macías, Inmaculada; García-España, Enrique; Albelda, María Teresa; Gutiérrez-Sánchez, Ramón; Sánchez-Moreno, Manuel; Arán, Vicente J

    2017-04-03

    The synthesis and antiprotozoal activity of some simple dialkyl pyrazole-3,5-dicarboxylates (compounds 2-6) and their sodium salts (pyrazolates) (compounds 7-9) against Trypanosoma cruzi, Leishmania infantum and Leishmania braziliensis are reported. In most cases the studied compounds showed, especially against the clinically significant amastigote forms, in vitro activities higher than those of the reference drugs (benznidazole for T. cruzi and glucantime for Leishmania spp.); furthermore, the low non-specific cytotoxicities against Vero cells and macrophages shown by these compounds led to good selectivity indexes, which are 8-72 times higher for T. cruzi amastigotes and 15-113 times higher for Leishmania spp. amastigotes than those of the respective reference drugs. The high efficiency of diethyl ester 3 and its sodium salt 8 against the mentioned protozoa was confirmed by further in vitro assays on infection rates and by an additional in vivo study in a murine model of acute and chronic Chagas disease. The inhibitory capacity of compounds 3 and 8 on the essential iron superoxide dismutase of the aforementioned parasites may be related to the observed anti-trypanosomatid activity. The low acute toxicity of compounds 3 and 8 in mice is also reported in this article.

  5. Phosphoinositide 5- and 3-phosphatase activities of a voltage-sensing phosphatase in living cells show identical voltage dependence

    PubMed Central

    Keum, Dongil; Kim, Dong-Il; Suh, Byung-Chang

    2016-01-01

    Voltage-sensing phosphatases (VSPs) are homologs of phosphatase and tensin homolog (PTEN), a phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2] and phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] 3-phosphatase. However, VSPs have a wider range of substrates, cleaving 3-phosphate from PI(3,4)P2 and probably PI(3,4,5)P3 as well as 5-phosphate from phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and PI(3,4,5)P3 in response to membrane depolarization. Recent proposals say these reactions have differing voltage dependence. Using Förster resonance energy transfer probes specific for different PIs in living cells with zebrafish VSP, we quantitate both voltage-dependent 5- and 3-phosphatase subreactions against endogenous substrates. These activities become apparent with different voltage thresholds, voltage sensitivities, and catalytic rates. As an analytical tool, we refine a kinetic model that includes the endogenous pools of phosphoinositides, endogenous phosphatase and kinase reactions connecting them, and four exogenous voltage-dependent 5- and 3-phosphatase subreactions of VSP. We show that apparent voltage threshold differences for seeing effects of the 5- and 3-phosphatase activities in cells are not due to different intrinsic voltage dependence of these reactions. Rather, the reactions have a common voltage dependence, and apparent differences arise only because each VSP subreaction has a different absolute catalytic rate that begins to surpass the respective endogenous enzyme activities at different voltages. For zebrafish VSP, our modeling revealed that 3-phosphatase activity against PI(3,4,5)P3 is 55-fold slower than 5-phosphatase activity against PI(4,5)P2; thus, PI(4,5)P2 generated more slowly from dephosphorylating PI(3,4,5)P3 might never accumulate. When 5-phosphatase activity was counteracted by coexpression of a phosphatidylinositol 4-phosphate 5-kinase, there was accumulation of PI(4,5)P2 in parallel to PI(3,4,5)P3 dephosphorylation

  6. Cephalosporin-NO-donor prodrug PYRRO-C3D shows β-lactam-mediated activity against Streptococcus pneumoniae biofilms.

    PubMed

    Allan, Raymond N; Kelso, Michael J; Rineh, Ardeshir; Yepuri, Nageshwar R; Feelisch, Martin; Soren, Odel; Brito-Mutunayagam, Sanjita; Salib, Rami J; Stoodley, Paul; Clarke, Stuart C; Webb, Jeremy S; Hall-Stoodley, Luanne; Faust, Saul N

    2017-05-01

    Bacterial biofilms show high tolerance towards antibiotics and are a significant problem in clinical settings where they are a primary cause of chronic infections. Novel therapeutic strategies are needed to improve anti-biofilm efficacy and support reduction in antibiotic use. Treatment with exogenous nitric oxide (NO) has been shown to modulate bacterial signaling and metabolic processes that render biofilms more susceptible to antibiotics. We previously reported on cephalosporin-3'-diazeniumdiolates (C3Ds) as NO-donor prodrugs designed to selectively deliver NO to bacterial infection sites following reaction with β-lactamases. With structures based on cephalosporins, C3Ds could, in principal, also be triggered to release NO following β-lactam cleavage mediated by transpeptidases/penicillin-binding proteins (PBPs), the antibacterial target of cephalosporin antibiotics. Transpeptidase-reactive C3Ds could potentially show both NO-mediated anti-biofilm properties and intrinsic (β-lactam-mediated) antibacterial effects. This dual-activity concept was explored using Streptococcus pneumoniae, a species that lacks β-lactamases but relies on transpeptidases for cell-wall synthesis. Treatment with PYRRO-C3D (a representative C3D containing the diazeniumdiolate NO donor PYRRO-NO) was found to significantly reduce viability of planktonic and biofilm pneumococci, demonstrating that C3Ds can elicit direct, cephalosporin-like antibacterial activity in the absence of β-lactamases. While NO release from PYRRO-C3D in the presence of pneumococci was confirmed, the anti-pneumococcal action of the compound was shown to arise exclusively from the β-lactam component and not through NO-mediated effects. The compound showed similar potency to amoxicillin against S. pneumoniae biofilms and greater efficacy than azithromycin, highlighting the potential of C3Ds as new agents for treating pneumococcal infections.

  7. Indonesian fire activity and smoke pollution in 2015 show persistent nonlinear sensitivity to El Niño-induced drought

    NASA Astrophysics Data System (ADS)

    Field, Robert D.; van der Werf, Guido R.; Fanin, Thierry; Fetzer, Eric J.; Fuller, Ryan; Jethva, Hiren; Levy, Robert; Livesey, Nathaniel J.; Luo, Ming; Torres, Omar; Worden, Helen M.

    2016-08-01

    The 2015 fire season and related smoke pollution in Indonesia was more severe than the major 2006 episode, making it the most severe season observed by the NASA Earth Observing System satellites that go back to the early 2000s, namely active fire detections from the Terra and Aqua Moderate Resolution Imaging Spectroradiometers (MODIS), MODIS aerosol optical depth, Terra Measurement of Pollution in the Troposphere (MOPITT) carbon monoxide (CO), Aqua Atmospheric Infrared Sounder (AIRS) CO, Aura Ozone Monitoring Instrument (OMI) aerosol index, and Aura Microwave Limb Sounder (MLS) CO. The MLS CO in the upper troposphere showed a plume of pollution stretching from East Africa to the western Pacific Ocean that persisted for 2 mo. Longer-term records of airport visibility in Sumatra and Kalimantan show that 2015 ranked after 1997 and alongside 1991 and 1994 as among the worst episodes on record. Analysis of yearly dry season rainfall from the Tropical Rainfall Measurement Mission (TRMM) and rain gauges shows that, due to the continued use of fire to clear and prepare land on degraded peat, the Indonesian fire environment continues to have nonlinear sensitivity to dry conditions during prolonged periods with less than 4 mm/d of precipitation, and this sensitivity appears to have increased over Kalimantan. Without significant reforms in land use and the adoption of early warning triggers tied to precipitation forecasts, these intense fire episodes will reoccur during future droughts, usually associated with El Niño events.

  8. Indonesian fire activity and smoke pollution in 2015 show persistent nonlinear sensitivity to El Niño-induced drought.

    PubMed

    Field, Robert D; van der Werf, Guido R; Fanin, Thierry; Fetzer, Eric J; Fuller, Ryan; Jethva, Hiren; Levy, Robert; Livesey, Nathaniel J; Luo, Ming; Torres, Omar; Worden, Helen M

    2016-08-16

    The 2015 fire season and related smoke pollution in Indonesia was more severe than the major 2006 episode, making it the most severe season observed by the NASA Earth Observing System satellites that go back to the early 2000s, namely active fire detections from the Terra and Aqua Moderate Resolution Imaging Spectroradiometers (MODIS), MODIS aerosol optical depth, Terra Measurement of Pollution in the Troposphere (MOPITT) carbon monoxide (CO), Aqua Atmospheric Infrared Sounder (AIRS) CO, Aura Ozone Monitoring Instrument (OMI) aerosol index, and Aura Microwave Limb Sounder (MLS) CO. The MLS CO in the upper troposphere showed a plume of pollution stretching from East Africa to the western Pacific Ocean that persisted for 2 mo. Longer-term records of airport visibility in Sumatra and Kalimantan show that 2015 ranked after 1997 and alongside 1991 and 1994 as among the worst episodes on record. Analysis of yearly dry season rainfall from the Tropical Rainfall Measurement Mission (TRMM) and rain gauges shows that, due to the continued use of fire to clear and prepare land on degraded peat, the Indonesian fire environment continues to have nonlinear sensitivity to dry conditions during prolonged periods with less than 4 mm/d of precipitation, and this sensitivity appears to have increased over Kalimantan. Without significant reforms in land use and the adoption of early warning triggers tied to precipitation forecasts, these intense fire episodes will reoccur during future droughts, usually associated with El Niño events.

  9. Indonesian fire activity and smoke pollution in 2015 show persistent nonlinear sensitivity to El Niño-induced drought

    PubMed Central

    Field, Robert D.; van der Werf, Guido R.; Fanin, Thierry; Fetzer, Eric J.; Fuller, Ryan; Jethva, Hiren; Levy, Robert; Livesey, Nathaniel J.; Luo, Ming; Torres, Omar; Worden, Helen M.

    2016-01-01

    The 2015 fire season and related smoke pollution in Indonesia was more severe than the major 2006 episode, making it the most severe season observed by the NASA Earth Observing System satellites that go back to the early 2000s, namely active fire detections from the Terra and Aqua Moderate Resolution Imaging Spectroradiometers (MODIS), MODIS aerosol optical depth, Terra Measurement of Pollution in the Troposphere (MOPITT) carbon monoxide (CO), Aqua Atmospheric Infrared Sounder (AIRS) CO, Aura Ozone Monitoring Instrument (OMI) aerosol index, and Aura Microwave Limb Sounder (MLS) CO. The MLS CO in the upper troposphere showed a plume of pollution stretching from East Africa to the western Pacific Ocean that persisted for 2 mo. Longer-term records of airport visibility in Sumatra and Kalimantan show that 2015 ranked after 1997 and alongside 1991 and 1994 as among the worst episodes on record. Analysis of yearly dry season rainfall from the Tropical Rainfall Measurement Mission (TRMM) and rain gauges shows that, due to the continued use of fire to clear and prepare land on degraded peat, the Indonesian fire environment continues to have nonlinear sensitivity to dry conditions during prolonged periods with less than 4 mm/d of precipitation, and this sensitivity appears to have increased over Kalimantan. Without significant reforms in land use and the adoption of early warning triggers tied to precipitation forecasts, these intense fire episodes will reoccur during future droughts, usually associated with El Niño events. PMID:27482096

  10. What Do Blood Tests Show?

    MedlinePlus

    ... Range Results* Red blood cell (varies with altitude) Male: 5 to 6 million cells/mcL Female: 4 to 5 million cells/mcL ... cells/mcL Platelets 140,000 to 450,000 cells/mcL Hemoglobin (varies with altitude) Male: 14 to 17 gm/dL Female: 12 to ...

  11. Motor Skills and Free-Living Physical Activity Showed No Association Among Preschoolers in 2012 U.S. National Youth Fitness Survey.

    PubMed

    Loprinzi, Paul D; Frith, Emily

    2017-04-01

    Albeit limited, some emerging work, using convenience-based samples, has demonstrated that greater motor skill development is associated with higher physical activity among preschool-aged children. The purpose of this study was to evaluate this topic using data from the 2012 National Youth Fitness Survey that included 329 preschool-aged children (3-5 years). Parents proxy-reported their child's physical activity, with motor skill level assessed from the Test of Gross Motor Development-Second Edition (TGMD2). Motor skill levels (Gross Motor Quotient, locomotor or object control) were not associated with preschool free-living physical activity in any analytic model. Thus, in this large sample of preschoolers, contrary to research with older children, motor skill level was not associated with physical activity. Findings are discussed in terms of study limitations of (a) a reliance on parent report of children's physical activity levels and (b) the possibility that physical activity data within the national survey were too limited in range to show possible associations to motor skill development with higher levels of free-living physical activity in preschoolers.

  12. Portosystemic hepatic encephalopathy model shows reversal learning impairment and dysfunction of neural activity in the prefrontal cortex and regions involved in motivated behavior.

    PubMed

    Méndez, M; Méndez-López, M; López, L; Aller, M A; Arias, J; Arias, J L

    2011-05-01

    Hepatic encephalopathy (HE) is a neurological complication that affects attention and memory. Experimental animal models have been used to study HE, the most frequent being the portacaval shunt (PCS). In order to investigate learning impairment and brain functional alterations in this model, we assessed reversal learning and neural metabolic activity in a PCS rat model. PCS and sham-operated rats were tested for reversal learning in the Morris water maze. Brains were then processed for cytochrome oxidase (CO) histochemistry. The PCS group had reversal learning impairment and a reduction in CO activity in the prefrontal cortex, ventral tegmental area and accumbens shell nucleus. These results suggest that this model of portosystemic HE shows learning impairments that could be linked to dysfunction in neural activity in the prefrontal cortex and regions involved in motivated behavior.

  13. "The Show"

    ERIC Educational Resources Information Center

    Gehring, John

    2004-01-01

    For the past 16 years, the blue-collar city of Huntington, West Virginia, has rolled out the red carpet to welcome young wrestlers and their families as old friends. They have come to town chasing the same dream for a spot in what many of them call "The Show". For three days, under the lights of an arena packed with 5,000 fans, the…

  14. Rat supraoptic magnocellular neurones show distinct large conductance, Ca2+-activated K+ channel subtypes in cell bodies versus nerve endings

    PubMed Central

    Dopico, Alejandro M; Widmer, Hélène; Wang, Gang; Lemos, José R; Treistman, Steven N

    1999-01-01

    Large conductance, Ca2+-activated K+ (BK) channels were identified in freshly dissociated rat supraoptic neurones using patch clamp techniques. The single channel conductance of cell body BK channels, recorded from inside-out patches in symmetric 145 mM K+, was 246.1 pS, compared with 213 pS in nerve ending BK channels (P < 0.01). At low open probability (Po), the reciprocal of the slope in the ln(NPo)-voltage relationship (N, number of available channels in the patch) for cell body and nerve ending channels were similar: 11 vs. 14 mVper e-fold change in NPo, respectively. At 40 mV, the [Ca2+]i producing half-maximal activation was 273 nM, as opposed to > 1.53 μM for the neurohypophysial channel, indicating the higher Ca2+ sensitivity of the cell body isochannel. Cell body BK channels showed fast kinetics (open time constant, 8.5 ms; fast closed time constant, 1.6 and slow closed time constant, 12.7 ms), identifying them as ‘type I’ isochannels, as opposed to the slow gating (type II) of neurohypophysial BK channels. Cell body BK activity was reduced by 10 nM charybdotoxin (NPo, 37 % of control), or 10 nM iberiotoxin (NPo, 5 % of control), whereas neurohypophysial BK channels are insensitive to charybdotoxin at concentrations as high as 360 nM. Whilst blockade of nerve ending BK channels markedly slowed the repolarization of evoked single spikes, blockade of cell body channels was without effect on repolarization of evoked single spikes. Ethanol reversibly increased neurohypophysial BK channel activity (EC50, 22 mM; maximal effect, 100 mM). In contrast, ethanol (up to 100 mM) failed to increase cell body BK channel activity. In conclusion, we have characterized BK channels in supraoptic neuronal cell bodies, and demonstrated that they display different electrophysiological and pharmacological properties from their counterparts in the nerve endings. PMID:10432342

  15. Antinociceptive activity of atranorin in mice orofacial nociception tests.

    PubMed

    Siqueira, Rosana S; Bonjardim, Leonardo R; Araújo, Adriano A S; Araújo, Bruno E S; Melo, Marcélia G D; Oliveira, Marília G B; Gelain, Daniel P; Silva, Francilene A; DeSantana, Josimari M; Albuquerque-Júnior, Ricardo L C; Rocha, Ricardo F; Moreira, José C F; Antoniolli, Angelo R; Quintans-Júnior, Lucindo J

    2010-01-01

    Physicochemical characterization and antinociceptive and anti-inflammatory activities of atranorin (AT) extracted from Cladina kalbii Ahti in formalin- and capsaicin-induced orofacial pain and anti-inflammatory tests in rodents were studied. Physicochemical characterization showed that AT has the general formula C19H18O8. Male Swiss mice were pretreated with AT (100, 200, and 400 mg/kg, i.p.), morphine (3 mg/kg, i.p.), or vehicle (0.9% saline with two drops of 0.2% Tween 80) before formalin (20 microl, 2%) or capsaicin (20 microl, 2.5 microg) were injected into the right vibrissa. Our results showed that i.p. treatment with AT displayed marked inhibitory effects in different orofacial pain tests in mice. AT (400 mg/kg, i.p.) was effective in reducing the nociceptive face-rubbing behavioural response in both phases of the formalin test, which was also naloxone-sensitive. Additionally, AT produced a significant antinociceptive effect at all doses in the capsaicin test. Such results were unlikely to be provoked by motor abnormality, since AT-treated mice exhibited no performance alteration on the rota rod apparatus. AT exhibited significant anti-inflammatory activity in the acute model of inflammation (leukocyte migration to the peritoneal cavity), carrageenan- and arachidonic acid-induced hind paw edema in rats. Additionally, AT exhibited a dose-dependent antioxidant activity in vitro, as assessed by total radical-trapping antioxidant parameter and total antioxidant reactivity assays. All these findings suggest that AT might represent an important tool for the management of orofacial pain and/or inflammatory disorders.

  16. Epidihydropinidine, the main piperidine alkaloid compound of Norway spruce (Picea abies) shows promising antibacterial and anti-Candida activity.

    PubMed

    Fyhrquist, Pia; Virjamo, Virpi; Hiltunen, Eveliina; Julkunen-Tiitto, Riitta

    2017-03-01

    This study reports for the first time promising antibacterial and antifungal effects of epidihydropinidine, the major piperidine alkaloid in the needles and bark of Norway spruce, Picea abies (L.) Karsten. Epidihydropinidine was growth inhibitory against all bacterial and fungal strains used in our investigation, showing the lowest MIC value of 5.37μg/mL against Pseudomonas aeruginosa, Enterococcus faecalis, Candida glabrata and C. albicans. Epidihydropinidine was nearly three times more active than tetracycline against P. aeruginosa and E. faecalis. Promising antibacterial effects were also recorded against Staphylococcus aureus and Bacillus cereus (MIC 10.75μg/mL) as well as against Salmonella enterica (MIC and MBC 43μg/mL). Our preliminary results suggest that epidihydropinidine as well related alkaloids of Norway spruce could be powerful candidates for new antibiotics and for preventing food spoilage.

  17. Goldstone field test activities: Target search

    NASA Technical Reports Server (NTRS)

    Tarter, J.

    1986-01-01

    In March of this year prototype SETI equipment was installed at DSS13, the 26 meter research and development antenna at NASA's Goldstone complex of satellite tracking dishes. The SETI equipment will remain at this site at least through the end of the summer so that the hardware and software developed for signal detection and recognition can be fully tested in a dynamic observatory environment. The field tests are expected to help understand which strategies for observing and which signal recognition algorithms perform best in the presence of strong man-made interfering signals (RFI) and natural astronomical sources.

  18. Novel triterpenoid saponins from residual seed cake of Camellia oleifera Abel. show anti-proliferative activity against tumor cells.

    PubMed

    Zong, Jianfa; Wang, Ruilong; Bao, Guanhu; Ling, Tiejun; Zhang, Liang; Zhang, Xinfu; Hou, Ruyan

    2015-07-01

    Four oleanane-type triterpenoid saponins were isolated from the seed cake of Camellia oleifera Abel.: camelliasaponin B1 and three new saponins, oleiferasaponin C1-C3 (1-3). Their structures were identified as 22-O-angeloyl-camelliagenin B 3-O-[β-d-galactopyranosyl-(1→2)]-[β-d-galactopyranosyl-(1→2)-α-l-arabinopyranosyl-(1→3)]-β-d-glucopyranosiduronic acid methyl ester (1); 22-O-angeloyl-camelliagenin A 3-O-[β-d-galactopyranosyl-(1→2)]-[β-d-glucopyranosyl-(1→2)-β-d-galactopyranosyl-(1→3)]-β-d-glucopyranosiduronic acid methyl ester (2); and 28-O-cinnamoyl-camelliagenin B 3-O-[β-d-galactopyranosylz-(1→2)] [β-d-galactopyranosyl(1→2)-α-l-arabinopyranosyl-(1→3)]-β-d-glucopyranosiduronic acid methyl ester (3) through 1D and 2D NMR, HR-ESI-MS, as well as GC-MS spectroscopic methods. The anti-proliferative activities of these four compounds were investigated on five human tumor cell lines (BEL-7402, BGC-823, MCF-7, HL-60 and KB). Compounds 1 and 2 and camelliasaponin B1 showed significant cytotoxic activities.

  19. Wind Tunnel Test of the SMART Active Flap Rotor

    NASA Technical Reports Server (NTRS)

    Straub, Friedrich K.; Anand, Vaidyanthan R.; Birchette, Terrence S.; Lau, Benton H.

    2009-01-01

    Boeing and a team from Air Force, NASA, Army, DARPA, MIT, UCLA, and U. of Maryland have successfully completed a wind-tunnel test of the smart material actuated rotor technology (SMART) rotor in the 40- by 80-foot wind-tunnel of the National Full-Scale Aerodynamic Complex at NASA Ames Research Center. The Boeing SMART rotor is a full-scale, five-bladed bearingless MD 900 helicopter rotor modified with a piezoelectric-actuated trailing edge flap on each blade. The eleven-week test program evaluated the forward flight characteristics of the active-flap rotor at speeds up to 155 knots, gathered data to validate state-of-the-art codes for rotor aero-acoustic analysis, and quantified the effects of open and closed loop active flap control on rotor loads, noise, and performance. The test demonstrated on-blade smart material control of flaps on a full-scale rotor for the first time in a wind tunnel. The effectiveness of the active flap control on noise and vibration was conclusively demonstrated. Results showed significant reductions up to 6dB in blade-vortex-interaction and in-plane noise, as well as reductions in vibratory hub loads up to 80%. Trailing-edge flap deflections were controlled within 0.1 degrees of the commanded value. The impact of the active flap on control power, rotor smoothing, and performance was also demonstrated. Finally, the reliability of the flap actuation system was successfully proven in more than 60 hours of wind-tunnel testing.

  20. An Overview of Follow-On Testing Activities of the A-3 Subscale Diffuser Test Project

    NASA Technical Reports Server (NTRS)

    Ryan, James E.

    2009-01-01

    An overview of NASA Stennis Space Center's (SSC) A-3 Subscale Diffuser Test (SDT) Project is presented. The original scope of the SDT Project, conducted from April 2007 to January 2008, collected data to support mitigation of risk associated with design and procurement activities of the A-3 Test Stand Project, an effort to construct a simulated altitude test facility at SSC in support of NASA's Constellation Program. Follow-on tests were conducted from May 2008 through August 2009, utilizing the SDT test setup as a testbed for additional risk mitigation activities. Included are descriptions of the Subscale Diffuser (SD) test article, the test facility configuration, and test approaches.

  1. Discovery of SMP-304, a novel benzylpiperidine derivative with serotonin transporter inhibitory activity and 5-HT1A weak partial agonistic activity showing the antidepressant-like effect.

    PubMed

    Yoshinaga, Hidefumi; Masumoto, Shuji; Koyama, Koji; Kinomura, Naoya; Matsumoto, Yuji; Kato, Taro; Baba, Satoko; Matsumoto, Kenji; Horisawa, Tomoko; Oki, Hitomi; Yabuuchi, Kazuki; Kodo, Toru

    2017-01-01

    We report the discovery of a novel benzylpiperidine derivative with serotonin transporter (SERT) inhibitory activity and 5-HT1A receptor weak partial agonistic activity showing the antidepressant-like effect. The 3-methoxyphenyl group and the phenethyl group of compound 1, which has weak SERT binding activity, but potent 5-HT1A binding activity, were optimized, leading to compound 35 with potent and balanced dual SERT and 5-HT1A binding activity, but also potent CYP2D6 inhibitory activity. Replacement of the methoxy group in the left part of compound 35 with a larger alkoxy group, such as ethoxy, isopropoxy or methoxy-ethoxy group ameliorated CYP2D6 inhibition, giving SMP-304 as a candidate. SMP-304 with serotonin uptake inhibitory activity and 5-HT1A weak partial agonistic activity, which could work as a 5-HT1A antagonist, displayed faster onset of antidepressant-like effect than a representative SSRI paroxetine in an animal model.

  2. Recovery Efficiency Test Project: Phase 1, Activity report

    SciTech Connect

    Overbey, W.K. Jr.; Wilkins, D.W.; Keltch, B.; Saradji, B.; Salamy, S.P.

    1988-04-01

    This report is the second volume of the Recovery Efficiency Test Phase I Report of Activities. Volume 1 covered selection, well planning, drilling, coring, logging and completion operations. This volume reports on well testing activities, reclamation activities on the drilling site and access roads, and the results of physical and mechanical properties tests on the oriented core material obtained from a horizontal section of the well. 3 refs., 21 figs., 10 tabs.

  3. Bid chimeras indicate that most BH3-only proteins can directly activate Bak and Bax, and show no preference for Bak versus Bax

    PubMed Central

    Hockings, C; Anwari, K; Ninnis, R L; Brouwer, J; O'Hely, M; Evangelista, M; Hinds, M G; Czabotar, P E; Lee, E F; Fairlie, W D; Dewson, G; Kluck, R M

    2015-01-01

    The mitochondrial pathway of apoptosis is initiated by Bcl-2 homology region 3 (BH3)-only members of the Bcl-2 protein family. On upregulation or activation, certain BH3-only proteins can directly bind and activate Bak and Bax to induce conformation change, oligomerization and pore formation in mitochondria. BH3-only proteins, with the exception of Bid, are intrinsically disordered and therefore, functional studies often utilize peptides based on just their BH3 domains. However, these reagents do not possess the hydrophobic membrane targeting domains found on the native BH3-only molecule. To generate each BH3-only protein as a recombinant protein that could efficiently target mitochondria, we developed recombinant Bid chimeras in which the BH3 domain was replaced with that of other BH3-only proteins (Bim, Puma, Noxa, Bad, Bmf, Bik and Hrk). The chimeras were stable following purification, and each immunoprecipitated with full-length Bcl-xL according to the specificity reported for the related BH3 peptide. When tested for activation of Bak and Bax in mitochondrial permeabilization assays, Bid chimeras were ~1000-fold more effective than the related BH3 peptides. BH3 sequences from Bid and Bim were the strongest activators, followed by Puma, Hrk, Bmf and Bik, while Bad and Noxa were not activators. Notably, chimeras and peptides showed no apparent preference for activating Bak or Bax. In addition, within the BH3 domain, the h0 position recently found to be important for Bax activation, was important also for Bak activation. Together, our data with full-length proteins indicate that most BH3-only proteins can directly activate both Bak and Bax. PMID:25906158

  4. PASylated Coversin, a C5-Specific Complement Inhibitor with Extended Pharmacokinetics, Shows Enhanced Anti-Hemolytic Activity in Vitro.

    PubMed

    Kuhn, Nadine; Schmidt, Christoph Q; Schlapschy, Martin; Skerra, Arne

    2016-10-19

    The Ornithodoros moubata Complement Inhibitor (OmCI) binds complement component 5 (C5) with high affinity and, thus, selectively prevents proteolytic activation of the terminal lytic complement pathway. A recombinant version of OmCI (also known as Coversin and rEV576) has proven efficacious in several animal models of complement-mediated diseases and successfully completed a phase Ia clinical trial. Coversin is a small 17 kDa lipocalin protein which has a very short plasma half-life if not bound to C5; therefore, the drug requires frequent dosing. We have improved the pharmacokinetics of Coversin by N-terminal translational conjugation with a 600 residue polypeptide composed of Pro, Ala, and Ser (PAS) residues. To this end, PAS-Coversin as well as the unmodified Coversin were functionally expressed in the cytoplasm of E. coli and purified to homogeneity. Both versions showed identical affinity to human C5, as determined by surface plasmon resonance measurements, and revealed similar complement inhibitory activity, as measured in ELISAs with human serum. In line with the PEG-like biophysical properties, PASylation dramatically prolonged the plasma half-life of uncomplexed Coversin by a factor ≥50 in mice. In a clinically relevant in vitro model of the complement-mediated disease paroxysmal nocturnal hemoglobinuria (PNH) both versions of Coversin effectively reduced erythrocyte lysis. Unexpectedly, while the IC50 values were comparable, PAS-Coversin reached a substantially lower plateau of residual lysis at saturating inhibitor concentrations. Taken together, our data demonstrate two clinically relevant improvements of PASylated Coversin: markedly increased plasma half-life and considerably reduced background hemolysis of erythrocytes with PNH-induced phenotype.

  5. Active testing for face detection and localization.

    PubMed

    Sznitman, Raphael; Jedynak, Bruno

    2010-10-01

    We provide a novel search technique which uses a hierarchical model and a mutual information gain heuristic to efficiently prune the search space when localizing faces in images. We show exponential gains in computation over traditional sliding window approaches, while keeping similar performance levels.

  6. Exploring the transferase activity of Ffase from Schwanniomyces occidentalis, a β-fructofuranosidase showing high fructosyl-acceptor promiscuity.

    PubMed

    Piedrabuena, David; Míguez, Noa; Poveda, Ana; Plou, Francisco J; Fernández-Lobato, María

    2016-10-01

    The β-fructofuranosidase from the yeast Schwanniomyces occidentalis (Ffase) produces the prebiotic sugars 6-kestose and 1-kestose by transfructosylation of sucrose, which makes it of biotechnological interest. In this study, the hydrolase and transferase activity of this enzyme was kinetically characterized and its potential to synthesize new fructosylated products explored. A total of 40 hydroxylated compounds were used as potential fructosyl-acceptor alternatives to sucrose. Only 17 of them, including some monosaccharides, disaccharides, and oligosaccharides as well as alditols and glycosides were fructosylated. The best alternative acceptors were the alditols. The major transfer product of the reaction including mannitol was purified and characterized as 1-O-β-D-fructofuranosyl-D-mannitol, whose maximum concentration reached 44 g/L, representing about 7.3 % of total compounds in the mixture and 89 % of all products generated by transfructosylation. The reactions including erythritol produced 35 g/L of an isomer mixture comprising 1- and 4-O-β-D-fructofuranosyl-D-erythritol. In addition, Ffase produced 24 g/L of the disaccharide blastose by direct fructosylation of glucose, which makes it the first enzyme characterized from yeast showing this ability. Thus, novel fructosylated compounds with potential applications in food and pharmaceutical industries can be obtained due to the Ffase fructosyl-acceptor promiscuity.

  7. Tryptophan prenyltransferases showing higher catalytic activities for Friedel-Crafts alkylation of o- and m-tyrosines than tyrosine prenyltransferases.

    PubMed

    Fan, Aili; Xie, Xiulan; Li, Shu-Ming

    2015-07-21

    Tryptophan prenyltransferases FgaPT2, 5-DMATS, 6-DMATSSv and 7-DMATS catalyse regiospecific C-prenylations on the indole ring, while tyrosine prenyltransferases SirD and TyrPT catalyse the O-prenylation of the phenolic hydroxyl group. In this study, we report the Friedel-Crafts alkylation of L-o-tyrosine by these enzymes. Surprisingly, no conversion was detected with SirD and three tryptophan prenyltransferases showed significantly higher activity than another tyrosine prenyltransferase TyrPT. C5-prenylated L-o-tyrosine was identified as a unique product of these enzymes. Using L-m-tyrosine as the prenylation substrate, product formation was only observed with the tryptophan prenyltransferases FgaPT2 and 7-DMATS. C4- and C6-prenylated derivatives were identified in the reaction mixture of FgaPT2. These results provided additional evidence for the similarities and differences between these two subgroups within the DMATS superfamily in their catalytic behaviours.

  8. Centipede venom peptide SsmTX-I with two intramolecular disulfide bonds shows analgesic activities in animal models.

    PubMed

    Wang, Ying; Li, Xiaojie; Yang, Meifeng; Wu, Chunyun; Zou, Zhirong; Tang, Jing; Yang, Xinwang

    2017-03-01

    Pain is a major symptom of many diseases and results in enormous pressures on human body or society. Currently, clinically used analgesic drugs, including opioids and nonsteroidal anti-inflammatory drugs, have adverse reactions, and thus, the development of new types of analgesic drug candidates is urgently needed. Animal venom peptides have proven to have potential as new types of analgesic medicine. In this research, we describe the isolation and characterization of an analgesic peptide from the crude venom of centipede, Scolopendra subspinipes mutilans. The amino acid sequence of this peptide was identical with SsmTX-I that was previously reported as a specific Kv2.1 ion channel blocker. Our results revealed that SsmTX-I was produced by posttranslational processing of a 73-residue prepropeptide. The intramolecular disulfide bridge motifs of SsmTX-I was Cys1-Cys3 and Cys2-Cys4. Functional assay revealed that SsmTX-I showed potential analgesic activities in formalin-induced paw licking, thermal pain, and acetic acid-induced abdominal writhing mice models. Our research provides the first report of cDNA sequences, disulfide motif, successful synthesis, and analgesic potential of SsmTX-I for the development of pain-killing drugs. It indicates that centipede peptide toxins could be a treasure trove for the search of novel analgesic drug candidates. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

  9. Plasma membrane of Beta vulgaris storage root shows high water channel activity regulated by cytoplasmic pH and a dual range of calcium concentrations.

    PubMed

    Alleva, Karina; Niemietz, Christa M; Sutka, Moira; Maurel, Christophe; Parisi, Mario; Tyerman, Stephen D; Amodeo, Gabriela

    2006-01-01

    Plasma membrane vesicles isolated by two-phase partitioning from the storage root of Beta vulgaris show atypically high water permeability that is equivalent only to those reported for active aquaporins in tonoplast or animal red cells (Pf=542 microm s(-1)). The values were determined from the shrinking kinetics measured by stopped-flow light scattering. This high Pf was only partially inhibited by mercury (HgCl2) but showed low activation energy (Ea) consistent with water permeation through water channels. To study short-term regulation of water transport that could be the result of channel gating, the effects of pH, divalent cations, and protection against dephosphorylation were tested. The high Pf observed at pH 8.3 was dramatically reduced by medium acidification. Moreover, intra-vesicular acidification (corresponding to the cytoplasmic face of the membrane) shut down the aquaporins. De-phosphorylation was discounted as a regulatory mechanism in this preparation. On the other hand, among divalent cations, only calcium showed a clear effect on aquaporin activity, with two distinct ranges of sensitivity to free Ca2+ concentration (pCa 8 and pCa 4). Since the normal cytoplasmic free Ca2+ sits between these ranges it allows for the possibility of changes in Ca2+ to finely up- or down-regulate water channel activity. The calcium effect is predominantly on the cytoplasmic face, and inhibition corresponds to an increase in the activation energy for water transport. In conclusion, these findings establish both cytoplasmic pH and Ca2+ as important regulatory factors involved in aquaporin gating.

  10. An Echinococcus multilocularis Antigen B3 Proteoform That Shows Specific Antibody Responses to Active-Stage Alveolar Echinococcosis

    PubMed Central

    Ahn, Chun-Seob; Cai, Huixia; Kim, Jeong-Geun; Han, Xiumin; Ma, Xiao; Bae, Young-An; Yang, Hyun-Jong; Kang, Insug; Wang, Hu

    2015-01-01

    Alveolar echinococcosis (AE), caused by the Echinococcus multilocularis metacestode, represents one of the most frequently fatal zoonoses. Early diagnosis significantly reduces morbidity and mortality associated with AE. Diagnosis of AE largely depends on a combination of imaging and serological tests due to its minimal clinical manifestations. Several antigens derived from the whole worm and protoscolex have been targeted for AE serodiagnosis, while the antigenic properties of E. multilocularis hydatid fluid (EmHF) are unclear. We observed two AE-specific 6- and 8-kDa antigen proteoforms through an immunoproteome array of the EmHF. We identified these proteins as representing an E. multilocularis antigen B3 (EmAgB3) isoform, and the proteins were shown to be encoded by the same gene. We cloned the gene and expressed the recombinant EmAgB3 protein (rEmAgB3) in Escherichia coli. rEmAgB3 exhibited sensitivity of 90.9% (80/88 cases) and specificity of 98.5% (597/606 samples) by immunoblotting. The positive and negative predictive values were 89.9% and 98.6%, respectively. The protein did not show antibody responses to 33 AE sera collected during posttreatment follow-up monitoring. Mouse sera experimentally infected with AE protoscoleces began to demonstrate specific antibody responses to native and recombinant EmAgB3 6 months after infection. At that stage, fully mature metacestode vesicles that harbored the brood capsule, primary cell, and protoscolex were observed within an AE mass(es). The response declined along with worm degeneration. Our results demonstrate that the immune responses to this EmAgB3 isoform were highly correlated with worm viability accompanied with AE progression. rEmAgB3 is a promising biomarker for serological assessment of AE patients. PMID:26269620

  11. Endophytic Bacteria Isolated from Common Bean (Phaseolus vulgaris) Exhibiting High Variability Showed Antimicrobial Activity and Quorum Sensing Inhibition.

    PubMed

    Lopes, Ralf Bruno Moura; Costa, Leonardo Emanuel de Oliveira; Vanetti, Maria Cristina Dantas; de Araújo, Elza Fernandes; de Queiroz, Marisa Vieira

    2015-10-01

    Endophytic bacteria play a key role in the biocontrol of phytopathogenic microorganisms. In this study, genotypic diversity was analyzed via repetitive element PCR (rep-PCR) of endophytic isolates of the phylum Actinobacteria that were previously collected from leaves of cultivars of common bean (Phaseolus vulgaris). Considerable variability was observed, which has not been reported previously for this phylum of endophytic bacteria of the common bean. Furthermore, the ethanol extracts from cultures of various isolates inhibited the growth of pathogenic bacteria in vitro, especially Gram-positive pathogens. Extracts from cultures of Microbacterium testaceum BAC1065 and BAC1093, which were both isolated from the 'Talismã' cultivar, strongly inhibited most of the pathogenic bacteria tested. Bean endophytic bacteria were also demonstrated to have the potential to inhibit the quorum sensing of Gram-negative bacteria. This mechanism may regulate the production of virulence factors in pathogens. The ability to inhibit quorum sensing has also not been reported previously for endophytic microorganisms of P. vulgaris. Furthermore, M. testaceum with capacity to inhibit quorum sensing appears to be widespread in common bean. The genomic profiles of M. testaceum were also analyzed via pulsed-field gel electrophoresis, and greater differentiation was observed using this method than rep-PCR; in general, no groups were formed based on the cultivar of origin. This study showed for the first time that endophytic bacteria from common bean plants exhibit high variability and may be useful for the development of strategies for the biological control of diseases in this important legume plant.

  12. Severe Accident Test Station Activity Report

    SciTech Connect

    Pint, Bruce A.; Terrani, Kurt A.

    2015-06-01

    Enhancing safety margins in light water reactor (LWR) severe accidents is currently the focus of a number of international R&D programs. The current UO2/Zr-based alloy fuel system is particularly susceptible since the Zr-based cladding experiences rapid oxidation kinetics in steam at elevated temperatures. Therefore, alternative cladding materials that offer slower oxidation kinetics and a smaller enthalpy of oxidation can significantly reduce the rate of heat and hydrogen generation in the core during a coolant-limited severe accident. In the U.S. program, the high temperature steam oxidation performance of accident tolerant fuel (ATF) cladding solutions has been evaluated in the Severe Accident Test Station (SATS) at Oak Ridge National Laboratory (ORNL) since 2012. This report summarizes the capabilities of the SATS and provides an overview of the oxidation kinetics of several candidate cladding materials. A suggested baseline for evaluating ATF candidates is a two order of magnitude reduction in the steam oxidation resistance above 1000ºC compared to Zr-based alloys. The ATF candidates are categorized based on the protective external oxide or scale that forms during exposure to steam at high temperature: chromia, alumina, and silica. Comparisons are made to literature and SATS data for Zr-based alloys and other less-protective materials.

  13. Basophil activation test with food additives in chronic urticaria patients.

    PubMed

    Kang, Min-Gyu; Song, Woo-Jung; Park, Han-Ki; Lim, Kyung-Hwan; Kim, Su-Jung; Lee, Suh-Young; Kim, Sae-Hoon; Cho, Sang-Heon; Min, Kyung-Up; Chang, Yoon-Seok

    2014-01-01

    The role of food additives in chronic urticaria (CU) is still under investigation. In this study, we aimed to explore the association between food additives and CU by using the basophil activation test (BAT). The BAT using 15 common food additives was performed for 15 patients with CU who had a history of recurrent urticarial aggravation following intake of various foods without a definite food-specific IgE. Of the 15 patients studied, two (13.3%) showed positive BAT results for one of the tested food additives. One patient responded to monosodium glutamate, showing 18.7% of CD203c-positive basophils. Another patient showed a positive BAT result to sodium benzoate. Both patients had clinical correlations with the agents, which were partly determined by elimination diets. The present study suggested that at least a small proportion of patients with CU had symptoms associated with food additives. The results may suggest the potential utility of the BAT to identity the role of food additives in CU.

  14. Designing and testing the activities of TAL effector nucleases.

    PubMed

    Lin, Yanni; Cradick, Thomas J; Bao, Gang

    2014-01-01

    Transcription activator-like effector nucleases (TALENs) have rapidly developed into a powerful tool for genome editing. To avoid labor-intensive and time-consuming experimental screening for active TALENs, a scoring system can help select optimal target sites. Here we describe a procedure to design active TALENs using a scoring system named Scoring Algorithm for Predicted TALEN Activity (SAPTA) and a method to test the activity of individual and pairs of TALENs.

  15. Genotoxicity testing of the herbicide Roundup and its active ingredient glyphosate isopropylamine using the mouse bone marrow micronucleus test, Salmonella mutagenicity test, and Allium anaphase-telophase test.

    PubMed

    Rank, J; Jensen, A G; Skov, B; Pedersen, L H; Jensen, K

    1993-06-01

    The genotoxic potential of the herbicide Roundup and its active agent, glyphosate isopropylamine salt, was studied in three different assays. No clastogenic effects were found in the mouse bone marrow micronucleus test for either of the two agents. In the Salmonella assay only Roundup was tested. It showed a weak mutagenic effect for the concentrations 360 micrograms/plate in TA98 (without S9) and 720 micrograms/plate in TA100 (with S9). These concentrations are close to the toxic level. The anaphase-telophase Allium test showed no effect for the glyphosate isopropylamine salt, but a significant increase in chromosome aberrations appeared after treatment with Roundup at concentrations of 1.44 and 2.88 mg/l when calculated as glyphosate isopropylamine. The most frequent aberrations observed could be characterized as disturbances of the spindle.

  16. Active Learning Facilitated by Using a Game-Show Format or Who Doesn't Want to Be a Millionaire?

    ERIC Educational Resources Information Center

    Sarason, Yolanda; Banbury, Catherine

    2004-01-01

    University faculty are increasingly called on to be less of a sage on the stage and more a guide on the side. This discussion introduces the underlying philosophy and assumptions of active learning theory. With this shift in pedagogical philosophy, there has been an increasing call for tools that actively engage students in the learning process. A…

  17. Physical Activity in the Life of a Woman with Severe Cerebral Palsy: Showing Competence and Being Socially Connected

    ERIC Educational Resources Information Center

    Gaskin, Cadeyrn J.; Andersen, Mark B.; Morris, Tony

    2009-01-01

    We used a life-history approach to investigate the meanings and experiences of physical activity in the life of a 25-year-old woman with severe cerebral palsy (Amy). Amy and her mother were interviewed about Amy's life and her involvement in physical activity. The conversation was audio-recorded and transcribed verbatim. We interpreted Amy's story…

  18. Imidazopyridine-Based Fatty Acid Synthase Inhibitors That Show Anti-HCV Activity and in Vivo Target Modulation

    PubMed Central

    2012-01-01

    Potent imidazopyridine-based inhibitors of fatty acid synthase (FASN) are described. The compounds are shown to have antiviral (HCV replicon) activities that track with their biochemical activities. The most potent analogue (compound 19) also inhibits rat FASN and inhibits de novo palmitate synthesis in vitro (cell-based) as well as in vivo. PMID:24900571

  19. Healthy children show gender differences in correlations between nonverbal cognitive ability and brain activation during visual perception.

    PubMed

    Asano, Kohei; Taki, Yasuyuki; Hashizume, Hiroshi; Sassa, Yuko; Thyreau, Benjamin; Asano, Michiko; Takeuchi, Hikaru; Kawashima, Ryuta

    2014-08-08

    Humans perceive textual and nontextual information in visual perception, and both depend on language. In childhood education, students exhibit diverse perceptual abilities, such that some students process textual information better and some process nontextual information better. These predispositions involve many factors, including cognitive ability and learning preference. However, the relationship between verbal and nonverbal cognitive abilities and brain activation during visual perception has not yet been examined in children. We used functional magnetic resonance imaging to examine the relationship between nonverbal and verbal cognitive abilities and brain activation during nontextual visual perception in large numbers of children. A significant positive correlation was found between nonverbal cognitive abilities and brain activation in the right temporoparietal junction, which is thought to be related to attention reorienting. This significant positive correlation existed only in boys. These findings suggested that male brain activation differed from female brain activation, and that this depended on individual cognitive processes, even if there was no gender difference in behavioral performance.

  20. Fusion peptide P15-CSP shows antibiofilm activity and pro-osteogenic activity when deposited as a coating on hydrophilic but not hydrophobic surfaces.

    PubMed

    Li, Xian; Contreras-Garcia, Angel; LoVetri, Karen; Yakandawala, Nandadeva; Wertheimer, Michael R; De Crescenzo, Gregory; Hoemann, Caroline D

    2015-12-01

    In the context of porous bone void filler for oral bone reconstruction, peptides that suppress microbial growth and promote osteoblast function could be used to enhance the performance of a porous bone void filler. We tested the hypothesis that P15-CSP, a novel fusion peptide containing collagen-mimetic osteogenic peptide P15, and competence-stimulating peptide (CSP), a cationic antimicrobial peptide, has emerging properties not shared by P15 or CSP alone. Peptide-coated surfaces were tested for antimicrobial activity toward Streptoccocus mutans, and their ability to promote human mesenchymal stem cell (MSC) attachment, spreading, metabolism, and osteogenesis. In the osteogenesis assay, peptides were coated on tissue culture plastic and on thin films generated by plasma-enhanced chemical vapor deposition to have hydrophilic or hydrophobic character (water contact angles 63°, 42°, and 92°, respectively). S. mutans planktonic growth was specifically inhibited by CSP, whereas biofilm formation was inhibited by P15-CSP. MSC adhesion and actin stress fiber formation was strongly enhanced by CSP, P15-CSP, and fibronectin coatings and modestly enhanced by P15 versus uncoated surfaces. Metabolic assays revealed that CSP was slightly cytotoxic to MSCs. MSCs developed alkaline phosphatase activity on all surfaces, with or without peptide coatings, and consistently deposited the most biomineralized matrix on hydrophilic surfaces coated with P15-CSP. Hydrophobic thin films completely suppressed MSC biomineralization, consistent with previous findings of suppressed osteogenesis on hydrophobic bioplastics. Collective data in this study provide new evidence that P15-CSP has unique dual capacity to suppress biofilm formation, and to enhance osteogenic activity as a coating on hydrophilic surfaces.

  1. Forebrain-specific constitutively active CaMKKα transgenic mice show deficits in hippocampus-dependent long-term memory.

    PubMed

    Kaitsuka, Taku; Li, Sheng-Tian; Nakamura, Kenji; Takao, Keizo; Miyakawa, Tsuyoshi; Matsushita, Masayuki

    2011-09-01

    The Ca(2+)/calmodulin (CaM) kinase cascade is activated by Ca(2+) influx through the voltage-dependent Ca(2+) channels and the NMDA receptor. CaM kinase kinase (CaMKK), the most upstream kinase of the CaM kinase cascade, phosphorylates and activates both CaM kinase I (CaMKI) and CaMKIV, resulting in activation of cyclic AMP-responsive element binding protein (CREB)-dependent gene transcription. Using transgenic techniques, we created mutant mice in which a constitutively active form of CaMKK1, the autoinhibitory domain truncated protein, is over-expressed specifically in the forebrain. In these mice, although performance was normal in basal activity and short-term memory, specific impairments were shown in hippocampus-dependent long-term memory after training in spatial memory tasks and after contextual fear conditioning. In cultured neurons of these mice, phosphorylation of CaMKI was significantly increased in basal states, whereas the activity range of CaMKI phosphorylation by brain-derived neurotrophic factor (BDNF) and KCl stimulation was significantly diminished in mutant mice. Our results define a critical role for CaMKKα in synaptic plasticity and the retention of hippocampus-dependent long-term memory.

  2. Tc-99 Adsorption on Selected Activated Carbons - Batch Testing Results

    SciTech Connect

    Mattigod, Shas V.; Wellman, Dawn M.; Golovich, Elizabeth C.; Cordova, Elsa A.; Smith, Ronald M.

    2010-12-01

    CH2M HILL Plateau Remediation Company (CHPRC) is currently developing a 200-West Area groundwater pump-and-treat system as the remedial action selected under the Comprehensive Environmental Response, Compensation, and Liability Act Record of Decision for Operable Unit (OU) 200-ZP-1. This report documents the results of treatability tests Pacific Northwest National Laboratory researchers conducted to quantify the ability of selected activated carbon products (or carbons) to adsorb technetium-99 (Tc-99) from 200-West Area groundwater. The Tc-99 adsorption performance of seven activated carbons (J177601 Calgon Fitrasorb 400, J177606 Siemens AC1230AWC, J177609 Carbon Resources CR-1240-AW, J177611 General Carbon GC20X50, J177612 Norit GAC830, J177613 Norit GAC830, and J177617 Nucon LW1230) were evaluated using water from well 299-W19-36. Four of the best performing carbons (J177606 Siemens AC1230AWC, J177609 Carbon Resources CR-1240-AW, J177611 General Carbon GC20X50, and J177613 Norit GAC830) were selected for batch isotherm testing. The batch isotherm tests on four of the selected carbons indicated that under lower nitrate concentration conditions (382 mg/L), Kd values ranged from 6,000 to 20,000 mL/g. In comparison. Under higher nitrate (750 mg/L) conditions, there was a measureable decrease in Tc-99 adsorption with Kd values ranging from 3,000 to 7,000 mL/g. The adsorption data fit both the Langmuir and the Freundlich equations. Supplemental tests were conducted using the two carbons that demonstrated the highest adsorption capacity to resolve the issue of the best fit isotherm. These tests indicated that Langmuir isotherms provided the best fit for Tc-99 adsorption under low nitrate concentration conditions. At the design basis concentration of Tc 0.865 µg/L(14,700 pCi/L), the predicted Kd values from using Langmuir isotherm constants were 5,980 mL/g and 6,870 mL/g for for the two carbons. These Kd values did not meet the target Kd value of 9,000 mL/g. Tests

  3. Saraca indica Bark Extract Shows In Vitro Antioxidant, Antibreast Cancer Activity and Does Not Exhibit Toxicological Effects

    PubMed Central

    Yadav, Navneet Kumar; Saini, Karan Singh; Hossain, Zakir; Omer, Ankur; Sharma, Chetan; Gayen, Jiaur R.; Singh, Poonam; Arya, K. R.; Singh, R. K.

    2015-01-01

    Medicinal plants are used as a complementary and alternative medicine in treatment of various diseases including cancer worldwide, because of their ease of accessibility and cost effectiveness. Multicomposed mixture of compounds present in a plant extract has synergistic activity, increases the therapeutic potential many folds, compensates toxicity, and increases bioavailability. Saraca indica (family Caesalpiniaceae) is one of the most ancient sacred plants with medicinal properties, exhibiting a number of pharmacological effects. Antioxidant, antibreast cancer activity and toxicological evaluation of Saraca indica bark extract (SIE) were carried out in the present study. The results of the study indicated that this herbal preparation has antioxidant and antibreast cancer activity. Toxicological studies suggest that SIE is safer to use and may have a potential to be used as complementary and alternative medicine for breast cancer therapy. PMID:25861411

  4. NASA Stennis Space Center Test Technology Branch Activities

    NASA Technical Reports Server (NTRS)

    Solano, Wanda M.

    2000-01-01

    This paper provides a short history of NASA Stennis Space Center's Test Technology Laboratory and briefly describes the variety of engine test technology activities and developmental project initiatives. Theoretical rocket exhaust plume modeling, acoustic monitoring and analysis, hand held fire imaging, heat flux radiometry, thermal imaging and exhaust plume spectroscopy are all examples of current and past test activities that are briefly described. In addition, recent efforts and visions focused on accomodating second, third, and fourth generation flight vehicle engine test requirements are discussed.

  5. Transformation of Lettuce with rol ABC Genes: Extracts Show Enhanced Antioxidant, Analgesic, Anti-Inflammatory, Antidepressant, and Anticoagulant Activities in Rats.

    PubMed

    Ismail, Hammad; Dilshad, Erum; Waheed, Mohammad Tahir; Mirza, Bushra

    2017-03-01

    Lettuce is an edible crop that is well known for dietary and antioxidant benefits. The present study was conducted to investigate the effects of rol ABC genes on antioxidant and medicinal potential of lettuce by Agrobacterium-mediated transformation. Transgene integration and expression was confirmed through PCR and real-time RT-PCR, respectively. The transformed plants showed 91-102 % increase in total phenolic contents and 53-65 % increase in total flavonoid contents compared to untransformed plants. Total antioxidant capacity and total reducing power increased up to 112 and 133 % in transformed plants, respectively. Results of DPPH assay showed maximum 51 % increase, and lipid peroxidation assay exhibited 20 % increase in antioxidant activity of transformed plants compared to controls. Different in vivo assays were carried out in rats. The transgenic plants showed up to 80 % inhibition in both hot plate analgesic assay and carrageenan-induced hind paw edema test, while untransformed plants showed only 45 % inhibition. Antidepressant and anticoagulant potential of transformed plants was also significantly enhanced compared to untransformed plants. Taken together, the present work highlights the use of rol genes to enhance the secondary metabolite production in lettuce and improve its analgesic, anti-inflammatory, antidepressant, and anticoagulatory properties.

  6. A new class of peroxisome proliferator-activated receptor agonists with a novel binding epitope shows antidiabetic effects.

    PubMed

    Ostberg, Tove; Svensson, Stefan; Selén, Göran; Uppenberg, Jonas; Thor, Markus; Sundbom, Maj; Sydow-Bäckman, Mona; Gustavsson, Anna-Lena; Jendeberg, Lena

    2004-09-24

    The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the NR1 subfamily of nuclear receptors. The PPARs play key roles in the control of glucose and lipid homeostasis, and the synthetic isoform-specific PPAR agonists are used clinically to improve insulin sensitivity and to lower serum triglyceride levels. All of the previously reported PPAR agonists form the same characteristic interactions with the receptor, which have been postulated to be important for the induction of agonistic activity. Here we describe a new class of PPARalpha/gamma modulators, the 5-substituted 2-benzoylaminobenzoic acids (2-BABAs). As shown by x-ray crystallography, the representative compounds BVT.13, BVT.762, and BVT.763, utilize a novel binding epitope and lack the agonist-characteristic interactions. Despite this, some compounds within the 2-BABA family are potent agonists in a cell-based reporter gene assay. Furthermore, BVT.13 displays antidiabetic effects in ob/ob mice. We concluded that the 2-BABA binding mode can be used to design isoform-specific PPAR modulators with biological activity in vivo.

  7. Individuals with low working memory spans show greater interference from irrelevant information because of poor source monitoring, not greater activation.

    PubMed

    Lilienthal, Lindsey; Rose, Nathan S; Tamez, Elaine; Myerson, Joel; Hale, Sandra

    2015-04-01

    Although individuals with high and low working memory (WM) span appear to differ in the extent to which irrelevant information interferes with their performance on WM tasks, the locus of this interference is not clear. The present study investigated whether, when performing a WM task, high- and low-span individuals differ in the activation of formerly relevant, but now irrelevant items, and/or in their ability to correctly identify such irrelevant items. This was done in two experiments, both of which used modified complex WM span tasks. In Experiment 1, the span task included an embedded lexical decision task designed to obtain an implicit measure of the activation of both currently and formerly relevant items. In Experiment 2, the span task included an embedded recognition judgment task designed to obtain an explicit measure of both item and source recognition ability. The results of these experiments indicate that low-span individuals do not hold irrelevant information in a more active state in memory than high-span individuals, but rather that low-span individuals are significantly poorer at identifying such information as irrelevant at the time of retrieval. These results suggest that differences in the ability to monitor the source of information, rather than differences in the activation of irrelevant information, are the more important determinant of performance on WM tasks.

  8. Glycosynthase Mutants of Endoglycosidase S2 Show Potent Transglycosylation Activity and Remarkably Relaxed Substrate Specificity for Antibody Glycosylation Remodeling.

    PubMed

    Li, Tiezheng; Tong, Xin; Yang, Qiang; Giddens, John P; Wang, Lai-Xi

    2016-08-05

    Glycosylation can exert a profound impact on the structures and biological functions of antibodies. Glycosylation remodeling using the endoglycosidase-catalyzed deglycosylation and transglycosylation approach is emerging as a promising platform to produce homogeneous glycoforms of antibodies, but the broad application of this method will require the availability of highly efficient glycosynthase mutants. We describe in this paper a systematic site-directed mutagenesis of an endoglycosidase from Streptococcus pyogenes of serotype M49 (Endo-S2) and the evaluation of the resulting mutants for their hydrolysis and transglycosylation activities. We found that mutations at the Asp-184 residue gave mutants that demonstrated significantly different properties, some possessed potent transglycosylation activity with diminished hydrolysis activity but others did not, which would be otherwise difficult to predict without the comparative study. In contrast to the previously reported Endo-S mutants that are limited to action on complex type N-glycans, the Endo-S2 glycosynthases described here, including D184M and D184Q, were found to have remarkably relaxed substrate specificity and were capable of transferring three major types (complex, high-mannose, and hybrid type) of N-glycans for antibody glycosylation remodeling. In addition, the Endo-S2 glycosynthase mutants were found to be much more active in general than the Endo-S mutants for transglycosylation. The usefulness of these Endo-S2 glycosynthase mutants was exemplified by an efficient glycosylation remodeling of two therapeutic monoclonal antibodies, rituximab and trastuzumab (Herceptin).

  9. Oral Therapy with Amlodipine and Lacidipine, 1,4-Dihydropyridine Derivatives Showing Activity against Experimental Visceral Leishmaniasis.

    PubMed

    Palit, Partha; Ali, Nahid

    2008-01-01

    Amlodipine and lacidipine, conventional antihypertensive drugs, inhibited Leishmania donovani infection in vitro and in BALB/c mice when administered orally. These 1,4-dihydropyridine derivatives functioned through dose-dependent inhibition of oxygen consumption, triggering caspase 3-like activation-mediated programmed cell death of the parasites.

  10. Camptothecin analog (CPT-11)-sensitive human pancreatic tumor cell line QGP-1N shows resistance to SN-38, an active metabolite of CPT-11.

    PubMed

    Takeda, S; Shimazoe, T; Kuga, H; Sato, K; Kono, A

    1992-10-15

    In the course of our study to determine the cross-sensitivity between CPT-11 and its active metabolite, SN-38, we found a SN-38-resistant human pancreatic tumor cell line, QGP-1N, which shows sensitivity to CPT-11. The IC50 of SN-38 was 152 times greater for QGP-1N than for SUIT-2, also a human pancreatic tumor cell line, whose IC50 of CPT-11 was similar to that for QGP-1N. The uptakes of CPT-11 and SN-38 and the intracellular conversion of CPT-11 to SN-38 could not explain the difference in sensitivity. DNA synthesis of QGP-1N cells was inhibited by CPT-11 which did not affect that of SUIT-2, while SN-38 inhibited the DNA synthesis of SUIT-2 at lower concentrations than that of QGP-1N. The inhibition test of topoisomerase I catalytic activity by CPT-11 or SN-38 revealed no difference in the biochemical properties of the topoisomerase I enzymes to the compounds between these two cell lines. These results indicate that CPT-11 should have its own inhibitory effect on DNA synthesis through a yet unknown mechanism in QGP-1N cells, although SN-38 plays an essential role in the antitumor activity of CPT-11 in SUIT-2 cells. In some cases, the antitumor effect of CPT-11 might be consequent not only on SN-38 but also on CPT-11 itself.

  11. Phthalazine derivatives containing imidazole rings behave as Fe-SOD inhibitors and show remarkable anti-T. cruzi activity in immunodeficient-mouse mode of infection.

    PubMed

    Sánchez-Moreno, Manuel; Gómez-Contreras, Fernando; Navarro, Pilar; Marín, Clotilde; Olmo, Francisco; Yunta, María J R; Sanz, Ana María; Rosales, María José; Cano, Carmen; Campayo, Lucrecia

    2012-11-26

    A series of new phthalazine derivatives 1-4 containing imidazole rings were prepared. The monoalkylamino substituted derivatives 2 and 4 were more active in vitro against T. cruzi and less toxic against Vero cells than both their disubstituted analogues and the reference drug benznidazole. Compounds 2 and 4 highly inhibited the antioxidant parasite enzyme Fe-SOD, and molecular modeling suggested that they interact with the H-bonding system of the iron atom moiety. In vivo tests on the acute phase of Chagas disease gave parasitemia inhibition values twice those of benznidazole, and a remarkable decrease in the reactivation of parasitemia was found in the chronic phase for immunodeficient mice. Glucose metabolism studies showed that compounds 1-4 did not affect the succinate pathway but originated important changes in the excretion of pyruvate metabolites. The morphological alterations found in epimastigotes treated with 1-4 confirmed extensive cytoplasm damage and a high mortality rate of parasites.

  12. Energy-efficiency testing activities of the Mobile Energy Laboratory

    SciTech Connect

    Parker, G.B.

    1991-01-01

    This report summarizes energy-efficiency testing activities during the first and second quarters of fiscal year 1990 applying the Mobile Energy Laboratory (MEL) testing capabilities. Four MELs, developed by the US Department of Energy (DOE) Federal Energy Management Program (FEMP), are administered by Pacific Northwest Laboratory (PNL) for energy testing and program support functions at federal facilities. The using agencies principally fund MEL applications, while DOE/FEMP funds program administration and capability enhancement activities. This report fulfills the requirements established in the MEL Use Plan (PNL-6861) for semiannual reporting on energy-efficiency testing activities using the MEL capabilities. The MEL Use Committee, formally established in 1989, developed the MEL Use Plan and meets semiannually to establish priorities for energy-efficient testing applications using the MEL capabilities.

  13. A statistical algorithm showing coenzyme Q10 and citrate synthase as biomarkers for mitochondrial respiratory chain enzyme activities.

    PubMed

    Yubero, D; Adin, A; Montero, R; Jou, C; Jiménez-Mallebrera, C; García-Cazorla, A; Nascimento, A; O'Callaghan, M M; Montoya, J; Gort, L; Navas, P; Ribes, A; Ugarte, M D; Artuch, R

    2016-12-01

    Laboratory data interpretation for the assessment of complex biological systems remains a great challenge, as occurs in mitochondrial function research studies. The classical biochemical data interpretation of patients versus reference values may be insufficient, and in fact the current classifications of mitochondrial patients are still done on basis of probability criteria. We have developed and applied a mathematic agglomerative algorithm to search for correlations among the different biochemical variables of the mitochondrial respiratory chain in order to identify populations displaying correlation coefficients >0.95. We demonstrated that coenzyme Q10 may be a better biomarker of mitochondrial respiratory chain enzyme activities than the citrate synthase activity. Furthermore, the application of this algorithm may be useful to re-classify mitochondrial patients or to explore associations among other biochemical variables from different biological systems.

  14. Adrenal cryptococcosis in an immunosuppressed patient showing intensely increased metabolic activity on (18)F-FDG PET/CT.

    PubMed

    Papadakis, Georgios Z; Holland, Steven M; Quezado, Martha; Patronas, Nicholas J

    2016-12-01

    Disseminated cryptococcosis most commonly occurs in immunosuppressed patients and can rarely affect the adrenal glands. We report on a patient with biopsy proven bilateral adrenal cryptococcosis resulting in primary adrenal insufficiency, which was evaluated with whole-body positron emission tomography/computed tomography scan using (18)F-FDG. Both enlarged adrenal glands presented intensely increased (18)F-FDG activity in the periphery, while central necrotic regions were photopenic. Although diagnosis was established by adrenal gland biopsy, (18)F-FDG positron emission tomography/computed tomography scan can significantly contribute to the assessment of disease activity and monitoring of treatment response. Furthermore, fungal infections should always be considered when encountering hypermetabolic adrenal masses, especially in the setting of immunodeficient patients.

  15. Launch Deployment Assembly Extravehicular Activity Neutral Buoyancy Development Test Report

    NASA Technical Reports Server (NTRS)

    Loughead, T.

    1996-01-01

    This test evaluated the Launch Deployment Assembly (LDA) design for Extravehicular Activity (EVA) work sites (setup, igress, egress), reach and visual access, and translation required for cargo item removal. As part of the LDA design, this document describes the method and results of the LDA EVA Neutral Buoyancy Development Test to ensure that the LDA hardware support the deployment of the cargo items from the pallet. This document includes the test objectives, flight and mockup hardware description, descriptions of procedures and data collection used in the testing, and the results of the development test at the National Aeronautics and Space Administrations (NASA) Marshall Space Flight Center (MSFC) Neutral Buoyancy Simulator (NBS).

  16. Syringe test (modified larval immersion test): a new bioassay for testing acaricidal activity of plant extracts against Rhipicephalus microplus.

    PubMed

    Sindhu, Zia-ud-Din; Jonsson, Nicholas N; Iqbal, Zafar

    2012-09-10

    We report a new bioassay "syringe test" (modified larval immersion test) for in vitro evaluation of acaricidal activity of crude plant extracts. Prepared syringes, containing eggs of tick, were incubated until 14 d after hatching of eggs, when the bioassay was performed on the larvae. Lethal concentrations for 50% of larvae (LC(50)), LC(90) and LC(99) values were calculated for each tested product. 95% confidence intervals for LC(50) were very narrow, indicating a high degree of repeatability for the new bioassay on larvae of R. microplus. Bioassays were applied to six crude aqueous-methanol extracts from five plants (Acacia nilotica, Buxus papillosa, Fumaria parviflora, Juniperus excelsa, and Operculina turpethum), of which three showed discernible effects. Twenty-four hours post exposure, LC(99) values were 11.9% (w/v) for F. parviflora, 20.8% (w/v) and 29.2% (w/v) for B. papillosa and A. nilotica, respectively. After six days of exposure these values were; 9.1% (w/v), 9.2% (w/v) and 15.5 (w/v) for F. parviflora, A. nilotica and B. papillosa, respectively.

  17. The BACHD Rat Model of Huntington Disease Shows Signs of Fronto-Striatal Dysfunction in Two Operant Conditioning Tests of Short-Term Memory

    PubMed Central

    Clemensson, Laura Emily; Riess, Olaf; Nguyen, Huu Phuc

    2017-01-01

    The BACHD rat is a recently developed transgenic animal model of Huntington disease, a progressive neurodegenerative disorder characterized by extensive loss of striatal neurons. Cognitive impairments are common among patients, and characterization of similar deficits in animal models of the disease is therefore of interest. The present study assessed the BACHD rats' performance in the delayed alternation and the delayed non-matching to position test, two Skinner box-based tests of short-term memory function. The transgenic rats showed impaired performance in both tests, indicating general problems with handling basic aspects of the tests, while short-term memory appeared to be intact. Similar phenotypes have been found in rats with fronto-striatal lesions, suggesting that Huntington disease-related neuropathology might be present in the BACHD rats. Further analyses indicated that the performance deficit in the delayed alternation test might be due to impaired inhibitory control, which has also been implicated in Huntington disease patients. The study ultimately suggests that the BACHD rats might suffer from neuropathology and cognitive impairments reminiscent of those of Huntington disease patients. PMID:28045968

  18. The BACHD Rat Model of Huntington Disease Shows Signs of Fronto-Striatal Dysfunction in Two Operant Conditioning Tests of Short-Term Memory.

    PubMed

    Clemensson, Erik Karl Håkan; Clemensson, Laura Emily; Riess, Olaf; Nguyen, Huu Phuc

    2017-01-01

    The BACHD rat is a recently developed transgenic animal model of Huntington disease, a progressive neurodegenerative disorder characterized by extensive loss of striatal neurons. Cognitive impairments are common among patients, and characterization of similar deficits in animal models of the disease is therefore of interest. The present study assessed the BACHD rats' performance in the delayed alternation and the delayed non-matching to position test, two Skinner box-based tests of short-term memory function. The transgenic rats showed impaired performance in both tests, indicating general problems with handling basic aspects of the tests, while short-term memory appeared to be intact. Similar phenotypes have been found in rats with fronto-striatal lesions, suggesting that Huntington disease-related neuropathology might be present in the BACHD rats. Further analyses indicated that the performance deficit in the delayed alternation test might be due to impaired inhibitory control, which has also been implicated in Huntington disease patients. The study ultimately suggests that the BACHD rats might suffer from neuropathology and cognitive impairments reminiscent of those of Huntington disease patients.

  19. Mono- and dinuclear manganese(III) complexes showing efficient catechol oxidase activity: syntheses, characterization and spectroscopic studies.

    PubMed

    Banu, Kazi Sabnam; Chattopadhyay, Tanmay; Banerjee, Arpita; Mukherjee, Madhuparna; Bhattacharya, Santanu; Patra, Goutam Kumar; Zangrando, Ennio; Das, Debasis

    2009-10-28

    Four side-off compartmental ligands L1-L4 [L1 = N,N'-ethylenebis(3-formyl-5-methyl-salicylaldimine), L2 = N,N'-1-methylethylenebis(3-formyl-5-methylsalicylaldimine), L3 = N,N'-1,1-dimethylethylenebis(3-formyl-5-methylsalicylaldimine) and L4= N,N'-cyclohexenebis(3-formyl-5-methylsalicylaldimine)] having two binding sites, N2O2 and O4, have been chosen to synthesize mononuclear and dinuclear manganese(III) complexes with the aim to study their catecholase activity using 3,5-di-tert-butylcatechol (3,5-DTBC) as substrate in the presence of molecular oxygen. In all cases only mononuclear manganese complexes (1-4) were obtained, with manganese coordination taking place at the N2O2 binding site only, irrespective of the amount of manganese salt used. All these complexes have been characterized by routine physico-chemical techniques. Complex MnL2Cl.4H2O (2) has further been structurally characterized by X-ray single crystal structure analysis. Four dinuclear manganese complexes, 5-8, were obtained after condensing the two pending formyl groups on each ligand (L1-L4) with aniline followed by reaction with MnCl2 to put the second Mn atom onto another N2O2 site. The catalytic activity of all complexes 1-8 has been investigated following the oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC) to 3,5-di-tert-butylbenzoquinone (3,5-DTBQ) with molecular oxygen in two different solvents, methanol and acetonitrile. The study reveals that the catalytic activity is influenced by the solvent and to a significant extent by the backbone of the diamine and the behavior seems to be related mainly to steric rather than electronic factors. Experimental data suggest that a correlation, the lower the E(1/2) value the higher the catalytic activity, can be drawn between E(1/2) and Vmax of the complexes in a particular solvent. The EPR measurements suggest that the catalytic property of the complexes is related to the metal center(s) participation rather than to a radical mechanism.

  20. Alpha-momorcharin, a RIP produced by bitter melon, enhances defense response in tobacco plants against diverse plant viruses and shows antifungal activity in vitro.

    PubMed

    Zhu, Feng; Zhang, Ping; Meng, Yan-Fa; Xu, Fei; Zhang, Da-Wei; Cheng, Jian; Lin, Hong-Hui; Xi, De-Hui

    2013-01-01

    Alpha-momorcharin (α-MMC) is type-1 ribosome inactivating proteins (RIPs) with molecular weight of 29 kDa and has lots of biological activity. Our recent study indicated that the α-MMC purified from seeds of Momordica charantia exhibited distinct antiviral and antifungal activity. Tobacco plants pre-treated with 0.5 mg/mL α-MMC 3 days before inoculation with various viruses showed less-severe symptom and less reactive oxygen species (ROS) accumulation compared to that inoculated with viruses only. Quantitative real-time PCR analysis revealed that the replication levels of viruses were lower in the plants treated with the α-MMC than control plants at 15 days post inoculation. Moreover, the coat protein expression of viruses was almost completely inhibited in plants which were treated with the α-MMC compared with control plants. Furthermore, the SA-responsive defense-related genes including non-expressor of pathogenesis-related genes 1 (NPR1), PR1, PR2 were up-regulated and activities of some antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), peroxidase (POD) were increased after the α-MMC treatment. In addition, the α-MMC (500 μg/mL) revealed remarkable antifungal effect against phytopathogenic fungi, in the growth inhibition range 50.35-67.21 %, along with their MIC values ranging from 100 to 500 μg/mL. The α-MMC had also a strong detrimental effect on spore germination of all the tested plant pathogens along with concentration as well as time-dependent kinetic inhibition of Sclerotinia sclerotiorum. The α-MMC showed a remarkable antiviral and antifungal effect and hence could possibly be exploited in crop protection for controlling certain important plant diseases.

  1. Effects of Vigorous Intensity Physical Activity on Mathematics Test Performance

    ERIC Educational Resources Information Center

    Phillips, David S.; Hannon, James C.; Castelli, Darla M.

    2015-01-01

    The effect of an acute bout of physical activity on academic performance in school-based settings is under researched. The purpose of this study was to examine associations between a single, vigorous (70-85%) bout of physical activity completed during physical education on standardized mathematics test performance among 72, eighth grade students…

  2. Physical Activity and Cervical Cancer Testing among American Indian Women

    ERIC Educational Resources Information Center

    Muus, Kyle J.; Baker-Demaray, Twyla B.; Bogart, T. Andy; Duncan, Glen E.; Jacobsen, Clemma; Buchwald, Dedra S.; Henderson, Jeffrey A.

    2012-01-01

    Purpose: Studies have shown that women who engage in high levels of physical activity have higher rates of cancer screening, including Papanicalaou (Pap) tests. Because American Indian (AI) women are at high risk for cervical cancer morbidity and mortality, we examined Pap screening prevalence and assessed whether physical activity was associated…

  3. Antagonist activities of mecamylamine and nicotine show reciprocal dependence on beta subunit sequence in the second transmembrane domain.

    PubMed

    Webster, J C; Francis, M M; Porter, J K; Robinson, G; Stokes, C; Horenstein, B; Papke, R L

    1999-07-01

    We show that a portion of the TM2 domain regulates the sensitivity of beta subunit-containing rat neuronal nicotinic AChR to the ganglionic blocker mecamylamine, such that the substitution of 4 amino acids of the muscle beta subunit sequence into the neuronal beta4 sequence decreases the potency of mecamylamine by a factor of 200 and eliminates any long-term effects of this drug on receptor function. The same exchange of sequence that decreases inhibition by mecamylamine produces a comparable potentiation of long-term inhibition by nicotine. Inhibition by mecamylamine is voltage-dependent, suggesting a direct interaction of mecamylamine with sequence elements within the membrane field. We have previously shown that sensitivity to TMP (tetramethylpiperidine) inhibitors is controlled by the same sequence elements that determine mecamylamine sensitivity. However, inhibition by bis-TMP compounds is independent of voltage. Our experiments did not show any influence of voltage on the inhibition of chimeric receptors by nicotine, suggesting that the inhibitory effects of nicotine are mediated by binding to a site outside the membrane's electric field. An analysis of point mutations indicates that the residues at the 6' position within the beta subunit TM2 domain may be important for determining the effects of both mecamylamine and nicotine in a reciprocal manner. Single mutations at the 10' position are not sufficient to produce effects, but 6' 10' double mutants show more effect than do the 6' single mutants.

  4. In Vitro and In Vivo Antimalarial Activity Assays of Seeds from Balanites aegyptiaca: Compounds of the Extract Show Growth Inhibition and Activity against Plasmodial Aminopeptidase

    PubMed Central

    Kusch, Peter; Deininger, Susanne; Specht, Sabine; Maniako, Rudeka; Haubrich, Stefanie; Pommerening, Tanja; Lin, Paul Kong Thoo; Hoerauf, Achim; Kaiser, Annette

    2011-01-01

    Balanites aegyptiaca (Balanitaceae) is a widely grown desert plant with multiuse potential. In the present paper, a crude extract from B. aegyptiaca seeds equivalent to a ratio of 1 : 2000 seeds to the extract was screened for antiplasmodial activity. The determined IC50 value for the chloroquine-susceptible Plasmodium falciparum NF54 strain was 68.26 μg/μL ± 3.5. Analysis of the extract by gas chromatography-mass spectrometry detected 6-phenyl-2(H)-1,2,4-triazin-5-one oxime, an inhibitor of the parasitic M18 Aspartyl Aminopeptidase as one of the compounds which is responsible for the in vitro antiplasmodial activity. The crude plant extract had a Ki of 2.35 μg/μL and showed a dose-dependent response. After depletion of the compound, a significantly lower inhibition was determined with a Ki of 4.8 μg/μL. Moreover, two phenolic compounds, that is, 2,6-di-tert-butyl-phenol and 2,4-di-tert-butyl-phenol, with determined IC50 values of 50.29 μM ± 3 and 47.82 μM ± 2.5, respectively, were detected. These compounds may contribute to the in vitro antimalarial activity due to their antioxidative properties. In an in vivo experiment, treatment of BALB/c mice with the aqueous Balanite extract did not lead to eradication of the parasites, although a reduced parasitemia at day 12 p.i. was observed. PMID:21687598

  5. Map showing recent and historic landslide activity on coastal bluffs of Puget Sound between Shilshole Bay and Everett, Washington

    USGS Publications Warehouse

    Baum, R.L.; Harp, E.L.; Hultman, W.A.

    2000-01-01

    Many landslides occurred on the coastal bluffs between Seattle and Everett, Washington during the winters of 1996 and 1997. Shallow earth slides and debris flows were the most common, but a few deep-seated rotational earth slides also occurred. The landslides caused significant property damage and interfered with rail traffic; future landslides in the area pose significant hazards to property and public safety. Field observations indicate that ground-water seepage, runoff concentration, and dumping at the tops of the bluffs all contributed to instability of the bluffs. Most landslides in the study area occurred in colluvium, residuum, and landslide deposits derived from the Vashon Drift, particularly the advance outwash. In the northern part of the area, colluvium derived from the Pleistocene Whidbey Formation was also involved in shallow landslides. Comparison of recent activity with historic records in the southern part of the map area indicates that landslides tend to occur in many of the same areas as previous landslides.

  6. 2,8-bis(trifluoromethyl)quinoline analogs show improved anti-Zika virus activity, compared to mefloquine.

    PubMed

    Barbosa-Lima, Giselle; Moraes, Adriana M; Araújo, Adriele da S; da Silva, Emerson T; de Freitas, Caroline S; Vieira, Yasmine R; Marttorelli, Andressa; Neto, José Cerbino; Bozza, Patrícia T; de Souza, Marcus V N; Souza, Thiago Moreno L

    2017-02-15

    Zika virus (ZIKV), an arthropod-born Flavivirus, has been associated with a wide range of neurological diseases in adults, foetuses and neonates. Since no vaccine is available, repurposing of antiviral drugs currently in medical use is necessary. Mefloquine has confirmed anti-ZIKV activity. We used medicinal chemistry-driven approaches to synthesize and evaluate the ability of a series of new 2,8-bis(trifluoromethyl)quinoline derivatives to inhibit ZIKV replication in vitro, in order to improve the potency of mefloquine. We found that quinoline derivatives 3a and 4 were the most potent compounds within this series, both with mean EC50 values of 0.8 μM, which represents a potency 5 times that of mefloquine. These results indicate that new 2,8-bis(trifluoromethyl)quinoline chemical structures may be promising for the development of novel anti-ZIKV drugs.

  7. Mucin-depleted foci are modulated by dietary treatments and show deregulation of proliferative activity in carcinogen-treated rodents.

    PubMed

    Femia, Angelo Pietro; Caderni, Giovanna; Bottini, Consuelo; Salvadori, Maddalena; Dolara, Piero; Tessitore, Luciana

    2007-06-01

    The correlation between mucin-depleted foci (MDF) and colon carcinogenesis was studied in F344 rats initiated with 1,2-dimethylhydrazine and treated with a chemopreventive regimen (polyethylene glycol, PEG) or with a promoting diet (high-corn oil). High corn oil diet increased MDF, while PEG reduced them. The expression of p27 and p16, inhibitors of cyclin-dependent kinases, which inhibit the progression of the cell cycle, was studied by immunohistochemistry in MDF and in aberrant crypt foci (ACF) of control rats. In both MDF and ACF, the nuclear expression of p27 was markedly reduced, while p16 was reduced to a lower extent. Mitotic activity was higher in MDF and ACF than in normal mucosa of control rats. MDF were also identified in azoxymethane-initiated SWR/J mice. These results further confirm that MDF are preneoplastic lesions and could be useful biomarkers of colon carcinogenesis.

  8. Synthesis of analogues of the Des-Phe-NH2 C-terminal hexapeptide of cholecystokinin showing gastrin antagonist activity.

    PubMed

    Laur, J; Rodriguez, M; Aumelas, A; Bali, J P; Martinez, J

    1986-04-01

    Four analogues of Z-CCK-27-32-NH2, Z-Tyr(SO3-)-Met-Gly-Trp-Met-Asp-NH2, a cholecystokinin receptor antagonist have been synthesized by solution methodology. In these analogues, Z-Tyr(SO3-)-Nle-Gly-Trp-Met-Asp-NH2 16, Z-Tyr(SO3-)-Nle-Gly-Trp-Nle-Asp-NH2 17, BOC-Tyr(SO3-)-Met-Gly-Trp-Met-Asp-NH2 24 and Boc-Tyr(SO3-)-Met-Gly-Trp-Nle-Asp-NH2 25 methionyl residues were replaced by norleucyl residues. Preliminary biological activity on gastrin-induced acid secretion, in rat, are reported. These derivatives proved to antagonize the action of gastrin, with ED 50 of between 0.5 and 3 mg/kg.

  9. The adult pituitary shows stem/progenitor cell activation in response to injury and is capable of regeneration.

    PubMed

    Fu, Qiuli; Gremeaux, Lies; Luque, Raul M; Liekens, Daisy; Chen, Jianghai; Buch, Thorsten; Waisman, Ari; Kineman, Rhonda; Vankelecom, Hugo

    2012-07-01

    The pituitary gland constitutes, together with the hypothalamus, the regulatory core of the endocrine system. Whether the gland is capable of cell regeneration after injury, in particular when suffered at adult age, is unknown. To investigate the adult pituitary's regenerative capacity and the response of its stem/progenitor cell compartment to damage, we constructed a transgenic mouse model to conditionally destroy pituitary cells. GHCre/iDTR mice express diphtheria toxin (DT) receptor after transcriptional activation by Cre recombinase, which is driven by the GH promoter. Treatment with DT for 3 d leads to gradual GH(+) (somatotrope) cell obliteration with a final ablation grade of 80-90% 1 wk later. The stem/progenitor cell-clustering side population promptly expands after injury, concordant with the immediate increase in Sox2(+) stem/progenitor cells. In addition, folliculo-stellate cells, previously designated as pituitary stem/progenitor cells and significantly overlapping with Sox2(+) cells, also increase in abundance. In situ examination reveals expansion of the Sox2(+) marginal-zone niche and appearance of remarkable Sox2(+) cells that contain GH. When mice are left after the DT-provoked lesion, GH(+) cells considerably regenerate during the following months. Double Sox2(+)/GH(+) cells are observed throughout the regenerative period, suggesting recovery of somatotropes from stem/progenitor cells, as further supported by 5-ethynyl-2'-deoxyuridine (EdU) pulse-chase lineage tracing. In conclusion, our study demonstrates that the adult pituitary gland holds regenerative competence and that tissue repair follows prompt activation and plausible involvement of the stem/progenitor cells.

  10. Active Protection of an MgB2 Test Coil

    PubMed Central

    Park, Dong Keun; Hahn, Seungyong; Bascuñán, Juan; Iwasa, Yukikazu

    2011-01-01

    This paper presents results of a study, experimental and computational, of a detect-and-activate-the-heater protection technique applied to a magnesium diboride (MgB2) test coil operated in semi-persistent mode. The test coil with a winding ID of 25 cm and wound with ~500-m long reacted MgB2 wire was operated at 4.2 K immersed in a bath of liquid helium. In this active technique, upon the initiation of a “hot spot” of a length ~10 cm, induced by a “quench heater,” a “protection heater” (PH) of ~600-cm long planted within the test coil is activated. The normal zone created by the PH is large enough to absorb the test coil’s entire initial stored energy and still keeps the peak temperature within the winding below ~260 K. PMID:22081754

  11. Ozonated saline shows activity against planktonic and biofilm growing Staphylococcus aureus in vitro: a potential irrigant for infected wounds.

    PubMed

    Al-Saadi, Hayder; Potapova, Inga; Rochford, Edward Tj; Moriarty, Thomas F; Messmer, Peter

    2016-10-01

    Infections associated with deep wounds require extensive surgical and medical care. New adjunctive treatments are required to aid in the eradication of the bacterial biofilms found on infected wounds and, in particular, any underlying hardware. Ozone has been used as a safe and efficient disinfectant in water treatment plants for many years. The purpose of this study is to investigate the anti-biofilm potential of ozonated saline against biofilms of Staphylococcus aureus, a microorganism commonly implicated in wound infections. A custom-made bacterial biofilm bioreactor was used to grow S. aureus biofilms on discs of medical grade titanium alloy. An ozone generator was connected in-line and biofilms and planktonic bacteria were exposed to ozone in saline. Cytotoxicity was assessed against primary ovine osteoblasts in the same system. In tests against planktonic S. aureus, a 99% reduction in bacterial numbers was detected within 15 minutes of exposure. S. aureus biofilms were significantly more resistant to ozone, although complete eradication of the biofilm was eventually achieved within 5 hours. Ozonated saline was not found to be cytotoxic to primary ovine osteoblasts. Ozonated saline may be suitable as an adjuvant therapy to treat patients as an instillation fluid for wound irrigation and sterilisation.

  12. Mycobactericidal activity of selected disinfectants using a quantitative suspension test.

    PubMed

    Griffiths, P A; Babb, J R; Fraise, A P

    1999-02-01

    In this study, a quantitative suspension test carried out under both clean and dirty conditions was used to assess the activity of various instrument and environmental disinfectants against the type strain NCTC 946 and an endoscope washer disinfector isolate of Mycobacterium chelonae, Mycobacterium fortuitum NCTC 10,394, Mycobacterium tuberculosis H37 Rv NCTC 7416 and a clinical isolate of Mycobacterium avium-intracellulare (MAI). The disinfectants tested were; a chlorine releasing agent, sodium dichloroisocyanurate (NaDCC) at 1000 ppm and 10,000 ppm av Cl; chlorine dioxide at 1100 ppm av ClO2 (Tristel, MediChem International Limited); 70% industrial methylated spirits (IMS); 2% alkaline glutaraldehyde (Asep, Galan); 10% succinedialdehyde and formaldehyde mixture (Gigasept, Schulke & Mayr); 0.35% peracetic acid (NuCidex, Johnson & Johnson); and a peroxygen compound at 1% and 3% (Virkon, Antec International). Results showed that the clinical isolate of MAI was much more resistant than M. tuberculosis to all the disinfectants, while the type strains of M. chelonae and M. fortuitum were far more sensitive. The washer disinfector isolate of M. chelonae was extremely resistant to 2% alkaline activated glutaraldehyde and appeared to be slightly more resistant than the type strain to Nu-Cidex, Gigasept, Virkon and the lower concentration of NaDCC. This study has shown peracetic acid (Nu-Cidex), chlorine dioxide (Tristel), alcohol (IMS) and high concentrations of a chlorine releasing agent (NaDCC) are rapidly mycobactericidal. Glutaraldehyde, although effective, is a slow mycobactericide. Gigasept and Virkon are poor mycobactericidal agents and are not therefore recommended for instruments or spillage if mycobacteria are likely to be present.

  13. Nanorods of a new metal-biomolecule coordination polymer showing novel bidirectional electrocatalytic activity and excellent performance in electrochemical sensing.

    PubMed

    Yang, Jiao; Zhou, Bo; Yao, Jie; Jiang, Xiao-Qing

    2015-05-15

    Metal organic coordination polymers (CPs), as most attractive multifunctional materials, have been studied extensively in many fields. However, metal-biomolecule CPs and CPs' electrochemical properties and applications were studied much less. We focus on this topic aiming at electrochemical biosensors with excellent performance and high biocompatibility. A new nanoscaled metal-biomolecule CP, Mn-tyr, containing manganese and tyrosine, was synthesized hydrothermally and characterized by various techniques, including XRD, TEM, EDS, EDX mapping, elemental analysis, XPS, and IR. Electrode modified with Mn-tyr showed novel bidirectional electrocatalytic ability toward both reduction and oxidation of H2O2, which might be due to Mn. With the assistance of CNTs, the sensing performance of Mn-tyr/CNTs/GCE was improved to a much higher level, with high sensitivity of 543 mA mol(-1) L cm(-2) in linear range of 1.00×10(-6)-1.02×10(-4) mol L(-1), and detection limit of 3.8×10(-7) mol L(-1). Mn-tyr/CNTs/GCE also showed fast response, high selectivity, high steadiness and reproducibility. The excellent performance implies that the metal-biomolecule CPs are promising candidates for using in enzyme-free electrochemical biosensing.

  14. Immobilized MAS1 lipase showed high esterification activity in the production of triacylglycerols with n-3 polyunsaturated fatty acids.

    PubMed

    Wang, Xiumei; Li, Daoming; Qu, Man; Durrani, Rabia; Yang, Bo; Wang, Yonghua

    2017-02-01

    Immobilization of lipase MAS1 from marine Streptomyces sp. strain W007 and its application in catalyzing esterification of n-3 polyunsaturated fatty acids (PUFA) with glycerol were investigated. The resin XAD1180 was selected as a suitable support for the immobilization of lipase MAS1, and its absorption ability was 75mg/g (lipase/resin ratio) with initial buffer pH value of 8.0. The thermal stability of immobilized MAS1 was improved significantly compared with that of the free lipase. Immobilized MAS1 had no regiospecificity in the hydrolysis of triolein. The highest esterification degree (99.31%) and TAG content (92.26%) by immobilized MAS1-catalyzed esterification were achieved under the optimized conditions, which were significantly better than those (82.16% and 47.26%, respectively) by Novozym 435. More than 92% n-3 PUFA was incorporated into TAG that had similar fatty acids composition to the substrate (n-3 PUFA). The immobilized MAS1 exhibited 50% of its initial activity after being used for five cycles.

  15. Ecotoxicological assessment of solar cell leachates: Copper indium gallium selenide (CIGS) cells show higher activity than organic photovoltaic (OPV) cells.

    PubMed

    Brun, Nadja Rebecca; Wehrli, Bernhard; Fent, Karl

    2016-02-01

    Despite the increasing use of photovoltaics their potential environmental risks are poorly understood. Here, we compared ecotoxicological effects of two thin-film photovoltaics: established copper indium gallium selenide (CIGS) and organic photovoltaic (OPV) cells. Leachates were produced by exposing photovoltaics to UV light, physical damage, and exposure to environmentally relevant model waters, representing mesotrophic lake water, acidic rain, and seawater. CIGS cell leachates contained 583 μg L(-1) molybdenum at lake water, whereas at acidic rain and seawater conditions, iron, copper, zinc, molybdenum, cadmium, silver, and tin were present up to 7219 μg L(-1). From OPV, copper (14 μg L(-1)), zinc (87 μg L(-1)) and silver (78 μg L(-1)) leached. Zebrafish embryos were exposed until 120 h post-fertilization to these extracts. CIGS leachates produced under acidic rain, as well as CIGS and OPV leachates produced under seawater conditions resulted in a marked hatching delay and increase in heart edema. Depending on model water and solar cell, transcriptional alterations occurred in genes involved in oxidative stress (cat), hormonal activity (vtg1, ar), metallothionein (mt2), ER stress (bip, chop), and apoptosis (casp9). The effects were dependent on the concentrations of cationic metals in leachates. Addition of ethylenediaminetetraacetic acid protected zebrafish embryos from morphological and molecular effects. Our study suggests that metals leaching from damaged CIGS cells, may pose a potential environmental risk.

  16. An Agrobacterium tumefaciens Strain with Gamma-Aminobutyric Acid Transaminase Activity Shows an Enhanced Genetic Transformation Ability in Plants

    PubMed Central

    Nonaka, Satoko; Someya, Tatsuhiko; Zhou, Sha; Takayama, Mariko; Nakamura, Kouji; Ezura, Hiroshi

    2017-01-01

    Agrobacterium tumefaciens has the unique ability to mediate inter-kingdom DNA transfer, and for this reason, it has been utilized for plant genetic engineering. To increase the transformation frequency in plant genetic engineering, we focused on gamma-aminobutyric acid (GABA), which is a negative factor in the Agrobacterium-plant interaction. Recent studies have shown contradictory results regarding the effects of GABA on vir gene expression, leading to the speculation that GABA inhibits T-DNA transfer. In this study, we examined the effect of GABA on T-DNA transfer using a tomato line with a low GABA content. Compared with the control, the T-DNA transfer frequency was increased in the low-GABA tomato line, indicating that GABA inhibits T-DNA transfer. Therefore, we bred a new A. tumefaciens strain with GABA transaminase activity and the ability to degrade GABA. The A. tumefaciens strain exhibited increased T-DNA transfer in two tomato cultivars and Erianthus arundinacues and an increased frequency of stable transformation in tomato. PMID:28220841

  17. A major EBNA1 variant from Asian EBV isolates shows enhanced transcriptional activity compared to prototype B95.8.

    PubMed

    Do, Nguyen-Van; Ingemar, Ernberg; Phi, Phan-Thi Phi; Jenny, Almqvist; Chinh, Tran-Thi; Zeng, Yixin; Hu, Lifu

    2008-03-01

    Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) has an instrumental role in maintaining EBV latent infection by controlling EBV episome replication and regulating viral transcription. It is a ubiquitously expressed protein during latent viral infection and in EBV-associated tumors. The EBNA1 C-terminus interacts functionally with the Qp and Cp that control viral gene expression in latency I/II and III, respectively. EBNA1 has been classified into five subtypes due to sequence variation in the DNA-interacting C-terminus. By DNA sequence analysis of its C-terminus, we detected a main sub-variant (V-val-v1) of EBNA1 with valine located in both positions 487 and 528 from matched samples including NPC biopsies and peripheral blood taken from Vietnamese (9), Chinese (12) NPC patients and healthy donors (5). In the FR-region of oriP from nine NPC biopsies from Vietnam we also frequently found substitutions, deletions and variable numbers of repeats. Using a luciferase reporter system, EBNA1 and FR both derived from Asian isolates induced higher transcriptional activity than those from B95-8 virus.

  18. Healthy working school teachers with high effort-reward-imbalance and overcommitment show increased pro-inflammatory immune activity and a dampened innate immune defence.

    PubMed

    Bellingrath, Silja; Rohleder, Nicolas; Kudielka, Brigitte M

    2010-11-01

    To test whether chronic work stress is accompanied by altered immune functioning, changes in lymphocyte subsets and in lymphocyte production of cytokines were examined in reaction to acute psychosocial stress. Work stress was measured according to Siegrist's effort-reward-imbalance (ERI) model. ERI reflects stress due to a lack of reciprocity between costs and gains at work. Overcommitment (OC) is conceptualized as a dysfunctional coping pattern mainly characterized by the inability to withdraw from work obligations. Fifty-five healthy teachers (34 women, 21 men, mean age 50.0 ± 8.47 years) were exposed to a standardized laboratory stressor (Trier Social Stress Test). Lymphocyte subset counts and lymphocyte production of tumor-necrosis-factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-2, -4, -6 and -10 were measured before and after challenge. High levels of ERI and OC were associated with lower natural killer (NK) cell (CD16+/56+) numbers whereas high levels of OC were related to a lower increase in T-helper cells (CD4+) after stress. Furthermore, subjects with higher ERI showed an overall increased pro-inflammatory activity, with higher TNF-α production at both time points and elevated pre-stress IL-6 production. IL-10 production decreased with higher ERI after stress. The ratios of TNF-α/IL-10 and IL-6/IL-10 were significantly increased in subjects high on ERI. Finally, OC was associated with higher IL-2 production post-stress. The present findings suggest a dampened innate immune defence, reflected in lower NK cell numbers together with an increased pro-inflammatory activity in teachers high on ERI and OC. Such pathways could partly be responsible for the increased vulnerability for stress-related diseases in individuals suffering from chronic work stress.

  19. Crack users show high rates of antisocial personality disorder, engagement in illegal activities and other psychosocial problems.

    PubMed

    Paim Kessler, Felix Henrique; Barbosa Terra, Mauro; Faller, Sibele; Ravy Stolf, Anderson; Carolina Peuker, Ana; Benzano, Daniela; Pechansky, Flavio

    2012-01-01

    The aim of this study was to compare three groups of Brazilian psychoactive substance (PAS) abuse patients (crack cocaine users, cocaine snorters, and non-cocaine PAS users) in terms of psychiatric comorbidities and severity of psychosocial problems. A cross-sectional, multi-center study was conducted at five Brazilian research centers. A total of 738 current PAS abusers seeking specialized treatment (outpatient and inpatient clinics) were assessed using the sixth version of the Addiction Severity Index (ASI-6): 293 patients using crack cocaine were compared with 126 using powder cocaine and 319 using non-cocaine PAS (mostly alcohol and marijuana). Psychiatric comorbidities were assessed in a smaller sample (290 cases), originating from three of the centers, using the Mini International Neuropsychiatric Interview Plus (MINI-Plus). Crack and powder cocaine users were significantly younger than non-cocaine PAS users (31.1 ± 8.1 and 32.9 ± 8.8 vs. 42.4 ± 12, respectively; p < .001). Crack users presented a higher rate of antisocial personality disorder (25%) than powder cocaine (9%) and non-cocaine PAS users (9%), even when adjusted for confounding factors (Pr = 2.6; 95% CI 1.10-6.40). According to ASI-6 summary scores, crack users presented a significantly higher rate of occupational, family, and legal problems and reported more illegal and violent activities such as burglary and theft (23%) and threatening or assaulting (32%) than non-cocaine PAS users. Our findings, combined with the recent increase observed in the prevalence of crack use in Brazil, highlight the severity of psychiatric symptoms and psychosocial problems related to this powerful drug and corroborate the already suggested association between crack/cocaine, violence, and legal problems. Treatment programs for crack users should routinely consider the possibility of associated psychiatric comorbidities, such as antisocial personality disorder, which may affect treatment outcomes.

  20. Poly(amidoamine) dendrimers show carbonic anhydrase inhibitory activity against α-, β-, γ- and η-class enzymes.

    PubMed

    Carta, Fabrizio; Osman, Sameh M; Vullo, Daniela; AlOthman, Zeid; Del Prete, Sonia; Capasso, Clemente; Supuran, Claudiu T

    2015-11-01

    Four generations of poly(amidoamine) (PAMAM) dendrimers incorporating benzenesulfonamide moieties were investigated as inhibitors of carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the α-, β-, γ- and η-classes which are present in pathogenic bacteria, fungi or protozoa. The following bacterial, fungal and protozoan organisms were included in the study: Vibrio cholerae, Trypanosoma cruzi, Leishmania donovani chagasi, Porphyromonas gingivalis, Cryptococcus neoformans, Candida glabrata, and Plasmodium falciparum. The eight pathozymes present in these organisms were efficiently inhibited by the four generations PAMAM-sulfonamide dendrimers, but multivalency effects were highly variable among the different enzyme classes. The Vibrio enzyme VchCA was best inhibited by the G3 dendrimer incorporating 32 sulfamoyl moieties. The Trypanosoma enzyme TcCA on the other hand was best inhibited by the first generation dendrimer G0 (with 4 sulfamoyl groups), whereas for other enzymes the optimal inhibitory power was observed for the G1 or G2 dendrimers, with 8 and 16 sulfonamide functionalities. This study thus proves that the multivalency may be highly relevant for enzyme inhibition for some but not all CAs from pathogenic organisms. On the other hand, some dendrimers investigated here showed a better inhibitory power compared to acetazolamide for enzymes from widespread pathogens, such as the η-CA from Plasmodium falciparum. Overall, the main conclusion is that this class of molecules may lead to important developments in the field of anti-infective CA inhibitors.

  1. Virus infection and interferon can activate gene expression through a single synthetic element, but endogenous genes show distinct regulation.

    PubMed

    Raj, N B; Engelhardt, J; Au, W C; Levy, D E; Pitha, P M

    1989-10-05

    Virus inducible elements (IE) in promoters of mouse alpha-interferon and human beta 1-interferon genes contain multiple copies of the hexanucleotide sequence AGT-GAA or its variants which are also found in the interferon-stimulated response element of genes transcriptionally induced by interferon. We have examined the similarities between virus and interferon induction of gene expression and the role of AGTGAA and AAT-GAA hexamers in these responses. Hybrid plasmids were constructed by inserting the IE region, the alpha 4 promoter, or the multiple copies of AGTGAA or AAT-GAA 5' to the inactive-45 human immunodeficiency-chloramphenicol acetyltransferase hybrid gene, and their inducible expression was studied in a transient expression assay. In L-cells, multiple hexamers were efficiently induced both by infection with Newcastle disease virus and by interferon treatment; while the alpha 4 promoter and the IE inducible region were induced predominantly by virus rather than by interferon. In order to dissociate the effect of virus and endogenous interferon on the induction process, we examined the gene expression in Vero cells, which have undergone homozygous deletion of type 1 interferon genes, and in VNPT-159 cells, which were derived from Vero cells by insertion of an inducible human interferon beta 1 gene. The results show that while the alpha 4 promoter was efficiently induced only by virus in both cell types, the constructs containing shorter segments of the IE were induced by both virus and interferon in Vero cells. However, the inducibility by interferon was not detected in VNPT-159 cells, suggesting that the presence of endogenous interferon suppresses interferon-induced expression of hexanucleotide repeats and the short inducible region. In contrast, virus inducibility of endogenous interferon-stimulated genes, ISG-15 and ISG-54, was about 100-fold more efficient in VNPT-159 cells than in Vero cells, suggesting that this induction is largely mediated through

  2. Space Shuttle Orbiter Approach and Landing Test Evaluation Report. Captive-Active Flight Test Summary

    NASA Technical Reports Server (NTRS)

    1977-01-01

    Captive-active tests consisted of three mated carrier aircraft/Orbiter flights with an active manned Orbiter. The objectives of this series of flights were to (1) verify the separation profile, (2) verify the integrated structure, aerodynamics, and flight control system, (3) verify Orbiter integrated system operations, and (4) refine and finalize carrier aircraft, Orbiter crew, and ground procedures in preparation for free flight tests. A summary description of the flights is presented with assessments of flight test requirements, and of the performance operations, and of significant flight anomalies is included.

  3. Simultaneous and intercontinental tests show synchronism between the local gravimetric tide and the ultra-weak photon emission in seedlings of different plant species.

    PubMed

    Gallep, Cristiano M; Barlow, Peter W; Burgos, Rosilene C R; van Wijk, Eduard P A

    2017-01-01

    In order to corroborate the hypothesis that variations in the rate of spontaneous ultra-weak photon emission (UPE) from germinating seedlings are related to local variations of the lunisolar tidal force, a series of simultaneous tests was performed using the time courses of UPE collected from three plant species-corn, wheat and sunflower-and also from wheat samples whose grains were transported between continents, from Brazil to The Netherlands and vice versa. All tests which were run in parallel showed coincident inflections within the UPE time courses not only between seedlings of the same species but also between the different species. In most cases, the UPE inflections were synchronised with the turning points in the local gravimetric tidal variation. Statistical tests using the local Pearson correlation verified these coincidences in the two time series. The results therefore support the hypothesis of a relationship between UPE emissions and, in the oscillations, the local gravimetric tide. This applies to both the emissions from seedlings of different species and to the seedlings raised from transported grain samples of the same species.

  4. Shuttle active thermal control system development testing. Volume 6: Water ejector plume tests

    NASA Technical Reports Server (NTRS)

    Mcginnis, F. K.; Summerhays, R. M.

    1973-01-01

    Results are given of vacuum testing of nozzles designed to eject water vapor away from the space shuttle to prevent contamination of the spacecraft surfaces and payload. The water vapor is generated by an active cooling system which evaporates excess fuel cell water to supplement a modular radiator system (MRS). The complete heat rejection system including the MRS, flash evaporator or sublimator and nozzle were first tested to demonstrate the system operational characteristics. The plume tests were performed in two phases and the objectives of this test series were: (1) to determine the effectiveness of a supersonic nozzle and a plugged nozzle in minimizing impingement upon the spacecraft of water vapor exhausted by an active device (flash evaporator or sublimator); and (2) to obtain basic data on the flow fields of exhaust plumes generated by these active devices, both with and without nozzles installed.

  5. Methanogenic activity tests by Infrared Tunable Diode Laser Absorption Spectroscopy.

    PubMed

    Martinez-Cruz, Karla; Sepulveda-Jauregui, Armando; Escobar-Orozco, Nayeli; Thalasso, Frederic

    2012-10-01

    Methanogenic activity (MA) tests are commonly carried out to estimate the capability of anaerobic biomass to treat effluents, to evaluate anaerobic activity in bioreactors or natural ecosystems, or to quantify inhibitory effects on methanogenic activity. These activity tests are usually based on the measurement of the volume of biogas produced by volumetric, pressure increase or gas chromatography (GC) methods. In this study, we present an alternative method for non-invasive measurement of methane produced during activity tests in closed vials, based on Infrared Tunable Diode Laser Absorption Spectroscopy (MA-TDLAS). This new method was tested during model acetoclastic and hydrogenotrophic methanogenic activity tests and was compared to a more traditional method based on gas chromatography. From the results obtained, the CH(4) detection limit of the method was estimated to 60 ppm and the minimum measurable methane production rate was estimated to 1.09(.)10(-3) mg l(-1) h(-1), which is below CH(4) production rate usually reported in both anaerobic reactors and natural ecosystems. Additionally to sensitivity, the method has several potential interests compared to more traditional methods among which short measurements time allowing the measurement of a large number of MA test vials, non-invasive measurements avoiding leakage or external interferences and similar cost to GC based methods. It is concluded that MA-TDLAS is a promising method that could be of interest not only in the field of anaerobic digestion but also, in the field of environmental ecology where CH(4) production rates are usually very low.

  6. Phosphatase activity of the voltage-sensing phosphatase, VSP, shows graded dependence on the extent of activation of the voltage sensor.

    PubMed

    Sakata, Souhei; Okamura, Yasushi

    2014-03-01

    The voltage-sensing phosphatase (VSP) consists of a voltage sensor and a cytoplasmic phosphatase region, and the movement of the voltage sensor is coupled to the phosphatase activity. However, its coupling mechanisms still remain unclear. One possible scenario is that the phosphatase is activated only when the voltage sensor is in a fully activated state. Alternatively, the enzymatic activity of single VSP proteins could be graded in distinct activated states of the voltage sensor, and partial activation of the voltage sensor could lead to partial activation of the phosphatase. To distinguish between these two possibilities, we studied a voltage sensor mutant of zebrafish VSP, where the voltage sensor moves in two steps as evidenced by analyses of charge movements of the voltage sensor and voltage clamp fluorometry. Measurements of the phosphatase activity toward phosphatidylinositol 4,5-bisphosphate revealed that both steps of voltage sensor activation are coupled to the tuning of phosphatase activities, consistent with the idea that the phosphatase activity is graded by the magnitude of the movement of the voltage sensor.

  7. Development and testing of an active platen for IC manufacturing

    SciTech Connect

    Redmond, J.; Barney, P.; Smith, T.; Darnold, J.

    1998-11-01

    The conflicting demands for finer features and increased production rates in integrated circuit manufacturing have emphasized the need for improved wafer positioning technology. In this paper we present operational test results from a magnetically levitated platen with structurally integrated piezoelectric acctuators. The strain based actuators provide active damping of the platen`s flexible body modes, enabling increased bandwidth on the mag-lev positioning system. Test results reveal a dramatic reduction in steady state positioning error and settling time through implementation of active vibration control.

  8. Electromechanical simulation and testing of actively controlled rotordynamic systems with piezoelectric actuators

    NASA Technical Reports Server (NTRS)

    Lin, Reng Rong; Palazzolo, A. B.; Kascak, A. F.; Montague, G. T.

    1991-01-01

    A method is presented for simulating the coupled 'electromechanical' system to predict rotordynamic stability and unbalance response along with control system stability. The piezoelectric actuators and their amplifiers are represented as equivalent linear electrical circuits. The electromechanical system modeling approach is utilized to correlate test results from a double overhung rotor rig. The test results also show the effectiveness of the control system for suppressing the unbalance response of two modes using active stiffness and active damping.

  9. Bootstrap testing for cross-correlation under low firing activity.

    PubMed

    González-Montoro, Aldana M; Cao, Ricardo; Espinosa, Nelson; Cudeiro, Javier; Mariño, Jorge

    2015-06-01

    A new cross-correlation synchrony index for neural activity is proposed. The index is based on the integration of the kernel estimation of the cross-correlation function. It is used to test for the dynamic synchronization levels of spontaneous neural activity under two induced brain states: sleep-like and awake-like. Two bootstrap resampling plans are proposed to approximate the distribution of the test statistics. The results of the first bootstrap method indicate that it is useful to discern significant differences in the synchronization dynamics of brain states characterized by a neural activity with low firing rate. The second bootstrap method is useful to unveil subtle differences in the synchronization levels of the awake-like state, depending on the activation pathway.

  10. Automated Activation and Deactivation of a System Under Test

    NASA Technical Reports Server (NTRS)

    Poff, Mark A.

    2006-01-01

    The MPLM Automated Activation/Deactivation application (MPLM means Multi-Purpose Logistic Module) was created with a three-fold purpose in mind: 1. To reduce the possibility of human error in issuing commands to, or interpreting telemetry from, the MPLM power, computer, and environmental control systems; 2. To reduce the amount of test time required for the repetitive activation/deactivation processes; and 3. To reduce the number of on-console personnel required for activation/ deactivation. All of these have been demonstrated with the release of the software. While some degree of automated end-item commanding had previously been performed for space-station hardware in the test environment, none approached the functionality and flexibility of this application. For MPLM activation, it provides mouse-click selection of the hardware complement to be activated, activates the desired hardware and verifies proper feedbacks, and alerts the user when telemetry indicates an error condition or manual intervention is required. For MPLM deactivation, the product senses which end items are active and deactivates them in the proper sequence. For historical purposes, an on-line log is maintained of commands issued and telemetry points monitored. The benefits of the MPLM Automated Activation/ Deactivation application were demonstrated with its first use in December 2002, when it flawlessly performed MPLM activation in 8 minutes (versus as much as 2.4 hours for previous manual activations), and performed MPLM deactivation in 3 minutes (versus 66 minutes for previous manual deactivations). The number of test team members required has dropped from eight to four, and in actuality the software can be operated by a sole (knowledgeable) system engineer.

  11. Charpy impact test results for low-activation ferritic alloys

    SciTech Connect

    Cannon, N.S.; Hu, W.L.; Gelles, D.S.

    1987-05-01

    The objective of this work is to evaluate the shift of the ductile to brittle transition temperature (DBTT) and the reduction of the upper shelf energy (USE) due to neutron irradiation of low activation ferritic alloys. Six low activation ferritic alloys have been tested following irradiation at 365/sup 0/C to 10 dpa and compared with control specimens in order to assess the effect of irradiation on Charpy impact properties.

  12. Effects of physical activity on exercise tests and respiratory function

    PubMed Central

    Cheng, Y; Macera, C; Addy, C; Sy, F; Wieland, D; Blair, S

    2003-01-01

    Background: Exercise is an important component of pulmonary rehabilitation for patients with chronic lung disease. Objective: To explore the role of physical activity in maintaining cardiac and respiratory function in healthy people. Methods: Cardiorespiratory fitness was measured by a maximal treadmill test (MTT), and respiratory function was tested by spirometry. The cross sectional study included data from 24 536 healthy persons who were examined at the Cooper Clinic between 1971 and 1995; the longitudinal study included data from 5707 healthy persons who had an initial visit between 1971 and 1995 and a subsequent visit during the next five years. All participants were aged 25–55 years and completed a cardiorespiratory test and a medical questionnaire. Results: In the cross sectional study, after controlling for covariates, being active and not being a recent smoker were associated with better cardiorespiratory fitness and respiratory function in both men and women. In the follow up study, persons who remained or became active had better MTT than persons who remained or became sedentary. Men who remained active had higher forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) than the other groups. Smoking was related to lower cardiorespiratory fitness and respiratory function. Conclusions: Physical activity and non-smoking or smoking cessation is associated with maintenance of cardiorespiratory fitness. Change in physical activity habits is associated with change in cardiorespiratory fitness, but respiratory function contributed little to this association during a five year follow up. PMID:14665592

  13. Spacecraft Environmental Testing SMAP (Soil, Moisture, Active, Passive)

    NASA Technical Reports Server (NTRS)

    Fields, Keith

    2014-01-01

    Testing a complete full up spacecraft to verify it will survive the environment, in which it will be exposed to during its mission, is a formidable task in itself. However, the ''test like you fly'' philosophy sometimes gets compromised because of cost, design and or time. This paper describes the thermal-vacuum and mass properties testing of the Soil Moisture Active Passive (SMAP) earth orbiting satellite. SMAP will provide global observations of soil moisture and freeze/thaw state (the hydrosphere state). SMAP hydrosphere state measurements will be used to enhance understanding of processes that link the water, energy, and carbon cycles, and to extend the capabilities of weather and climate prediction models. It will explain the problems encountered, and the solutions developed, which minimized the risk typically associated with such an arduous process. Also discussed, the future of testing on expensive long lead-time spacecraft. Will we ever reach the ''build and shoot" scenario with minimal or no verification testing?

  14. Alpha casein micelles show not only molecular chaperone-like aggregation inhibition properties but also protein refolding activity from the denatured state.

    PubMed

    Sakono, Masafumi; Motomura, Konomi; Maruyama, Tatsuo; Kamiya, Noriho; Goto, Masahiro

    2011-01-07

    Casein micelles are a major component of milk proteins. It is well known that casein micelles show chaperone-like activity such as inhibition of protein aggregation and stabilization of proteins. In this study, it was revealed that casein micelles also possess a high refolding activity for denatured proteins. A buffer containing caseins exhibited higher refolding activity for denatured bovine carbonic anhydrase than buffers including other proteins. In particular, a buffer containing α-casein showed about a twofold higher refolding activity compared with absence of α-casein. Casein properties of surface hydrophobicity, a flexible structure and assembly formation are thought to contribute to this high refolding activity. Our results indicate that casein micelles stabilize milk proteins by both chaperone-like activity and refolding properties.

  15. Activated carbon testing for the 200 area effluent treatment facility

    SciTech Connect

    Wagner, R.N.

    1997-01-17

    This report documents pilot and laboratory scale testing of activated carbon for use in the 200 Area Effluent Treatment Facility peroxide decomposer columns. Recommendations are made concerning column operating conditions and hardware design, the optimum type of carbon for use in the plant, and possible further studies.

  16. Maps showing mines, quarries, oil and gas activity, and sample localities in and near the Sipsey Wilderness and additions, Lawrence and Winston counties, Alabama

    USGS Publications Warehouse

    Mory, Peter C.; Behum, Paul T.; Ross, Robert B.

    1982-01-01

    No mining activities are being conducted in the study area at present.  Previous mining has been limited to small-scale production of limestone and coal.  Two oil and gas test holes have been drilled inside the study area.

  17. Genome-Wide Identification of Mitogen-Activated Protein Kinase Gene Family across Fungal Lineage Shows Presence of Novel and Diverse Activation Loop Motifs

    PubMed Central

    Mohanta, Tapan Kumar; Mohanta, Nibedita; Parida, Pratap; Panda, Sujogya Kumar; Ponpandian, Lakshmi Narayanan; Bae, Hanhong

    2016-01-01

    The mitogen-activated protein kinase (MAPK) is characterized by the presence of the T-E-Y, T-D-Y, and T-G-Y motifs in its activation loop region and plays a significant role in regulating diverse cellular responses in eukaryotic organisms. Availability of large-scale genome data in the fungal kingdom encouraged us to identify and analyse the fungal MAPK gene family consisting of 173 fungal species. The analysis of the MAPK gene family resulted in the discovery of several novel activation loop motifs (T-T-Y, T-I-Y, T-N-Y, T-H-Y, T-S-Y, K-G-Y, T-Q-Y, S-E-Y and S-D-Y) in fungal MAPKs. The phylogenetic analysis suggests that fungal MAPKs are non-polymorphic, had evolved from their common ancestors around 1500 million years ago, and are distantly related to plant MAPKs. We are the first to report the presence of nine novel activation loop motifs in fungal MAPKs. The specificity of the activation loop motif plays a significant role in controlling different growth and stress related pathways in fungi. Hence, the presences of these nine novel activation loop motifs in fungi are of special interest. PMID:26918378

  18. A review of DOE HEPA filter component test activities

    SciTech Connect

    Slawski, J.W.; Bresson, J.F.; Scripsick, R.C.

    1997-08-01

    All HEPA filters purchased for installation in DOE nuclear facilities are required to be tested at a Filter Test Facility (FTF) prior to installation. The number of HEPA filters purchased by DOE has been reduced so much that the Hanford FTF was closed. From Fiscal Year (FY) 1992 to 1994, funding was not provided to the FTF Technical Support Group (TSG) at the Los Alamos National Laboratory. As a consequence, Round Robin Tests (RRTs), performed twice each year by the FTFs to assess constituency of test results among the FTFs, were not performed in FY 1992 and FY 1993. The Annual Reports of FTF test activities were not prepared for FY 1992 - 1995. Technical support provided to the FTFs was minimal. There is talk of closing a second FTF, and ongoing discussions as to whether DOE will continue to fund operation of the FTFs. In FY 1994, DOE Defense Programs commenced funding the TSG. RRT data for FY 1994 and 1995 have been entered into the database; the FY 1994 RRT report has been issued; and the FY 1995 RRT report is in progress. Data from semiannual reports have been retrieved and entered into the database. Standards related to HEPA filter test and procurement activities are now scheduled for issuance by FY 1996. Continuation of these activities depends on whether DOE will continue to support the HEPA filter test program. The history and activities of the FTFs and the TSG at Los Alamos have been reported at previous Air Cleaning Conferences. Data from the FY 1991 Annual Report of FTF activities was presented at the 1992 Air Cleaning Conference. Preparation of the Annual Reports was temporarily suspended in 1992. However, all of the FTF Semiannual report data have been retrieved and entered into the data base. This paper focuses primarily on the results of HEPA filter tests conducted by FTFs during FY 1992 - FY 1995, and the possible effects of the DOE program uncertainties on the quality of HEPA filters for installation at the DOE sites. 15 refs., 13 tabs.

  19. Shuttle active thermal control system development testing. Volume 5: Integrated radiator/expendable cooling system tests

    NASA Technical Reports Server (NTRS)

    Scheps, P. B.

    1974-01-01

    Tests were conducted to gather data on a space shuttle active control system (ATCS) incorporating both radiators and an expendable cooling device to provide vehicle heat removal. Two systems were tested and design information was provided for both nominal and limit conditions. The tests verified the concept that an integrated radiator/expendable cooling system can adequately maintain desired water quantities while responding to variations in heat loads and environments. In addition, the need for duct heating was demonstrated, while exhaust nozzle heating was also shown to be unnecessary.

  20. Benign hormone-secreting adenoma within a larger adrenocortical mass showing intensely increased activity on (18)F-FDG PET/CT.

    PubMed

    Papadakis, Georgios Z; Millo, Corina; Stratakis, Constantine A

    2016-10-01

    Adrenal adenomas usually show (18)F-FDG activity less than that of the liver parenchyma. However, lipid-poor and hormone-secreting adenomas have been reported to show mild (18)F-FDG avidity. We report on a 51-year-old female with clinical symptoms of hypercortisolemia and a large right adrenal mass detected on CT. Post-contrast CT images showed an enhancing focus in the lower pole of the mass, with corresponding markedly increased activity on (18)F-FDG PET/CT. Right adrenalectomy was performed and histology revealed a benign adenoma, indicating that functioning benign adenomas can show intensely increased metabolic activity on (18)F-FDG mimicking malignancy.

  1. The active flexible wing aeroservoelastic wind-tunnel test program

    NASA Technical Reports Server (NTRS)

    Noll, Thomas; Perry, Boyd

    1989-01-01

    For a specific application of aeroservoelastic technology, Rockwell International Corporation developed a concept known as the Active Flexible Wing (AFW). The concept incorporates multiple active leading-and trailing-edge control surfaces with a very flexible wing such that wing shape is varied in an optimum manner resulting in improved performance and reduced weight. As a result of a cooperative program between the AFWAL's Flight Dynamics Laboratory, Rockwell, and NASA LaRC, a scaled aeroelastic wind-tunnel model of an advanced fighter was designed, fabricated, and tested in the NASA LaRC Transonic Dynamics Tunnel (TDT) to validate the AFW concept. Besides conducting the wind-tunnel tests NASA provided a design of an Active Roll Control (ARC) System that was implemented and evaluated during the tests. The ARC system used a concept referred to as Control Law Parameterization which involves maintaining constant performance, robustness, and stability while using different combinations of multiple control surface displacements. Since the ARC system used measured control surface stability derivatives during the design, the predicted performance and stability results correlated very well with test measurements.

  2. Male rats with same sex preference show high experimental anxiety and lack of anxiogenic-like effect of fluoxetine in the plus maze test.

    PubMed

    García-Cárdenas, Nallely; Olvera-Hernández, Sandra; Gómez-Quintanar, Blanca Nelly; Fernández-Guasti, Alonso

    2015-08-01

    Homosexual men show a 2-4 higher risk to suffer anxiety in comparison with heterosexuals. It is unknown if biological factors collaborate to increase such incidence. Fluoxetine produces differential brain activation in homosexuals as compared with heterosexuals, suggesting that it may produce a divergent behavioral effect dependant on sex-preference. The first aim was to evaluate experimental anxiety in male rats that show same-sex preference in the elevated plus maze (EPM). The second goal explored the putative differential effect of fluoxetine (10mg/kg) in male rats with female and same-sex preference in the EPM. To induce same-sex preference males were prenatally treated with letrozole (0.56μg/kg, 10-20 gestation days), while controls were males prenatally treated with letrozole that retain female-preference or which mothers received oil. In both groups we found animals with male preference, but the proportion was higher in males that prenatally received letrozole (10 vs. 27%). Males with same-sex preference spent less time and showed lower number of entries to the open arms of the EPM than males that prefer females, regardless of the prenatal treatment. In males with female preference, fluoxetine reduced the time spent and number of entries to the open arms that was absent in males with same-sex preference. These data suggest that biological factors contribute to the high levels of anxiety in subjects with same-sex preference and that fluoxetine in men may produce a divergent action depending on sexual orientation.

  3. Taming Test Anxiety: The Activation of Failure-Related Concepts Enhances Cognitive Test Performance of Test-Anxious Students

    ERIC Educational Resources Information Center

    Tempel, Tobias; Neumann, Roland

    2016-01-01

    We investigated processes underlying performance decrements of highly test-anxious persons. Three experiments contrasted conditions that differed in the degree of activation of concepts related to failure. Participants memorized a list of words either containing words related to failure or containing no words related to failure in Experiment 1. In…

  4. Heavy metals testing in active pharmaceutical ingredients: an alternate approach.

    PubMed

    Raghuram, P; Soma Raju, I V; Sriramulu, J

    2010-01-01

    The principle of the pharmacopoeial heavy metals test is detection and estimation of the metallic impurities colored by sulfide ion by comparison against lead standard. The test suffers from a loss of analytes upon ashing and from having varied responses for various metals. An inductively coupled plasma-optical emission spectroscopy (ICP-OES) for estimating 23 metals in active pharmaceutical ingredients is being proposed. The method covers the metals listed in USP, Ph. Eur and EMEA guidance on "Residues of Metal Catalysts or Metal Reagents".

  5. The Activity of Antimicrobial Surfaces Varies by Testing Protocol Utilized

    PubMed Central

    Campos, Matias D.; Zucchi, Paola C.; Phung, Ann; Leonard, Steven N.; Hirsch, Elizabeth B.

    2016-01-01

    Background Contaminated hospital surfaces are an important source of nosocomial infections. A major obstacle in marketing antimicrobial surfaces is a lack of efficacy data based on standardized testing protocols. Aim We compared the efficacy of multiple testing protocols against several “antimicrobial” film surfaces. Methods Four clinical isolates were used: one Escherichia coli, one Klebsiella pneumoniae, and two Staphylococcus aureus strains. Two industry methods (modified ISO 22196 and ASTM E2149), a “dried droplet”, and a “transfer” method were tested against two commercially available antimicrobial films, one film in development, an untreated control, and a positive (silver) control film. At 2 (only ISO) and 24 hours following inoculation, bacteria were collected from film surfaces and enumerated. Results Compared to untreated films in all protocols, there were no significant differences in recovery on either commercial brand at 2 or 24 hours after inoculation. The silver surface demonstrated significant microbicidal activity (mean loss 4.9 Log10 CFU/ml) in all methods and time points with the exception of 2 hours in the ISO protocol and the transfer method. Using our novel droplet method, no differences between placebo and active surfaces were detected. The surface in development demonstrated variable activity depending on method, organism, and time point. The ISO demonstrated minimal activity at 2 hours but significant activity at 24 hours (mean 4.5 Log10 CFU/ml difference versus placebo). The ASTEM protocol exhibited significant differences in recovery of staphylococci (mean 5 Log10 CFU/ml) but not Gram-negative isolates (10 fold decrease). Minimal activity was observed with this film in the transfer method. Conclusions Varying results between protocols suggested that efficacy of antimicrobial surfaces cannot be easily and reproducibly compared. Clinical use should be considered and further development of representative methods is needed. PMID

  6. Chimpanzees show a developmental increase in susceptibility to contagious yawning: a test of the effect of ontogeny and emotional closeness on yawn contagion.

    PubMed

    Madsen, Elainie Alenkær; Persson, Tomas; Sayehli, Susan; Lenninger, Sara; Sonesson, Göran

    2013-01-01

    Contagious yawning has been reported for humans, dogs and several non-human primate species, and associated with empathy in humans and other primates. Still, the function, development and underlying mechanisms of contagious yawning remain unclear. Humans and dogs show a developmental increase in susceptibility to yawn contagion, with children showing an increase around the age of four, when also empathy-related behaviours and accurate identification of others' emotions begin to clearly evince. Explicit tests of yawn contagion in non-human apes have only involved adult individuals and examined the existence of conspecific yawn contagion. Here we report the first study of heterospecific contagious yawning in primates, and the ontogeny of susceptibility thereto in chimpanzees, Pan troglodytes verus. We examined whether emotional closeness, defined as attachment history with the yawning model, affected the strength of contagion, and compared the contagiousness of yawning to nose-wiping. Thirty-three orphaned chimpanzees observed an unfamiliar and familiar human (their surrogate human mother) yawn, gape and nose-wipe. Yawning, but not nose-wiping, was contagious for juvenile chimpanzees, while infants were immune to contagion. Like humans and dogs, chimpanzees are subject to a developmental trend in susceptibility to contagious yawning, and respond to heterospecific yawn stimuli. Emotional closeness with the model did not affect contagion. The familiarity-biased social modulatory effect on yawn contagion previously found among some adult primates, seem to only emerge later in development, or be limited to interactions with conspecifics. The influence of the 'chameleon effect', targeted vs. generalised empathy, perspective-taking and visual attention on contagious yawning is discussed.

  7. Chimpanzees Show a Developmental Increase in Susceptibility to Contagious Yawning: A Test of the Effect of Ontogeny and Emotional Closeness on Yawn Contagion

    PubMed Central

    Madsen, Elainie Alenkær; Persson, Tomas; Sayehli, Susan; Lenninger, Sara; Sonesson, Göran

    2013-01-01

    Contagious yawning has been reported for humans, dogs and several non-human primate species, and associated with empathy in humans and other primates. Still, the function, development and underlying mechanisms of contagious yawning remain unclear. Humans and dogs show a developmental increase in susceptibility to yawn contagion, with children showing an increase around the age of four, when also empathy-related behaviours and accurate identification of others’ emotions begin to clearly evince. Explicit tests of yawn contagion in non-human apes have only involved adult individuals and examined the existence of conspecific yawn contagion. Here we report the first study of heterospecific contagious yawning in primates, and the ontogeny of susceptibility thereto in chimpanzees, Pan troglodytes verus. We examined whether emotional closeness, defined as attachment history with the yawning model, affected the strength of contagion, and compared the contagiousness of yawning to nose-wiping. Thirty-three orphaned chimpanzees observed an unfamiliar and familiar human (their surrogate human mother) yawn, gape and nose-wipe. Yawning, but not nose-wiping, was contagious for juvenile chimpanzees, while infants were immune to contagion. Like humans and dogs, chimpanzees are subject to a developmental trend in susceptibility to contagious yawning, and respond to heterospecific yawn stimuli. Emotional closeness with the model did not affect contagion. The familiarity-biased social modulatory effect on yawn contagion previously found among some adult primates, seem to only emerge later in development, or be limited to interactions with conspecifics. The influence of the ‘chameleon effect’, targeted vs. generalised empathy, perspective-taking and visual attention on contagious yawning is discussed. PMID:24146848

  8. Mice lacking acid-sensing ion channels (ASIC) 1 or 2, but not ASIC3, show increased pain behaviour in the formalin test.

    PubMed

    Staniland, Amelia A; McMahon, Stephen B

    2009-07-01

    Extracellular acidification is a component of the inflammatory process and may be a factor driving the pain accompanying it. Acid-sensing ion channels (ASICs) are neuronal proton sensors and evidence suggests they are involved in signalling inflammatory pain. The aims of this study were to (1) clarify the role of ASICs in nociception and (2) confirm their involvement in inflammatory pain and determine whether this was subunit specific. This was achieved by (1) direct comparison of the sensitivity of ASIC1, ASIC2, ASIC3 and TRPV1 knockout mice versus wildtype littermates to acute thermal and mechanical noxious stimuli and (2) studying the behavioural responses of each transgenic strain to hind paw inflammation with either complete Freund's adjuvant (CFA) or formalin. Naïve ASIC1(-/-) and ASIC2(-/-) mice responded normally to acute noxious stimuli, whereas ASIC3(-/-) mice were hypersensitive to high intensity thermal stimuli. CFA injection decreased mechanical and thermal withdrawal thresholds for up to 8 days. ASIC2(-/-) mice had increased mechanical sensitivity on day 1 post-CFA compared to wildtype controls. TRPV1(-/-) mice had significantly reduced thermal, but not mechanical, hyperalgesia on all days after inflammation. Following formalin injection, ASIC1(-/-) and ASIC2(-/-), but not ASIC3(-/-) or TRPV1(-/-), mice showed enhanced pain behaviour, predominantly in the second phase of the test. These data suggest that whilst ASICs may play a role in mediating inflammatory pain, this role is likely to be modulatory and strongly dependent on channel subtype.

  9. Relaxation training affects success and activation on a teaching test.

    PubMed

    Helin, P; Hänninen, O

    1987-12-01

    We studied the effects of an audiocassette-relaxation training period (ART) and its timing on success at a teaching test (lecture type), on observed tension and on a number of physiological responses. The electrical activity of the upper trapezius muscle (EMG), heart rate (HR) and blood pressure (BP), of female and male instructor candidates, were examined before, during and after the teaching test as well as during its critique. The relaxation period (18 min) was presented either on the preceding night (ARTnt) or immediately before the teaching test (ARTimm). The influence of personality (types A-B and extrovert-introvert) was also studied. ART improved success at the teaching test in both sexes. In males (but not in females), ARTimm decreased EMG level during the test, but ARTnt increased EMG at the test period as compared to the control group. In females, both ARTnt and ARTimm lowered HR more than in the control group. ARTimm lowered systolic BP in both sexes. Personality types affected the ART responses; ART was more beneficial for type A than B subjects.

  10. Rats with minimal hepatic encephalopathy show reduced cGMP-dependent protein kinase activity in hypothalamus correlating with circadian rhythms alterations.

    PubMed

    Felipo, Vicente; Piedrafita, Blanca; Barios, Juan A; Agustí, Ana; Ahabrach, Hanan; Romero-Vives, María; Barrio, Luis C; Rey, Beatriz; Gaztelu, Jose M; Llansola, Marta

    2015-01-01

    Patients with liver cirrhosis show disturbances in sleep and in its circadian rhythms which are an early sign of minimal hepatic encephalopathy (MHE). The mechanisms of these disturbances are poorly understood. Rats with porta-caval shunt (PCS), a model of MHE, show sleep disturbances reproducing those of cirrhotic patients. The aims of this work were to characterize the alterations in circadian rhythms in PCS rats and analyze the underlying mechanisms. To reach these aims, we analyzed in control and PCS rats: (a) daily rhythms of spontaneous and rewarding activity and of temperature, (b) timing of the onset of activity following turning-off the light, (c) synchronization to light after a phase advance and (d) the molecular mechanisms contributing to these alterations in circadian rhythms. PCS rats show altered circadian rhythms of spontaneous and rewarding activities (wheel running). PCS rats show more rest bouts during the active phase, more errors in the onset of motor activity and need less time to re-synchronize after a phase advance than control rats. Circadian rhythm of body temperature is also slightly altered in PCS rats. The internal period length (tau) of circadian rhythm of motor activity is longer in PCS rats. We analyzed some mechanisms by which hypothalamus modulate circadian rhythms. PCS rats show increased content of cGMP in hypothalamus while the activity of cGMP-dependent protein kinase was reduced by 41% compared to control rats. Altered cGMP-PKG pathway in hypothalamus would contribute to altered circadian rhythms and synchronization to light.

  11. A Disease-associated Mutant of NLRC4 Shows Enhanced Interaction with SUG1 Leading to Constitutive FADD-dependent Caspase-8 Activation and Cell Death.

    PubMed

    Raghawan, Akhouri Kishore; Sripada, Anand; Gopinath, Gayathri; Pushpanjali, Pendyala; Kumar, Yatender; Radha, Vegesna; Swarup, Ghanshyam

    2017-01-27

    Nod-like receptor family card containing 4 (NLRC4)/Ipaf is involved in recognition of pathogen-associated molecular patterns leading to caspase-1 activation and cytokine release, which mediate protective innate immune response. Point mutations in NLRC4 cause autoinflammatory syndromes. Although all the mutations result in constitutive caspase-1 activation, their phenotypic presentations are different, implying that these mutations cause different alterations in properties of NLRC4. NLRC4 interacts with SUG1 and induces caspase-8-mediated cell death. Here, we show that one of the autoinflammatory syndrome-causing mutants of NLRC4, H443P, but not T337A and V341A, constitutively activates caspase-8 and induces apoptotic cell death in human lung epithelial cells. Compared with wild type NLRC4, the H443P mutant shows stronger interaction with SUG1 and with ubiquitinated cellular proteins. Phosphorylation of NLRC4 at Ser(533) plays a crucial role in caspase-8 activation and cell death. However, H443P mutant does not require Ser(533) phosphorylation for caspase-8 activation and cell death. Caspase-8 activation by NLRC4 and its H443P mutant are dependent on the adaptor protein FADD. A phosphomimicking mutant of NLRC4, S533D does not require SUG1 activity for inducing cell death. Ubiquitin-tagged NLRC4 could induce cell death and activate caspase-8 independent of Ser(533) phosphorylation. Our work suggests that SUG1-mediated signaling results in enhanced ubiquitination and regulates FADD-dependent caspase-8 activation by NLRC4. We show that the autoinflammation-associated H443P mutant is altered in interaction with SUG1 and ubiquitinated proteins, triggering constitutive caspase-8-mediated cell death dependent on FADD but independent of Ser(533) phosphorylation.

  12. 55P0110, a Novel Synthetic Compound Developed from a Plant Derived Backbone Structure, Shows Promising Anti-Hyperglycaemic Activity in Mice.

    PubMed

    Brunmair, Barbara; Lehner, Zsuzsanna; Stadlbauer, Karin; Adorjan, Immanuel; Frobel, Klaus; Scherer, Thomas; Luger, Anton; Bauer, Leonhardt; Fürnsinn, Clemens

    2015-01-01

    Starting off with a structure derived from the natural compound multiflorine, a derivatisation program aimed at the discovery and initial characterisation of novel compounds with antidiabetic potential. Design and discovery of the structures was guided by oral bioactivities obtained in oral glucose tolerance tests in mice. 55P0110, one among several new compounds with distinct anti-hyperglycaemic activity, was further examined to characterise its pharmacology and mode of action. Whereas a single oral dose of 55P0110 did not affect basal glycaemia, it markedly improved the glucose tolerance of healthy and diabetic mice (peak blood glucose in glucose tolerance test, mmol/l: healthy mice with 90 mg/kg 55P0110, 17.0 ± 1.2 vs. 10.1 ± 1.1; diabetic mice with 180 mg/kg 55P0110, 23.1 ± 0.9 vs. 11.1 ± 1.4; p<0.001 each). Closer examination argued against retarded glucose resorption from the gut, increased glucose excretion in urine, acute insulin-like or insulin sensitising properties, and direct inhibition of dipeptidyl peptidase-4 as the cause of glucose lowering. Hence, 55P0110 seems to act via a target not exploited by any drug presently approved for the treatment of diabetes mellitus. Whereas the insulinotropic sulfonylurea gliclazide (16 mg/kg) distinctly increased the circulating insulin-per-glucose ratio under basal conditions, 55P0110 (90 mg/kg) lacked such an effect (30 min. after dosing, nmol/mol: vehicle, 2.49 ± 0.27; 55P0110, 2.99 ± 0.35; gliclazide, 8.97 ± 0.49; p<0.001 each vs. gliclazide). Under an exogenous glucose challenge, however, 55P0110 increased this ratio to the same extent as gliclazide (20 min. after glucose feeding: vehicle, 2.53 ± 0.41; 55P0110, 3.80 ± 0.46; gliclazide, 3.99 ± 0.26; p<0.05 each vs. vehicle). By augmenting the glucose stimulated increase in plasma insulin, 55P0110 thus shows distinct anti-hyperglycaemic action in combination with low risk for fasting hypoglycaemia in mice. In summary, we have discovered a novel class of

  13. A Model for Aryl Hydrocarbon Receptor-Activated Gene Expression Shows Potency and Efficacy Changes and Predicts Squelching Due to Competition for Transcription Co-Activators

    PubMed Central

    Simon, Ted W.; Budinsky, Robert A.; Rowlands, J. Craig

    2015-01-01

    A stochastic model of nuclear receptor-mediated transcription was developed based on activation of the aryl hydrocarbon receptor (AHR) by 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and subsequent binding the activated AHR to xenobiotic response elements (XREs) on DNA. The model was based on effects observed in cells lines commonly used as in vitro experimental systems. Following ligand binding, the AHR moves into the cell nucleus and forms a heterodimer with the aryl hydrocarbon nuclear translocator (ARNT). In the model, a requirement for binding to DNA is that a generic coregulatory protein is subsequently bound to the AHR-ARNT dimer. Varying the amount of coregulator available within the nucleus altered both the potency and efficacy of TCDD for inducing for transcription of CYP1A1 mRNA, a commonly used marker for activation of the AHR. Lowering the amount of available cofactor slightly increased the EC50 for the transcriptional response without changing the efficacy or maximal response. Further reduction in the amount of cofactor reduced the efficacy and produced non-monotonic dose-response curves (NMDRCs) at higher ligand concentrations. The shapes of these NMDRCs were reminiscent of the phenomenon of squelching. Resource limitations for transcriptional machinery are becoming apparent in eukaryotic cells. Within single cells, nuclear receptor-mediated gene expression appears to be a stochastic process; however, intercellular communication and other aspects of tissue coordination may represent a compensatory process to maintain an organism’s ability to respond on a phenotypic level to various stimuli within an inconstant environment. PMID:26039703

  14. Preference as a Function of Active Interresponse Times: A Test of the Active Time Model

    ERIC Educational Resources Information Center

    Misak, Paul; Cleaveland, J. Mark

    2011-01-01

    In this article, we describe a test of the active time model for concurrent variable interval (VI) choice. The active time model (ATM) suggests that the time since the most recent response is one of the variables controlling choice in concurrent VI VI schedules of reinforcement. In our experiment, pigeons were trained in a multiple concurrent…

  15. Sesquiterpene lactone containing extracts from two cultivars of forage chicory (Cichorium intybus) show distinctive chemical profiles and in vitro activity against Ostertagia ostertagi.

    PubMed

    Peña-Espinoza, Miguel; Boas, Ulrik; Williams, Andrew R; Thamsborg, Stig M; Simonsen, Henrik T; Enemark, Heidi L

    2015-12-01

    The study investigated direct anthelmintic effects of sesquiterpene lactones (SL)-containing extracts from forage chicory against free-living and parasitic stages of Ostertagia ostertagi. Freeze-dried leaves from chicory cultivars 'Spadona' and 'Puna II' were extracted using methanol/water. Total SL were further fractionated by solid-phase extraction and resulting extracts were characterised by high-performance liquid chromatography (HPLC). O. ostertagi eggs from faeces of mono-infected calves were hatched and L1 were used in a larval feeding inhibition assay (LFIA), while cultured L3 were used in a larval exsheathment inhibition assay (LEIA). Adult worms were immediately recovered after slaughter and used for motility inhibition assays (AMIA). Electron microscopy (EM) was performed on adult O. ostertagi exposed to 1000 μg extract mL(-1) of both chicory cultivars. In all assays, decreasing concentrations of SL-containing extracts in PBS (1% DMSO) were tested in replicates with 1% DMSO in PBS as negative controls. HPLC demonstrated similar concentrations of most SL in both extracts. However, Spadona-extract contained significantly higher concentrations of 11, 13-dihydro-8-deoxylactucin (P = 0.01), while Puna II-extract had increased levels of 11, 13-dihydrolactucin (P < 0.0001). In the LFIA, both extracts reduced larval feeding at increasing concentrations, but Spadona-extract showed higher potency confirmed by significantly lower EC50 (P < 0.0001). In the LEIA, neither of the two extracts interfered with the exsheathment of L3 (P > 0.05). In the AMIA, both SL-containing extracts induced a dose-dependent effect but Spadona-extract showed greater activity and exerted faster worm paralysis than Puna II-extract with significantly lower EC50 (P < 0.0001). No cuticular damage was observed by EM in worms exposed to any of the extracts. We have demonstrated that SL-containing extracts from forage chicory can inhibit feeding of free-living larvae and exert

  16. Sesquiterpene lactone containing extracts from two cultivars of forage chicory (Cichorium intybus) show distinctive chemical profiles and in vitro activity against Ostertagia ostertagi

    PubMed Central

    Peña-Espinoza, Miguel; Boas, Ulrik; Williams, Andrew R.; Thamsborg, Stig M.; Simonsen, Henrik T.; Enemark, Heidi L.

    2015-01-01

    The study investigated direct anthelmintic effects of sesquiterpene lactones (SL)-containing extracts from forage chicory against free-living and parasitic stages of Ostertagia ostertagi. Freeze-dried leaves from chicory cultivars ‘Spadona’ and ‘Puna II’ were extracted using methanol/water. Total SL were further fractionated by solid-phase extraction and resulting extracts were characterised by high-performance liquid chromatography (HPLC). O. ostertagi eggs from faeces of mono-infected calves were hatched and L1 were used in a larval feeding inhibition assay (LFIA), while cultured L3 were used in a larval exsheathment inhibition assay (LEIA). Adult worms were immediately recovered after slaughter and used for motility inhibition assays (AMIA). Electron microscopy (EM) was performed on adult O. ostertagi exposed to 1000 μg extract mL−1 of both chicory cultivars. In all assays, decreasing concentrations of SL-containing extracts in PBS (1% DMSO) were tested in replicates with 1% DMSO in PBS as negative controls. HPLC demonstrated similar concentrations of most SL in both extracts. However, Spadona-extract contained significantly higher concentrations of 11, 13-dihydro-8-deoxylactucin (P = 0.01), while Puna II-extract had increased levels of 11, 13-dihydrolactucin (P < 0.0001). In the LFIA, both extracts reduced larval feeding at increasing concentrations, but Spadona-extract showed higher potency confirmed by significantly lower EC50 (P < 0.0001). In the LEIA, neither of the two extracts interfered with the exsheathment of L3 (P > 0.05). In the AMIA, both SL-containing extracts induced a dose-dependent effect but Spadona-extract showed greater activity and exerted faster worm paralysis than Puna II-extract with significantly lower EC50 (P < 0.0001). No cuticular damage was observed by EM in worms exposed to any of the extracts. We have demonstrated that SL-containing extracts from forage chicory can inhibit feeding of free-living larvae and

  17. But the Scores Don't Show How I Really Function: A Feedback Method to Reveal Cognitive Distortions Regarding Normal Neuropsychological Test Performance.

    PubMed

    Carone, Dominic A

    2017-01-01

    Neuropsychologists commonly provide feedback to patients with a high degree of cognitive complaints in the context of normal neuropsychological test performance. Patients are sometimes not reassured by this feedback because they blame external factors (e.g., the tests are wrong) and do not develop insight about internal factors (e.g., distorted self-perception) that could lead to better understanding about why high symptom reporting is present in the context of normal test results. This article presents the first formal feedback model for neuropsychologists to use with such patients that helps reveal the presence of cognitive distortions that result in high cognitive complaints. The critical elements of this model incorporate self-ratings of neuropsychological test performance, comparing those ratings to actual test performance, and presenting discrepancies to patients in an objective, professional, and respectful manner. Ways in which this feedback model may lead to improved patient outcomes and reductions in healthcare costs are discussed.

  18. Cocaine users with comorbid Cluster B personality disorders show dysfunctional brain activation and connectivity in the emotional regulation networks during negative emotion maintenance and reappraisal.

    PubMed

    Albein-Urios, Natalia; Verdejo-Román, Juan; Soriano-Mas, Carles; Asensio, Samuel; Martínez-González, José Miguel; Verdejo-García, Antonio

    2013-12-01

    Cocaine dependence often co-occurs with Cluster B personality disorders. Since both disorders are characterized by emotion regulation deficits, we predicted that cocaine comorbid patients would exhibit dysfunctional patterns of brain activation and connectivity during reappraisal of negative emotions. We recruited 18 cocaine users with comorbid Cluster B personality disorders, 17 cocaine users without comorbidities and 21 controls to be scanned using functional magnetic resonance imaging (fMRI) during performance on a reappraisal task in which they had to maintain or suppress the emotions induced by negative affective stimuli. We followed region of interest (ROI) and whole-brain approaches to investigate brain activations and connectivity associated with negative emotion experience and reappraisal. Results showed that cocaine users with comorbid personality disorders had reduced activation of the subgenual anterior cingulate cortex during negative emotion maintenance and increased activation of the lateral orbitofrontal cortex and the amygdala during reappraisal. Amygdala activation correlated with impulsivity and antisocial beliefs in the comorbid group. Connectivity analyses showed that in the cocaine comorbid group the subgenual cingulate was less efficiently connected with the amygdala and the fusiform gyri and more efficiently connected with the anterior insula during maintenance, whereas during reappraisal the left orbitofrontal cortex was more efficiently connected with the amygdala and the right orbitofrontal cortex was less efficiently connected with the dorsal striatum. We conclude that cocaine users with comorbid Cluster B personality disorders have distinctive patterns of brain activation and connectivity during maintenance and reappraisal of negative emotions, which correlate with impulsivity and dysfunctional beliefs.

  19. Identification of the immunoglobulin class active in the Rose Bengal plate test for bovine brucellosis

    PubMed Central

    Corbel, M. J.

    1972-01-01

    The antibodies active in the Rose Bengal plate test (RBPT) for bovine brucellosis have been studied. The results of fractionation experiments showed that RBPT activity was associated with fractions containing immunoglobulin of the IgG1 class; other immunoglobulin classes were inactive in this respect although active in other tests. These results were confirmed by inhibition tests with specific antisera and by elution of the antibody from agglutinated RBPT antigen. The major proportion of the serum complement-fixing activity was also present in the IgG1 fraction and it is suggested that the RBPT and CF reactions are probably mediated by the same antibodies. ImagesFig. 1Fig. 2Fig. 3Plate 2Plate 2 PMID:4630606

  20. Active Matrix Organic Light Emitting Diode (AMOLED) Environmental Test Report

    NASA Technical Reports Server (NTRS)

    Salazar, George A.

    2013-01-01

    This report focuses on the limited environmental testing of the AMOLED display performed as an engineering evaluation by The NASA Johnson Space Center (JSC)-specifically. EMI. Thermal Vac, and radiation tests. The AMOLED display is an active-matrix Organic Light Emitting Diode (OLED) technology. The testing provided an initial understanding of the technology and its suitability for space applications. Relative to light emitting diode (LED) displays or liquid crystal displays (LCDs), AMOLED displays provide a superior viewing experience even though they are much lighter and smaller, produce higher contrast ratio and richer colors, and require less power to operate than LCDs. However, AMOLED technology has not been demonstrated in a space environment. Therefore, some risks with the technology must be addressed before they can be seriously considered for human spaceflight. The environmental tests provided preliminary performance data on the ability of the display technology to handle some of the simulated induced space/spacecraft environments that an AMOLED display will see during a spacecraft certification test program. This engineering evaluation is part of a Space Act Agreement (SM) between The NASA/JSC and Honeywell International (HI) as a collaborative effort to evaluate the potential use of AMOLED technology for future human spaceflight missions- both government-led and commercial. Under this SM, HI is responsible for doing optical performance evaluation, as well as temperature and touch screen studies. The NASA/JSC is responsible for performing environmental testing comprised of EMI, Thermal Vac, and radiation tests. Additionally, as part of the testing, limited optical data was acquired to assess performance as the display was subjected to the induced environments. The NASA will benefit from this engineering evaluation by understanding AMOLED suitability for future use in space as well as becoming a smarter buyer (or developer) of the technology. HI benefits

  1. Detection of bacterial phosphatase activity by means of an original and simple test.

    PubMed Central

    Satta, G; Grazi, G; Varaldo, P E; Fontana, R

    1979-01-01

    A new test for the detection of bacterial phosphatase activity has been devised. The test is performed using agar media containing both methyl green (MG) and phenolphthalein diphosphate (PDP); in these media phosphatase-producing strains grow deep-green-stained colonies whereas non-producing strains do not. A total of 739 different strains were tested, including 593 staphylococci, 95 micrococci, 11 streptococci, 10 corynebacteria, 14 enterobacteria, and 16 candidae. All strains found phosphatase-positive according to the conventional phosphatase test displayed deep-green-stained colonies on MG-PDP media, whereas all phosphatase-negative strains showed unstained colonies on the same media. The main advantages of the present phosphatase test as compared with other conventional ones are that it is more simple to perform, it can reveal the phosphatase activity of colonies grown in deep agar, and can be incorporated into commercial multitest kits. PMID:87403

  2. Varenicline has antidepressant-like activity in the forced swim test and augments sertraline's effect.

    PubMed

    Rollema, Hans; Guanowsky, Victor; Mineur, Yann S; Shrikhande, Alka; Coe, Jotham W; Seymour, Patricia A; Picciotto, Marina R

    2009-03-01

    Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist developed as a smoking cessation aid, showed antidepressant-like activity in the forced swim test in two mouse strains. In addition, a low varenicline dose significantly enhanced the effects of moderately active doses of the selective serotonin reuptake inhibitor sertraline. These findings are consistent with the notion that reducing alpha4beta2 nicotinic acetylcholine receptor activity either by antagonists or by partial agonists that can partially activate or desensitize acetylcholine receptors is associated with antidepressant-like properties. These data suggest that varenicline may have antidepressant potential and can, when combined, augment antidepressant responses of selective serotonin reuptake inhibitors.

  3. Cenicriviroc, a Novel CCR5 (R5) and CCR2 Antagonist, Shows In Vitro Activity against R5 Tropic HIV-2 Clinical Isolates

    PubMed Central

    Visseaux, Benoit; Charpentier, Charlotte; Collin, Gilles; Bertine, Mélanie; Peytavin, Gilles; Damond, Florence; Matheron, Sophie; Lefebvre, Eric; Brun-Vézinet, Françoise; Descamps, Diane

    2015-01-01

    Background Maraviroc activity against HIV-2, a virus naturally resistant to different HIV-1 antiretroviral drugs, has been recently demonstrated. The aim of this study was to assess HIV-2 susceptibility to cenicriviroc, a novel, once-daily, dual CCR5 and CCR2 antagonist that has completed Phase 2b development in HIV-1 infection. Methods Cenicriviroc phenotypic activity has been tested using a PBMC phenotypic susceptibility assay against four R5-, one X4- and one dual-tropic HIV-2 clinical primary isolates. All isolates were obtained by co-cultivation of PHA-activated PBMC from distinct HIV-2-infected CCR5-antagonist-naïve patients included in the French HIV-2 cohort and were previously tested for maraviroc susceptibility using the same protocol. HIV-2 tropism was determined by phenotypic assay using Ghost(3) cell lines. Results Regarding the 4 R5 HIV-2 clinical isolates tested, effective concentration 50% EC50 for cenicriviroc were 0.03, 0.33, 0.45 and 0.98 nM, similar to those observed with maraviroc: 1.13, 0.58, 0.48 and 0.68 nM, respectively. Maximum percentages of inhibition (MPI) of cenicriviroc were 94, 94, 93 and 98%, similar to those observed with maraviroc (93, 90, 82, 100%, respectively). The dual- and X4-tropic HIV-2 strains were resistant to cenicriviroc with EC50 >1000 nM and MPI at 33% and 4%, respectively. Conclusions In this first study assessing HIV-2 susceptibility to cenicriviroc, we observed an in vitro activity against HIV-2 R5-tropic strains similar to that observed with maraviroc. Thus, cenicriviroc may offer a once-daily treatment opportunity in the limited therapeutic arsenal for HIV-2. Clinical studies are warranted. PMID:26247470

  4. Active Blade Vibration Control Being Developed and Tested

    NASA Technical Reports Server (NTRS)

    Johnson, Dexter

    2003-01-01

    Gas turbine engines are currently being designed to have increased performance, lower weight and manufacturing costs, and higher reliability. Consequently, turbomachinery components, such as turbine and compressor blades, have designs that are susceptible to new vibration problems and eventual in-service failure due to high-cycle fatigue. To address this problem, researchers at the NASA Glenn Research Center are developing and testing innovative active blade vibration control concepts. Preliminary results of using an active blade vibration control system, involving a rotor supported by an active magnetic bearing in Glenn's Dynamic Spin Rig, indicate promising results (see the photograph). Active blade vibration control was achieved using feedback of blade strain gauge signals within the magnetic bearing control loop. The vibration amplitude was reduced substantially (see the graphs). Also, vibration amplitude amplification was demonstrated; this could be used to enhance structural mode identification, if desired. These results were for a nonrotating two-bladed disk. Tests for rotating blades are planned. Current and future active blade vibration control research is planned to use a fully magnetically suspended rotor and smart materials. For the fully magnetically suspended rotor work, three magnetic bearings (two radial and one axial) will be used as actuators instead of one magnetic bearing. This will allow additional degrees of freedom to be used for control. For the smart materials work, control effectors located on and off the blade will be considered. Piezoelectric materials will be considered for on-the-blade actuation, and actuator placement on a stator vane, or other nearby structure, will be investigated for off-the-blade actuation. Initial work will focus on determining the feasibility of these methods by performing basic analysis and simple experiments involving feedback control.

  5. The 5'-flanking region of the RP58 coding sequence shows prominent promoter activity in multipolar cells in the subventricular zone during corticogenesis.

    PubMed

    Ohtaka-Maruyama, C; Hirai, S; Miwa, A; Takahashi, A; Okado, H

    2012-01-10

    Pyramidal neurons of the neocortex are produced from progenitor cells located in the neocortical ventricular zone (VZ) and subventricular zone (SVZ) during embryogenesis. RP58 is a transcriptional repressor that is strongly expressed in the developing brain and plays an essential role in corticogenesis. The expression of RP58 is strictly regulated in a time-dependent and spatially restricted manner. It is maximally expressed in E15-16 embryonic cerebral cortex, localized specifically to the cortical plate and SVZ of the neocortex, hippocampus, and parts of amygdala during brain development, and found in glutamatergic but not GABAergic neurons. Identification of the promoter activity underlying specific expression patterns provides important clues to their mechanisms of action. Here, we show that the RP58 gene promoter is activated prominently in multipolar migrating cells, the first in vivo analysis of RP58 promoter activity in the brain. The 5.3 kb 5'-flanking genomic DNA of the RP58 coding region demonstrates promoter activity in neurons both in vitro and in vivo. This promoter is highly responsive to the transcription factor neurogenin2 (Ngn2), which is a direct upstream activator of RP58 expression. Using in utero electroporation, we demonstrate that RP58 gene promoter activity is first detected in a subpopulation of pin-like VZ cells, then prominently activated in migrating multipolar cells in the multipolar cell accumulation zone (MAZ) located just above the VZ. In dissociated primary cultured cortical neurons, RP58 promoter activity mimics in vivo expression patterns from a molecular standpoint that RP58 is expressed in a fraction of Sox2-positive progenitor cells, Ngn2-positive neuronal committed cells, and Tuj1-positive young neurons, but not in Dlx2-positive GABAergic neurons. Finally, we show that Cre recombinase expression under the control of the RP58 gene promoter is a feasible tool for conditional gene switching in post-mitotic multipolar migrating

  6. The basophil activation test: a sensitive test in the diagnosis of allergic immediate hypersensitivity to pristinamycin.

    PubMed

    Viel, Sébastien; Garnier, Lorna; Joly, Elodie; Rouzaire, Paul; Nosbaum, Audrey; Pralong, Pauline; Faudel, Amélie; Rioufol, Catherine; Bienvenu, Françoise; Bienvenu, Jacques; Berard, Frédéric

    2015-01-01

    Immediate hypersensitivity (IHS) reactions to macrolides and to macrolide-derived antibiotics like pristinamycin are uncommon. In this context, there is little data available to appreciate the true value of biological tools regarding the diagnosis of immediate allergy to pristinamycin. Here we assess the clinical usefulness of the basophil activation test (BAT) to differentiate allergic from nonallergic IHS to pristinamycin. Thirty-six patients were tested with skin tests as the gold standard and BAT. The BAT achieved a sensitivity of 76% and a specificity of 100%, implying an absence of false positive results. Multicenter studies remain to be performed to better define the sensitivity, specificity and interlaboratory variation of BAT in the diagnosis of allergy to pristinamycin and macrolides.

  7. An alpha2,6-sialyltransferase cloned from Photobacterium leiognathi strain JT-SHIZ-119 shows both sialyltransferase and neuraminidase activity.

    PubMed

    Mine, Toshiki; Katayama, Sakurako; Kajiwara, Hitomi; Tsunashima, Masako; Tsukamoto, Hiroshi; Takakura, Yoshimitsu; Yamamoto, Takeshi

    2010-02-01

    We cloned, expressed, and characterized a novel beta-galactoside alpha2,6-sialyltransferase from Photobacterium leiognathi strain JT-SHIZ-119. The protein showed 56-96% identity to the marine bacterial alpha2,6-sialyltransferases classified into glycosyltransferase family 80. The sialyltransferase activity of the N-terminal truncated form of the recombinant enzyme was 1477 U/L of Escherichia coli culture. The truncated recombinant enzyme was purified as a single band by sodium dodecyl sulfate polyacrylamide gel electrophoresis through 3 column chromatography steps. The enzyme had distinct activity compared with known marine bacterial alpha2,6-sialyltransferases. Although alpha2,6-sialyltransferases cloned from marine bacteria, such as Photobacterium damselae strain JT0160, P. leiognathi strain JT-SHIZ-145, and Photobacterium sp. strain JT-ISH-224, show only alpha2,6-sialyltransferase activity, the recombinant enzyme cloned from P. leiognathi strain JT-SHIZ-119 showed both alpha2,6-sialyltransferase and alpha2,6-linkage-specific neuraminidase activity. Our results provide important information toward a comprehensive understanding of the bacterial sialyltransferases belonging to the group 80 glycosyltransferase family in the CAZy database.

  8. Piperidinols that show anti-tubercular activity as inhibitors of arylamine N-acetyltransferase: an essential enzyme for mycobacterial survival inside macrophages.

    PubMed

    Abuhammad, Areej; Fullam, Elizabeth; Lowe, Edward D; Staunton, David; Kawamura, Akane; Westwood, Isaac M; Bhakta, Sanjib; Garner, Alun Christopher; Wilson, David L; Seden, Peter T; Davies, Stephen G; Russell, Angela J; Garman, Elspeth F; Sim, Edith

    2012-01-01

    Latent M. tuberculosis infection presents one of the major obstacles in the global eradication of tuberculosis (TB). Cholesterol plays a critical role in the persistence of M. tuberculosis within the macrophage during latent infection. Catabolism of cholesterol contributes to the pool of propionyl-CoA, a precursor that is incorporated into cell-wall lipids. Arylamine N-acetyltransferase (NAT) is encoded within a gene cluster that is involved in the cholesterol sterol-ring degradation and is essential for intracellular survival. The ability of the NAT from M. tuberculosis (TBNAT) to utilise propionyl-CoA links it to the cholesterol-catabolism pathway. Deleting the nat gene or inhibiting the NAT enzyme prevents intracellular survival and results in depletion of cell-wall lipids. TBNAT has been investigated as a potential target for TB therapies. From a previous high-throughput screen, 3-benzoyl-4-phenyl-1-methylpiperidinol was identified as a selective inhibitor of prokaryotic NAT that exhibited antimycobacterial activity. The compound resulted in time-dependent irreversible inhibition of the NAT activity when tested against NAT from M. marinum (MMNAT). To further evaluate the antimycobacterial activity and the NAT inhibition of this compound, four piperidinol analogues were tested. All five compounds exert potent antimycobacterial activity against M. tuberculosis with MIC values of 2.3-16.9 µM. Treatment of the MMNAT enzyme with this set of inhibitors resulted in an irreversible time-dependent inhibition of NAT activity. Here we investigate the mechanism of NAT inhibition by studying protein-ligand interactions using mass spectrometry in combination with enzyme analysis and structure determination. We propose a covalent mechanism of NAT inhibition that involves the formation of a reactive intermediate and selective cysteine residue modification. These piperidinols present a unique class of antimycobacterial compounds that have a novel mode of action different from

  9. Piperidinols That Show Anti-Tubercular Activity as Inhibitors of Arylamine N-Acetyltransferase: An Essential Enzyme for Mycobacterial Survival Inside Macrophages

    PubMed Central

    Abuhammad, Areej; Fullam, Elizabeth; Lowe, Edward D.; Staunton, David; Kawamura, Akane; Westwood, Isaac M.; Bhakta, Sanjib; Garner, Alun Christopher; Wilson, David L.; Seden, Peter T.; Davies, Stephen G.; Russell, Angela J.; Garman, Elspeth F.; Sim, Edith

    2012-01-01

    Latent M. tuberculosis infection presents one of the major obstacles in the global eradication of tuberculosis (TB). Cholesterol plays a critical role in the persistence of M. tuberculosis within the macrophage during latent infection. Catabolism of cholesterol contributes to the pool of propionyl-CoA, a precursor that is incorporated into cell-wall lipids. Arylamine N-acetyltransferase (NAT) is encoded within a gene cluster that is involved in the cholesterol sterol-ring degradation and is essential for intracellular survival. The ability of the NAT from M. tuberculosis (TBNAT) to utilise propionyl-CoA links it to the cholesterol-catabolism pathway. Deleting the nat gene or inhibiting the NAT enzyme prevents intracellular survival and results in depletion of cell-wall lipids. TBNAT has been investigated as a potential target for TB therapies. From a previous high-throughput screen, 3-benzoyl-4-phenyl-1-methylpiperidinol was identified as a selective inhibitor of prokaryotic NAT that exhibited antimycobacterial activity. The compound resulted in time-dependent irreversible inhibition of the NAT activity when tested against NAT from M. marinum (MMNAT). To further evaluate the antimycobacterial activity and the NAT inhibition of this compound, four piperidinol analogues were tested. All five compounds exert potent antimycobacterial activity against M. tuberculosis with MIC values of 2.3–16.9 µM. Treatment of the MMNAT enzyme with this set of inhibitors resulted in an irreversible time-dependent inhibition of NAT activity. Here we investigate the mechanism of NAT inhibition by studying protein-ligand interactions using mass spectrometry in combination with enzyme analysis and structure determination. We propose a covalent mechanism of NAT inhibition that involves the formation of a reactive intermediate and selective cysteine residue modification. These piperidinols present a unique class of antimycobacterial compounds that have a novel mode of action different

  10. Information Technology Measurement and Testing Activities at NIST

    PubMed Central

    Hogan, Michael D.; Carnahan, Lisa J.; Carpenter, Robert J.; Flater, David W.; Fowler, James E.; Frechette, Simon P.; Gray, Martha M.; Johnson, L. Arnold; McCabe, R. Michael; Montgomery, Douglas; Radack, Shirley M.; Rosenthal, Robert; Shakarji, Craig M.

    2001-01-01

    Our high technology society continues to rely more and more upon sophisticated measurements, technical standards, and associated testing activities. This was true for the industrial society of the 20th century and remains true for the information society of the 21st century. Over the last half of the 20th century, information technology (IT) has been a powerful agent of change in almost every sector of the economy. The complexity and rapidly changing nature of IT have presented unique technical challenges to the National Institute of Standards and Technology (NIST) and to the scientific measurement community in developing a sound measurement and testing infrastructure for IT. This measurement and testing infrastructure for the important non-physical and non-chemical properties associated with complex IT systems is still in an early stage of development. This paper explains key terms and concepts of IT metrology, briefly reviews the history of the National Bureau of Standards/National Institute of Standards and Technology (NBS/NIST) in the field of IT, and reviews NIST’s current capabilities and work in measurement and testing for IT. It concludes with a look at what is likely to occur in the field of IT over the next ten years and what metrology roles NIST is likely to play. PMID:27500026

  11. Information Technology Measurement and Testing Activities at NIST.

    PubMed

    Hogan, M D; Carnahan, L J; Carpenter, R J; Flater, D W; Fowler, J E; Frechette, S P; Gray, M M; Johnson, L A; McCabe, R M; Montgomery, D; Radack, S M; Rosenthal, R; Shakarji, C M

    2001-01-01

    Our high technology society continues to rely more and more upon sophisticated measurements, technical standards, and associated testing activities. This was true for the industrial society of the 20th century and remains true for the information society of the 21st century. Over the last half of the 20th century, information technology (IT) has been a powerful agent of change in almost every sector of the economy. The complexity and rapidly changing nature of IT have presented unique technical challenges to the National Institute of Standards and Technology (NIST) and to the scientific measurement community in developing a sound measurement and testing infrastructure for IT. This measurement and testing infrastructure for the important non-physical and non-chemical properties associated with complex IT systems is still in an early stage of development. This paper explains key terms and concepts of IT metrology, briefly reviews the history of the National Bureau of Standards/National Institute of Standards and Technology (NBS/NIST) in the field of IT, and reviews NIST's current capabilities and work in measurement and testing for IT. It concludes with a look at what is likely to occur in the field of IT over the next ten years and what metrology roles NIST is likely to play.

  12. Boron-10 ABUNCL Prototype Models And Initial Active Testing

    SciTech Connect

    Kouzes, Richard T.; Ely, James H.; Lintereur, Azaree T.; Siciliano, Edward R.

    2013-04-23

    The Department of Energy Office of Nuclear Safeguards and Security (NA-241) is supporting the project Coincidence Counting With Boron-Based Alternative Neutron Detection Technology at Pacific Northwest National Laboratory (PNNL) for the development of a 3He proportional counter alternative neutron coincidence counter. The goal of this project is to design, build and demonstrate a system based upon 10B-lined proportional tubes in a configuration typical for 3He-based coincidence counter applications. This report provides results from MCNPX model simulations and initial testing of the active mode variation of the Alternative Boron-Based Uranium Neutron Coincidence Collar (ABUNCL) design built by General Electric Reuter-Stokes. Initial experimental testing of the as-delivered passive ABUNCL was previously reported.

  13. Uranium Adsorption on Granular Activated Carbon – Batch Testing

    SciTech Connect

    Parker, Kent E.; Golovich, Elizabeth C.; Wellman, Dawn M.

    2013-09-01

    The uranium adsorption performance of two activated carbon samples (Tusaar Lot B-64, Tusaar ER2-189A) was tested using unadjusted source water from well 299-W19-36. These batch tests support ongoing performance optimization efforts to use the best material for uranium treatment in the Hanford Site 200 West Area groundwater pump-and-treat system. A linear response of uranium loading as a function of the solution-to-solid ratio was observed for both materials. Kd values ranged from ~380,000 to >1,900,000 ml/g for the B-64 material and ~200,000 to >1,900,000 ml/g for the ER2-189A material. Uranium loading values ranged from 10.4 to 41.6 μg/g for the two Tusaar materials.

  14. Utilisation of Wearable Computing for Space Programmes Test Activities Optimasation

    NASA Astrophysics Data System (ADS)

    Basso, V.; Lazzari, D.; Alemanni, M.

    2004-08-01

    New technologies are assuming a relevant importance in the Space business domain also in the Assembly Integration and Test (AIT) activities allowing process optimization and capability that were unthinkable only few years ago. This paper has the aim to describe Alenia Spazio (ALS) gained experience on the remote interaction techniques as a results of collaborations established both on European Communities (EC) initiatives, with Alenia Aeronautica (ALA) and Politecnico of Torino (POLITO). The H/W and S/W components performances increase and costs reduction due to the home computing massive utilization (especially demanded by the games business) together with the network technology possibility (offered by the web as well as the hi-speed links and the wireless communications) allow today to re-think the traditional AIT process activities in the light of the multimedia data exchange: graphical, voice video and by sure more in the future. Aerospace business confirm its innovation vocation which in the year '80 represents the cradle of the CAD systems and today is oriented to the 3D data visualization/ interaction technologies and remote visualisation/ interaction in collaborative way on a much more user friendly bases (i.e. not for specialists). Fig. 1 collects AIT extended scenario studied and adopted by ALS in these years. ALS experimented two possibilities of remote visualization/interaction: Portable [e.g. Fig.2 Personal Digital Assistant (PDA), Wearable] and walls (e.g.VR-Lab) screens as both 2D/3D visualisation and interaction devices which could support many types of traditional (mainly based on EGSE and PDM/CAD utilisation/reports) company internal AIT applications: 1. design review support 2. facility management 3. storage management 4. personnel training 5. integration sequences definition 6. assembly and test operations follow up 7. documentation review and external access to AIT activities for remote operations (e.g. tele-testing) EGSE Portable Clean room

  15. Chemistry Game Shows

    NASA Astrophysics Data System (ADS)

    Campbell, Susan; Muzyka, Jennifer

    2002-04-01

    We present a technological improvement to the use of game shows to help students review for tests. Our approach uses HTML files interpreted with a browser on a computer attached to an LCD projector. The HTML files can be easily modified for use of the game in a variety of courses.

  16. Standards Development Activities at White Sands Test Facility

    NASA Technical Reports Server (NTRS)

    Baker, D. L.; Beeson, H. D.; Saulsberry, R. L.; Julien, H. L.; Woods, S. S.

    2003-01-01

    The development of standards and standard activities at the JSC White Sands Test Facility (WSTF) has been expanded to include the transfer of technology and standards to voluntary consensus organizations in five technical areas of importance to NASA. This effort is in direct response to the National Technology Transfer Act designed to accelerate transfer of technology to industry and promote government-industry partnerships. Technology transfer is especially important for WSTF, whose longterm mission has been to develop and provide vital propellant safety and hazards information to aerospace designers, operations personnel, and safety personnel. Meeting this mission is being accomplished through the preparation of consensus guidelines and standards, propellant hazards analysis protocols, and safety courses for the propellant use of hydrogen, oxygen, and hypergols, as well as the design and inspection of spacecraft pressure vessels and the use of pyrovalves in spacecraft propulsion systems. The overall WSTF technology transfer program is described and the current status of technology transfer activities are summarized.

  17. Trabectedin and its C subunit modified analogue PM01183 attenuate nucleotide excision repair and show activity toward platinum-resistant cells.

    PubMed

    Soares, Daniele G; Machado, Miriana S; Rocca, Céline J; Poindessous, Virginie; Ouaret, Djamila; Sarasin, Alain; Galmarini, Carlos M; Henriques, João A P; Escargueil, Alexandre E; Larsen, Annette K

    2011-08-01

    PM01183 is a novel marine-derived covalent DNA binder in clinical development. PM01183 is structurally similar to trabectedin (yondelis, ecteinascidin-743) except for the C subunit, and this modification is accompanied by different pharmacokinetics in cancer patients. We here characterize the interaction of PM01183 with the nucleotide excision repair (NER) pathway in comparison with trabectedin. Our results show for the first time that although neither PM01183 nor trabectedin is repaired by NER, both compounds are able to interfere with the NER machinery thereby attenuating the repair of specific NER substrates. We further show that the NER activity is increased in 3 of 4 cellular models with acquired resistance to cisplatin or oxaliplatin, confirming the involvement of NER in the resistance to platinum derivatives. Importantly, both PM01183 and trabectedin show unchanged or even enhanced activity toward all 4 cisplatin- and oxaliplatin-resistant cell lines. We finally show that combinations of PM01183 and cisplatin were mostly synergistic toward both parental and cisplatin-resistant ovarian carcinoma cells as indicated by Chou and Talalay analysis. These data show that the C subunit of trabectedin can be subjected to at least some structural modifications without loss of activity or NER interaction. While PM01183 and trabectedin appear functionally similar in cellular models, it is likely that the differences in pharmacokinetics may allow different dosing and scheduling of PM01183 in the clinic that could lead to novel and/or increased antitumor activity. Taken together, our results provide a mechanistic basis to support clinical trials of PM01183 alone or in combination with cisplatin.

  18. Shuttle active thermal control system development testing. Volume 2: Modular radiator system tests

    NASA Technical Reports Server (NTRS)

    Scheps, P. B.; Howell, H. R.; Voss, F. E.

    1973-01-01

    Tests were designed to investigate the validity of the "modular" approach to space radiator system design for space shuttle and future applications by gathering performance data on various systems comprised of different numbers of identical panels, subject to nominal and extreme heat loads and environments. Both one-sided and two-sided radiation was tested, and engineering data was gathered on simulated low a/e coatings and system response to changes in outlet temperature control point. The results of the testing showed system stability throughout nominal orbital transients, unrealistically skewed environments, freeze-thaw transients, and rapid changes in outlet temperature control point. Various alternative panel plumbing arrangements were tested with no significant changes in performance being observed. With the MRS panels arranged to represent the shuttle baseline system, a maximum heat rejection of 76,600 Btu/hr was obtained in segmented tests under the expected worst case design environments. Testing of an alternate smaller two-sided radiation configuration yielded a maximum heat rejection of 52,931 Btu/hr under the maximum design environments.

  19. Antidepressant-like activity of liposomal formulation containing nimodipine treatment in the tail suspension test, forced swim test and MAOB activity in mice.

    PubMed

    Moreno, Lina Clara Gayoso E Almendra Ibiapina; Rolim, Hercília Maria Lins; Freitas, Rivelilson Mendes; Santos-Magalhães, Nereide Stela

    2016-09-01

    Previous studies have shown that intracellular calcium ion dysfunction may be an etiological factor in affective illness. Nimodipine (NMD) is a Ca(2+) channel blocker that has been extensively investigated for therapy of central nervous system (CNS) disorders. In this work, we have evaluated the antidepressant-like activity of nimodipine encapsulated into liposomes (NMD-Lipo) in mice through tail suspension and forced swim assays, as well as MAOB activity. During the tail suspension test, the administration of NMD-Lipo at 0.1, 1 and 10mg/kg was able to promote a reduction in the immobility time of animals greater than the positive control (imipramine). In the forced swim test, the immobility time of mice treated with NMD-Lipo was reduced. This reduction was significantly greater than that found in the animals treated with imipramine and paroxetine. This may suggest that NMD-Lipo provides more antidepressant-like activity than in positive controls. The groups that received a combination of liposomal NMD and antidepressant drugs showed lower immobility time than the groups, which were treated only with imipramine or paroxetine. The mice treated with the combination of NMD-Lipo and reserpine presented an increase in the time of immobility compared with animals treated only with NMD-Lipo. There was a significant decrease in MAOB activity in animals treated with NMD-Lipo compared with untreated animals. The results of the tail suspension test, forced swim test and MAOB activity suggested that the antidepressant activity of NMD-Lipo may be related to an increase in the cerebral monoamine concentrations.

  20. External validation and prediction employing the predictive squared correlation coefficient test set activity mean vs training set activity mean.

    PubMed

    Schüürmann, Gerrit; Ebert, Ralf-Uwe; Chen, Jingwen; Wang, Bin; Kühne, Ralph

    2008-11-01

    The external prediction capability of quantitative structure-activity relationship (QSAR) models is often quantified using the predictive squared correlation coefficient, q (2). This index relates the predictive residual sum of squares, PRESS, to the activity sum of squares, SS, without postprocessing of the model output, the latter of which is automatically done when calculating the conventional squared correlation coefficient, r (2). According to the current OECD guidelines, q (2) for external validation should be calculated with SS referring to the training set activity mean. Our present findings including a mathematical proof demonstrate that this approach yields a systematic overestimation of the prediction capability that is triggered by the difference between the training and test set activity means. Example calculations with three regression models and data sets taken from literature show further that for external test sets, q (2) based on the training set activity mean may become even larger than r (2). As a consequence, we suggest to always use the test set activity mean when quantifying the external prediction capability through q (2) and to revise the respective OECD guidance document accordingly. The discussion includes a comparison between r (2) and q (2) value ranges and the q (2) statistics for cross-validation.

  1. A follow-up study on three caries activity tests.

    PubMed

    Shi, Sizhen; Deng, Qing; Hayashi, Yoshihiro; Yakushiji, Masashi; Machida, Yukio; Liang, Qin

    2003-01-01

    The purpose of this research was to study the efficacy of three CAT's (Dentocult SM, Dentocult LB and Dentobuff Strip) in revealing caries condition and predicting caries progress, and provide a reference for application by comparing the three tests. Oral condition and results of the three CAT's of 82 children aged 3 to 4 were recorded and followed up. The examination was checked again two years later. The caries incidence, dft and CSI data from the two examinations were analyzed statistically. The results were that each Dentocult SM degree showed significant variances in incidence rate, as did the dft and CSI results in the second examination. The dft and CSI of both examinations exhibited a high degree of statistical significance. The same may be said of the Dentocult LB findings for the two years. No noticeable variances in caries incidence rate, dft and CSI from the Dentobuff Strip test were observed in both years' study, nor was there any statistical significance drawn from the findings, except for those of the second exam. No gender differences were observed in the distribution by degree with the three CATs The conclusion is that Dentocult SM is the best of the three tests for the diagnosis of the presence of caries and prognosis of its progress, Dentocult LB is second best whereas the Dentobuff Strip shows no detection capability. The findings serve as an application reference.

  2. A GPBAR1 (TGR5) Small Molecule Agonist Shows Specific Inhibitory Effects on Myeloid Cell Activation In Vitro and Reduces Experimental Autoimmune Encephalitis (EAE) In Vivo

    PubMed Central

    Lewis, Nuruddeen D.; Patnaude, Lori A.; Pelletier, Josephine; Souza, Donald J.; Lukas, Susan M.; King, F. James; Hill, Jonathan D.; Stefanopoulos, Dimitria E.; Ryan, Kelli; Desai, Sudha; Skow, Donna; Kauschke, Stefan G.; Broermann, Andre; Kuzmich, Daniel; Harcken, Christian; Hickey, Eugene R.; Modis, Louise K.

    2014-01-01

    GPBAR1 is a G protein-coupled receptor that is activated by certain bile acids and plays an important role in the regulation of bile acid synthesis, lipid metabolism, and energy homeostasis. Recent evidence suggests that GPBAR1 may also have important effects in reducing the inflammatory response through its expression on monocytes and macrophages. To further understand the role of GPBAR1 in inflammation, we generated a novel, selective, proprietary GPBAR1 agonist and tested its effectiveness at reducing monocyte and macrophage activation in vitro and in vivo. We have used this agonist, together with previously described agonists to study agonism of GPBAR1, and shown that they can all induce cAMP and reduce TLR activation-induced cytokine production in human monocytes and monocyte-derived macrophages in vitro. Additionally, through the usage of RNA sequencing (RNA-Seq), we identified a select set of genes that are regulated by GPBAR1 agonism during LPS activation. To further define the in vivo role of GPBAR1 in inflammation, we assessed GPBAR1 expression and found high levels on circulating mouse monocytes. Agonism of GPBAR1 reduced LPS-induced cytokine production in mouse monocytes ex vivo and serum cytokine levels in vivo. Agonism of GPBAR1 also had profound effects in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis, where monocytes play an important role. Mice treated with the GPBAR1 agonist exhibited a significant reduction in the EAE clinical score which correlated with reduced monocyte and microglial activation and reduced trafficking of monocytes and T cells into the CNS. These data confirm the importance of GPBAR1 in controlling monocyte and macrophage activation in vivo and support the rationale for selective agonists of GPBAR1 in the treatment of inflammatory diseases. PMID:24967665

  3. Complex Parts, Complex Data: Why You Need to Understand What Radiation Single Event Testing Data Does and Doesn't Show and the Implications Thereof

    NASA Technical Reports Server (NTRS)

    LaBel, Kenneth A.; Berg, Melanie D.

    2015-01-01

    Electronic parts (integrated circuits) have grown in complexity such that determining all failure modes and risks from single particle event testing is impossible. In this presentation, the authors will present why this is so and provide some realism on what this means. Its all about understanding actual risks and not making assumptions.

  4. Marine Mammal Active Sonar Test 2004 (MAST 2004)

    NASA Astrophysics Data System (ADS)

    Stein, Peter J.; Vandiver, Amy; Edelson, Geoffrey S.; Frankel, Adam S.; Clark, Christopher W.

    2004-05-01

    The Marine Mammal Active Sonar Test was conducted in January 2004 off the central California coast during the gray whale migration. The purpose of the test was to collect data to significantly advance active sonar detection, classification, and tracking of marine mammals out to ranges of 1 mile. The R/V NEW HORIZON was moored in the migration path. Two different sonar systems operating between 210 and 220 dB were deployed off the vessel, the IMAPS phased array sonar system that operates from 20-30 kHz and the MAST mechanical system that uses rotating parabolic transducers operating from 30 to 40 kHz. Marine mammal observers were deployed on the bluffs overlooking the experiment and aboard the NEW HORIZON. The observers tracked the whales using electronic theodelites, providing ground truth for the sonar systems. They also looked for any severe reactions from the animals, and called for a shutdown if any marine mammals were observed within 100 m of the sonar. Here, we discuss the experiment and the results to date, including any reaction of the whales to the sonar system. We will also touch on the legal battle to conduct the experiment, and lessons learned.

  5. Indole-2-carboxamide-based MmpL3 Inhibitors Show Exceptional Antitubercular Activity in an Animal Model of Tuberculosis Infection.

    PubMed

    Stec, Jozef; Onajole, Oluseye K; Lun, Shichun; Guo, Haidan; Merenbloom, Benjamin; Vistoli, Giulio; Bishai, William R; Kozikowski, Alan P

    2016-07-14

    Our team had previously identified certain indolecarboxamides that represented a new chemical scaffold that showed promising anti-TB activity at both an in vitro and in vivo level. Based on mutational analysis using bacteria found resistant to one of these indolecarboxamides, we identified the trehalose monomycolate transporter MmpL3 as the likely target of these compounds. In the present work, we now further elaborate on the SAR of these compounds, which has led in turn to the identification of a new analog, 4,6-difluoro-N-((1R,2R,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]heptan-3-yl)-1H-indole-2-carboxamide (26), that shows excellent activity against drug-sensitive (MIC = 0.012 μM; SI ≥ 16000), multidrug-resistant (MDR), and extensively drug-resistant (XDR) Mycobacterium tuberculosis strains, has superior ADMET properties, and shows excellent activity in the TB aerosol lung infection model. Compound 26 is also shown to work in synergy with rifampin. Because of these properties, we believe that indolecarboxamide 26 is a possible candidate for advancement to human clinical trials.

  6. Showing What They Know

    ERIC Educational Resources Information Center

    Cech, Scott J.

    2008-01-01

    Having students show their skills in three dimensions, known as performance-based assessment, dates back at least to Socrates. Individual schools such as Barrington High School--located just outside of Providence--have been requiring students to actively demonstrate their knowledge for years. The Rhode Island's high school graduating class became…

  7. The Ozone Show.

    ERIC Educational Resources Information Center

    Mathieu, Aaron

    2000-01-01

    Uses a talk show activity for a final assessment tool for students to debate about the ozone hole. Students are assessed on five areas: (1) cooperative learning; (2) the written component; (3) content; (4) self-evaluation; and (5) peer evaluation. (SAH)

  8. What Do Maps Show?

    ERIC Educational Resources Information Center

    Geological Survey (Dept. of Interior), Reston, VA.

    This curriculum packet, appropriate for grades 4-8, features a teaching poster which shows different types of maps (different views of Salt Lake City, Utah), as well as three reproducible maps and reproducible activity sheets which complement the maps. The poster provides teacher background, including step-by-step lesson plans for four geography…

  9. German National Galileo Public Regulated Service (PRS) Testing Activities

    NASA Astrophysics Data System (ADS)

    Habrich, Heinz; Söhne, Wolfgang

    2013-04-01

    The European Global Navigation System (GNSS) Galileo is going to be established in the near future. Currently, four satellites are in place forming the In-Orbit-Testing (IOT) phase. Within the next years, the constellation will be filled. Full Operational Capability (FOC) will be reached 2019. Beside the Open Service (OS) which is comparable to other OS of existing GNSS, e.g., GPS C/A, there is a so-called Public Regulated Service (PRS) included in the IOT satellites already. The PRS will have improved robustness, i.e. robust signals which will be resistant against involuntary interferences, jamming and spoofing. The PRS signal is encrypted and there will be a restricted access to authorized users, e.g. safety and emergency services, authorities with security task, critical infrastructure organizations etc. The access to the PRS which will be controlled through a special key management will be managed and supervised within the European Union (EU) Member States (MS) by national authorities, the Competent PRS Authority (CPA). But a set of Common Minimum Standards (CMS) will define the minimum requirements applicable to each PRS participant. Nevertheless, each MS is responsible for its national key management. This presentation will inform about the testing activities for Galileo PRS in Germany. The coarse concept for the testing is explained, the schedule is outlined. Finally, the paper will formulate some expectations to the Galileo PRS, e.g. for international cooperation.

  10. Test and theory for piezoelectric actuator-active vibration control of rotating machinery

    NASA Technical Reports Server (NTRS)

    Palazzolo, A. B.; Lin, R. R.; Alexander, R. M.; Kascak, A. F.; Montague, J.

    1989-01-01

    The application of piezoelectric actuators for active vibration control (AVC) of rotating machinery is examined. Theory is derived and the resulting predictions are shown to agree closely with results of tests performed on an air turbine driven-overhung rotor. The test results show significant reduction in unbalance, transient and sub-synchronous responses. Results from a 30-hour endurance test support the AVD system reliability. Various aspects of the electro-mechanical stability of the control system are also discussed and illustrated. Finally, application of the AVC system to an actual jet engine is discussed.

  11. Diffuse large B-cell lymphoma with concurrent high MYC and BCL2 expression shows evidence of active B-cell receptor signaling by quantitative immunofluorescence

    PubMed Central

    Kovach, Alexandra E.; Le, Long P.; Feng, Derek; Baxter, Richard H. G.; Sohani, Aliyah R.

    2017-01-01

    B-cell receptor (BCR)-mediated signaling plays an important role in the pathogenesis of a subset of diffuse large B-cell lymphoma (DLBCL), and novel agents targeting this pathway are now in clinical use. We have previously identified a signature of active BCR signaling on formalin-fixed paraffin-embedded specimens using quantitative immunofluorescence, allowing for identification of patients who might benefit from anti-BCR therapies. We sought to characterize the clinicopathologic significance of active BCR signaling in DLBCL by correlating measures of signaling intensity with clinical features and various tumor cell characteristics. High MYC and concurrent high MYC and BCL2 double-expression was positively correlated with individual markers of active BCR signaling and cases with MYC/BCL2 double-expression showed overall greater BCR activation compared to cases lacking double-expression. Our findings suggest that the BCR signaling pathway may be more active in MYC/BCL2 double-expressor DLBCL and may represent a rational therapeutic target in this aggressive DLBCL subgroup. PMID:28212447

  12. Laser active thermography for non-destructive testing

    NASA Astrophysics Data System (ADS)

    Semerok, A.; Grisolia, C.; Fomichev, S. V.; Thro, P.-Y.

    2013-11-01

    Thermography methods have found their applications in different fields of human activity. The non-destructive feature of these methods along with the additional advantage by automated remote control and tests of nuclear installations without personnel attendance in the contaminated zone are of particular interest. Laser active pyrometry and laser lock-in thermography for in situ non-destructive characterization of micrometric layers on graphite substrates from European tokamaks were under extensive experimental and theoretical studies in CEA (France). The studies were aimed to obtain layer characterization with cross-checking the layer thermal contact coefficients determined by active laser pyrometry and lock-in thermography. The experimental installation comprised a Nd-YAG pulsed repetition rate laser (1 Hz - 10 kHz repetition rate frequency, homogeneous spot) and a home-made pyrometer system based on two pyrometers for the temperature measurements in 500 - 2600 K range. For both methods, the layer characterization was provided by the best fit of the experimental results and simulations. The layer thermal contact coefficients determined by both methods were quite comparable. Though there was no gain in the measurements accuracy, lock-in measurements have proved their advantage as being much more rapid. The obtained experimental and theoretical results are presented. Some practical applications and possible improvements of the methods are discussed.

  13. The 46 kDa dimeric protein from Variovorax paradoxus shows faster methotrexate degrading activity in its nanoform compare to the native enzyme.

    PubMed

    Bayineni, Venkata Krishna; Venkatesh, Krishna; Sahu, Chandan Kumar; Kadeppagari, Ravi-Kumar

    2016-04-01

    Methotrexate degrading enzymes are required to overcome the toxicity of the methotrexate while treating the cancer. The enzyme from Variovorax paradoxus converts the methotrexate in to non toxic products. Methotrexate degrading enzyme from V. paradoxus is a dimeric protein with a molecular mass of 46 kDa and it acts on casein and gelatin. This enzyme is optimally active at pH 7.5 and 40°C and nanoparticles of this enzyme were prepared by desolvation-crosslinking method. Enzyme nanoparticles could degrade methotrexate faster than the native enzyme and they show lower Km compare to the native enzyme. Enzyme nanoparticles show better thermostability and they were stable for much longer time in the serum compare to the native enzyme. Enzyme nanoparticles show better functionality than the native enzyme while clearing the methotrexate added to the serum suggesting their advantage over the native enzyme for the therapeutic and biotechnological applications.

  14. B-Ring-Aryl Substituted Luotonin A Analogues with a New Binding Mode to the Topoisomerase 1-DNA Complex Show Enhanced Cytotoxic Activity

    PubMed Central

    González-Ruiz, Víctor; Pascua, Irene; Fernández-Marcelo, Tamara; Ribelles, Pascual; Bianchini, Giulia; Sridharan, Vellaisamy; Iniesta, Pilar; Ramos, M. Teresa; Olives, Ana I.; Martín, M. Antonia; Menéndez, J. Carlos

    2014-01-01

    Topoisomerase 1 inhibition is an important strategy in targeted cancer chemotherapy. The drugs currently in use acting on this enzyme belong to the family of the camptothecins, and suffer severe limitations because of their low stability, which is associated with the hydrolysis of the δ-lactone moiety in their E ring. Luotonin A is a natural camptothecin analogue that lacks this functional group and therefore shows a much-improved stability, but at the cost of a lower activity. Therefore, the development of luotonin A analogues with an increased potency is important for progress in this area. In the present paper, a small library of luotonin A analogues modified at their A and B rings was generated by cerium(IV) ammonium nitrate-catalyzed Friedländer reactions. All analogues showed an activity similar or higher than the natural luotonin A in terms of topoisomerase 1 inhibition and some compounds had an activity comparable to that of camptothecin. Furthermore, most compounds showed a better activity than luotonin A in cell cytotoxicity assays. In order to rationalize these results, the first docking studies of luotonin-topoisomerase 1-DNA ternary complexes were undertaken. Most compounds bound in a manner similar to luotonin A and to standard topoisomerase poisons such as topotecan but, interestingly, the two most promising analogues, bearing a 3,5-dimethylphenyl substituent at ring B, docked in a different orientation. This binding mode allows the hydrophobic moiety to be shielded from the aqueous environment by being buried between the deoxyribose belonging to the G(+1) guanine and Arg364 in the scissile strand and the surface of the protein and a hydrogen bond between the D-ring carbonyl and the basic amino acid. The discovery of this new binding mode and its associated higher inhibitory potency is a significant advance in the design of new topoisomerase 1 inhibitors. PMID:24830682

  15. 40-Hz EEG activity during hypnotic induction and hypnotic testing.

    PubMed

    DePascalis, V; Penna, P M

    1990-04-01

    The present study evaluates changes in left and right 40-Hz EEG production for 19 high and 20 low hypnotizable female Ss during the hypnotic induction and the administration of the Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C) of the Weitzenhoffer and Hilgard (1962). Scalp recorded 40-Hz EEG density was obtained from the middle of the O1-P3-T5 and O2-P4-T6 triangles. As the hypnotic induction proceeded, high hypnotizable Ss exhibited a shift to greater right-hemisphere activity as compared to a waking-state rest condition. In contrast, low hypnotizable Ss, showed a reduction in left- and right-hemisphere activity. No differences between groups for SHSS:C ideomotor items were observed. A main effect for Hypnotizability among SHSS:C imaginative items was found. A Hypnotizability x Hemisphere x Trial interaction was found for both sensory distortion and imaginative SHSS:C items. A comparison was made between low versus high hypnotizable Ss of 40-Hz EEG activity while they passed the same item. The results of these comparisons indicate that differences in brain activity might be partially related to the differences between experiencing a hypnotic suggestion or failing to do so. Significant relationships between 40-Hz EEG production and hypnotizability and 40-Hz EEG production and level of amnesia were also found.

  16. Plasma renin-angiotensin system-regulating aminopeptidase activities are modified in early stage Alzheimer's disease and show gender differences but are not related to apolipoprotein E genotype.

    PubMed

    Puertas, María Del Carmen; Martínez-Martos, José Manuel; Cobo, Manuela; Lorite, Pedro; Sandalio, Rosa María; Palomeque, Teresa; Torres, María Isabel; Carrera-González, María Pilar; Mayas, María Dolores; Ramírez-Expósito, María Jesús

    2013-06-01

    Alterations in blood pressure and components of the renin-angiotensin system (RAS) contribute to the development and progression of Alzheimer's disease (AD), resulting in changes that can lead or contribute to cognitive decline. Aspartyl aminopeptidase (ASAP), aminopeptidase A (APA), aminopeptidase N (APN) and aminopeptidase B (APB) catabolise circulating angiotensins, whereas insulin-regulated aminopeptidase (IRAP) has been described as the AT4 receptor. We have found in AD patients a significant decrease of APA activity in men but not in women, and of APN, APB and IRAP in both genders, when compared with control subjects. No changes were found in ASAP activity. Also, APN, APB and IRAP but not APA correlated with the Mini-Mental test, but no relationship with APOE genotype was found. We conclude that several components of the RAS are modified in AD patients, with gender differences. Furthermore, ROC analysis indicates that APN, APB and IRAP activities could be useful non-invasive biomarkers of AD from the earliest stages.

  17. Do collaborative practical tests encourage student-centered active learning of gross anatomy?

    PubMed

    Green, Rodney A; Cates, Tanya; White, Lloyd; Farchione, Davide

    2016-05-06

    Benefits of collaborative testing have been identified in many disciplines. This study sought to determine whether collaborative practical tests encouraged active learning of anatomy. A gross anatomy course included a collaborative component in four practical tests. Two hundred and seven students initially completed the test as individuals and then worked as a team to complete the same test again immediately afterwards. The relationship between mean individual, team, and difference (between team and individual) test scores to overall performance on the final examination (representing overall learning in the course) was examined using regression analysis. The overall mark in the course increased by 9% with a decreased failure rate. There was a strong relationship between individual score and final examination mark (P < 0.001) but no relationship for team score (P = 0.095). A longitudinal analysis showed that the test difference scores increased after Test 1 which may be indicative of social loafing and this was confirmed by a significant negative relationship between difference score on Test 4 (indicating a weaker student) and final examination mark (P < 0.001). It appeared that for this cohort, there was little peer-to-peer learning occurring during the collaborative testing and that weaker students gained the benefit from team marks without significant active learning taking place. This negative outcome may be due to insufficient encouragement of the active learning strategies that were expected to occur during the collaborative testing process. An improved understanding of the efficacy of collaborative assessment could be achieved through the inclusion of questionnaire based data to allow a better interpretation of learning outcomes. Anat Sci Educ 9: 231-237. © 2015 American Association of Anatomists.

  18. Novel Antiviral Characteristics of Nanosized Copper(I) Iodide Particles Showing Inactivation Activity against 2009 Pandemic H1N1 Influenza Virus

    PubMed Central

    Sato, Tetsuya; Hayata, Taishi; Nagao, Tomokazu; Nakayama, Mikio; Nakayama, Tsuruo; Sugamata, Ryuichi; Suzuki, Kazuo

    2012-01-01

    We investigated the antiviral activity of nanosized copper(I) iodide (CuI) particles having an average size of 160 nm. CuI particles showed aqueous stability and generated hydroxyl radicals, which were probably derived from monovalent copper (Cu+). We confirmed that CuI particles showed antiviral activity against an influenza A virus of swine origin (pandemic [H1N1] 2009) by plaque titration assay. The virus titer decreased in a dose-dependent manner upon incubation with CuI particles, with the 50% effective concentration being approximately 17 μg/ml after exposure for 60 min. SDS-PAGE analysis confirmed the inactivation of the virus due to the degradation of viral proteins such as hemagglutinin and neuraminidase by CuI. Electron spin resonance (ESR) spectroscopy revealed that CuI generates hydroxyl radicals in aqueous solution, and radical production was found to be blocked by the radical scavenger N-acetylcysteine. Taken together, these findings indicate that CuI particles exert antiviral activity by generating hydroxyl radicals. Thus, CuI may be a useful material for protecting against viral attacks and may be suitable for applications such as filters, face masks, protective clothing, and kitchen cloths. PMID:22156433

  19. Mice repeatedly exposed to Group-A β-Haemolytic Streptococcus show perseverative behaviors, impaired sensorimotor gating, and immune activation in rostral diencephalon.

    PubMed

    Macrì, Simone; Ceci, Chiara; Onori, Martina Proietti; Invernizzi, Roberto William; Bartolini, Erika; Altabella, Luisa; Canese, Rossella; Imperi, Monica; Orefici, Graziella; Creti, Roberta; Margarit, Immaculada; Magliozzi, Roberta; Laviola, Giovanni

    2015-08-25

    Repeated exposure to Group-A β-Haemolytic Streptococcus (GAS) may constitute a vulnerability factor in the onset and course of pediatric motor disturbances. GAS infections/colonization can stimulate the production of antibodies, which may cross the blood brain barrier, target selected brain areas (e.g. basal ganglia), and exacerbate motor alterations. Here, we exposed developing SJL male mice to four injections with a GAS homogenate and evaluated the following domains: motor coordination; general locomotion; repetitive behaviors; perseverative responses; and sensorimotor gating (pre-pulse inhibition, PPI). To demonstrate that behavioral changes were associated with immune-mediated brain alterations, we analyzed, in selected brain areas, the presence of infiltrates and microglial activation (immunohistochemistry), monoamines (HPLC), and brain metabolites (in vivo Magnetic Resonance Spectroscopy). GAS-exposed mice showed increased repetitive and perseverative behaviors, impaired PPI, and reduced concentrations of serotonin in prefrontal cortex, a brain area linked to the behavioral domains investigated, wherein they also showed remarkable elevations in lactate. Active inflammatory processes were substantiated by the observation of infiltrates and microglial activation in the white matter of the anterior diencephalon. These data support the hypothesis that repeated GAS exposure may elicit inflammatory responses in brain areas involved in motor control and perseverative behavior, and result in phenotypic abnormalities.

  20. Mice repeatedly exposed to Group-A β-Haemolytic Streptococcus show perseverative behaviors, impaired sensorimotor gating, and immune activation in rostral diencephalon

    PubMed Central

    Macrì, Simone; Ceci, Chiara; Onori, Martina Proietti; Invernizzi, Roberto William; Bartolini, Erika; Altabella, Luisa; Canese, Rossella; Imperi, Monica; Orefici, Graziella; Creti, Roberta; Margarit, Immaculada; Magliozzi, Roberta; Laviola, Giovanni

    2015-01-01

    Repeated exposure to Group-A β-Haemolytic Streptococcus (GAS) may constitute a vulnerability factor in the onset and course of pediatric motor disturbances. GAS infections/colonization can stimulate the production of antibodies, which may cross the blood brain barrier, target selected brain areas (e.g. basal ganglia), and exacerbate motor alterations. Here, we exposed developing SJL male mice to four injections with a GAS homogenate and evaluated the following domains: motor coordination; general locomotion; repetitive behaviors; perseverative responses; and sensorimotor gating (pre-pulse inhibition, PPI). To demonstrate that behavioral changes were associated with immune-mediated brain alterations, we analyzed, in selected brain areas, the presence of infiltrates and microglial activation (immunohistochemistry), monoamines (HPLC), and brain metabolites (in vivo Magnetic Resonance Spectroscopy). GAS-exposed mice showed increased repetitive and perseverative behaviors, impaired PPI, and reduced concentrations of serotonin in prefrontal cortex, a brain area linked to the behavioral domains investigated, wherein they also showed remarkable elevations in lactate. Active inflammatory processes were substantiated by the observation of infiltrates and microglial activation in the white matter of the anterior diencephalon. These data support the hypothesis that repeated GAS exposure may elicit inflammatory responses in brain areas involved in motor control and perseverative behavior, and result in phenotypic abnormalities. PMID:26304458

  1. Erucin, a new promising cancer chemopreventive agent from rocket salads, shows anti-proliferative activity on human lung carcinoma A549 cells.

    PubMed

    Melchini, A; Costa, C; Traka, M; Miceli, N; Mithen, R; De Pasquale, R; Trovato, A

    2009-07-01

    Erucin (ER) is a dietary isothiocyanate present in cruciferous vegetables, such as rocket salads (Erucasativa Mill., Diplotaxis sp.), that has been recently considered a promising cancer chemopreventive phytochemical. Biological activity of ER was investigated on human lung adenocarcinoma A549 cells, analyzing its effects on molecular pathways involved in apoptosis and cell cycle arrest, such as PARP-1 cleavage, p53 and p21 protein expression. Our results show that ER affects the A549 cell proliferation, enhancing significantly p53 and p21 protein expression in a dose-dependent manner (p<0.001). PARP-1 cleavage occurs only after exposure to high concentrations of ER (50 microM), in accordance to previous studies showing similar bioactivity of other isothiocyanates (ITCs). Our study reports for the first time that the induction of p53, p21 and PARP-1 cleavage may participate in the anti-proliferative activity of ER in human lung adenocarcinoma A549 cells. Comparison of data with those obtained with the isothiocyanate sulforaphane (SF), structurally related to ER, underlines the strong relationship between structural analogy of ITCs and their biological activity. The ability of dietary compounds to modulate molecular mechanisms that affect cancer cell proliferation is certainly a key point of the cancer prevention potential by functional foods.

  2. Recovery Efficiency Test Project: Phase 1, Activity report

    SciTech Connect

    Overbey, W.K. Jr.; Carden, R.S.; Kirr, J.N.

    1987-04-01

    The recovery Efficiency Test well project addressed a number of technical issues. The primary objective was to determine the increased efficiency gas recovery of a long horizontal wellbore over that of a vertical wellbore and, more specifically, what improvements can be expected from inducing multiple hydraulic fractures from such a wellbore. BDM corporation located, planned, and drilled a long radius turn horizontal well in the Devonian shale Lower Huron section in Wayne County, West Virginia, demonstrating that state-of-the-art technology is capable of drilling such wells. BDM successfully tested drilling, coring, and logging in a horizontal well using air as the circulating medium; conducted reservoir modeling studies to protect flow rates and reserves in advance of drilling operations; observed two phase flow conditions in the wellbore not observed previously; cored a fracture zone which produced gas; observed that fractures in the core and the wellbore were not systematically spaced (varied from 5 to 68 feet in different parts of the wellbore); observed that highest gas show rates reported by the mud logger corresponded to zone with lowest fracture spacing (five feet) or high fracture frequency. Four and one-half inch casting was successfully installed in the borehole and was equipped to isolate the horizontal section into eight (8) zones for future testing and stimulation operations. 6 refs., 48 figs., 10 tabs.

  3. Evaluation of some biological tests as parameters for microbial activities in soils. II. Field investigations.

    PubMed

    Abd-El-Malek, Y; Monib, M; Rizk, S G; Shehata, S M

    1976-01-01

    Investigations were designed to study the effect of certain factors on the microbial activities in soil. The parameters, used as an index of the microbial activities, were total bacterial counts, dehydrogenase activity, oxidation of organic carbon, and CO2 evolved/7 days. Bahteem Farm clay soil was examined for determining the effects of depth, type of fertilization, and crop rotation on the microbial activities. It appears that the microbial activities, as indicated by the tested parameters, were more pronounced in the surface 15 cm-layer than in the subsurface layer (15-30 cm). Results of all the parameters tested showed markedly higher increases with farmyard manure than with nitrogenous fertilizer and in the control, without significant differences between the latter two. Moreover, the time of sampling had no effect on the results obtained for all parameters. Different types of rotations did not exert significant variation in total bacterial counts, though more than one crop per year increased the organic carbon content of soil and mostly the dehydrogenase activity, whereas the evolution of CO2 tended to decrease. At Gabal el-Asfar Farm, the effect of irrigation with sewage effluent, for long periods, on the microbial activities of sandy soil was investigated. Sewage water stimulated the total bacteria, raised the dehydrogenase activity, the organic carbon, and the production of CO2. In North El Tahreer and Mariut Sectors, the effect of both the type and age of cultivation on the microbial activities in the calcareous soils were examined. Cultivation raised the figures of all the tested parameters progressively with time of cultivation. It was also noticed that crops exerted more beneficial effects on microbial activities than orchards, and the dehydrogenase test was the most reliable parameter to reveal this fact.

  4. PP2A inhibition determines poor outcome and doxorubicin resistance in early breast cancer and its activation shows promising therapeutic effects

    PubMed Central

    Zazo, Sandra; Arpí, Oriol; Menéndez, Silvia; Manso, Rebeca; Lluch, Ana; Eroles, Pilar; Rovira, Ana; Albanell, Joan; García-Foncillas, Jesús; Madoz-Gúrpide, Juan; Rojo, Federico

    2015-01-01

    The protein phosphatase 2A (PP2A) is a key tumor suppressor which has emerged as a novel molecular target in some human cancers. Here, we show that PP2A inhibition is a common event in breast cancer and identified PP2A phosphorylation and deregulation SET and CIP2A as molecular contributing mechanisms to inactivate PP2A. Interestingly, restoration of PP2A activity after FTY720 treatment reduced cell growth, induced apoptosis and decreased AKT and ERK activation. Moreover, FTY720 led to PP2A activation then enhancing doxorubicin-induced antitumor effects both in vitro and in vivo. PP2A inhibition (CPscore: PP2A phosphorylation and/or CIP2A overexpression) was detected in 27% of cases (62/230), and associated with grade (p = 0.017), relapse (p < 0.001), negative estrogen (p < 0.001) and progesterone receptor expression (p < 0.001), HER2-positive tumors (p = 0.049), Ki-67 expression (p < 0.001), and higher AKT (p < 0.001) and ERK (p < 0.001) phosphorylation. Moreover, PP2A inhibition determined shorter overall (p = 0.006) and event-free survival (p = 0.003), and multivariate analysis confirmed its independent prognostic impact. Altogether, our results indicate that PP2A is frequently inactivated in breast cancer and determines worse outcome, and its restoration using PP2A activators represents an alternative therapeutic strategy in this disease. PMID:25726524

  5. PP2A inhibition determines poor outcome and doxorubicin resistance in early breast cancer and its activation shows promising therapeutic effects.

    PubMed

    Rincón, Raúl; Cristóbal, Ion; Zazo, Sandra; Arpí, Oriol; Menéndez, Silvia; Manso, Rebeca; Lluch, Ana; Eroles, Pilar; Rovira, Ana; Albanell, Joan; García-Foncillas, Jesús; Madoz-Gúrpide, Juan; Rojo, Federico

    2015-02-28

    The protein phosphatase 2A (PP2A) is a key tumor suppressor which has emerged as a novel molecular target in some human cancers. Here, we show that PP2A inhibition is a common event in breast cancer and identified PP2A phosphorylation and deregulation SET and CIP2A as molecular contributing mechanisms to inactivate PP2A. Interestingly, restoration of PP2A activity after FTY720 treatment reduced cell growth, induced apoptosis and decreased AKT and ERK activation. Moreover, FTY720 led to PP2A activation then enhancing doxorubicin-induced antitumor effects both in vitro and in vivo. PP2A inhibition (CPscore: PP2A phosphorylation and/or CIP2A overexpression) was detected in 27% of cases (62/230), and associated with grade (p = 0.017), relapse (p < 0.001), negative estrogen (p < 0.001) and progesterone receptor expression (p < 0.001), HER2-positive tumors (p = 0.049), Ki-67 expression (p < 0.001), and higher AKT (p < 0.001) and ERK (p < 0.001) phosphorylation. Moreover, PP2A inhibition determined shorter overall (p = 0.006) and event-free survival (p = 0.003), and multivariate analysis confirmed its independent prognostic impact. Altogether, our results indicate that PP2A is frequently inactivated in breast cancer and determines worse outcome, and its restoration using PP2A activators represents an alternative therapeutic strategy in this disease.

  6. Bacillus subtilis from Soybean Food Shows Antimicrobial Activity for Multidrug-Resistant Acinetobacter baumannii by Affecting the adeS Gene.

    PubMed

    Wang, Tieshan; Su, Jianrong

    2016-12-28

    Exploring novel antibiotics is necessary for multidrug-resistant pathogenic bacteria. Because the probiotics in soybean food have antimicrobial activities, we investigated their effects on multidrug-resistant Acinetobacter baumannii. Nineteen multidrug-resistant A. baumannii strains were clinifcally isolated as an experimental group and 11 multidrug-sensitive strains as controls. The growth rates of all bacteria were determined by using the analysis for xCELLigence Real-Time Cell. The combination of antibiotics showed synergistic effects on the strains in the control group but no effect on the strains in the experimental group. Efflux pump gene adeS was absent in all the strains from the control group, whereas it exists in all the strains from the experimental group. Furthermore, all the strains lost multidrug resistance when an adeS inhibitor was used. One strain of probiotics isolated from soybean food showed high antimicrobial activity for multidrug-resistant A. baumannii. The isolated strain belongs to Bacillus subtilis according to 16S RNA analysis. Furthermore, E. coli showed multidrug resistance when it was transformed with the adeS gene from A. baumannii whereas the resistant bacteria could be inhibited completely by isolated Bacillus subtilis. Thus, probiotics from soybean food provide potential antibiotics against multidrug-resistant pathogenic bacteria.

  7. Neutron activation analysis; A sensitive test for trace elements

    SciTech Connect

    Hossain, T.Z. . Ward Lab.)

    1992-01-01

    This paper discusses neutron activation analysis (NAA), an extremely sensitive technique for determining the elemental constituents of an unknown specimen. Currently, there are some twenty-five moderate-power TRIGA reactors scattered across the United States (fourteen of them at universities), and one of their principal uses is for NAA. NAA is procedurally simple. A small amount of the material to be tested (typically between one and one hundred milligrams) is irradiated for a period that varies from a few minutes to several hours in a neutron flux of around 10{sup 12} neutrons per square centimeter per second. A tiny fraction of the nuclei present (about 10{sup {minus}8}) is transmuted by nuclear reactions into radioactive forms. Subsequently, the nuclei decay, and the energy and intensity of the gamma rays that they emit can be measured in a gamma-ray spectrometer.

  8. Design, test, and evaluation of three active flutter suppression controllers

    NASA Technical Reports Server (NTRS)

    Adams, William M., Jr.; Christhilf, David M.; Waszak, Martin R.; Mukhopadhyay, Vivek; Srinathkumar, S.

    1992-01-01

    Three control law design techniques for flutter suppression are presented. Each technique uses multiple control surfaces and/or sensors. The first method uses traditional tools (such as pole/zero loci and Nyquist diagrams) for producing a controller that has minimal complexity and which is sufficiently robust to handle plant uncertainty. The second procedure uses linear combinations of several accelerometer signals and dynamic compensation to synthesize the model rate of the critical mode for feedback to the distributed control surfaces. The third technique starts with a minimum-energy linear quadratic Gaussian controller, iteratively modifies intensity matrices corresponding to input and output noise, and applies controller order reduction to achieve a low-order, robust controller. The resulting designs were implemented digitally and tested subsonically on the active flexible wing wind-tunnel model in the Langley Transonic Dynamics Tunnel. Only the traditional pole/zero loci design was sufficiently robust to errors in the nominal plant to successfully suppress flutter during the test. The traditional pole/zero loci design provided simultaneous suppression of symmetric and antisymmetric flutter with a 24-percent increase in attainable dynamic pressure. Posttest analyses are shown which illustrate the problems encountered with the other laws.

  9. The environmental chemical tributyltin chloride (TBT) shows both estrogenic and adipogenic activities in mice which might depend on the exposure dose

    SciTech Connect

    Penza, M.; Jeremic, M.; Marrazzo, E.; Maggi, A.; Ciana, P.; Rando, G.; Grigolato, P.G.; Di Lorenzo, D.

    2011-08-15

    Exposure during early development to chemicals with hormonal action may be associated with weight gain during adulthood because of altered body homeostasis. It is known that organotins affect adipose mass when exposure occurs during fetal development, although no knowledge of effects are available for exposures after birth. Here we show that the environmental organotin tributyltin chloride (TBT) exerts adipogenic action when peripubertal and sexually mature mice are exposed to the chemical. The duration and extent of these effects depend on the sex and on the dose of the compound, and the effects are relevant at doses close to the estimated human intake (0.5 {mu}g/kg). At higher doses (50-500 {mu}g/kg), TBT also activated estrogen receptors (ERs) in adipose cells in vitro and in vivo, based on results from acute and longitudinal studies in ERE/luciferase reporter mice. In 3T3-L1 cells (which have no ERs), transiently transfected with the ERE-dependent reporter plus or minus ER{alpha} or ER{beta}, TBT (in a dose range of 1-100 nM) directly targets each ER subtype in a receptor-specific manner through a direct mechanism mediated by ER{alpha} in undifferentiated preadipocytic cells and by ER{beta} in differentiating adipocytes. The ER antagonist ICI-182,780 inhibits this effect. In summary, the results of this work suggest that TBT is adipogenic at all ages and in both sexes and that it might be an ER activator in fat cells. These findings might help to resolve the apparent paradox of an adipogenic chemical being also an estrogen receptor activator by showing that the two apparently opposite actions are separated by the different doses to which the organism is exposed. - Research Highlights: > The environmental organotin tributyltin chloride shows dose-dependent estrogenic and adipogenic activities in mice. > The duration and extent of these effects depend on the sex and the dose of the compound. > The estrogenic and adipogenic effects of TBT occur at doses closed to

  10. The Loughborough Intermittent Shuttle Test: a field test that simulates the activity pattern of soccer.

    PubMed

    Nicholas, C W; Nuttall, F E; Williams, C

    2000-02-01

    The aims of this study were to describe and determine the test-retest reliability of an exercise protocol, the Loughborough Intermittent Shuttle Test (the LIST), which was designed to simulate the activity pattern characteristic of the game of soccer. The protocol consisted of two parts: Part A comprised a fixed period of variable-intensity shuttle running over 20 m; Part B consisted of continuous running, alternating every 20 m between 55% and 95% VO2max, until volitional fatigue. Seven trained games players (age 21.5+/-0.9 years, height 182+/-2 cm, body mass 80.1+/-3.6 kg, VO2max 59.0+/-1.9 ml x kg(-1) x min(-1); mean +/- s(x)) performed the test on two occasions (Trial 1 and Trial 2), at least 7 days apart, to determine the test-retest reliability of the sprint times and running capacity. The physiological and metabolic responses on both occasions were also monitored. The participants ingested water ad libitum during the first trial, and were then prescribed the same amount of water during the second trial. The 15 m sprint times during Trials 1 and 2 averaged 2.42+/-0.04 s and 2.43+/-0.04 s, respectively. Run time during Part B was 6.3+/-2.0 min for Trial 1 and 6.1+/-1.3 min for Trial 2. The 95% limits of agreement for sprint times and run times during Part B were -0.14 to 0.12 s and -3.19 to 2.16 min respectively. There were no differences between trials for heart rate, rating of perceived exertion, body mass change during exercise, or blood lactate and glucose concentrations during the test. Thus, we conclude that the sprint times and the Part B run times were reproducible within the limits previously stated. In addition, the activity pattern and the physiological and metabolic responses closely simulated the match demands of soccer.

  11. Tests of the Extension and Deadbolt Models of Integrin Activation*

    PubMed Central

    Zhu, Jieqing; Boylan, Brian; Luo, Bing-Hao; Newman, Peter J.; Springer, Timothy A.

    2007-01-01

    Despite extensive evidence that integrin conformational changes between bent and extended conformations regulate affinity for ligands, an alternative hypothesis has been proposed in which a “deadbolt” can regulate affinity for ligand in the absence of extension. Here, we tested both the deadbolt and the extension models. According to the deadbolt model, a hairpin loop in the β3 tail domain could act as a deadbolt to restrain the displacement of the β3 I domain β6-α7 loop and maintain integrin in the low affinity state. We found that mutating or deleting the β3 tail domain loop has no effect on ligand binding by either αIIbβ3 or αVβ3 integrins. In contrast, we found that mutations that lock integrins in the bent conformation with disulfide bonds resist inside-out activation induced by cytoplasmic domain mutation. Furthermore, we demonstrated that extension is required for accessibility to fibronectin but not smaller fragments. The data demonstrate that integrin extension is required for ligand binding during integrin inside-out signaling and that the deadbolt does not regulate integrin activation. PMID:17301049

  12. Rapid test for distinguishing membrane-active antibacterial agents.

    PubMed

    Prakash Singh, Maya

    2006-10-01

    In the search for antibacterial agents with a novel mode-of-action (MOA) many targeted cellular and cell-free assays are developed and used to screen chemical and natural product libraries. Frequently, hits identified by the primary screens include compounds with nonspecific activities that can affect the integrity and function of bacterial membrane. For a rapid dereplication of membrane-active compounds, a simple method was established using a commercially available Live/Dead(R) Bacterial Viability Kit. This method utilized two fluorescent nucleic acid stains, SYTO9 (stains all cells green) and propidium iodide (stains cells with damaged membrane red) for the drug-treated bacterial cells. The cells were then either examined visually by fluorescence microscopy or their fluorescence emissions were recorded using a multi-label plate reader set to measure emissions at two different wavelengths. The ratio of green versus red was compared to a standard curve indicating the percentage of live versus dead bacteria. Nine known antibiotics and 14 lead compounds from various antibacterial screens were tested with results consistent with their MOA.

  13. Assessment of CO₂ adsorption capacity on activated carbons by a combination of batch and dynamic tests.

    PubMed

    Balsamo, Marco; Silvestre-Albero, Ana; Silvestre-Albero, Joaquín; Erto, Alessandro; Rodríguez-Reinoso, Francisco; Lancia, Amedeo

    2014-05-27

    In this work, batch and dynamic adsorption tests are coupled for an accurate evaluation of CO2 adsorption performance of three different activated carbons (AC) obtained from olive stones by chemical activation followed by physical activation with CO2 at varying times (i.e., 20, 40, and 60 h). Kinetic and thermodynamic CO2 adsorption tests from simulated flue gas at different temperatures and CO2 pressures are carried out under both batch (a manometric equipment operating with pure CO2) and dynamic (a lab-scale fixed-bed column operating with a CO2/N2 mixture) conditions. The textural characterization of the AC samples shows a direct dependence of both micropore and ultramicropore volume on the activation time; hence, AC60 has the higher contribution. The adsorption tests conducted at 273 and 293 K showed that when CO2 pressure is lower than 0.3 bar, the lower the activation time, the higher CO2 adsorption capacity; a ranking of ω(eq)(AC20) > ω(eq)(AC40) > ω(eq)(AC60) can be exactly defined when T = 293 K. This result is likely ascribed to the narrower pore size distribution of the AC20 sample, whose smaller pores are more effective for CO2 capture at higher temperature and lower CO2 pressure, the latter representing operating conditions of major interest for decarbonation of flue gas effluent. Moreover, the experimental results obtained from dynamic tests confirm the results derived from the batch tests in terms of CO2 adsorption capacity. It is important to highlight the fact that the adsorption of N2 on the synthesized AC samples can be considered to be negligible. Finally, the importance of proper analysis for data characterization and adsorption experimental results is highlighted for the correct assessment of the CO2 removal performance of activated carbons at different CO2 pressures and operating temperatures.

  14. Whole scalp resting state EEG of oscillatory brain activity shows no parametric relationship with psychoacoustic and psychosocial assessment of tinnitus: A repeated measures study.

    PubMed

    Pierzycki, Robert H; McNamara, Adam J; Hoare, Derek J; Hall, Deborah A

    2016-01-01

    Tinnitus is a perception of sound that can occur in the absence of an external stimulus. A brief review of electroencephalography (EEG) and magnetoencephalography (MEG) literature demonstrates that there is no clear relationship between tinnitus presence and frequency band power in whole scalp or source oscillatory activity. Yet a preconception persists that such a relationship exists and that resting state EEG could be utilised as an outcome measure for clinical trials of tinnitus interventions, e.g. as a neurophysiological marker of therapeutic benefit. To address this issue, we first examined the test-retest correlation of EEG band power measures in tinnitus patients (n = 42). Second we examined the evidence for a parametric relationship between numerous commonly used tinnitus variables (psychoacoustic and psychosocial) and whole scalp EEG power spectra, directly and after applying factor reduction techniques. Test-retest correlation for both EEG band power measures and tinnitus variables were high. Yet we found no relationship between whole scalp EEG band powers and psychoacoustic or psychosocial variables. We conclude from these data that resting state whole scalp EEG should not be used as a biomarker for tinnitus and that greater caution should be exercised in regard to reporting of findings to avoid confirmation bias. The data was collected during a randomised controlled trial registered at ClinicalTrials.gov (Identifier: NCT01541969).

  15. Syringe test screening of microbial gas production activity: Cases denitrification and biogas formation.

    PubMed

    Østgaard, Kjetill; Kowarz, Viktoria; Shuai, Wang; Henry, Ingrid A; Sposob, Michal; Haugen, Hildegunn Hegna; Bakke, Rune

    2017-01-01

    Mass produced plastic syringes may be applied as vessels for cheap, simple and large scale batch culture testing. As illustrated for the cases of denitrification and of biogas formation, metabolic activity was monitored by direct reading of the piston movement due to the gas volume formed. Pressure buildup due to friction was shown to be moderate. A piston pull and slide back routine can be applied before recording gas volume to minimize experimental errors due to friction. Inoculum handling and activity may be conveniently standardized as illustrated by applying biofilm carriers. A robust set of positive as well as negative controls ("blanks") should be included to ensure quality of the actual testing. The denitrification test showed saturation response at increasing amounts of inoculum in the form of adapted moving bed biofilm reactor (MBBR) carriers, with well correlated nitrate consumption vs. gas volume formed. As shown, the denitrification test efficiently screened different inocula at standardized substrates. Also, different substrates were successfully screened and compared at standardized inocula. The biogas potential test showed efficient screening of different substrates with effects of relative amounts of carbohydrate, protein, fat. A second case with CO2 capture reclaimer waste as substrate demonstrated successful use of co-feeding to support waste treatment and how temperature effects on kinetics and stoichiometry can be observed. In total, syringe test screening of microbial gas production seems highly efficient at a low cost when properly applied.

  16. Modified high-density lipoproteins by artificial sweetener, aspartame, and saccharin, showed loss of anti-atherosclerotic activity and toxicity in zebrafish.

    PubMed

    Kim, Jae-Yong; Park, Ki-Hoon; Kim, Jihoe; Choi, Inho; Cho, Kyung-Hyun

    2015-01-01

    Safety concerns have been raised regarding the association of chronic consumption of artificial sweeteners (ASs) with metabolic disorders, especially in the heart and brain. There has been no information on the in vivo physiological effects of AS consumption in lipoprotein metabolism. High-dosage treatment (final 25, 50, and 100 mM) with AS (aspartame, acesulfame K, and saccharin) to human high-density lipoprotein (HDL) induced loss of antioxidant ability along with elevated atherogenic effects. Aspartame-treated HDL3 (final 100 mM) almost all disappeared due to putative proteolytic degradation. Aspartame- and saccharin-treated HDL3 showed more enhanced cholesteryl ester transfer activity, while their antioxidant ability was disappeared. Microinjection of the modified HDL3 exacerbated the inflammatory death in zebrafish embryos in the presence of oxLDL. These results show that AS treatment impaired the beneficial functions of HDL, resulting in loss of antioxidant and anti-atherogenic activities. These results suggest that aspartame and saccharin could be toxic to the human circulation system as well as embryonic development via impairment of lipoprotein function.

  17. C-terminal truncated cannabinoid receptor 1 coexpressed with G protein trimer in Sf9 cells exists in a precoupled state and shows constitutive activity.

    PubMed

    Chillakuri, Chandramouli Reddy; Reinhart, Christoph; Michel, Hartmut

    2007-12-01

    We have investigated the existence of a precoupled form of the distal C-terminal truncated cannabinoid receptor 1 (CB1-417) and heterotrimeric G proteins in a heterologous insect cell expression system. CB1-417 showed higher production levels than the full-length receptor. The production levels obtained in our expression system were double the values reported in the literature. We also observed that at least the distal C-terminus of the receptor was not involved in receptor dimerization, as was predicted in the literature. Using fluorescence resonance energy transfer, we found that CB1-417 and Galpha(i1)beta(1)gamma(2) proteins were colocalized in the cells. GTPgammaS binding assays with the Sf9 cell membranes containing CB1-417 and the G protein trimer showed that the receptor could constitutively activate the Galpha(i1) protein in the absence of agonists. A CB1-specific antagonist (SR 141716A) inhibited this constitutive activity of the truncated receptor. We found that the CB1-417/Galpha(i1)beta(1)gamma(2) complex could be solubilized from Sf9 cell membranes and coimmunoprecipitated. In this study, we have proven that the receptor and G proteins can be coexpressed in higher yields using Sf9 cells, and that the protein complex is stable in detergent solution. Thus, our system can be used to produce sufficient quantities of the protein complex to start structural studies.

  18. Catechins and procyanidins of Ginkgo biloba show potent activities towards the inhibition of β-amyloid peptide aggregation and destabilization of preformed fibrils.

    PubMed

    Xie, Haiyan; Wang, Jing-Rong; Yau, Lee-Fong; Liu, Yong; Liu, Liang; Han, Quan-Bin; Zhao, Zhongzhen; Jiang, Zhi-Hong

    2014-04-22

    Catechins and procyanidins, together with flavonoid glycosides and terpene trilactones, are three important categories of components in the standard extract of Ginkgo biloba leaves (EGb761). In this research, catechins and proanthocyanidins were found to exist in both the extract of Ginkgo leaves and Ginkgo products. By comparing with reference compounds, six of them were identified as (+)-catechin, (-)-epicatechin, (-)-gallocatechin, (-)-epigallocatechin and procyanidins B1 and B3. The activities of these polyphenols in the inhibition of Aβ42 aggregation and the destabilization of preformed fibrils were evaluated using biochemical assays, which showed that all six of the polyphenols, as well as a fraction of the extract of Ginkgo biloba leaves (EGb) containing catechins and procyanidins, exerted potent inhibitory activities towards Aβ42 aggregation and could also destabilize the performed fibrils. Catechins and procyanidins can therefore be regarded as the potent active constituents of EGb761 in terms of their inhibition of Aβ42 aggregation and destabilization of the fibrils. Although quantitative mass spectroscopic analysis revealed that the catechins and procyanidins are only present in low concentrations in EGb761, these components should be studied in greater detail because of their potent inhibitory effects towards Aβ42 aggregation and their ability to destabilize preformed fibrils, especially during the quality control of Ginkgo leaves and the manufacture of Ginkgo products.

  19. Polysaccharides from the Medicinal Mushroom Cordyceps taii Show Antioxidant and Immunoenhancing Activities in a D-Galactose-Induced Aging Mouse Model

    PubMed Central

    Xiao, Jian-Hui; Xiao, Dai-Min; Chen, Dai-Xiong; Xiao, Yu; Liang, Zong-Qi; Zhong, Jian-Jiang

    2012-01-01

    Cordyceps taii, an edible medicinal mushroom native to south China, is recognized as an unparalleled resource of healthy foods and drug discovery. In the present study, the antioxidant pharmacological properties of C. taii were systematically investigated. In vitro assays revealed the scavenging activities of the aqueous extract and polysaccharides of C. taii against various free radicals, that is, 1,1-diphenyl-2-picrylhydrazyl radical, hydroxyl radical, and superoxide anion radical. The EC50 values for superoxide anion-free radical ranged from 2.04 mg/mL to 2.49 mg/mL, which was at least 2.6-fold stronger than that of antioxidant thiourea. The polysaccharides also significantly enhanced the antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase) and markedly decreased the malondialdehyde production of lipid peroxidation in a D-galactose-induced aging mouse model. Interestingly, the immune function of the administration group was significantly boosted compared with the D-galactose-induced aging model group. Therefore, the C. taii polysaccharides possessed potent antioxidant activity closely associated with immune function enhancement and free radical scavenging. These findings suggest that the polysaccharides are a promising source of natural antioxidants and antiaging drugs. Consequently, a preliminary chemical investigation was performed using gas chromatography-mass spectroscopy and revealed that the polysaccharides studied were mainly composed of glucose, mannose, and galactose. Fourier-transform infrared spectra also showed characteristic polysaccharide absorption bands. PMID:22536281

  20. HAL/S-360 compiler test activity report

    NASA Technical Reports Server (NTRS)

    Helmers, C. T.

    1974-01-01

    The levels of testing employed in verifying the HAL/S-360 compiler were as follows: (1) typical applications program case testing; (2) functional testing of the compiler system and its generated code; and (3) machine oriented testing of compiler implementation on operational computers. Details of the initial test plan and subsequent adaptation are reported, along with complete test results for each phase which examined the production of object codes for every possible source statement.

  1. microRNA-454 shows anti-angiogenic and anti-metastatic activity in pancreatic ductal adenocarcinoma by targeting LRP6

    PubMed Central

    Fan, Yue; Shi, Chenye; Li, Tianyu; Kuang, Tiantao

    2017-01-01

    Our previous work has shown that microRNA-454 (miR-454) can inhibit the growth of pancreatic ductal adenocarcinoma (PDAC) by blocking the recruitment of bone marrow-derived macrophages. In the present study, we aimed to explore its role in the proliferation, invasion, and pro-angiogenic activity of PDAC cells in vitro and lung metastasis in vivo. PANC-1 and MiaPaCa-2 cells were transfected with a miR-454-expressing plasmid and tested for cell proliferation, colony formation, cell cycle distribution, invasion, and pro-angiogenic activity. The target gene(s) that mediated the action of miR-454 was identified. The effect of miR-454 overexpression on lung metastasis of PDAC was evaluated in nude mice. Of note, overexpression of miR-454 significantly inhibited PDAC cell proliferation and colony formation and arrests PDAC cells at the G2/M phase. Decreased invasiveness was observed in miR-454-overexpressing PDAC cells. Conditioned media from miR-454-overexpressing PANC-1 cells contained lower levels of vascular endothelial growth factor and had reduced capacity to induce endothelial cell tube-like structure formation. Mechanistically, miR-454 was found to target the mRNA of LRP6 and inhibit the activation of Wnt/β-catenin signaling in PDAC cells. Ectopic expression of LRP6 significantly reversed the suppressive effects of miR-454 on PDAC cells. In vivo studies confirmed that miR-454-overexpressing PANC-1 cells formed significantly less lung metastases than control cells. Altogether, miR-454 functions as a suppressor in tumor growth, angiogenesis, and metastasis in PDAC, likely through downregulation of LRP6. PMID:28123855

  2. Testing the applicability of rapid on-site enzymatic activity detection for surface water monitoring

    NASA Astrophysics Data System (ADS)

    Stadler, Philipp; Vogl, Wolfgang; Juri, Koschelnik; Markus, Epp; Maximilian, Lackner; Markus, Oismüller; Monika, Kumpan; Peter, Strauss; Regina, Sommer; Gabriela, Ryzinska-Paier; Farnleitner Andreas, H.; Matthias, Zessner

    2015-04-01

    On-site detection of enzymatic activities has been suggested as a rapid surrogate for microbiological pollution monitoring of water resources (e.g. using glucuronidases, galactosidases, esterases). Due to the possible short measuring intervals enzymatic methods have high potential as near-real time water quality monitoring tools. This presentation describes results from a long termed field test. For twelve months, two ColiMinder devices (Vienna Water Monitoring, Austria) for on-site determination of enzymatic activity were tested for stream water monitoring at the experimental catchment HOAL (Hydrological Open Air Laboratory, Center for Water Resource Systems, Vienna University of Technology). The devices were overall able to follow and reflect the diverse hydrological and microbiological conditions of the monitored stream during the test period. Continuous data in high temporal resolution captured the course of enzymatic activity in stream water during diverse rainfall events. The method also proofed sensitive enough to determine diurnal fluctuations of enzymatic activity in stream water during dry periods. The method was able to capture a seasonal trend of enzymatic activity in stream water that matches the results gained from Colilert18 analysis for E. coli and coliform bacteria of monthly grab samples. Furthermore the comparison of ColiMinder data with measurements gained at the same test site with devices using the same method but having different construction design (BACTcontrol, microLAN) showed consistent measuring results. Comparative analysis showed significant differences between measured enzymatic activity (modified fishman units and pmol/min/100ml) and cultivation based analyses (most probable number, colony forming unit). Methods of enzymatic activity measures are capable to detect ideally the enzymatic activity caused by all active target bacteria members, including VBNC (viable but nonculturable) while cultivation based methods cannot detect VBNC

  3. Cytokinin-Deficient Transgenic Arabidopsis Plants Show Multiple Developmental Alterations Indicating Opposite Functions of Cytokinins in the Regulation of Shoot and Root Meristem Activity

    PubMed Central

    Werner, Tomáš; Motyka, Václav; Laucou, Valérie; Smets, Rafaël; Van Onckelen, Harry; Schmülling, Thomas

    2003-01-01

    Cytokinins are hormones that regulate cell division and development. As a result of a lack of specific mutants and biochemical tools, it has not been possible to study the consequences of cytokinin deficiency. Cytokinin-deficient plants are expected to yield information about processes in which cytokinins are limiting and that, therefore, they might regulate. We have engineered transgenic Arabidopsis plants that overexpress individually six different members of the cytokinin oxidase/dehydrogenase (AtCKX) gene family and have undertaken a detailed phenotypic analysis. Transgenic plants had increased cytokinin breakdown (30 to 45% of wild-type cytokinin content) and reduced expression of the cytokinin reporter gene ARR5:GUS (β-glucuronidase). Cytokinin deficiency resulted in diminished activity of the vegetative and floral shoot apical meristems and leaf primordia, indicating an absolute requirement for the hormone. By contrast, cytokinins are negative regulators of root growth and lateral root formation. We show that the increased growth of the primary root is linked to an enhanced meristematic cell number, suggesting that cytokinins control the exit of cells from the root meristem. Different AtCKX-green fluorescent protein fusion proteins were localized to the vacuoles or the endoplasmic reticulum and possibly to the extracellular space, indicating that subcellular compartmentation plays an important role in cytokinin biology. Analyses of promoter:GUS fusion genes showed differential expression of AtCKX genes during plant development, the activity being confined predominantly to zones of active growth. Our results are consistent with the hypothesis that cytokinins have central, but opposite, regulatory functions in root and shoot meristems and indicate that a fine-tuned control of catabolism plays an important role in ensuring the proper regulation of cytokinin functions. PMID:14555694

  4. The environmental chemical tributyltin chloride (TBT) shows both estrogenic and adipogenic activities in mice which might depend on the exposure dose.

    PubMed

    Penza, M; Jeremic, M; Marrazzo, E; Maggi, A; Ciana, P; Rando, G; Grigolato, P G; Di Lorenzo, D

    2011-08-15

    Exposure during early development to chemicals with hormonal action may be associated with weight gain during adulthood because of altered body homeostasis. It is known that organotins affect adipose mass when exposure occurs during fetal development, although no knowledge of effects are available for exposures after birth. Here we show that the environmental organotin tributyltin chloride (TBT) exerts adipogenic action when peripubertal and sexually mature mice are exposed to the chemical. The duration and extent of these effects depend on the sex and on the dose of the compound, and the effects are relevant at doses close to the estimated human intake (0.5μg/kg). At higher doses (50-500μg/kg), TBT also activated estrogen receptors (ERs) in adipose cells in vitro and in vivo, based on results from acute and longitudinal studies in ERE/luciferase reporter mice. In 3T3-L1 cells (which have no ERs), transiently transfected with the ERE-dependent reporter plus or minus ERα or ERβ, TBT (in a dose range of 1-100nM) directly targets each ER subtype in a receptor-specific manner through a direct mechanism mediated by ERα in undifferentiated preadipocytic cells and by ERβ in differentiating adipocytes. The ER antagonist ICI-182,780 inhibits this effect. In summary, the results of this work suggest that TBT is adipogenic at all ages and in both sexes and that it might be an ER activator in fat cells. These findings might help to resolve the apparent paradox of an adipogenic chemical being also an estrogen receptor activator by showing that the two apparently opposite actions are separated by the different doses to which the organism is exposed.

  5. Hedgehog Signaling Pathway Is Active in GBM with GLI1 mRNA Expression Showing a Single Continuous Distribution Rather than Discrete High/Low Clusters

    PubMed Central

    Biswas, Nidhan K.; Rote, Sarang; Chatterjee, Uttara; Ghosh, Samarendra N.; Deb, Sumit; Saha, Suniti K.; Chowdhury, Anup K.; Ghosh, Subhashish; Rudin, Charles M.; Mukherjee, Ankur; Basu, Analabha; Dhara, Surajit

    2015-01-01

    Hedgehog (Hh) signaling pathway is a valid therapeutic target in a wide range of malignancies. We focus here on glioblastoma multiforme (GBM), a lethal malignancy of the central nervous system (CNS). By analyzing RNA-sequencing based transcriptomics data on 149 clinical cases of TCGA-GBM database we show here a strong correlation (r = 0.7) between GLI1 and PTCH1 mRNA expression—as a hallmark of the canonical Hh-pathway activity in this malignancy. GLI1 mRNA expression varied in 3 orders of magnitude among the GBM patients of the same cohort showing a single continuous distribution—unlike the discrete high/low-GLI1 mRNA expressing clusters of medulloblastoma (MB). When compared with MB as a reference, the median GLI1 mRNA expression in GBM appeared 14.8 fold lower than that of the “high-Hh” cluster of MB but 5.6 fold higher than that of the “low-Hh” cluster of MB. Next, we demonstrated statistically significant up- and down-regulation of GLI1 mRNA expressions in GBM patient-derived low-passage neurospheres in vitro by sonic hedgehog ligand-enriched conditioned media (shh-CM) and by Hh-inhibitor drug vismodegib respectively. We also showed clinically achievable dose (50 μM) of vismodegib alone to be sufficient to induce apoptosis and cell cycle arrest in these low-passage GBM neurospheres in vitro. Vismodegib showed an effect on the neurospheres, both by down-regulating GLI1 mRNA expression and by inducing apoptosis/cell cycle arrest, irrespective of their relative endogenous levels of GLI1 mRNA expression. We conclude from our study that this single continuous distribution pattern of GLI1 mRNA expression technically puts almost all GBM patients in a single group rather than discrete high- or low-clusters in terms of Hh-pathway activity. That is suggestive of therapies with Hh-pathway inhibitor drugs in this malignancy without a need for further stratification of patients on the basis of relative levels of Hh-pathway activity among them. PMID:25775002

  6. Novel Gal3 proteins showing altered Gal80p binding cause constitutive transcription of Gal4p-activated genes in Saccharomyces cerevisiae.

    PubMed Central

    Blank, T E; Woods, M P; Lebo, C M; Xin, P; Hopper, J E

    1997-01-01

    Gal4p-mediated activation of galactose gene expression in Saccharomyces cerevisiae normally requires both galactose and the activity of Gal3p. Recent evidence suggests that in cells exposed to galactose, Gal3p binds to and inhibits Ga180p, an inhibitor of the transcriptional activator Gal4p. Here, we report on the isolation and characterization of novel mutant forms of Gal3p that can induce Gal4p activity independently of galactose. Five mutant GAL3(c) alleles were isolated by using a selection demanding constitutive expression of a GAL1 promoter-driven HIS3 gene. This constitutive effect is not due to overproduction of Gal3p. The level of constitutive GAL gene expression in cells bearing different GAL3(c) alleles varies over more than a fourfold range and increases in response to galactose. Utilizing glutathione S-transferase-Gal3p fusions, we determined that the mutant Gal3p proteins show altered Gal80p-binding characteristics. The Gal3p mutant proteins differ in their requirements for galactose and ATP for their Gal80p-binding ability. The behavior of the novel Gal3p proteins provides strong support for a model wherein galactose causes an alteration in Gal3p that increases either its ability to bind to Gal80p or its access to Gal80p. With the Gal3p-Gal80p interaction being a critical step in the induction process, the Gal3p proteins constitute an important new reagent for studying the induction mechanism through both in vivo and in vitro methods. PMID:9111326

  7. Identification of prefrontal cortex (BA10) activation while performing Stroop test using diffuse optical tomography

    NASA Astrophysics Data System (ADS)

    Khadka, Sabin; Chityala, Srujan R.; Tian, Fenghua; Liu, Hanli

    2011-03-01

    Stroop test is commonly used as a behavior-testing tool for psychological examinations that are related to attention and cognitive control of the human brain. Studies have shown activations in Broadmann area 10 (BA10) of prefrontal cortex (PFC) during attention and cognitive process. The use of diffuse optical tomography (DOT) for human brain mapping is becoming more prevalent. In this study we expect to find neural correlates between the performed cognitive tasks and hemodynamic signals detected by a DOT system. Our initial observation showed activation of oxy-hemoglobin concentration in BA 10, which is consistent with some results seen by positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Our study demonstrates the possibility of combining DOT with Stroop test to quantitatively investigate cognitive functions of the human brain at the prefrontal cortex.

  8. Dual fatty acid synthase and HER2 signaling blockade shows marked antitumor activity against breast cancer models resistant to anti-HER2 drugs.

    PubMed

    Blancafort, Adriana; Giró-Perafita, Ariadna; Oliveras, Glòria; Palomeras, Sònia; Turrado, Carlos; Campuzano, Òscar; Carrión-Salip, Dolors; Massaguer, Anna; Brugada, Ramon; Palafox, Marta; Gómez-Miragaya, Jorge; González-Suárez, Eva; Puig, Teresa

    2015-01-01

    Blocking the enzyme Fatty Acid Synthase (FASN) leads to apoptosis of HER2-positive breast carcinoma cells. The hypothesis is that blocking FASN, in combination with anti-HER2 signaling agents, would be an effective antitumor strategy in preclinical HER2+ breast cancer models of trastuzumab and lapatinib resistance. We developed and molecularly characterized in vitro HER2+ models of resistance to trastuzumab (SKTR), lapatinib (SKLR) and both (SKLTR). The cellular interactions of combining anti-FASN polyphenolic compounds (EGCG and the synthetic G28UCM) with anti-HER2 signaling drugs (trastuzumab plus pertuzumab and temsirolimus) were analyzed. Tumor growth inhibition after treatment with EGCG, pertuzumab, temsirolimus or the combination was evaluated in two in vivo orthoxenopatients: one derived from a HER2+ patient and another from a patient who relapsed on trastuzumab and lapatinib-based therapy. SKTR, SKLR and SKLTR showed hyperactivation of EGFR and p-ERK1/2 and PI3KCA mutations. Dual-resistant cells (SKLTR) also showed hyperactivation of HER4 and recovered levels of p-AKT compared with mono-resistant cells. mTOR, p-mTOR and FASN expression remained stable in SKTR, SKLR and SKLTR. In vitro, anti-FASN compounds plus pertuzumab showed synergistic interactions in lapatinib- and dual- resistant cells and improved the results of pertuzumab plus trastuzumab co-treatment. FASN inhibitors combined with temsirolimus displayed the strongest synergistic interactions in resistant cells. In vivo, both orthoxenopatients showed strong response to the antitumor activity of the combination of EGCG with pertuzumab or temsirolimus, without signs of toxicity. We showed that the simultaneous blockade of FASN and HER2 pathways is effective in cells and in breast cancer models refractory to anti-HER2 therapies.

  9. Dual Fatty Acid Synthase and HER2 Signaling Blockade Shows Marked Antitumor Activity against Breast Cancer Models Resistant to Anti-HER2 Drugs

    PubMed Central

    Blancafort, Adriana; Giró-Perafita, Ariadna; Oliveras, Glòria; Palomeras, Sònia; Turrado, Carlos; Campuzano, Òscar; Carrión-Salip, Dolors; Massaguer, Anna; Brugada, Ramon; Palafox, Marta; Gómez-Miragaya, Jorge; González-Suárez, Eva; Puig, Teresa

    2015-01-01

    Blocking the enzyme Fatty Acid Synthase (FASN) leads to apoptosis of HER2-positive breast carcinoma cells. The hypothesis is that blocking FASN, in combination with anti-HER2 signaling agents, would be an effective antitumor strategy in preclinical HER2+ breast cancer models of trastuzumab and lapatinib resistance. We developed and molecularly characterized in vitro HER2+ models of resistance to trastuzumab (SKTR), lapatinib (SKLR) and both (SKLTR). The cellular interactions of combining anti-FASN polyphenolic compounds (EGCG and the synthetic G28UCM) with anti-HER2 signaling drugs (trastuzumab plus pertuzumab and temsirolimus) were analyzed. Tumor growth inhibition after treatment with EGCG, pertuzumab, temsirolimus or the combination was evaluated in two in vivo orthoxenopatients: one derived from a HER2+ patient and another from a patient who relapsed on trastuzumab and lapatinib-based therapy. SKTR, SKLR and SKLTR showed hyperactivation of EGFR and p-ERK1/2 and PI3KCA mutations. Dual-resistant cells (SKLTR) also showed hyperactivation of HER4 and recovered levels of p-AKT compared with mono-resistant cells. mTOR, p-mTOR and FASN expression remained stable in SKTR, SKLR and SKLTR. In vitro, anti-FASN compounds plus pertuzumab showed synergistic interactions in lapatinib- and dual- resistant cells and improved the results of pertuzumab plus trastuzumab co-treatment. FASN inhibitors combined with temsirolimus displayed the strongest synergistic interactions in resistant cells. In vivo, both orthoxenopatients showed strong response to the antitumor activity of the combination of EGCG with pertuzumab or temsirolimus, without signs of toxicity. We showed that the simultaneous blockade of FASN and HER2 pathways is effective in cells and in breast cancer models refractory to anti-HER2 therapies. PMID:26107737

  10. Estrogenic and mutagenic activities of Crotalaria pallida measured by recombinant yeast assay and Ames test

    PubMed Central

    2013-01-01

    Background Crotalaria pallida Ailton is a plant belonging to the Fabaceae family, popularly known as “rattle or rattlesnake” and used in traditional medicine to treat swelling of the joints and as a vermifuge. Previous pharmacological studies have also reported anti-inflammatory, antimicrobial and antifungal activities. Nevertheless, scientific information regarding this species is scarce, and there are no reports related to its possible estrogenic and mutagenic effects. Thus, the purpose of the present study was to investigate the estrogenic potential of C. pallida leaves by means of the Recombinant Yeast Assay (RYA), seeking an alternative for estrogen replacement therapy during menopause; and to reflect on the safe use of natural products to assess the mutagenic activity of the crude extract from C. pallida leaves, the dichloromethane fraction and stigmasterol by means of the Ames test. Methods The recombinant yeast assay with the strain BY4741 of Saccharomyces cerevisiae, was performed with the ethanolic extract, dichloromethane fraction and stigmasterol isolated from the leaves of C. pallida. Mutagenic activity was evaluated by the Salmonella/microsome assay (Ames test), using the Salmonella typhimurium tester strains TA100, TA98, TA97 and TA102, with (+S9) and without (-S9) metabolization, by the preincubation method. Results All samples showed estrogenic activity, mainly stigmasterol. The ethanolic extract from C. pallida leaves showed mutagenic activity in the TA98 strain (-S9), whereas dichloromethane fraction and stigmasterol were found devoid of activity. Conclusion Considering the excellent estrogenic activity performed by stigmasterol in the RYA associated with the absence of mutagenic activity when evaluated by the Ames test, stigmasterol becomes a strong candidate to be used in hormone replacement therapy during menopause. PMID:24134316

  11. A Test of Learned Industriousness in the Physical Activity Domain

    PubMed Central

    Bustamante, Eduardo E.; Davis, Catherine L.; Marquez, David X.

    2015-01-01

    Background The Theory of Learned Industriousness states that durable individual differences in industriousness are due in part to differences in the extent to which individuals were rewarded for high effort at an earlier time. Individuals rewarded for high effort during training are thought to generalize greater persistence to subsequent tasks than those rewarded for low effort. This study tested whether rewarded physical and/or mental effort at different intensities generalized to greater persistence at a subsequent mental task. Methods 80 inactive 18–25 year-olds were randomized into four groups: Low Mental Effort, High Mental Effort, Low Physical Effort, and High Physical Effort. Each completed group-specific effort training and a mental persistence task at baseline and posttest. Results Factorial analysis of covariance revealed a significant domain x effort interaction on persistence (F[1,75]=4.93, p=.029). High Mental Effort and Low Mental Effort groups demonstrated similar gains in persistence (d=-0.08, p>.05) and points earned (d=0.11, p>.05) following effort training. High Physical Effort and Low Physical Effort diverged on persistence (d=-0.49, p=.004) but not points earned (d =-0.12, p>.05). Conclusions Findings suggest either that training and test stimuli were too dissimilar to cue effects of associative learning in physical effort groups, or that effects were present but overpowered by the affective and neurocognitive consequences of an acute bout of intense aerobic physical activity. Findings do not support the Theory of Learned Industriousness nor generalization of effort across physical and mental domains. PMID:26052372

  12. Organometallic cyclic polyphenols derived from 1,2-(alpha-keto tri or tetra methylene) ferrocene show strong antiproliferative activity on hormone-independent breast cancer cells.

    PubMed

    Plazuk, Damian; Top, Siden; Vessières, Anne; Plamont, Marie-Aude; Huché, Michel; Zakrzewski, Janusz; Makal, Anna; Woźniak, Krzysztof; Jaouen, Gérard

    2010-08-28

    We have previously shown that achiral ferrocenyl diphenol butene derivatives are strong antitumor agents against both hormone-dependent and -independent breast cancer cell lines. We report now examples of a new series of two planar chiral diphenol derivatives, namely 1,2-[1-[1,1-bis(4-hydroxyphenyl)methylidene]trimethylene] ferrocene (4), and 1,2-[1-[1,1-bis(4-hydroxyphenyl)methylidene]tetramethylene]ferrocene (5). They were prepared under racemic form from a McMurry coupling reaction with 30% and 16% yields, respectively. Compound 5 gave crystals suitable for X-ray structural analysis. Compounds 4 and 5 were tested for ERalpha and ERbeta affinity, lipophilicity, and proliferative/antiproliferative effects against the hormone-dependent breast cancer cell line MCF-7, and the hormone-independent breast cancer cell line MDA-MB-231. Both compounds exhibit better affinity for ERbeta (16.4 +/- 0.1, and 7.0 +/- 0.4, respectively) than for ERalpha (6.4 +/- 0.2, and 6.6 +/- 0.2). The test on hormone-independent breast cancer cell line MDA-MB-231 showed that 4 with a 5-membered ring gives an IC50 value of 2.7 microM while with 5 in which the ring has 6 carbons, the value is reduced to IC50 = 1.23 microM.

  13. Development of an Active Twist Rotor for Wind: Tunnel Testing (NLPN97-310

    NASA Technical Reports Server (NTRS)

    Cesnik, Carlos E. S.; Shin, SangJoon; Hagood, Nesbitt W., IV

    1998-01-01

    The development of the Active Twist Rotor prototype blade for hub vibration and noise reduction studies is presented in this report. Details of the modeling, design, and manufacturing are explored. The rotor blade is integrally twisted by direct strain actuation. This is accomplished by distributing embedded piezoelectric fiber composites along the span of the blade. The development of the analysis framework for this type of active blade is presented. The requirements for the prototype blade, along with the final design results are also presented. A detail discussion on the manufacturing aspects of the prototype blade is described. Experimental structural characteristics of the prototype blade compare well with design goals, and preliminary bench actuation tests show lower performance than originally predicted. Electrical difficulties with the actuators are also discussed. The presented prototype blade is leading to a complete fully articulated four-blade active twist rotor system for future wind tunnel tests.

  14. Testing Unification Models in Dual Active Galactic Nuclei

    NASA Astrophysics Data System (ADS)

    Muller-Sanchez, Francisco

    Dual active galactic nuclei (AGNs), which are kpc-scale separation AGN pairs in galaxy mergers, are ideal targets for testing unification models and models of galaxy evolution. By definition, the AGN nature of the two nuclei suggests that they must be consistent with standard unification models (i.e, a dusty torus obscures the central engine in type 2 AGN). At the same time, they are the result of merger-induced nuclear activity. Galaxy evolution models suggest that merger-induced AGNs are heavily obscured for long periods by the high gas densities powering them. Eventually, feedback drives away material, creating a brief window in time in which the AGN is not obscured. Therefore, in these models, there is no need for a small-scale torus. We are constructing for the first time the spectral energy distributions (SEDs) of the two AGNs in dual AGN systems using data from Hubble and Chandra telescopes, in combination with VLA, Keck and VLT data. However, a critical missing component is dust emission at 30-40 microns, which can only be achieved by SOFIA. We propose FORCAST 31.5 and 37.1 microns observations of the complete sample of 5 confirmed dual AGNs with angular separations >3.5". As suggested by current models, the best wavelength to detect thermal emission from a torus would be between 30-40 microns, where both the non-thermal core and the stellar emission sharply decline, and the torus emission peaks. Thus, FORCAST provides 1) the best angular resolution between 30-40 microns of the current suite of instruments, crucial to separate the emission from the two AGNs, and 2) the largest constraining power for torus models, crucial to characterize the properties of the torus in AGNs.

  15. Corrosion Testing of Low-Activity Waste Glasses Fiscal Year 1998 Summary Report

    SciTech Connect

    BP McGrail; CW Lindenmeier; HT Schaef; PF Martin

    1998-11-25

    Analytical results are presented on the chemical composition and other physical properties of a glass, given the identification BNFL-A-S98, made at Pacific Northwest National Laboratory' that is representative of the low-activity waste glass composition proposed by BNFL, Inc.* for immobilization of envelope A double-shell tank wastes at the Hanford Site. This glass was prepared for use in a testing program to be conducted at Pacific Northwest National Laboratory and at Argonne National Laboratory for the purpose of characterizing its long-term corrosion behavior. Detailed examination of the glass microstructure using transmission electron microscopy showed structural features indicative of amorphous phase separation. A remelt was performed on a smaller batch (100 g) to ensure rapid cooling. The glass microstructure was reexamined and showed no evidence of phase separation. Selected long-term (some to 860 d) product consistency tests were terminated, and the leachates were analyzed on tests with three other representative low-activity waste glass formulations (L8- 1, L8-3, and L8-7). The results showed no evidence of corrosion rate acceleration at three times the duration of tests where another well-studied glass, LD6-5412, had been completely altered under identical test conditions. These tests (and others not discussed in this report) provide clear evidence that low-activity waste glasses with at least 20 mass% Na20 can be made that have excellent long-term corrosion resistance. However, glass composition has a large impact on long-term behavior and so careful experiments with several different techniques are essential to ensuring that a particular glass will have good long-term corrosion resistance.

  16. In vitro genotoxicity of neutral red after photo-activation and metabolic activation in the Ames test, the micronucleus test and the comet assay.

    PubMed

    Guérard, Melanie; Zeller, Andreas; Singer, Thomas; Gocke, Elmar

    2012-07-04

    Neutral red (Nr) is relatively non-toxic and is widely used as indicator dye in many biological test systems. It absorbs visible light and is known to act as a photosensitizer, involving the generation of reactive oxygen species (type-I reaction) and singlet oxygen (type-II reaction). The mutagenicity of Nr was determined in the Ames test (with Salmonella typhimurium strains TA1535, TA97, TA98, TA98NR, TA100, and TA102) with and without metabolic activation, and with and without photo-activation on agar plates. Similarly to the situation following metabolic activation, photo-mutagenicity of Nr was seen with all Salmonella strains tested, albeit with different effects between these strains. To our knowledge, Nr is the only photo-mutagen showing such a broad action. Since the effects are also observed in strains not known to be responsive to ROS, this indicates that ROS production is not the sole mode of action that leads to photo-genotoxicity. The reactive species produced by irradiation are short-lived as pre-irradiation of an Nr solution did not produce mutagenic effects when added to the bacteria. In addition, mutagenicity in TA98 following irradiation was stronger than in the nitroreductase-deficient strain TA98NR, indicating that nitro derivatives that are transformed by bacterial nitroreductase to hydroxylamines appear to play a role in the photo-mutagenicity of Nr. Photo-genotoxicity of Nr was further investigated in the comet assay and micronucleus test in L5178Y cells. Concentration-dependent increases in primary DNA damage and in the frequency of micronuclei were observed after irradiation.

  17. Rapid toxicity testing based on mitochondrial respiratory activity

    SciTech Connect

    Haubenstricker, M.E. ); Holodnick, S.E.; Mancy, K.H. ); Brabec, M.J. )

    1990-05-01

    The need exists for rapid and inexpensive methods to determine the health effects of environmental contaminants on biological systems. One of the current research approaches for assessing cytotoxicity is to monitor the respiratory activity of the mitochondrion, a sensitive, nonspecific subcellular target site. Detected changes in mitochondrial function after the addition of a test chemical could be correlated to toxic effects. Mitochondrial respiration can be characterized by three indices: state 3 and state 4 respiratory rates, and the respiratory control ratio (RCR). State 4, the idle or resting state, results when coupled mitochondrial respire in a medium containing inorganic phosphate and a Kreb's cycle substrate in the absence of a phosphate acceptor such as adenosine diphosphate (ADP). In the presence of ADP the respiration rate increases to a maximum (state 3), accompanied by phosphorylation of ADP to adenosine triphosphate (ATP). The ratio of state 3 to state 4, or RCR, indicates how tightly the oxidative phosphorylation process is coupled. The synthesis of ATP by mitochondria is influenced by a number of compounds, most of which are either uncouplers or inhibitors.

  18. T-cell lines from 2 patients with adenosine deaminase (ADA) deficiency showed the restoration of ADA activity resulted from the reversion of an inherited mutation.

    PubMed

    Ariga, T; Oda, N; Yamaguchi, K; Kawamura, N; Kikuta, H; Taniuchi, S; Kobayashi, Y; Terada, K; Ikeda, H; Hershfield, M S; Kobayashi, K; Sakiyama, Y

    2001-05-01

    Inherited deficiency of adenosine deaminase (ADA) results in one of the autosomal recessive forms of severe combined immunodeficiency. This report discusses 2 patients with ADA deficiency from different families, in whom a possible reverse mutation had occurred. The novel mutations were identified in the ADA gene from the patients, and both their parents were revealed to be carriers. Unexpectedly, established patient T-cell lines, not B-cell lines, showed half-normal levels of ADA enzyme activity. Reevaluation of the mutations in these T-cell lines indicated that one of the inherited ADA gene mutations was reverted in both patients. At least one of the patients seemed to possess the revertant cells in vivo; however, the mutant cells might have overcome the revertant after receiving ADA enzyme replacement therapy. These findings may have significant implications regarding the prospects for stem cell gene therapy for ADA deficiency.

  19. Wing Torsional Stiffness Tests of the Active Aeroelastic Wing F/A-18 Airplane

    NASA Technical Reports Server (NTRS)

    Lokos, William A.; Olney, Candida D.; Crawford, Natalie D.; Stauf, Rick; Reichenbach, Eric Y.

    2002-01-01

    The left wing of the Active Aeroelastic Wing (AAW) F/A-18 airplane has been ground-load-tested to quantify its torsional stiffness. The test has been performed at the NASA Dryden Flight Research Center in November 1996, and again in April 2001 after a wing skin modification was performed. The primary objectives of these tests were to characterize the wing behavior before the first flight, and provide a before-and-after measurement of the torsional stiffness. Two streamwise load couples have been applied. The wing skin modification is shown to have more torsional flexibility than the original configuration has. Additionally, structural hysteresis is shown to be reduced by the skin modification. Data comparisons show good repeatability between the tests.

  20. Leprosy Reactions Show Increased Th17 Cell Activity and Reduced FOXP3+ Tregs with Concomitant Decrease in TGF-β and Increase in IL-6

    PubMed Central

    Saini, Chaman; Siddiqui, Anisuddin; Ramesh, Venkatesh; Nath, Indira

    2016-01-01

    Background 50% of leprosy patients suffer from episodes of Type 1/ reversal reactions (RR) and Type 2/ Erythema Nodosum Leprosum (ENL) reactions which lead to morbidity and nerve damage. CD4+ subsets of Th17 cells and CD25+FOXP3+ regulatory T cells (Tregs) have been shown to play a major role in disease associated immunopathology and in stable leprosy as reported by us and others. The aim of our study was to analyze their role in leprosy reactions. Methodology and Principle Findings Quantitative reverse transcribed PCR (qPCR), flowcytometry and ELISA were used to respectively investigate gene expression, cell phenotypes and supernatant levels of cytokines in antigen stimulated PBMC cultures in patients with stable disease and those undergoing leprosy reactions. Both types of reactions are associated with significant increase of Th17 cells and associated cytokines IL-17A, IL-17F, IL-21, IL-23 and chemokines CCL20, CCL22 as compared to matching stable forms of leprosy. Concurrently patients in reactions show reduction in FOXP3+ Treg cells as well as reduction in TGF-β and increase in IL-6. Moreover, expression of many T cell markers, cytokines, chemokines and signaling factors were observed to be increased in RR as compared to ENL reaction patients. Conclusions Patients with leprosy reactions show an imbalance in Th17 and Treg populations. The reduction in Treg suppressor activity is associated withhigherTh17cell activity. The combined effect of reduced TGF-β and enhanced IL-6, IL-21 cytokines influence the balance between Th17 or Treg cells in leprosy reactions as reported in the murine models and autoimmune diseases. The increase in Th17 cell associated cytokines may contribute to lesional inflammation. PMID:27035913

  1. Structural analysis of the alcohol acyltransferase protein family from Cucumis melo shows that enzyme activity depends on an essential solvent channel.

    PubMed

    Galaz, Sebastián; Morales-Quintana, Luis; Moya-León, María Alejandra; Herrera, Raúl

    2013-03-01

    Alcohol acyltransferases (AAT) play a key role in ester biosynthesis. In Cucumis melo var. cantalupensis, AATs are encoded by a gene family of four members (CmAAT1-4). CmAAT1, CmAAT3 and CmAAT4 are capable of synthesizing esters, with CmAAT1 the most active. CmAAT2 is inactive and has an Ala268 residue instead of a threonine which is present in all other active AATs, although the role of this residue is still unclear. The present work aims to understand the molecular mechanism involved in ester biosynthesis in melon fruit and to clarify the importance of the Ala268 residue. First, structural models for each protein were built by comparative modelling methodology. Afterwards, conformational interaction between the protein and several ligands, alcohols and acyl-CoAs was explored by molecular docking and molecular dynamics simulation. Structural analysis showed that CmAATs share a similar structure. Also, well-defined solvent channels were described in the CmAATs except for CmAAT2 which does not have a proper channel and instead has a small pocket around Ala268. Residues of the catalytic HxxxD motif interact with substrates within the solvent channel, with Ser363 also important. Strong binding interaction energies were described for the best substrate couple of each CmAAT (hexyl-, benzyl- and cinnamyl-acetate for CmAAT1, 3 and 4 respectively). CmAAT1 and CmAAT2 protein surfaces share similar electrostatic potentials; nevertheless the entrance channels for the substrates differ in location and electrostatic character, suggesting that Ala268 might be responsible for that. This could partly explain the major differences in activity reported for these two enzymes.

  2. Healthy co-twins of patients with affective disorders show reduced risk-related activation of the insula during a monetary gambling task

    PubMed Central

    Macoveanu, Julian; Miskowiak, Kamilla; Kessing, Lars Vedel; Vinberg, Maj; Siebner, Hartwig Roman

    2016-01-01

    Background Healthy first-degree relatives of patients with affective disorders are at increased risk for affective disorders and express discrete structural and functional abnormalities in the brain reward system. However, value-based decision making is not well understood in these at-risk individuals. Methods We investigated healthy monozygotic and dizygotic twins with or without a co-twin history of affective disorders (high-risk and low-risk groups, respectively) using functional MRI during a gambling task. We assessed group differences in activity related to gambling risk over the entire brain. Results We included 30 monozygotic and 37 dizygotic twins in our analysis. Neural activity in the anterior insula and ventral striatum increased linearly with the amount of gambling risk in the entire cohort. Individual neuroticism scores were positively correlated with the neural response in the ventral striatum to increasing gambling risk and negatively correlated with individual risk-taking behaviour. Compared with low-risk twins, the high-risk twins showed a bilateral reduction of risk-related activity in the middle insula extending into the temporal cortex with increasing gambling risk. Post hoc analyses revealed that this effect was strongest in dizygotic twins. Limitations The relatively old average age of the mono- and dizygotic twin cohort (49.2 yr) may indicate an increased resilience to affective disorders. The size of the monozygotic high-risk group was relatively small (n = 13). Conclusion The reduced processing of risk magnitude in the middle insula may indicate a deficient integration of exteroceptive information related to risk-related cues with interoceptive states in individuals at familial risk for affective disorders. Impaired risk processing might contribute to increased vulnerability to affective disorders. PMID:26395812

  3. Saroglitazar, a novel PPARα/γ agonist with predominant PPARα activity, shows lipid-lowering and insulin-sensitizing effects in preclinical models

    PubMed Central

    Jain, Mukul R; Giri, Suresh R; Trivedi, Chitrang; Bhoi, Bibhuti; Rath, Akshyaya; Vanage, Geeta; Vyas, Purvi; Ranvir, Ramchandra; Patel, Pankaj R

    2015-01-01

    Saroglitazar is a novel nonthiazolidinediones (TZD) and nonfibric acid derivative designed to act as dual regulator of lipids and glucose metabolism by activating peroxisome proliferator-activated receptors (PPAR). These studies evaluate the efficacy and safety profile of Saroglitazar in preclinical in vitro and in vivo models. The EC50 values of Saroglitazar assessed in HepG2 cells using PPAR transactivation assay for hPPARα and hPPARγ were 0.65 pmol/L and 3 nmol/L, respectively. In db/db mice, 12-day treatment with Saroglitazar (0.01–3 mg/kg per day, orally) caused dose-dependent reductions in serum triglycerides (TG), free fatty acids (FFA), and glucose. The ED50 for these effects was found to be 0.05, 0.19, and 0.19 mg/kg, respectively with highly significant (91%) reduction in serum insulin and AUC-glucose following oral glucose administration (59%) at 1 mg/kg dose. Significant reduction in serum TG (upto 90%) was also observed in Zucker fa/fa rats, Swiss albino mice, and in high fat -high cholesterol (HF-HC)-fed Golden Syrian hamsters. LDL cholesterol was significantly lowered in hApoB100/hCETP double transgenic mice and HF-HC diet fed Golden Syrian Hamsters. Hyperinsulinemic-Euglycemic clamp study in Zucker fa/fa rats demonstrated potent insulin-sensitizing activity. Saroglitazar also showed a significant decrease in SBP (22 mmHg) and increase (62.1%) in serum adiponectin levels in Zucker fa/fa rats. A 90-day repeated dose comparative study in Wistar rats and marmosets confirmed efficacy (TG lowering) potential of Saroglitazar and has indicated low risk of PPAR-associated side effects in humans. Based on efficacy and safety profile, Saroglitazar appears to have good potential as novel therapeutic agent for treatment of dyslipidemia and diabetes. PMID:26171220

  4. Methotrexate-conjugated PEGylated dendrimers show differential patterns of deposition and activity in tumor-burdened lymph nodes after intravenous and subcutaneous administration in rats.

    PubMed

    Kaminskas, Lisa M; McLeod, Victoria M; Ascher, David B; Ryan, Gemma M; Jones, Seth; Haynes, John M; Trevaskis, Natalie L; Chan, Linda J; Sloan, Erica K; Finnin, Benjamin A; Williamson, Mark; Velkov, Tony; Williams, Elizabeth D; Kelly, Brian D; Owen, David J; Porter, Christopher J H

    2015-02-02

    The current study sought to explore whether the subcutaneous administration of lymph targeted dendrimers, conjugated with a model chemotherapeutic (methotrexate, MTX), was able to enhance anticancer activity against lymph node metastases. The lymphatic pharmacokinetics and antitumor activity of PEGylated polylysine dendrimers conjugated to MTX [D-MTX(OH)] via a tumor-labile hexapeptide linker was examined in rats and compared to a similar system where MTX was α-carboxyl O-tert-butylated [D-MTX(OtBu)]. The latter has previously been shown to exhibit longer plasma circulation times. D-MTX(OtBu) was well absorbed from the subcutaneous injection site via the lymph, and 3 to 4%/g of the dose was retained by sentinel lymph nodes. In contrast, D-MTX(OH) showed limited absorption from the subcutaneous injection site, but absorption was almost exclusively via the lymph. The retention of D-MTX(OH) by sentinel lymph nodes was also significantly elevated (approximately 30% dose/g). MTX alone was not absorbed into the lymph. All dendrimers displayed lower lymph node targeting after intravenous administration. Despite significant differences in the lymph node retention of D-MTX(OH) and D-MTX(OtBu) after subcutaneous and intravenous administration, the growth of lymph node metastases was similarly inhibited. In contrast, the administration of MTX alone did not significantly reduce lymph node tumor growth. Subcutaneous administration of drug-conjugated dendrimers therefore provides an opportunity to improve drug deposition in downstream tumor-burdened lymph nodes. In this case, however, increased lymph node biodistribution did not correlate well with antitumor activity, possibly suggesting constrained drug release at the site of action.

  5. Reduced Expression of the Retinoblastoma Protein Shows That the Related Signaling Pathway Is Essential for Mediating the Antineoplastic Activity of Erufosine

    PubMed Central

    Zaharieva, Maya M.; Kirilov, Milen; Chai, Minquang; Berger, Stefan M.; Konstantinov, Spiro; Berger, Martin R.

    2014-01-01

    Erufosine is a new antineoplastic agent of the group of alkylphosphocholines, which interferes with signal transduction and induces apoptosis in various leukemic and tumor cell lines. The present study was designed to examine for the first time the mechanism of resistance to erufosine in malignant cells with permanently reduced expression of the retinoblastoma (Rb) protein. Bearing in mind the high number of malignancies with reduced level of this tumor-suppressor, this investigation was deemed important for using erufosine, alone or in combination, in patients with compromised RB1 gene expression. For this purpose, clones of the leukemic T-cell line SKW-3 were used, which had been engineered to constantly express differently low Rb levels. The alkylphosphocholine induced apoptosis, stimulated the expression of the cyclin dependent kinase inhibitor p27Kip1 and inhibited the synthesis of cyclin D3, thereby causing a G2 phase cell cycle arrest and death of cells with wild type Rb expression. In contrast, Rb-deficiency impeded the changes induced by eru-fosine in the expression of these proteins and abrogated the induction of G2 arrest, which was correlated with reduced antiproliferative and anticlonogenic activities of the compound. In conclusion, analysis of our results showed for the first time that the Rb signaling pathway is essential for mediating the antineoplastic activity of erufosine and its efficacy in patients with malignant diseases may be predicted by determining the Rb status. PMID:24987858

  6. Surface modification with multiphilic ligands at detectable well defined active positions of nano-object of giant wheel shaped molybdenum blue showing third-order nonlinear optical properties

    NASA Astrophysics Data System (ADS)

    Zhang, Lijuan; Li, Yuhao; Zhou, Yunshan

    2010-04-01

    The reaction of an aqueous solution of sodium molybdate with L-tyrosine in the presence of reducing agent results in the formation of a new compound of the formula of Na 8Co 3[Mo VI126 Mo V28O 462H 14(H 2O) 46(HOC 6H 4CH 2CH( NH3+)COO -) 12]·ca. 200H 2O. The compound contains nanosized ring-shaped clusters with tyrosine ligands possessing different types of functional groups (one -CO 2, one -NH3+ and one -ArOH) coordinated through the carboxylate groups at the active sites of the inner cavity. Importantly, the result demonstrates that not only active sites/areas of the cluster surface under a specified condition can be directly monitored and detected but also novel type surfaces within the cavity of a nano-structured ring-shaped cluster can be generated simultaneously. The nonlinear optical properties of the new cluster are studied using the well-known Z-scan technique at a wavelength of 532 nm with laser pulse duration of 18 ps. The results show that the new cluster exhibits interesting self-focusing nonlinear optical response with the real and imaginary parts of the third-order nonlinear optical susceptibility χ(3) being 1.069 × 10 -13(esu) and 2.529 × 10 -15(esu), respectively, which may find application in material science.

  7. LOW ACTIVITY WASTE FEED SOLIDS CARACTERIZATION AND FILTERABILITY TESTS

    SciTech Connect

    McCabe, D.; Crawford, C.; Duignan, M.; Williams, M.; Burket, P.

    2014-04-03

    The primary treatment of the tank waste at the DOE Hanford site will be done in the Waste Treatment and Immobilization Plant (WTP) that is currently under construction. The baseline plan for the WTP Pretreatment facility is to treat the waste, splitting it into High Level Waste (HLW) feed and Low Activity Waste (LAW) feed. Both waste streams are then separately vitrified as glass and sealed in canisters. The LAW glass will be disposed onsite in the Integrated Disposal Facility (IDF). There are currently no plans to treat the waste to remove technetium in the WTP Pretreatment facility, so its disposition path is the LAW glass. Options are being explored to immobilize the LAW portion of the tank waste, i.e., the LAW feed from the WTP Pretreatment facility. Removal of {sup 99}Tc from the LAW Feed, followed by off-site disposal of the {sup 99}Tc, would eliminate a key risk contributor for the IDF Performance Assessment (PA) for supplemental waste forms, and has potential to reduce treatment and disposal costs. Washington River Protection Solutions (WRPS) is developing some conceptual flow sheets for LAW treatment and disposal that could benefit from technetium removal. One of these flowsheets will specifically examine removing {sup 99}Tc from the LAW feed stream to supplemental immobilization. The conceptual flow sheet of the {sup 99}Tc removal process includes a filter to remove insoluble solids prior to processing the stream in an ion exchange column, but the characteristics and behavior of the liquid and solid phases has not previously been investigated. This report contains results of testing of a simulant that represents the projected composition of the feed to the Supplemental LAW process. This feed composition is not identical to the aqueous tank waste fed to the Waste Treatment Plant because it has been processed through WTP Pretreatment facility and therefore contains internal changes and recycle streams that will be generated within the WTP process. Although

  8. Are nest sites actively chosen? Testing a common assumption for three non-resource limited birds

    NASA Astrophysics Data System (ADS)

    Goodenough, A. E.; Elliot, S. L.; Hart, A. G.

    2009-09-01

    Many widely-accepted ecological concepts are simplified assumptions about complex situations that remain largely untested. One example is the assumption that nest-building species choose nest sites actively when they are not resource limited. This assumption has seen little direct empirical testing: most studies on nest-site selection simply assume that sites are chosen actively (and seek explanations for such behaviour) without considering that sites may be selected randomly. We used 15 years of data from a nestbox scheme in the UK to test the assumption of active nest-site choice in three cavity-nesting bird species that differ in breeding and migratory strategy: blue tit ( Cyanistes caeruleus), great tit ( Parus major) and pied flycatcher ( Ficedula hypoleuca). Nest-site selection was non-random (implying active nest-site choice) for blue and great tits, but not for pied flycatchers. We also considered the relative importance of year-specific and site-specific factors in determining occupation of nest sites. Site-specific factors were more important than year-specific factors for the tit species, while the reverse was true for pied flycatchers. Our results show that nest-site selection, in birds at least, is not always the result of active choice, such that choice should not be assumed automatically in studies of nesting behaviour. We use this example to highlight the need to test key ecological assumptions empirically, and the importance of doing so across taxa rather than for single "model" species.

  9. New sub-family of lysozyme-like proteins shows no catalytic activity: crystallographic and biochemical study of STM3605 protein from Salmonella Typhimurium

    SciTech Connect

    Michalska, Karolina; Brown, Roslyn N.; Li, Hui; Jedrzejczak, Robert; Niemann, George; Heffron, Fred; Cort, John R.; Adkins, Joshua N.; Babnigg, Gyorgy; Joachimiak, Andrzej

    2013-03-01

    Phage viruses that infect prokaryotes integrate their genome into the host chromosome; thus, microbial genomes typically contain genetic remnants of both recent and ancient phage infections. Often phage genes occur in clusters of atypical G+C content that reflect integration of the foreign DNA. However, some phage genes occur in isolation without other phage gene neighbors, probably resulting from horizontal gene transfer. In these cases, the phage gene product is unlikely to function as a component of a mature phage particle, and instead may have been co-opted by the host for its own benefit. The product of one such gene from Salmonella enterica serovar Typhimurium, STM3605, encodes a protein with modest sequence similarity to phage-like lysozyme (N-acetylmuramidase) but appears to lack essential catalytic residues that are strictly conserved in all lysozymes. Close homologs in other bacteria share this characteristic. The structure of the STM3605 protein was characterized by X-ray crystallography, and functional assays showed that it is a stable, folded protein whose structure closely resembles lysozyme. However, this protein is unlikely to hydrolyze peptidoglycan. Instead, STM3605 is presumed to have evolved an alternative function because it shows some lytic activity and partitions to micelles.

  10. Macrophages in T cell/histiocyte rich large B cell lymphoma strongly express metal-binding proteins and show a bi-activated phenotype.

    PubMed

    Hartmann, Sylvia; Tousseyn, Thomas; Döring, Claudia; Flüchter, Patricia; Hackstein, Holger; Herreman, An; Ponzoni, Maurilio; de Wolf-Peeters, Chris; Facchetti, Fabio; Gascoyne, Randy D; Küppers, Ralf; Steidl, Christian; Hansmann, Martin-Leo

    2013-12-01

    Abundant macrophage infiltration in tumors often correlates with a poor prognosis. T cell/histiocyte rich large B cell lymphoma (THRLBCL) is a distinct aggressive B cell lymphoma entity showing a high macrophage content. To further elucidate the role of tumor-associated macrophages in THRLBCL, we performed gene expression profiling of microdissected histiocyte subsets of THRLBCL, nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), Piringer lymphadenitis, sarcoidosis, nonspecific lymphadenitis and monocytes from peripheral blood. In a supervised principal component analysis, histiocytes from THRLBCL were most closely related to epithelioid cells from NLPHL, with both types of cells expressing genes related to proinflammatory and regulatory macrophage activity. Moreover, histiocytes from THRLBCL strongly expressed metal-binding proteins like MT2A, by which histiocytes of THRLBCL can be distinguished from the other histiocyte subsets investigated. Interestingly, the validation at the protein level showed a strong expression of TXN, CXCL9, MT2A and SOD2 not only in macrophages of THRLBCL but also in the tumor cells of NLPHL and classical Hodgkin lymphoma (cHL). Overall, the present findings indicate that macrophages in the microenvironment of THRLBCL have acquired a distinct gene expression pattern that is characterized by a mixed M1/M2 phenotype and a strong expression of several metal binding proteins. The microenvironments in NLPHL and THRLBCL appear to have a similar influence on the macrophage phenotype. The high expression of metal binding proteins in histiocytes of THRLBCL may be diagnostically useful, but a potential pathophysiological role remains to be identified.

  11. Exhaustive mutagenesis of six secondary active-site residues in Escherichia coli chorismate mutase shows the importance of hydrophobic side chains and a helix N-capping position for stability and catalysis.

    PubMed

    Lassila, Jonathan Kyle; Keeffe, Jennifer R; Kast, Peter; Mayo, Stephen L

    2007-06-12

    Secondary active-site residues in enzymes, including hydrophobic amino acids, may contribute to catalysis through critical interactions that position the reacting molecule, organize hydrogen-bonding residues, and define the electrostatic environment of the active site. To ascertain the tolerance of an important model enzyme to mutation of active-site residues that do not directly hydrogen bond with the reacting molecule, all 19 possible amino acid substitutions were investigated in six positions of the engineered chorismate mutase domain of the Escherichia coli chorismate mutase-prephenate dehydratase. The six secondary active-site residues were selected to clarify results of a previous test of computational enzyme design procedures. Five of the positions encode hydrophobic side chains in the wild-type enzyme, and one forms a helix N-capping interaction as well as a salt bridge with a catalytically essential residue. Each mutant was evaluated for its ability to complement an auxotrophic chorismate mutase deletion strain. Kinetic parameters and thermal stabilities were measured for variants with in vivo activity. Altogether, we find that the enzyme tolerated 34% of the 114 possible substitutions, with a few mutations leading to increases in the catalytic efficiency of the enzyme. The results show the importance of secondary amino acid residues in determining enzymatic activity, and they point to strengths and weaknesses in current computational enzyme design procedures.

  12. Active Thermal Control Experiments for LISA Ground Verification Testing

    NASA Astrophysics Data System (ADS)

    Higuchi, Sei; DeBra, Daniel B.

    2006-11-01

    The primary mission goal of LISA is detecting gravitational waves. LISA uses laser metrology to measure the distance between proof masses in three identical spacecrafts. The total acceleration disturbance to each proof mass is required to be below 3 × 10-15 m/s2√Hz . Optical path length variations on each optical bench must be kept below 40 pm/√Hz over 1 Hz to 0.1 mHz. Thermal variations due to, for example, solar radiation or temperature gradients across the proof mass housing will distort the spacecraft causing changes in the mass attraction and sensor location. We have developed a thermal control system developed for the LISA gravitational reference sensor (GRS) ground verification testing which provides thermal stability better than 1 mK/√Hz to f < 1 mHz and which by extension is suitable for in-flight thermal control for the LISA spacecraft to compensate solar irradiation. Thermally stable environment is very demanded for LISA performance verification. In a lab environment specifications can be met with considerable amount of insulation and thermal mass. For spacecraft, the very limited thermal mass calls for an active control system which can meet disturbance rejection and stability requirements simultaneously in the presence of long time delay. A simple proportional plus integral control law presently provides approximately 1 mK/√Hz of thermal stability for over 80 hours. Continuing development of a model predictive feed-forward algorithm will extend performance to below 1 mK/√Hz at f < 1 mHz and lower.

  13. Xenobiotic metabolizing enzyme activities in cells used for testing skin sensitization in vitro.

    PubMed

    Fabian, E; Vogel, D; Blatz, V; Ramirez, T; Kolle, S; Eltze, T; van Ravenzwaay, B; Oesch, F; Landsiedel, R

    2013-09-01

    For ethical and regulatory reasons, in vitro tests for scoring potential toxicities of cosmetics are essential. A test strategy for investigating potential skin sensitization using two human keratinocytic and two human dendritic cell lines has been developed (Mehling et al. Arch Toxicol 86:1273–1295, 2012). Since prohaptens may be metabolically activated in the skin, information on xenobiotic metabolizing enzyme (XME) activities in these cell lines is of high interest. In this study, XME activity assays, monitoring metabolite or cofactor, showed the following: all three passages of keratinocytic (KeratinoSens® and LuSens) and dendritic (U937 und THP-1) cells displayed N-acetyltransferase 1 (NAT1) activities (about 6–60 nmol/min/mg S9-protein for acetylation of para-aminobenzoic acid). This is relevant since reactive species of many cosmetics are metabolically controlled by cutaneous NAT1. Esterase activities of about 1–4 nmol fluorescein diacetate/min/mg S9-protein were observed in all passages of investigated keratinocytic and about 1 nmol fluorescein diacetate/min/mg S9-protein in dendritic cell lines. This is also of practical relevance since many esters and amides are detoxified and others activated by cutaneous esterases. In both keratinocytic cell lines, activities of aldehyde dehydrogenase (ALDH) were observed (5–17 nmol product/min/mg cytosolic protein). ALDH is relevant for the detoxication of reactive aldehydes. Activities of several other XME were below detection, namely the investigated cytochrome P450-dependent alkylresorufin O-dealkylases 7-ethylresorufin O-deethylase, 7-benzylresorufin O-debenzylase and 7-pentylresorufin O-depentylase (while NADPH cytochrome c reductase activities were much above the limit of quantification), the flavin-containing monooxygenase, the alcohol dehydrogenase as well as the UDP glucuronosyl transferase activities.

  14. Evaluation of fine-particle catalysts: Activity testing results and phase identification using Mossbauer spectroscopy

    SciTech Connect

    Stohl, F.V.; Diegert, K.V.; Goodnow, D.; Rao, K.R.P.M.; Huggins, F.; Huffman, G.P.

    1994-10-01

    To evaluate and compare the activities/selectivities of fine- particle size catalysts being developed in the DOE/PETC Advanced Research (AR) Coal Liquefaction program by using standard coal liquefaction activity test procedures. Previously reported results have described the standard test procedure that was developed at Sandia to evaluate fine-particle size iron catalysts being developed in DOE/PETC`s AR Coal Liquefaction Program. This test uses DECS-17 Blind Canyon Coal, phenanthrene as the reaction solvent, and a factorial experimental design that enables evaluation of a catalyst over ranges of temperature (350 to 400{degrees}C), time (20 to 60 minutes), and catalyst loading (0 to 1 wt% on a dmmf coal basis). Testing has been performed on Pacific Northwest Laboratories` (PNL) 6-line ferrihydrite catalyst. Results showed that this catalyst is more active than the University of Pittsburgh`s sulfated iron oxide catalyst that was evaluated previously. PNL has also produced two additional batches of catalyst in an effort to optimize their preparation procedures for larger batches. Sandia has observed significant differences in activities among these three catalysts; these differences might be due to particle size effects, the type of drying procedure, or the amount of moisture present. Mossbauer characterization of the iron phases in the coal, catalyst precursors, and tetrahydrofuran (THF) insoluble material from liquefaction reactions has been performed on the University of Pittsburgh`s catalyst and the first PNL catalyst that was tested at Sandia. The Mossbauer results were obtained at the University of Kentucky and will be presented. Future work will include testing additional catalysts being developed in the AR Coal Liquefaction Program, developing procedures to characterize reaction products, and determining the kinetics of the reactions.

  15. Monkey Feeding Assay for Testing Emetic Activity of Staphylococcal Enterotoxin.

    PubMed

    Seo, Keun Seok

    2016-01-01

    Staphylococcal enterotoxins (SEs) are unique bacterial toxins that cause gastrointestinal toxicity as well as superantigenic activity. Since systemic administration of SEs induces superantigenic activity leading to toxic shock syndrome that may mimic enterotoxic activity of SEs such as vomiting and diarrhea, oral administration of SEs in the monkey feeding assay is considered as a standard method to evaluate emetic activity of SEs. This chapter summarizes and discusses practical considerations of the monkey feeding assay used in studies characterizing classical and newly identified SEs.

  16. Phenobarbital and propiconazole toxicogenomic profiles in mice show major similarities consistent with the key role that constitutive androstane receptor (CAR) activation plays in their mode of action.

    PubMed

    Currie, Richard A; Peffer, Richard C; Goetz, Amber K; Omiecinski, Curtis J; Goodman, Jay I

    2014-07-03

    Toxicogenomics (TGx) is employed frequently to investigate underlying molecular mechanisms of the compound of interest and, thus, has become an aid to mode of action determination. However, the results and interpretation of a TGx dataset are influenced by the experimental design and methods of analysis employed. This article describes an evaluation and reanalysis, by two independent laboratories, of previously published TGx mouse liver microarray data for a triazole fungicide, propiconazole (PPZ), and the anticonvulsant drug phenobarbital (PB). Propiconazole produced an increase incidence of liver tumors in male CD-1 mice only at a dose that exceeded the maximum tolerated dose (2500 ppm). Firstly, we illustrate how experimental design differences between two in vivo studies with PPZ and PB may impact the comparisons of TGx results. Secondly, we demonstrate that different researchers using different pathway analysis tools can come to different conclusions on specific mechanistic pathways, even when using the same datasets. Finally, despite these differences the results across three different analyses also show a striking degree of similarity observed for PPZ and PB treated livers when the expression data are viewed as major signaling pathways and cell processes affected. Additional studies described here show that the postulated key event of hepatocellular proliferation was observed in CD-1 mice for both PPZ and PB, and that PPZ is also a potent activator of the mouse CAR nuclear receptor. Thus, with regard to the events which are hallmarks of CAR-induced effects that are key events in the mode of action (MOA) of mouse liver carcinogenesis with PB, PPZ-induced tumors can be viewed as being promoted by a similar PB-like CAR-dependent MOA.

  17. The prolyl isomerase domain of PpiD from Escherichia coli shows a parvulin fold but is devoid of catalytic activity

    PubMed Central

    Weininger, Ulrich; Jakob, Roman P; Kovermann, Michael; Balbach, Jochen; Schmid, Franz X

    2010-01-01

    PpiD is a periplasmic folding helper protein of Escherichia coli. It consists of an N-terminal helix that anchors PpiD in the inner membrane near the SecYEG translocon, followed by three periplasmic domains. The second domain (residues 264–357) shows homology to parvulin-like prolyl isomerases. This domain is a well folded, stable protein and follows a simple two-state folding mechanism. In its solution structure, as determined by NMR spectroscopy, it resembles most closely the first parvulin domain of the SurA protein, which resides in the periplasm of E. coli as well. A previously reported prolyl isomerase activity of PpiD could not be reproduced when using improved protease-free peptide assays or assays with refolding proteins as substrates. The parvulin domain of PpiD interacts, however, with a proline-containing tetrapeptide, and the binding site, as identified by NMR resonance shift analysis, colocalized with the catalytic sites of other parvulins. In its structure, the parvulin domain of PpiD resembles most closely the inactive first parvulin domain of SurA, which is part of the chaperone unit of this protein and presumably involved in substrate recognition. PMID:19866485

  18. Partially resistant Cucurbita pepo showed late onset of the Zucchini yellow mosaic virus infection due to rapid activation of defense mechanisms as compared to susceptible cultivar.

    PubMed

    Nováková, Slavomíra; Flores-Ramírez, Gabriela; Glasa, Miroslav; Danchenko, Maksym; Fiala, Roderik; Skultety, Ludovit

    2015-01-01

    Zucchini yellow mosaic virus (ZYMV) is an emerging viral pathogen in cucurbit-growing areas wordwide. Infection causes significant yield losses in several species of the family Cucurbitaceae. To identify proteins potentially involved with resistance toward infection by the severe ZYMV-H isolate, two Cucurbita pepo cultivars (Zelena susceptible and Jaguar partially resistant) were analyzed using a two-dimensional gel electrophoresis-based proteomic approach. Initial symptoms on leaves (clearing veins) developed 6-7 days post-inoculation (dpi) in the susceptible C. pepo cv. Zelena. In contrast, similar symptoms appeared on the leaves of partially resistant C. pepo cv. Jaguar only after 15 dpi. This finding was confirmed by immune-blot analysis which showed higher levels of viral proteins at 6 dpi in the susceptible cultivar. Leaf proteome analyses revealed 28 and 31 spots differentially abundant between cultivars at 6 and 15 dpi, respectively. The variance early in infection can be attributed to a rapid activation of proteins involved with redox homeostasis in the partially resistant cultivar. Changes in the proteome of the susceptible cultivar are related to the cytoskeleton and photosynthesis.

  19. Partially resistant Cucurbita pepo showed late onset of the Zucchini yellow mosaic virus infection due to rapid activation of defense mechanisms as compared to susceptible cultivar

    PubMed Central

    Nováková, Slavomíra; Flores-Ramírez, Gabriela; Glasa, Miroslav; Danchenko, Maksym; Fiala, Roderik; Skultety, Ludovit

    2015-01-01

    Zucchini yellow mosaic virus (ZYMV) is an emerging viral pathogen in cucurbit-growing areas wordwide. Infection causes significant yield losses in several species of the family Cucurbitaceae. To identify proteins potentially involved with resistance toward infection by the severe ZYMV-H isolate, two Cucurbita pepo cultivars (Zelena susceptible and Jaguar partially resistant) were analyzed using a two-dimensional gel electrophoresis-based proteomic approach. Initial symptoms on leaves (clearing veins) developed 6–7 days post-inoculation (dpi) in the susceptible C. pepo cv. Zelena. In contrast, similar symptoms appeared on the leaves of partially resistant C. pepo cv. Jaguar only after 15 dpi. This finding was confirmed by immune-blot analysis which showed higher levels of viral proteins at 6 dpi in the susceptible cultivar. Leaf proteome analyses revealed 28 and 31 spots differentially abundant between cultivars at 6 and 15 dpi, respectively. The variance early in infection can be attributed to a rapid activation of proteins involved with redox homeostasis in the partially resistant cultivar. Changes in the proteome of the susceptible cultivar are related to the cytoskeleton and photosynthesis. PMID:25972878

  20. Mucin-depleted foci show strong activation of inflammatory markers in 1,2-dimethylhydrazine-induced carcinogenesis and are promoted by the inflammatory agent sodium dextran sulfate.

    PubMed

    Femia, Angelo Pietro; Dolara, Piero; Luceri, Cristina; Salvadori, Maddalena; Caderni, Giovanna

    2009-08-01

    Mucin-depleted foci (MDF), formed by dysplastic crypts devoid of mucins, have been identified in the colon of carcinogen-treated rodents and in humans at high risk for colon cancer. The lack of the protective layer of mucus may cause inflammation which has been linked to colon carcinogenesis, therefore, the expression of markers such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (i-NOS) and macrophage infiltration was studied with immunohistochemistry (IH) in MDF harvested from F344 rats treated with the colon carcinogen 1,2-dimethylhydrazine (DMH). The same determinations were performed in aberrant crypt foci (ACF) and, at a later time point, in tumours. A dramatic increase in COX-2, i-NOS and macrophage infiltration was observed in MDF but ACF showed a moderate increase compared with the paired normal mucosa. Tumours were positive for all the markers. RT-PCR experiments demonstrated that i-NOS RNA expression was increased in a set of MDF confirming the results obtained with immunohistochemistry. In an inflammation-cancer experimental model [mice treated with azoxymethane (AOM) and dextran sodium sulphate (DSS)], we observed that DSS-induced inflammation promoted MDF in a dose-dependent manner, whereas ACF were not affected. In conclusion, we report here for the first time a strong activation of the inflammatory process in MDF, which may contribute to the further progression of MDF to tumours.

  1. The Anxiolytic Etifoxine Binds to TSPO Ro5-4864 Binding Site with Long Residence Time Showing a High Neurosteroidogenic Activity.

    PubMed

    Costa, Barbara; Cavallini, Chiara; Da Pozzo, Eleonora; Taliani, Sabrina; Da Settimo, Federico; Martini, Claudia

    2017-04-04

    The low binding affinity of the approved anxiolytic drug etifoxine (Stresam) at the steroidogenic 18 kDa translocator protein (TSPO) has questioned the specific contribution of this protein in mediating the etifoxine neurosteroidogenic efficacy. Residence time (RT) at the binding site of the classical TSPO ligand PK11195 is emerging as a relevant neurosteroidogenic efficacy measure rather than the binding affinity. Here etifoxine was evaluated for (i) the in vitro neurosteroidogenic activity in comparison to poorly neurosteroidogenic reference TSPO ligands (PK11195 and Ro5-4864) and (ii) the affinity and RT at [(3)H]PK11195 and [(3)H]Ro5-4864 binding sites in rat kidney membranes. Etifoxine shows (i) high neurosteroidogenic efficacy and (ii) low affinity/short RT at the [(3)H]PK11195 site and low affinity/long RT at the [(3)H]Ro5-4864 site, at which etifoxine competitively bound. These findings suggest that the long RT of etifoxine at the Ro5-4864 binding site could account for its high neurosteroidogenic efficacy.

  2. Resonance Femtosecond-Stimulated Raman Spectroscopy without Actinic Excitation Showing Low-Frequency Vibrational Activity in the S2 State of All-Trans β-Carotene.

    PubMed

    Quick, Martin; Dobryakov, Alexander L; Kovalenko, Sergey A; Ernsting, Nikolaus P

    2015-04-02

    Raman scattering with stimulating femtosecond probe pulses (FSR) was used to observe vibrational activity of all-trans β-carotene in n-hexane. The short-lived excited electronic state S2 was accessed in two ways: (i) by transient FSR after an actinic pulse to populate the S2 state, exploiting resonance from an Sx ← S2 transition, and (ii) by FSR without actinic excitation, using S2 ↔ S0 resonance exclusively and narrow-band Raman/broad-band femtosecond probe pulses only. The two approaches have nonlinear optical susceptibilities χ((5)) and χ((3)), respectively. Both methods show low-frequency bands of the S2 state at 200, 400, and ∼600 cm(-1), which are reported for the first time. With (ii) the intensities of low-frequency vibrational resonances in S2 are larger compared to those in S0, implying strong anharmonicities/mode mixing in the excited state. In principle, for short-lived electronic states, the χ((3)) method should allow the best characterization of low-frequency modes.

  3. Proteasome inhibitor-adapted myeloma cells are largely independent from proteasome activity and show complex proteomic changes, in particular in redox and energy metabolism

    PubMed Central

    Soriano, G P; Besse, L; Li, N; Kraus, M; Besse, A; Meeuwenoord, N; Bader, J; Everts, B; den Dulk, H; Overkleeft, H S; Florea, B I; Driessen, C

    2016-01-01

    Adaptive resistance of myeloma to proteasome inhibition represents a clinical challenge, whose biology is poorly understood. Proteasome mutations were implicated as underlying mechanism, while an alternative hypothesis based on low activation status of the unfolded protein response was recently suggested (IRE1/XBP1-low model). We generated bortezomib- and carfilzomib-adapted, highly resistant multiple myeloma cell clones (AMO-BTZ, AMO-CFZ), which we analyzed in a combined quantitative and functional proteomic approach. We demonstrate that proteasome inhibitor-adapted myeloma cells tolerate subtotal proteasome inhibition, irrespective of a proteasome mutation, and uniformly show an 'IRE1/XBP1-low' signature. Adaptation of myeloma cells to proteasome inhibitors involved quantitative changes in >600 protein species with similar patterns in AMO-BTZ and AMO-CFZ cells: proteins involved in metabolic regulation, redox homeostasis, and protein folding and destruction were upregulated, while apoptosis and transcription/translation were downregulated. The quantitatively most upregulated protein in AMO-CFZ cells was the multidrug resistance protein (MDR1) protein ABCB1, and carfilzomib resistance could be overcome by MDR1 inhibition. We propose a model where proteasome inhibitor-adapted myeloma cells tolerate subtotal proteasome inhibition owing to metabolic adaptations that favor the generation of reducing equivalents, such as NADPH, which is supported by oxidative glycolysis. Proteasome inhibitor resistance may thus be targeted by manipulating the energy and redox metabolism. PMID:27118406

  4. Active sensor/actuator assemblies for vibration damping, compensation, measurement, and testing

    NASA Astrophysics Data System (ADS)

    Ryaboy, Vyacheslav M.; Kasturi, Prakash S.

    2010-04-01

    The vibration control module known as IQ damper had been developed as part of active vibration damping system for optical tables and other precision vibration isolated platforms. The present work describes steps to expand the application of these units to other tasks, namely, (1) dynamic testing of structures and (2) compensation of forced vibration in local areas. The sensor-actuator assembly, including signal conditioning circuits, is designed as a compact dynamically symmetric module with mechanical interface to an optical table. The test data show that the vibration control modules can be used to measure dynamic compliance characteristics of optical tables with precision comparable to that of dedicated vibration measurement systems. Stable concerted work of active vibration control modules compensating forced harmonic vibration is demonstrated experimentally.

  5. Reduced oxide soldering activation (ROSA) PWB solderability testing

    SciTech Connect

    Hernandez, C.L.; Hosking, F.M.; Reed, J.; Tench, D.M.; White, J.

    1996-02-01

    The effect of ROSA pretreatment on the solderability of environmentally stressed PWB test coupons was investigated. The PWB surface finish was an electroplated, reflowed solder. Test results demonstrated the ability to recover plated-through-hole fill of steam aged samples with solder after ROSA processing. ROSA offers an alternative method for restoring the solderability of aged PWB surfaces.

  6. Development and whirl tower test of the SMART active flap rotor

    NASA Astrophysics Data System (ADS)

    Straub, Friedrich K.; Kennedy, Dennis K.; Stemple, Alan D.; Anand, V. R.; Birchette, Terry S.

    2004-07-01

    A full scale Smart Material Actuated Rotor Technology (SMART) system with piezoelectric actuated blade flaps was developed and whirl tower tested. The development effort included design, fabrication, and component testing of rotor blades, trailing edge flaps, piezoelectric actuators, switching power amplifiers, and the data/power system. Simulations and model scale wind tunnel tests have shown that this system can provide 80% vibration reduction, 10dB noise reduction for a helicopter passing overhead, and substantial aerodynamic performance gains. Whirl tower testing of the 34-foot diameter rotor demonstrated the functionality, robustness, and required authority of the active flap system. The program involved extensive development work and risk reduction tests which resulted in a robust, high performance actuator and a tightly integrated actuator, flap, and blade system. The actuator demonstrated excellent performance during bench testing and has accumulated over 60 million cycles under a spectrum of loading conditions. The flight worthy active flap rotor blades were based on a modified design of the FAA certified MD900 Explorer production rotor blade. Whirl tower testing was conducted with full rotor instrumentation and a 5-component balance. The rotor was tested for 13 hours under a range of conditions, including 7 hours of flap operation. Flap inputs included open loop static and dynamic commands. The flaps showed excellent authority with oscillatory thrust greater than 10% of the steady baseline thrust. Various flap actuation frequency sweeps were run to investigate the dynamics of the rotor and the flap system. Limited closed loop tests used hub accelerations and hub loads for feedback. Proving the integration, robust operation, and authority of the flap system were the key objectives met by the whirl tower test. This success depended on tailoring the piezoelectric materials and actuator to the application and meeting actuator/blade integration requirements

  7. Increased Expression of CCN2, Epithelial Membrane Antigen, and Fibroblast Activation Protein in Hepatocellular Carcinoma with Fibrous Stroma Showing Aggressive Behavior

    PubMed Central

    Yoo, Jeong Eun; Ko, Jung Eun; Lee, Jee San; Kim, Hyunki; Choi, Jin Sub; Park, Young Nyun

    2014-01-01

    Tumor behavior is affected by the tumor microenvironment, composed of cancer-associated fibroblasts (CAFs). Meanwhile, hepatocellular carcinomas (HCC) with fibrous stroma reportedly exhibit aggressive behavior suggestive of tumor-stroma interaction. However, evidence of the crosstalk remains unclear. In this study, CCN2, epithelial membrane antigen (EMA), fibroblast activation protein (FAP), and keratin 19 (K19) expression was studied in 314 HCCs (cohort 1), 42 scirrhous HCCs (cohort 2), and 36 chronic hepatitis/cirrhosis specimens by immunohistochemistry. Clinicopathological parameters were analyzed according to the expressions of these markers. In tumor epithelial cells from cohort 1, CCN2 and EMA were expressed in 15.3% and 17.2%, respectively, and their expressions were more frequent in HCCs with fibrous stroma (≥5% of tumor area) than those without (P<0.05 for all); CCN2 expression was well correlated with K19 and EMA expression. In tumor stromal cells, FAP expression was found in 6.7%. In cohort 2, CCN2, EMA, and FAP expression was noted in 40.5%, 40.5%, and 66.7%, respectively, which was more frequent than that in cohort 1 (P<0.05 for all). Additionally, EMA expression was associated with the expression of K19, CCN2, and FAP (P<0.05 for all); EMA expressing tumor epithelial cells showed a topographic closeness to FAP-expressing CAFs. Analysis of disease-free survival revealed CCN2 expression to be a worse prognostic factor in both cohort 1 (P = 0.005) and cohort 2 (P = 0.023), as well as EMA as a worse prognostic factor in cohort 2 (P = 0.048). In conclusion, expression of CCN2, EMA, and FAP may be involved in the activation of CAFs in HCC, giving rise to aggressive behavior. Significant correlation between EMA-expressing tumor cells and FAP-expressing CAFs and their topographic closeness suggests possible cross-talk between tumor epithelial cells and stromal cells in the tumor microenvironment of HCC. PMID:25126747

  8. Manufacturing and thermomechanical testing of actively cooled all beryllium high heat flux test pieces

    SciTech Connect

    Vasiliev, N.N.; Sokolov, Yu.A.; Shatalov, G.E.

    1995-09-01

    One of the problems affiliated to ITER high heat flux elements development is a problem of interface of beryllium protection with heat sink routinely made of copper alloys. To get rid of this problem all beryllium elements could be used as heat receivers in places of enhanced thermal loads. In accordance with this objectives four beryllium test pieces of two types have been manufactured in {open_quotes}Institute of Beryllium{close_quotes} for succeeding thermomechanical testing. Two of them were manufactured in accordance with JET team design; they are round {open_quotes}hypervapotron type{close_quotes} test pieces. Another two ones are rectangular test sections with a twisted tape installed inside of the circular channel. Preliminary stress-strain analysis have been performed for both type of the test pieces. Hypervapotrons have been shipped to JET where they were tested on JET test bed. Thermomechanical testing of pieces of the type of {open_quotes}swirl tape inside of tube{close_quotes} have been performed on Kurchatov Institute test bed. Chosen beryllium grade properties, some details of manufacturing, results of preliminary stress-strain analysis and thermomechanical testing of the test pieces {open_quotes}swirl tape inside of tube{close_quotes} type are given in this report.

  9. Ibrutinib, a BTK inhibitor used for treatment of lymphoproliferative disorders, eliminates both aeroallergen skin test and basophil activation test reactivity.

    PubMed

    Regan, Jennifer A; Cao, Yun; Dispenza, Melanie C; Ma, Shuo; Gordon, Leo I; Petrich, Adam M; Bochner, Bruce S

    2017-04-04

    Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, was shown to eliminate skin test reactivity in vivo and IgE-dependent basophil activation testing ex vivo. Blockade of the BTK pathway may represent a novel therapeutic strategy for the effective reduction of allergic reactivity.

  10. Should soil testing services measure soil biological activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Health of agricultural soils depends largely on conservation management to promote soil organic C accumulation. Total soil organic C changes slowly, but active fractions are more dynamic. A key indicator of healthy soil is potential biological activity, which could be measured rapidly with soil te...

  11. Plutonium recycle test reactor characterization activities and results

    SciTech Connect

    Cornwell, B.C.

    1997-05-01

    Report contains results of PRTR core and associated structures characterization performed in January and February of 1997. Radiation survey data are presented, along with recommendations for stabilization activities before transitioning to a decontamination and decommissioning function. Recommendations are also made about handling the waste generated by the stabilization activities, and actions suggested by the Decontamination and Decommissioning organization.

  12. Clinical assessment of disease activity in rheumatoid arthritis: evaluation of a functional test.

    PubMed Central

    Kalla, A A; Kotze, T J; Meyers, O L; Parkyn, N D

    1988-01-01

    A cross sectional analysis of the correlation between clinical, laboratory, and radiological markers of disease activity in 98 patients with classical rheumatoid arthritis (RA) is reported. The median age was 38 years, the median age at onset of disease 29 years, and the median duration of disease seven years. The Keitel function test (KFT) showed good correlation with the Ritchie articular index (RAI) (p less than 0.0001; r = 0.5) and the disability questionnaire (DQ) (p less than 0.0001; r = 0.6). The RAI and DQ correlated weakly with laboratory variables, while the KFT showed significant correlation with the erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and plasma viscosity (PV) (p less than 0.001; r = 0.4; 0.3; 0.4). Only the KFT showed significant correlations with bone mass measurements (p less than 0.01; r = -0.3; -0.4), and the Larsen index at the right wrist (p less than 0.0001; r = 0.4). Consensus analysis suggested that the KFT is a useful single clinical test of disease activity in RA. The hand functional index (HFI), a component of the KFT, showed significant correlation with the total KFT (r = 0.9). Prospective drug trials are needed to establish the value of the HFI in the monitoring of patients with RA. PMID:3263089

  13. Stress Sensitive Healthy Females Show Less Left Amygdala Activation in Response to Withdrawal-Related Visual Stimuli under Passive Viewing Conditions

    ERIC Educational Resources Information Center

    Baeken, Chris; Van Schuerbeek, Peter; De Raedt, Rudi; Vanderhasselt, Marie-Anne; De Mey, Johan; Bossuyt, Axel; Luypaert, Robert

    2012-01-01

    The amygdalae are key players in the processing of a variety of emotional stimuli. Especially aversive visual stimuli have been reported to attract attention and activate the amygdalae. However, as it has been argued that passively viewing withdrawal-related images could attenuate instead of activate amygdalae neuronal responses, its role under…

  14. Risk-informed inservice test activities at the NRC

    SciTech Connect

    Fischer, D.; Cheok, M.; Hsia, A.

    1996-12-01

    The operational readiness of certain safety-related components is vital to the safe operation of nuclear power plants. Inservice testing (IST) is one of the mechanisms used by licensees to ensure this readiness. In the past, the type and frequency of IST have been based on the collective best judgment of the NRC and industry in an ASME Code consensus process and NRC rulemaking process. Furthermore, IST requirements have not explicitly considered unique component and system designs and contribution to overall plant risk. Because of the general nature of ASME Code test requirements and non-reliance on risk estimates, current IST requirements may not adequately emphasize testing those components that are most important to safety and may overly emphasize testing of less safety significant components. Nuclear power plant licensees are currently interested in optimizing testing by applying resources in more safety significant areas and, where appropriate, reducing measures in less safety-significant areas. They are interested in maintaining system availability and reducing overall maintenance costs in ways that do not adversely affect safety. The NRC has been interested in using probabilistic, as an adjunct to deterministic, techniques to help define the scope, type and frequency of IST. The development of risk-informed IST programs has the potential to optimize the use of NRC and industry resources without adverse affect on safety.

  15. Deep Borehole Field Test Research Activities at LBNL

    SciTech Connect

    Dobson, Patrick; Tsang, Chin-Fu; Kneafsey, Timothy; Borglin, Sharon; Piceno, Yvette; Andersen, Gary; Nakagawa, Seiji; Nihei, Kurt; Rutqvist, Jonny; Doughty, Christine; Reagan, Matthew

    2016-08-19

    The goal of the U.S. Department of Energy Used Fuel Disposition’s (UFD) Deep Borehole Field Test is to drill two 5 km large-diameter boreholes: a characterization borehole with a bottom-hole diameter of 8.5 inches and a field test borehole with a bottom-hole diameter of 17 inches. These boreholes will be used to demonstrate the ability to drill such holes in crystalline rocks, effectively characterize the bedrock repository system using geophysical, geochemical, and hydrological techniques, and emplace and retrieve test waste packages. These studies will be used to test the deep borehole disposal concept, which requires a hydrologically isolated environment characterized by low permeability, stable fluid density, reducing fluid chemistry conditions, and an effective borehole seal. During FY16, Lawrence Berkeley National Laboratory scientists conducted a number of research studies to support the UFD Deep Borehole Field Test effort. This work included providing supporting data for the Los Alamos National Laboratory geologic framework model for the proposed deep borehole site, conducting an analog study using an extensive suite of geoscience data and samples from a deep (2.5 km) research borehole in Sweden, conducting laboratory experiments and coupled process modeling related to borehole seals, and developing a suite of potential techniques that could be applied to the characterization and monitoring of the deep borehole environment. The results of these studies are presented in this report.

  16. Solar Energy Education. Home economics: student activities. Field test edition

    SciTech Connect

    Not Available

    1981-03-01

    A view of solar energy from the standpoint of home economics is taken in this book of activities. Students are provided information on solar energy resources while performing these classroom activities. Instructions for the construction of a solar food dryer and a solar cooker are provided. Topics for study include window treatments, clothing, the history of solar energy, vitamins from the sun, and how to choose the correct solar home. (BCS)

  17. 21 CFR 864.7140 - Activated whole blood clotting time tests.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Activated whole blood clotting time tests. 864....7140 Activated whole blood clotting time tests. (a) Identification. An activated whole blood clotting... pulmonary embolism by measuring the coagulation time of whole blood. (b) Classification. Class...

  18. 21 CFR 864.7140 - Activated whole blood clotting time tests.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Activated whole blood clotting time tests. 864....7140 Activated whole blood clotting time tests. (a) Identification. An activated whole blood clotting... pulmonary embolism by measuring the coagulation time of whole blood. (b) Classification. Class...

  19. 21 CFR 864.7140 - Activated whole blood clotting time tests.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Activated whole blood clotting time tests. 864....7140 Activated whole blood clotting time tests. (a) Identification. An activated whole blood clotting... pulmonary embolism by measuring the coagulation time of whole blood. (b) Classification. Class...

  20. 21 CFR 864.7140 - Activated whole blood clotting time tests.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Activated whole blood clotting time tests. 864....7140 Activated whole blood clotting time tests. (a) Identification. An activated whole blood clotting... pulmonary embolism by measuring the coagulation time of whole blood. (b) Classification. Class...

  1. 21 CFR 864.7140 - Activated whole blood clotting time tests.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Activated whole blood clotting time tests. 864....7140 Activated whole blood clotting time tests. (a) Identification. An activated whole blood clotting... pulmonary embolism by measuring the coagulation time of whole blood. (b) Classification. Class...

  2. A family of Fe(3+) based double-stranded helicates showing a magnetocaloric effect, and Rhodamine B dye and DNA binding activities.

    PubMed

    Adhikary, Amit; Jena, Himanshu Sekhar; Konar, Sanjit

    2015-09-21

    Herein, the synthesis, structural characterization, magnetic properties and guest binding activities of four Fe(3+) based double-stranded helicates namely; [Fe2(L)2](ClO4)(Cl)·4(CH3OH)·2(H2O) (), [Fe2(L)2](BF4)2·2(H2O) (), [Fe2(L)2](NO3)2·3(CH3OH)·2(H2O) (), and [Fe2(L)2](Cl)2·2(CH3OH)·4(H2O) () are reported. Complexes have been synthesized using the hydrazide-based ligand H2L (H2L = N'1,N'4-bis(2-hydroxybenzylidene)succinohydrazide) and the corresponding Fe(2+) salts. Each of the independent cationic complexes [Fe2(L)2](2+) shows double-stranded helicates from the self-assembly of the ligand and metal ions in a 2 : 2 ratio, where the individual Fe(3+) centre is lying on a C2-axis and the ligand strands wrap around it. In , ligand L adopts "pseudo-C" conformations and forms a double-stranded dinuclear helicate with a small cage in between them. Moreover, in , each of the independent cationic complexes [Fe2L2](2+) is inherently chiral and possesses P for right-hand and M for left-hand helicity and as a consequence is a racemic solid. Detailed magnetic studies of all the complexes reveal that the Fe(3+) centres are magnetically isolated and isotropic in nature. Estimation of the Magnetocaloric Effect (MCE) from magnetization data unveils a moderate MCE at a temperature of 3 K with magnetic entropy changes (-ΔSm) of 22.9, 27.7, 24.1, 26.5 J kg(-1) K(-1) at a magnetic field of 7 T for complexes , respectively. Also, the variation of the -ΔSm values was justified by considering the parameter of magnetization per unit mass. Stability of all the complexes in solution phase was confirmed by ESI-mass spectrometric analysis and liquid phase FT-IR spectroscopy. Further, the interaction of the complexes with Rhodamine B dye was examined by UV-vis and fluorescence spectroscopic study. The observed blue-shift in the fluorescence study and hyperchromicity and hypochromicity with the appearance of two isosbestic points in the UV-vis study ascertain the interactions of

  3. Shuttle active thermal control system development testing. Volume 7: Improved radiator coating adhesive tests

    NASA Technical Reports Server (NTRS)

    Reed, M. W.

    1973-01-01

    Silver/Teflon thermal control coatings have been tested on a modular radiator system projected for use on the space shuttle. Seven candidate adhesives have been evaluated in a thermal vacuum test on radiator panels similar to the anticipated flight hardware configuration. Several classes of adhesives based on polyester, silicone, and urethane resin systems were tested. These included contact adhesives, heat cured adhesives, heat and pressure cured adhesives, pressure sensitive adhesives, and two part paint on or spray on adhesives. The coatings attached with four of the adhesives, two silicones and two urethanes, had no changes develop during the thermal vacuum test. The two silicone adhesives, both of which were applied to the silver/Teflon as transfer laminates to form a tape, offered the most promise based on application process and thermal performance. Each of the successful silicone adhesives required a heat and pressure cure to adhere during the cryogenic temperature excursion of the thermal-vacuum test.

  4. TESTING GUIDELINES FOR TECHNETIUM-99 ABSORPTION ON ACTIVATED CARBON

    SciTech Connect

    BYRNES ME

    2010-09-08

    CH2M HILL Plateau Remediation Company (CHPRC) is currently evaluating the potential use of activated carbon adsorption for removing technetium-99 from groundwater as a treatment method for the Hanford Site's 200 West Area groundwater pump-and-treat system. The current pump-and-treat system design will include an ion-exchange (IX) system for selective removal of technetium-99 from selected wells prior to subsequent treatment of the water in the central treatment system. The IX resin selected for technetium-99 removal is Purolite A530E. The resin service life is estimated to be approximately 66.85 days at the design technetium-99 loading rate, and the spent resin must be replaced because it cannot be regenerated. The resulting operating costs associated with resin replacement every 66.85 days are estimated at $0.98 million/year. Activated carbon pre-treatment is being evaluated as a potential cost-saving measure to offset the high operating costs associated with frequent IX resin replacement. This document is preceded by the Literature Survey of Technetium-99 Groundwater Pre-Treatment Option Using Granular Activated Carbon (SGW-43928), which identified and evaluated prior research related to technetium-99 adsorption on activated carbon. The survey also evaluated potential operating considerations for this treatment approach for the 200 West Area. The preliminary conclusions of the literature survey are as follows: (1) Activated carbon can be used to selectively remove technetium-99 from contaminated groundwater. (2) Technetium-99 adsorption onto activated carbon is expected to vary significantly based on carbon types and operating conditions. For the treatment approach to be viable at the Hanford Site, activated carbon must be capable of achieving a designated minimum technetium-99 uptake. (3) Certain radionuclides known to be present in 200 West Area groundwater are also likely to adsorb onto activated carbon. (4) Organic solvent contaminants of concern (COCs) will

  5. Comparison of EMG activity between maximal manual muscle testing and cybex maximal isometric testing of the quadriceps femoris.

    PubMed

    Lin, Hui-Ting; Hsu, Ar-Tyan; Chang, Jia-Hao; Chien, Chi-Sheng; Chang, Guan-Liang

    2008-02-01

    Two methods have been used to produce a maximal voluntary isometric contraction (MVIC) of the superficial quadriceps femoris muscles for normalization of electromyographic (EMG) data. The purposes of this study were to compare the myoelectic activity of MVIC of manual muscle testing (MMT) versus Cybex maximal isometric testing. Eighteen normal subjects were recruited. MMT and Cybex testing for MVIC of the dominant leg were performed. EMG activities of the vastus medialis, vastus lateralis and rectus femoris were recorded during MMT and Cybex trials. EMG amplitude and median frequency obtained from the two methods (MMT and Cybex testing) were used for statistical analysis of these three muscles. Statistically, the difference in the mean of the EMG signal amplitude and median frequency between MMT and Cybex testing were not significant. Considering cost and time, MMT for MVIC technique appears to be reliable and highly valuable.

  6. Functional genomics analysis of big data identifies novel peroxisome proliferator–activated receptor gamma target single nucleotide polymorphisms showing association with cardiometabolic outcomes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background Cardiovascular disease and type 2 diabetes mellitus represent overlapping diseases where a large portion of the variation attributable to genetics remains unexplained. An important player in their pathogenesis is peroxisome proliferator–activated receptor gamma (PPARgamma) that is involve...

  7. Show Me Your Menu.

    ERIC Educational Resources Information Center

    Allen, Barbara

    2000-01-01

    Describes the importance of eating properly. Presents two middle school level activities: the first activity has students record what they eat for nine days; the second activity includes listing the foods according to the food pyramid and discussing their decisions. Recommends three Web sites. (YDS)

  8. Molecular basis for paradoxical carriers of adenosine deaminase (ADA) deficiency that show extremely low levels of ADA activity in peripheral blood cells without immunodeficiency.

    PubMed

    Ariga, T; Oda, N; Sanstisteban, I; Arredondo-Vega, F X; Shioda, M; Ueno, H; Terada, K; Kobayashi, K; Hershfield, M S; Sakiyama, Y

    2001-02-01

    Adenosine deaminase (ADA) deficiency causes an autosomal recessive form of severe combined immunodeficiency and also less severe phenotypes, depending to a large degree on genotype. In general, ADA activity in cells of carriers is approximately half-normal. Unexpectedly, healthy first-degree relatives of two unrelated ADA-deficient severe combined immunodeficient patients (mother and brother in family I; mother in family II) had only 1-2% of normal ADA activity in PBMC, lower than has previously been found in PBMC of healthy individuals with so-called "partial ADA deficiency." The level of deoxyadenosine nucleotides in erythrocytes of these paradoxical carriers was slightly elevated, but much lower than levels found in immunodeficient patients with ADA deficiency. ADA activity in EBV-lymphoblastoid cell lines (LCL) and T cell lines established from these carriers was 10-20% of normal. Each of these carriers possessed two mutated ADA alleles. Expression of cloned mutant ADA cDNAs in an ADA-deletion strain of Escherichia coli indicated that the novel mutations G239S and M310T were responsible for the residual ADA activity. ADA activity in EBV-LCL extracts of the paradoxical carriers was much more labile than ADA from normal EBV-LCL. Immunoblotting suggested that this lability was due to denaturation rather than to degradation of the mutant protein. These results further define the threshold level of ADA activity necessary for sustaining immune function.

  9. Isolation of glycopeptides with skin test activity from dermatophytes.

    PubMed Central

    Moser, S A; Pollack, J D

    1978-01-01

    By using ethylene glycol extraction of whole submerged cultures followed by Sephadex G-200 and diethylaminoethyl-Sephadex chromatography, we isolated four distinct glycopeptides from Trichophyton mentagrophytes, T. rubrum, and Microsporum canis. Chemical analyses revealed that these glycopeptides contained mostly carbohydrate (42.5 to 81.6%) and protein (4.3 to 11.3%), with lesser amounts of phosphorus (0.4 to 6.0%) and hexosamines (0.3 to 0.6%). Based upon total carbohydrate and monosaccharide content, these dermatophyte glycopeptides could be divided into two chemical groups: glucopeptides (DSI1) and mannopeptides (DSI2, DSII1, and DSII2). The mannopeptides and glucopeptides of each species of dermatophyte were not significantly different chemically from those derived from the other two dermatophyte species studied. Skin testing of DSI1-glycopeptides or DSI2-mannopeptides in immunized guinea pigs indicated that only the DSI2-mannopeptides elicited a delayed hypersensitivity reaction. Skin testing T. mentagrophytes 62-infected guinea pigs with the four purified DS-glycopeptides, as well as earlier fractions from the purification scheme, derived from T. mentagrophytes, T. rubrum, and M. canis, again indicated that only the DSI2-mannopeptides of the two Trichophyton species elicited a delayed hypersensitivity reaction. The number of infections or duration of infection had no effect on the size of the skin test response. DSI2-mannopeptides were non-cross-reactive between genera when tested in Trichophyton-immunized or -infected guinea pigs and Microsporum-immunized guinea pigs. Images PMID:640721

  10. CHANG'E-3 Active Particle-induced X-ray Spectrometer: ground verification test

    NASA Astrophysics Data System (ADS)

    Guo, Dongya; Peng, Wenxi; Cui, XingZhu; Wang, Huanyu

    The Active Particle-induced X-ray Spectrometer (APXS) is one of the payloads of Chang’E-3 rover Yutu, with which the major elemental composition of lunar soils and rocks can be measured on site. In order to assess the instrument performance and the accuracy of determination, ground verification test was carried out with two blind samples(basaltic rock, powder). Details of the experiments and data analysis method are discussed. The results show that the accuracy of quantitative analysis for major elements(Mg,Al,Si,K,Ca,Ti,Fe) is better than 15%.

  11. Development and Hover Testing of the Active Elevon Rotor

    DTIC Science & Technology

    2012-05-01

    IBC) of rotor pitch links (Refs. 2 and 3), and various on-blade controls – such as active flaps (Refs. 4, 5, 6, 7, and 8) and active twist (Ref. 9...It is a fully articulated, four bladed hub with coincident flap and lead-lag hinges with a 2.97 inch hinge offset. The pitch axis is further...frequency of the rotor regressing lag mode. The hub has a large deflection range, ±9o in lead-lag, ±24o in pitch and +11 to -8o in flapping . Hub

  12. Do Collaborative Practical Tests Encourage Student-Centered Active Learning of Gross Anatomy?

    ERIC Educational Resources Information Center

    Green, Rodney A.; Cates, Tanya; White, Lloyd; Farchione, Davide

    2016-01-01

    Benefits of collaborative testing have been identified in many disciplines. This study sought to determine whether collaborative practical tests encouraged active learning of anatomy. A gross anatomy course included a collaborative component in four practical tests. Two hundred and seven students initially completed the test as individuals and…

  13. Allosteric mutants show that PrfA activation is dispensable for vacuole escape but required for efficient spread and Listeria survival in vivo

    PubMed Central

    Deshayes, Caroline; Bielecka, Magdalena K; Cain, Robert J; Scortti, Mariela; de las Heras, Aitor; Pietras, Zbigniew; Luisi, Ben F; Núñez Miguel, Ricardo; Vázquez-Boland, José A

    2012-01-01

    The transcriptional regulator PrfA controls key virulence determinants of the facultative intracellular pathogen Listeria monocytogenes. PrfA-dependent gene expression is strongly induced within host cells. While the basis of this activation is unknown, the structural homology of PrfA with the cAMP receptor protein (Crp) and the finding of constitutively activated PrfA* mutants suggests it may involve ligand-induced allostery. Here, we report the identification of a solvent-accessible cavity within the PrfA N-terminal domain that may accommodate an activating ligand. The pocket occupies a similar position to the cAMP binding site in Crp but lacks the cyclic nucleotide-anchoring motif and has its entrance on the opposite side of the β-barrel. Site-directed mutations in this pocket impaired intracellular PrfA-dependent gene activation without causing extensive structural/functional alterations to PrfA. Two substitutions, L48F and Y63W, almost completely abolished intracellular virulence gene induction and thus displayed the expected phenotype for allosteric activation-deficient PrfA mutations. Neither PrfAallo substitution affected vacuole escape and initial intracellular growth of L. monocytogenes in epithelial cells and macrophages but caused defective cell-to-cell spread and strong attenuation in mice. Our data support the hypothesis that PrfA is allosterically activated during intracellular infection and identify the probable binding site for the effector ligand. They also indicate that PrfA allosteric activation is not required for early intracellular survival but is essential for full Listeria virulence and colonization of host tissues. PMID:22646689

  14. Crucible of Creativity: Testing Public Outreach Activities at the Phoenix Comicon

    NASA Astrophysics Data System (ADS)

    Horodyskyj, L.

    2015-12-01

    The Phoenix Comicon (PCC) is a growing four-day pop culture event that features guests, costuming, exhibits, and discussion panels for popular sci-fi, fantasy, horror, and anime franchises. The 2014 and 2015 shows (which drew 75,000+ unique attendees each) featured a science programming track coordinated and organized by Horodyskyj. The track consisted of discussion panels, mixers, shows, interactive displays, and signature events (over 30 hours of programming each year). Topics ranged from planetary sciences to biotechnology to artificial intelligence and event staff were recruited from all levels of experience in academia, industry, and STEM outreach. The PCC science programming track for both 2014 and 2015 received very positive feedback from the audience, PCC management, and even scientists who participated in the event. Panelists and staff received frequent unsolicited praise about the content and events, and surveys showed requests for more science content in future years. Demand for good science programming, especially the kind that links the audience to local scientists, is high. The unique organizational structure of PCC, which draws heavily on the fan community rather than industry professionals, provides a rich test bed for public outreach activities generated by scientists themselves. In 2014, we tested science-based game shows, such as the bloody Exoplanet Survivor. In 2015, we ran a science interactivity booth and an interactive stage show about forensics based on the BBC series Sherlock. I will detail some of the successes and failures of these various events and what we're planning for 2016.

  15. In vitro testing of African traditional medicines for cytotoxic, immune modulatory and anti-HIV activities.

    PubMed

    Gqaleni, Nceba; Ngcobo, Mlungisi; Parboosing, Raveen; Naidoo, Anneta

    2012-01-01

    African Traditional Medicines (ATMs) serve as a major source of primary healthcare for African people. The reasons for their use range from easy access, affordability, beliefs in traditional systems and long term safety. ATMs have been used to treat individuals infected with HIV and therefore need scientific validation; a view supported by Traditional Health Practitioners (THPs). This study aimed to evaluate the in vitro cytotoxicity, immune modulatory and anti-HIV activities of traditional multiple herbal preparations from local THPs. Ugambu, Ihashi, Product Nene, Product Blue, SPNa and SDKc ATM were supplied by local THPs. Changes in adenosine triphosphate (ATP) & glutathione (GSH) over 24 hours were measured using luminometry. Changes in 12 cytokines were assayed using an ELISA-based absorbance assay. Protective effects against HIV killing of MT-4 cells were tested using the XTT assay and antiviral activity was measured using an HIV-1 viral load assay. Cyclosporine and AZT were used as positive controls. Ugambu, Ihashi, Product Nene and SDKc induced a dose dependent toxicity on treated PBMCs by reducing ATP and GSH at high doses (p< 0.001). These medicinal preparations, along with SPNa, showed immunomodulatory activity by significantly (p< 0.001) changing the secretion of pro-inflammatory cytokines. Product Blue stimulated the levels of ATP and GSH in treated PBMCs at all doses however this product did not show any immunomodulatory activity on cytokine secretion when compared to control cells. Ugambu, Ihashi, Product Nene showed promising anti-HIV activity relative to AZT (p< 0.01). This study has shown that some of these traditional medicinal preparations have at least one or all the properties of immunostimulation, immunomodulation or antiretroviral effects. The mechanism of action of the shown activities should further be investigated.

  16. Transgenic Tobacco Lines Expressing Sense or Antisense FERROCHELATASE 1 RNA Show Modified Ferrochelatase Activity in Roots and Provide Experimental Evidence for Dual Localization of Ferrochelatase 1.

    PubMed

    Hey, Daniel; Ortega-Rodes, Patricia; Fan, Tingting; Schnurrer, Florian; Brings, Lea; Hedtke, Boris; Grimm, Bernhard

    2016-12-01

    In plants, two genes encode ferrochelatase (FC), which catalyzes iron chelation into protoporphyrin IX at the final step of heme biosynthesis. FERROCHELATASE1 (FC1) is continuously, but weakly expressed in roots and leaves, while FC2 is dominantly active in leaves. As a continuation of previous studies on the physiological consequences of FC2 inactivation in tobacco, we aimed to assign FC1 function in plant organs. While reduced FC2 expression leads to protoporphyrin IX accumulation in leaves, FC1 down-regulation and overproduction caused reduced and elevated FC activity in root tissue, respectively, but were not associated with changes in macroscopic phenotype, plant development or leaf pigmentation. In contrast to the lower heme content resulting from a deficiency of the dominant FC2 expression in leaves, a reduction of FC1 in roots and leaves does not significantly disturb heme accumulation. The FC1 overexpression was used for an additional approach to re-examine FC activity in mitochondria. Transgenic FC1 protein was immunologically shown to be present in mitochondria. Although matching only a small portion of total cellular FC activity, the mitochondrial FC activity in a FC1 overexpressor line increased 5-fold in comparison with wild-type mitochondria. Thus, it is suggested that FC1 contributes to mitochondrial heme synthesis.

  17. Solar Energy Education. Industrial arts: student activities. Field test edition

    SciTech Connect

    Not Available

    1981-02-01

    In this teaching manual several activities are presented to introduce students to information on solar energy through classroom instruction. Wind power is also included. Instructions for constructing demonstration models for passive solar systems, photovoltaic cells, solar collectors and water heaters, and a bicycle wheel wind turbine are provided. (BCS)

  18. The dipeptide H-Trp-Glu-OH (WE) shows agonistic activity to peroxisome proliferator-activated protein-α and reduces hepatic lipid accumulation in lipid-loaded H4IIE cells.

    PubMed

    Jia, Yaoyao; Kim, Jong-Ho; Nam, Bora; Kim, Jiyoung; Lee, Ji Hae; Hwang, Kwang-Yeon; Lee, Sung-Joon

    2014-07-01

    Dipeptides digested from dietary proteins can be directly absorbed by the intestine and delivered to the circulatory system. However, the dipeptides' metabolic roles and biological activities are largely unknown. Lipid-loaded HII4E cells stimulated with H-Trp-Glu-OH (WE) exhibited reduced lipid accumulation, of which the effect was abolished by peroxisome proliferator-activated receptor (PPAR) α gene knock down. A luciferase assay showed that the WE dipeptide induced PPARα transactivation in a dose-dependent manner. Surface plasmon resonance and time-resolved fluorescence resonance energy transfer analyses demonstrated that WE interacts directly with the PPARα ligand binding domain (KD, 120 μM; EC50, 83 μM). Cells stimulated with WE induced PPARα and its responsive genes and increased cellular fatty acid uptake. In conclusion, WE reduces hepatic lipid accumulation in lipid-loaded hepatocytes via the activation of PPARα by a direct interaction.

  19. Extra-Vehicular Activity (EVA) glove evaluation test protocol

    NASA Technical Reports Server (NTRS)

    Hinman-Sweeney, E. M.

    1994-01-01

    One of the most critical components of a space suit is the gloves, yet gloves have traditionally presented significant design challenges. With continued efforts at glove development, a method for evaluating glove performance is needed. This paper presents a pressure-glove evaluation protocol. A description of this evaluation protocol, and its development is provided. The protocol allows comparison of one glove design to another, or any one design to bare-handed performance. Gloves for higher pressure suits may be evaluated at current and future design pressures to drive out differences in performance due to pressure effects. Using this protocol, gloves may be evaluated during design to drive out design problems and determine areas for improvement, or fully mature designs may be evaluated with respect to mission requirements. Several different test configurations are presented to handle these cases. This protocol was run on a prototype glove. The prototype was evaluated at two operating pressures and in the unpressurized state, with results compared to bare-handed performance. Results and analysis from this test series are provided, as is a description of the configuration used for this test.

  20. Recovery Efficiency Test Project Phase 2 activity report, Volume 1

    SciTech Connect

    Overbey, W.K. Jr.; Salamy, S.P.; Locke, C.D.

    1989-02-01

    The purpose of Phase II operations of the Recovery Efficiency Test Project is to enhance the natural production of the well and evaluate the relative improvement as a function of the type of stimulation conducted. Another purpose is to compare the stimulated production performance of the horizontal well with vertical wells in the field. The objectives considered for Phase II operations and plans were: (1) Develop a rationale for a systematic approach to designing stimulations for the well. (2) Conduct a series of stimulations designed to optimize the fluids, injection rates, proppant volumes and general approach to stimulating a horizontal well with similar geologic conditions. (3) Develop and test a method or methods for determining the geometry of stimulation-induced fractures. (4) Conduct tests and analyze the results to determine the efficiency of stimulation operations. The technical approach pursued in developing plans to accomplish three objectives was to: (1) Review the data needs for all objectives and obtain that data first. (2) Identify the operating geologic, geomechanical, and reservoir parameters that need additional clarification or definition. (3) Investigate existing models which could be used to plan or evaluate stimulation on the well and the reservoir. (4) Plan for analysis and verification of models and approaches.

  1. Evaluation of the single-pass flow-through test to support a low-activity waste specification

    SciTech Connect

    McGrail, B.P.; Peeler, D.K.

    1995-09-01

    A series of single-pass flow-through (SPFT) tests was performed on five reference low-activity waste glasses and a reference glass from the National Institute of Standards and Technology to support a product specification for low-activity waste (LAW) forms. The results showed that the SPFT test provides a means to quantitatively distinguish among LAW glass forms in terms of their forward reaction rate at a given temperature and solution pH. Two of the test glasses were also subjected to SPFT testing at Argonne National Laboratory (ANL). Forward reaction rate constants calculated from the ANL test data were 100 to over 1,000 times larger than the values obtained from the SPFT tests conducted at PNL. An analysis of the ANL results showed that they were inconsistent with independent measurements done on glasses of similar composition, the known pH-dependence of the forward rate, and with the results from low surface-area-to-volume, short duration product consistency tests. Because the data set obtained from the SPFT tests done at PNL was consistent with each of these same factors, a detailed examination of the test procedures used at both laboratories was performed to determine the cause(s) of the discrepancy. The omission of background subtraction in the data analysis procedure and the short-duration (on the order of hours) of the ANL tests are factors that may have significantly affected the calculated rates.

  2. Fractionation and Composition Studies of Skin Test-Active Components of Sensitins from Coccidioides immitis

    PubMed Central

    Anderson, Kenneth L.; Wheat, Robert W.; Conant, Norman F.

    1971-01-01

    Coccidioidin skin-test activities from mycelial culture filtrates and autolysates were partially purified. Major chemical constituents included 3-O-methylmannose, mannose, and amino acids. PMID:5119201

  3. Phosphatidylinositol 3-kinase-δ inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals

    PubMed Central

    Herman, Sarah E. M.; Gordon, Amber L.; Wagner, Amy J.; Heerema, Nyla A.; Zhao, Weiqiang; Flynn, Joseph M.; Jones, Jeffrey; Andritsos, Leslie; Puri, Kamal D.; Lannutti, Brian J.; Giese, Neill A.; Zhang, Xiaoli; Wei, Lai; Byrd, John C.

    2010-01-01

    Targeted therapy with imatinib in chronic myeloid leukemia (CML) prompted a new treatment paradigm. Unlike CML, chronic lymphocytic leukemia (CLL) lacks an aberrant fusion protein kinase but instead displays increased phosphatidylinositol 3-kinase (PI3K) activity. To date, PI3K inhibitor development has been limited because of the requirement of this pathway for many essential cellular functions. Identification of the hematopoietic-selective isoform PI3K-δ unlocks a new therapeutic potential for B-cell malignancies. Herein, we demonstrate that PI3K has increased enzymatic activity and that PI3K-δ is expressed in CLL cells. A PI3K-δ selective inhibitor CAL-101 promoted apoptosis in primary CLL cells ex vivo in a dose- and time-dependent fashion that was independent of common prognostic markers. CAL-101–mediated cytotoxicity was caspase dependent and was not diminished by coculture on stromal cells. In addition, CAL-101 abrogated protection from spontaneous apoptosis induced by B cell–activating factors CD40L, TNF-α, and fibronectin. In contrast to malignant cells, CAL-101 does not promote apoptosis in normal T cells or natural killer cells, nor does it diminish antibody-dependent cellular cytotoxicity. However, CAL-101 did decrease activated T-cell production of various inflammatory and antiapoptotic cytokines. Collectively, these studies provide rationale for the clinical development of CAL-101 as a first-in-class targeted therapy for CLL and related B-cell lymphoproliferative disorders. PMID:20522708

  4. Maps showing mines, quarries, oil and gas activity, and sample localities in and near the Sipsey Wilderness and additions, Lawrence and Winston Counties, Alabama

    SciTech Connect

    Mory, P.C.; Behum, P.T.; Ross, R.B. Jr.

    1982-01-01

    This report presents the results of a mineral survey of the Sipsey Wilderness and additions, William B. Bankhead National Forest, Lawrence and Winston Counties, Alabama. The survey includes: limestone quarrying, coal mining, and oil and gas activity. 7 references, 5 figures, 2 tables.

  5. Towards the evaluation in an animal disease model: Fluorinated 17β-HSD1 inhibitors showing strong activity towards both the human and the rat enzyme.

    PubMed

    Abdelsamie, Ahmed S; Bey, Emmanuel; Gargano, Emanuele M; van Koppen, Chris J; Empting, Martin; Frotscher, Martin

    2015-10-20

    17β-Estradiol (E2), the most potent human estrogen, is known to be involved in the etiology of estrogen-dependent diseases (EDD) like breast cancer and endometriosis. 17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) catalyses the last step of E2 biosynthesis and is thus a promising target for the treatment of EDD. The previously described bicyclic substituted hydroxyphenylmethanones (BSHs) display high inhibitory potency towards human 17β-HSD1, but marginal activity towards rodent 17β-HSD1, precluding a proof of principle study in an animal endometriosis model. The aim of this work was to perform structural optimizations in the BSHs class to enhance inhibitory activity against rodent (mouse and rat) 17β-HSD1 while maintaining activity against the human enzyme. The introduction of fluorine atoms on the benzoyl moiety resulted in compounds with the desired properties. Molecular docking and homology modeling were applied to elucidate the binding mode and interspecies differences in activity. Compound 33 is the most potent inhibitor of both human and rat 17β-HSD1 up to date (IC₅₀ = 2 nM and 97 nM, respectively).

  6. Characterization of a heat-resistant extracellular protease from Pseudomonas fluorescens 07A shows that low temperature treatments are more effective in deactivating its proteolytic activity.

    PubMed

    Alves, Maura P; Salgado, Rafael L; Eller, Monique R; Vidigal, Pedro Marcus P; Fernandes de Carvalho, Antonio

    2016-10-01

    This work discusses the biological and biochemical characterization of an extracellular protease produced by Pseudomonas fluorescens. The enzyme has a molecular weight of 49.486 kDa and hydrolyzes gelatin, casein, and azocasein, but n