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  1. Philippines: decentralized approach shows results.

    PubMed

    1983-01-01

    In the Philippines several steps have been taken to meet the challenge of increasing population growth. Commencing with the Republic Act 6365, known as the Population Act (1971) program directives focus on achieving and maintaining population levels most conducive to the national welfare. In 1978 a Special Committee was constituted by the President to review the population program. Pursuant to the Committee's findings certain changes were adopted. The thrust is now towards longterm planning to ensure a more significant and perceptible demographic impact of development programs and policies. Increasing attention is paid to regional development and spatial distribution in the country. The 1978-82 Development Plan states more clearly the interaction between population and development. The National Economic and Development Authority, the central policy and planning agency of the government, takes charge of formulation and coordinating the broader aspects of population policy and integrating population with socioeconomic plans and policies. At present the National Economic and Development Authority (NEDA) is implementing a project known as the Population/Development Planning and Research (PDPR) project with financial support from the UN Fund for Population Activities (UNFPA). This project promotes and facilitates the integration of the population dimension in the planning process. It does this by maintaining linkages and instituting collaborative mechanisms with the different NEDA regional offices and sectoral ministries. It also trains government planners in ways of integrating population concerns into the development plan. PDPR promotes the use of population and development research for planning purposes and policy formation. The Philippine Development Plan, 1978-82, recognized that an improvement in the level of 1 sector reinforces the performance of the other sectors. Since the establishment of the National Population Program 12 years ago, population and family

  2. Arches showing UV flaring activity

    NASA Technical Reports Server (NTRS)

    Fontenla, J. M.

    1988-01-01

    The UVSP data obtained in the previous maximum activity cycle show the frequent appearance of flaring events in the UV. In many cases these flaring events are characterized by at least two footpoints which show compact impulsive non-simultaneous brightenings and a fainter but clearly observed arch developes between the footpoints. These arches and footpoints are observed in line corresponding to different temperatures, as Lyman alpha, N V, and C IV, and when observed above the limb display large Doppler shifts at some stages. The size of the arches can be larger than 20 arcsec.

  3. Storing CO2 underground shows promising results

    NASA Astrophysics Data System (ADS)

    Zweigel, Peter; Gale, John

    Long-term underground storage of CO2 is an important element in concepts to reduce atmospheric CO2 emissions as the use of fossil fuels continues. The first results of a multinational research project evaluating the injection of CO2 into a saline aquifer in the North Sea are validating this method of CO2 reduction, and are serving to further define the research needed to develop the technology for large-scale applicability. Reducing the emission of substances that have potentially harmful effects on global climate— for example, CO2—has become a central issue of environmental policy at least since the 1997 Kyoto conference on climate change.

  4. 14. DETAIL VIEW OF BUTTRESS 4 SHOWING THE RESULTS OF ...

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

    14. DETAIL VIEW OF BUTTRESS 4 SHOWING THE RESULTS OF INADEQUATE TAMPING. THE SIZE OF THE GRANITE AGGREGATE USED IN THE DAMS CONCRETE IS CLEARLY SHOWN. - Hume Lake Dam, Sequioa National Forest, Hume, Fresno County, CA

  5. 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,…

  6. 13. DETAIL VIEW OF BUTTRESS 4 SHOWING THE RESULTS OF ...

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

    13. DETAIL VIEW OF BUTTRESS 4 SHOWING THE RESULTS OF POOR CONSTRUCTION WORK. THOUGH NOT A SERIOUS STRUCTURAL DEFICIENCY, THE 'HONEYCOMB' TEXTURE OF THE CONCRETE SURFACE WAS THE RESULT OF INADEQUATE TAMPING AT THE TIME OF THE INITIAL 'POUR'. - Hume Lake Dam, Sequioa National Forest, Hume, Fresno County, CA

  7. Emerging Trends in Contextual Learning Show Positive Results for Students.

    ERIC Educational Resources Information Center

    WorkAmerica, 2001

    2001-01-01

    This issue focuses on contextual learning (CL), in which students master rigorous academic content in real-world or work-based learning experiences. "Emerging Trends in CL Show Positive Results for Students" discusses CL as an important strategy for improving student achievement. It describes: how CL raises the bar for all students, challenging…

  8. Breast vibro-acoustography: initial results show promise

    PubMed Central

    2012-01-01

    Introduction Vibro-acoustography (VA) is a recently developed imaging modality that is sensitive to the dynamic characteristics of tissue. It detects low-frequency harmonic vibrations in tissue that are induced by the radiation force of ultrasound. Here, we have investigated applications of VA for in vivo breast imaging. Methods A recently developed combined mammography-VA system for in vivo breast imaging was tested on female volunteers, aged 25 years or older, with suspected breast lesions on their clinical examination. After mammography, a set of VA scans was acquired by the experimental device. In a masked assessment, VA images were evaluated independently by 3 reviewers who identified mass lesions and calcifications. The diagnostic accuracy of this imaging method was determined by comparing the reviewers' responses with clinical data. Results We collected images from 57 participants: 7 were used for training and 48 for evaluation of diagnostic accuracy (images from 2 participants were excluded because of unexpected imaging artifacts). In total, 16 malignant and 32 benign lesions were examined. Specificity for diagnostic accuracy was 94% or higher for all 3 reviewers, but sensitivity varied (69% to 100%). All reviewers were able to detect 97% of masses, but sensitivity for detection of calcification was lower (≤ 72% for all reviewers). Conclusions VA can be used to detect various breast abnormalities, including calcifications and benign and malignant masses, with relatively high specificity. VA technology may lead to a new clinical tool for breast imaging applications. PMID:23021305

  9. Synthesis and evaluation of dioleoyl glyceric acids showing antitrypsin activity.

    PubMed

    Habe, Hiroshi; Fukuoka, Tokuma; Sato, Shun; Kitamoto, Dai; Sakaki, Keiji

    2011-01-01

    Previously, Lešová et al. reported the isolation and identification of metabolite OR-1, showing antitrypsin activity, produced during fermentation by Penicillium funiculosum. The structure of OR-1 was a mixture of glyceric acid (GA), esterified with C(14)-C(18) fatty acids, and oleic acid (C18:1) as the most predominant fatty acid (Folia Microbiol. 46, 21-23, 2001). In this study, dioleoyl D-GA and dioleoyl L-GA were synthesized via diesterification with oleoyl chloride, and their antitrypsin activities were evaluated using both a disk diffusion method and spectral absorption measurements. The results show that both compounds and their equivalent mixtures possess antitrypsin activities; however, their IC(50) values (approximately 2 mM) are much higher than that of OR-1 (4.25 µM), suggesting that dioleoyl GA does not play a major role in the OR-1 antitrypsin activity. PMID:21606621

  10. Sirt5 Deacylation Activities Show Differential Sensitivities to Nicotinamide Inhibition

    PubMed Central

    Suenkel, Benjamin; Lakshminarasimhan, Mahadevan; Schutkowski, Mike; Steegborn, Clemens

    2012-01-01

    Sirtuins are protein deacylases regulating metabolism and aging processes, and the seven human isoforms are considered attractive therapeutic targets. Sirtuins transfer acyl groups from lysine sidechains to ADP-ribose, formed from the cosubstrate NAD+ by release of nicotinamide, which in turn is assumed to be a general Sirtuin inhibitor. Studies on Sirtuin regulation have been hampered, however, by shortcomings of available assays. Here, we describe a mass spectrometry–based, quantitative deacylation assay not requiring any substrate labeling. Using this assay, we show that the deacetylation activity of human Sirt5 features an unusual insensitivity to nicotinamide inhibition. In contrast, we find similar values for Sirt5 and Sirt3 for the intrinsic NAD+ affinity as well as the apparent NAD+ affinity in presence of peptide. Structure comparison and mutagenesis identify an Arg neighboring to the Sirt5 nicotinamide binding pocket as a mediator of nicotinamide resistance, and statistical sequence analyses along with testing further Sirtuins reveal a network of coevolved residues likely defining a nicotinamide-insensitive Sirtuin deacetylase family. The same Arg was recently reported to render Sirt5 a preferential desuccinylase, and we find that this Sirt5 activity is highly sensitive to nicotinamide inhibition. Analysis of Sirt5 structures and activity data suggest that an Arg/succinate interaction is the molecular basis of the differential nicotinamide sensitivities of the two Sirt5 activities. Our results thus indicate a Sirtuin subfamily with nicotinamide-insensitive deacetylase activity and suggest that the molecular features determining nicotinamide sensitivity overlap with those dominating deacylation specificity, possibly suggesting that other subfamily members might also prefer other acylations than acetylations. PMID:23028781

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

    PubMed

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

    2015-10-01

    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 Ca(2+), 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

  13. 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.

  14. 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 registering…

  15. 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

  16. 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

  17. 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.

  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. PMID:27014154

  19. 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

  20. 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.

  1. Phenolic compounds from leaves of Casimiroa edulis showed adipogenesis activity.

    PubMed

    Nagai, Hiroyuki; Tanaka, Toshiyuki; Goto, Tsuyoshi; Kusudo, Tatsuya; Takahashi, Nobuyuki; Kawada, Teruo

    2014-01-01

    Casimiroa edulis is known as cochitzapotl, and it belongs to a species of tropical fruiting tree in the family Rutaceae, native to eastern Mexico and Central America south to Costa Rica. In this study, we isolated two furocoumarins and two polymethoxyflavones from leaves of C. edulis and evaluated the functions of glucose and lipid metabolism activity with 3T3-L1 adipocytes. We discovered that the addition of furocoumarins increased glucose uptake and lipid accumulation in 3T3-L1 adipocyte. These results suggest that furocoumarin compounds can be used as functional food-derived compounds, to regulate adipocyte functioning for the management of metabolic syndrome, which is associated with dysfunctions of glucose and lipid metabolism. PMID:25036684

  2. 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.

  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 (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.

  4. 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...

  5. Ultraviolet imaging spectroscopy shows an active saturnian system.

    PubMed

    Esposito, Larry W; Colwell, Joshua E; Larsen, Kristopher; McClintock, William E; Stewart, A Ian F; Hallett, Janet Tew; Shemansky, Donald E; Ajello, Joseph M; Hansen, Candice J; Hendrix, Amanda R; West, Robert A; Keller, H Uwe; Korth, Axel; Pryor, Wayne R; Reulke, Ralf; Yung, Yuk L

    2005-02-25

    Neutral oxygen in the saturnian system shows variability, and the total number of oxygen atoms peaks at 4 x 10(34). Saturn's aurora brightens in response to solar-wind forcing, and the auroral spectrum resembles Jupiter's. Phoebe's surface shows variable water-ice content, and the data indicate it originated in the outer solar system. Saturn's rings also show variable water abundance, with the purest ice in the outermost A ring. This radial variation is consistent with initially pure water ice bombarded by meteors, but smaller radial structures may indicate collisional transport and recent renewal events in the past 10(7) to 10(8) years.

  6. 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

  7. 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.

  8. Sulfur dioxide: episodic injection shows evidence for active venus volcanism.

    PubMed

    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.

  9. Data for behavioral results and brain regions showing a time effect during pair-association retrieval.

    PubMed

    Jimura, Koji; Hirose, Satoshi; Wada, Hiroyuki; Yoshizawa, Yasunori; Imai, Yoshio; Akahane, Masaaki; Machida, Toru; Shirouzu, Ichiro; Koike, Yasuharu; Konishi, Seiki

    2016-09-01

    The current data article provides behavioral and neuroimaging data for the research article "Relatedness-dependent rapid development of brain activity in anterior temporal cortex during pair-association retrieval" (Jimura et al., 2016) [1]. Behavioral performance is provided in a table. Fig. 2 of the article is based on this table. Brain regions showing time effect are provided in a table. A statistical activation map for the time effect is shown in Fig. 3C of the article. PMID:27508239

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

    ERIC Educational Resources Information Center

    LoPresto, Michael C.

    2007-01-01

    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…

  11. Gun shows and gun violence: fatally flawed study yields misleading results.

    PubMed

    Wintemute, Garen J; Hemenway, David; Webster, Daniel; Pierce, Glenn; Braga, Anthony A

    2010-10-01

    A widely publicized but unpublished study of the relationship between gun shows and gun violence is being cited in debates about the regulation of gun shows and gun commerce. We believe the study is fatally flawed. A working paper entitled "The Effect of Gun Shows on Gun-Related Deaths: Evidence from California and Texas" outlined this study, which found no association between gun shows and gun-related deaths. We believe the study reflects a limited understanding of gun shows and gun markets and is not statistically powered to detect even an implausibly large effect of gun shows on gun violence. In addition, the research contains serious ascertainment and classification errors, produces results that are sensitive to minor specification changes in key variables and in some cases have no face validity, and is contradicted by 1 of its own authors' prior research. The study should not be used as evidence in formulating gun policy.

  12. Hybrid [FeFe]-hydrogenases with modified active sites show remarkable residual enzymatic activity.

    PubMed

    Siebel, Judith F; Adamska-Venkatesh, Agnieszka; Weber, Katharina; Rumpel, Sigrun; Reijerse, Edward; Lubitz, Wolfgang

    2015-02-24

    [FeFe]-hydrogenases are to date the only enzymes for which it has been demonstrated that the native inorganic binuclear cofactor of the active site Fe2(adt)(CO)3(CN)2 (adt = azadithiolate = [S-CH2-NH-CH2-S](2-)) can be synthesized on the laboratory bench and subsequently inserted into the unmaturated enzyme to yield fully functional holo-enzyme (Berggren, G. et al. (2013) Nature 499, 66-70; Esselborn, J. et al. (2013) Nat. Chem. Biol. 9, 607-610). In the current study, we exploit this procedure to introduce non-native cofactors into the enzyme. Mimics of the binuclear subcluster with a modified bridging dithiolate ligand (thiodithiolate, N-methylazadithiolate, dimethyl-azadithiolate) and three variants containing only one CN(-) ligand were inserted into the active site of the enzyme. We investigated the activity of these variants for hydrogen oxidation as well as proton reduction and their structural accommodation within the active site was analyzed using Fourier transform infrared spectroscopy. Interestingly, the monocyanide variant with the azadithiolate bridge showed ∼50% of the native enzyme activity. This would suggest that the CN(-) ligands are not essential for catalytic activity, but rather serve to anchor the binuclear subsite inside the protein pocket through hydrogen bonding. The inserted artificial cofactors with a propanedithiolate and an N-methylazadithiolate bridge as well as their monocyanide variants also showed residual activity. However, these activities were less than 1% of the native enzyme. Our findings indicate that even small changes in the dithiolate bridge of the binuclear subsite lead to a rather strong decrease of the catalytic activity. We conclude that both the Brønsted base function and the conformational flexibility of the native azadithiolate amine moiety are essential for the high catalytic activity of the native enzyme. PMID:25633077

  13. 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.

  14. Long-Term Trial Results Show No Mortality Benefit from Annual Prostate Cancer Screening

    Cancer.gov

    Thirteen year follow-up data from the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial show higher incidence but similar mortality among men screened annually with the prostate-specific antigen (PSA) test and digital rectal examination

  15. Comparison of some results of program SHOW with other solar hot water computer programs

    NASA Astrophysics Data System (ADS)

    Young, M. F.; Baughn, J. W.

    Subroutines and the driver program for the simulation code SHOW (solar hot water) for solar thermosyphon systems are discussed, and simulations are compared with predictions by the F-CHART and TRNSYS codes. SHOW has the driver program MAIN, which defines the system control logic for choosing the appropriate system subroutine for analysis. Ten subroutines are described, which account for the solar system physical parameters, the weather data, the manufacturer-supplied system specifications, mass flow rates, pumped systems, total transformed radiation, load use profiles, stratification in storage, an electric water heater, and economic analyses. The three programs are employed to analyze a thermosiphon installation in Sacramento with two storage tanks. TRNSYS and SHOW were in agreement and lower than F-CHARt for annual predictions, although significantly more computer time was necessary to make TRNSYS converge.

  16. Meropenem-clavulanic acid shows activity against Mycobacterium tuberculosis in vivo.

    PubMed

    England, Kathleen; Boshoff, Helena I M; Arora, Kriti; Weiner, Danielle; Dayao, Emmanuel; Schimel, Daniel; Via, Laura E; Barry, Clifton E

    2012-06-01

    The carbapenems imipenem and meropenem in combination with clavulanic acid reduced the bacterial burden in Mycobacterium tuberculosis-infected macrophages by 2 logs over 6 days. Despite poor stability in solution and a short half-life in rodents, treatment of chronically infected mice revealed significant reductions of bacterial burden in the lungs and spleens. Our results show that meropenem has activity in two in vivo systems, but stability and pharmacokinetics of long-term administration will offer significant challenges to clinical evaluation.

  17. 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.

  18. Stem cells show promising results for lymphoedema treatment--a literature review.

    PubMed

    Toyserkani, Navid Mohamadpour; Christensen, Marlene Louise; Sheikh, Søren Paludan; Sørensen, Jens Ahm

    2015-04-01

    Lymphoedema is a debilitating condition, manifesting in excess lymphatic fluid and swelling of subcutaneous tissues. Lymphoedema is as of yet still an incurable condition and current treatment modalities are not satisfactory. The capacity of mesenchymal stem cells to promote angiogenesis, secrete growth factors, regulate the inflammatory process, and differentiate into multiple cell types make them a potential ideal therapy for lymphoedema. Adipose tissue is the richest and most accessible source of mesenchymal stem cells and they can be harvested, isolated, and used for therapy in a single stage procedure as an autologous treatment. The aim of this paper was to review all studies using mesenchymal stem cells for lymphoedema treatment with a special focus on the potential use of adipose-derived stem cells. A systematic search was performed and five preclinical and two clinical studies were found. Different stem cell sources and lymphoedema models were used in the described studies. Most studies showed a decrease in lymphoedema and an increased lymphangiogenesis when treated with stem cells and this treatment modality has so far shown great potential. The present studies are, however, subject to bias and more preclinical studies and large-scale high quality clinical trials are needed to show if this emerging therapy can satisfy expectations.

  19. Sapphyrins induce apoptosis in hematopoietic tumor-derived cell lines and show in vivo antitumor activity.

    PubMed

    Naumovski, Louie; Ramos, Jason; Sirisawad, Mint; Chen, Jun; Thiemann, Patti; Lecane, Philip; Magda, Darren; Wang, Zhong; Cortez, Cecilia; Boswell, Garry; Gyu Cho, Dong; Sessler, Jonathan; Miller, Richard

    2005-06-01

    Sapphyrins are pentapyrrolic, metal-free, expanded porphyrins. In the present study, the activity of sapphyrins as anticancer agents in hematopoietic-derived tumor cells was explored. It was found that a dihydroxylated water-soluble sapphyrin derivative (PCI-2000) is a potent inducer of apoptosis in a wide variety of tumor cell lines including lymphoma (Ramos, DHL-4, and HF-1), leukemia (Jurkat and HL-60), and myeloma (8226/S, 1-310, C2E3, and 1-414). PCI-2000 triggers an apoptotic pathway in these tumor cells as shown by release of cytochrome c from mitochondria; activation of caspases 9, 8, and 3; cleavage of the caspase substrate poly(ADP-ribose) polymerase; and Annexin V binding. Apoptosis can be partially inhibited by overexpression of the antiapoptotic protein Bcl-2 or treatment with benzyloxycarbonyl-valine-alanine-aspartic acid-fluoromethylketone, a cell-permeable caspase inhibitor. Both PCI-2000 and PCI-2010, a tetrahydroxy bis-carbamate derivative of PCI-2000, result in increased levels of phosphorylated p38 mitogen-activated protein kinase. Inhibition of p38 mitogen-activated protein kinase phosphorylation resulted in a synergistic increase of PCI-2000 cytotoxicity. PCI-2010 showed less toxicity in mice than PCI-2000 and was active in slowing the growth of Ramos and HL-60 tumor xenografts in nude mice. These results provide preclinical rationale for the further study of sapphyrins for potential use in the treatment of hematopoietic-derived tumors.

  20. 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.

  1. 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

  2. Aortic emboli show surprising size dependent predilection for cerebral arteries: Results from computational fluid dynamics

    NASA Astrophysics Data System (ADS)

    Carr, Ian; Schwartz, Robert; Shadden, Shawn

    2012-11-01

    Cardiac emboli can have devastating consequences if they enter the cerebral circulation, and are the most common cause of embolic stroke. Little is known about relationships of embolic origin/density/size to cerebral events; as these relationships are difficult to observe. To better understand stoke risk from cardiac and aortic emboli, we developed a computational model to track emboli from the heart to the brain. Patient-specific models of the human aorta and arteries to the brain were derived from CT angiography from 10 MHIF patients. Blood flow was modeled by the Navier-Stokes equations using pulsatile inflow at the aortic valve, and physiologic Windkessel models at the outlets. Particulate was injected at the aortic valve and tracked using modified Maxey-Riley equations with a wall collision model. Results demonstrate aortic emboli that entered the cerebral circulation through the carotid or vertebral arteries were localized to specific locations of the proximal aorta. The percentage of released particles embolic to the brain markedly increased with particle size from 0 to ~1-1.5 mm in all patients. Larger particulate became less likely to traverse the cerebral vessels. These findings are consistent with sparse literature based on transesophageal echo measurements. This work was supported in part by the National Science Foundation, award number 1157041.

  3. Animation shows promise in initiating timely cardiopulmonary resuscitation: results of a pilot study.

    PubMed

    Attin, Mina; Winslow, Katheryn; Smith, Tyler

    2014-04-01

    Delayed responses during cardiac arrest are common. Timely interventions during cardiac arrest have a direct impact on patient survival. Integration of technology in nursing education is crucial to enhance teaching effectiveness. The goal of this study was to investigate the effect of animation on nursing students' response time to cardiac arrest, including initiation of timely chest compression. Nursing students were randomized into experimental and control groups prior to practicing in a high-fidelity simulation laboratory. The experimental group was educated, by discussion and animation, about the importance of starting cardiopulmonary resuscitation upon recognizing an unresponsive patient. Afterward, a discussion session allowed students in the experimental group to gain more in-depth knowledge about the most recent changes in the cardiac resuscitation guidelines from the American Heart Association. A linear mixed model was run to investigate differences in time of response between the experimental and control groups while controlling for differences in those with additional degrees, prior code experience, and basic life support certification. The experimental group had a faster response time compared with the control group and initiated timely cardiopulmonary resuscitation upon recognition of deteriorating conditions (P < .0001). The results demonstrated the efficacy of combined teaching modalities for timely cardiopulmonary resuscitation. Providing opportunities for repetitious practice when a patient's condition is deteriorating is crucial for teaching safe practice.

  4. Bipolar I disorder and major depressive disorder show similar brain activation during depression

    PubMed Central

    Cerullo, Michael A; Eliassen, James C; Smith, Christopher T; Fleck, David E; Nelson, Erik B; Strawn, Jeffrey R; Lamy, Martine; DelBello, Melissa P; Adler, Caleb M; Strakowski, Stephen M

    2014-01-01

    Objectives Despite different treatments and course of illness, depressive symptoms appear similar in major depressive disorder (MDD) and bipolar I disorder (BP-I). This similarity of depressive symptoms suggests significant overlap in brain pathways underlying neurovegetative, mood, and cognitive symptoms of depression. These shared brain regions might be expected to exhibit similar activation in individuals with MDD and BP-I during functional magnetic resonance imaging (fMRI). Methods fMRI was used to compare regional brain activation in participants with BP-I (n = 25) and MDD (n = 25) during a depressive episode as well as 25 healthy comparison (HC) participants. During the scans, participants performed an attentional task that incorporated emotional pictures. Results During the viewing of emotional images, subjects with BP-I showed decreased activation in the middle occipital gyrus, lingual gyrus, and middle temporal gyrus compared to both subjects with MDD and HC participants. During attentional processing, participants with MDD had increased activation in the parahippocampus, parietal lobe, and postcentral gyrus. However, among these regions, only the postcentral gyrus also showed differences between MDD and HC participants. Conclusions No differences in cortico-limbic regions were found between participants with BP-I and MDD during depression. Instead, the major differences occurred in primary and secondary visual processing regions with decreased activation in these regions in BP-I compared to major depression. These differences were driven by abnormal decreases in activation seen in the participants with BP-I. Posterior activation changes are a common finding in studies across mood states in participants with BP-I. PMID:24990479

  5. 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.

  6. 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. PMID:26692481

  7. 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.

  8. Commercial runs show TiO/sub 2/ Claus catalyst retains activity

    SciTech Connect

    Nougayrede, J.; Philippe, A.; Quesmerel, E.; Vermeersch, R.

    1987-08-10

    Commercial data are given for the CRS 31 Claus catalyst, jointly developed by Rhone Poulenc and Societe Nationale Elf Aquitane (Production) (SNEA). The data confirm laboratory results that show the catalyst's ability to deliver more complete hydrolysis in the first reactor of Claus sulfur recovery plants, and its ability to maintain activity in the second and third reactors. The most important losses in sulfur yields in Claus plants generally come from COS and CS/sub 2/ formed in the thermal steps of the process in the first reactor, and from the low Claus activity of alumina-based catalysts in the second and third reactors. In the first reactor, loaded with alumina-based catalyst, hydrolysis is only partial. Low Claus activity in second and third reactors is caused by the inevitable sulfation of the alumina. Catalytic-activity decrease of aluminas is caused particularly by the presence of oxygen, even in trace amounts, in the Claus gases. Therefore, in the first reactor, the CS/sub 2/ hydrolysis rate is lowered in the subsequent reactors, the H/sub 2/ + SO/sub 2/ conversion significantly drops. The chemical composition of CRS 31, TiO/sub 2/ only, in the same operating conditions, causes a significant improvement in activity because of its increased resistance to sulfation. The economics of the process are given.

  9. Side Chain Degradable Cationic-Amphiphilic Polymers with Tunable Hydrophobicity Show in Vivo Activity.

    PubMed

    Uppu, Divakara S S M; Samaddar, Sandip; Hoque, Jiaul; Konai, Mohini M; Krishnamoorthy, Paramanandham; Shome, Bibek R; Haldar, Jayanta

    2016-09-12

    Cationic-amphiphilic antibacterial polymers with optimal amphiphilicity generally target the bacterial membranes instead of mammalian membranes. To date, this balance has been achieved by varying the cationic charge or side chain hydrophobicity in a variety of cationic-amphiphilic polymers. Optimal hydrophobicity of cationic-amphiphilic polymers has been considered as the governing factor for potent antibacterial activity yet minimal mammalian cell toxicity. However, the concomitant role of hydrogen bonding and hydrophobicity with constant cationic charge in the interactions of antibacterial polymers with bacterial membranes is not understood. Also, degradable polymers that result in nontoxic degradation byproducts offer promise as safe antibacterial agents. Here we show that amide- and ester (degradable)-bearing cationic-amphiphilic polymers with tunable side chain hydrophobicity can modulate antibacterial activity and cytotoxicity. Our results suggest that an amide polymer can be a potent antibacterial agent with lower hydrophobicity whereas the corresponding ester polymer needs a relatively higher hydrophobicity to be as effective as its amide counterpart. Our studies reveal that at higher hydrophobicities both amide and ester polymers have similar profiles of membrane-active antibacterial activity and mammalian cell toxicity. On the contrary, at lower hydrophobicities, amide and ester polymers are less cytotoxic, but the former have potent antibacterial and membrane activity compared to the latter. Incorporation of amide and ester moieties made these polymers side chain degradable, with amide polymers being more stable than the ester polymers. Further, the polymers are less toxic, and their degradation byproducts are nontoxic to mice. More importantly, the optimized amide polymer reduces the bacterial burden of burn wound infections in mice models. Our design introduces a new strategy of interplay between the hydrophobic and hydrogen bonding interactions

  10. Meropenem-Clavulanic Acid Shows Activity against Mycobacterium tuberculosis In Vivo

    PubMed Central

    England, Kathleen; Boshoff, Helena I. M.; Arora, Kriti; Weiner, Danielle; Dayao, Emmanuel; Schimel, Daniel; Via, Laura E.

    2012-01-01

    The carbapenems imipenem and meropenem in combination with clavulanic acid reduced the bacterial burden in Mycobacterium tuberculosis-infected macrophages by 2 logs over 6 days. Despite poor stability in solution and a short half-life in rodents, treatment of chronically infected mice revealed significant reductions of bacterial burden in the lungs and spleens. Our results show that meropenem has activity in two in vivo systems, but stability and pharmacokinetics of long-term administration will offer significant challenges to clinical evaluation. PMID:22450968

  11. Plant vermicides of Haitian Vodou show in vitro activity against larval hookworm.

    PubMed

    Wolpert, Beverly J; Beauvoir, Max G; Wells, Elizabeth Fortson; Hawdon, John M

    2008-10-01

    Haitian Vodou priests (houngans) and priestesses (mambos) use plant remedies to treat many illnesses, including intestinal parasite infections. The present study screened 12 plants used in Vodou treatments for intestinal parasites to detect in vitro activity against infective-stage larvae of the hookworm Ancylostoma caninum. Water-soluble extracts of 4 of the 12 plants inhibited serum-stimulated feeding by larval A. caninum in a dose-dependent manner. All 4 plant extracts inhibited feeding induced by the muscarinic agonist arecoline, suggesting that these plant extracts may inhibit the insulin-like signaling pathway involved in the recovery and resumption of development of arrested A. caninum larvae. These results indicate that at least some of the plants used in traditional Haitian medicine as vermifuges show activity against nematode physiological processes.

  12. 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

  13. 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

  14. 26 CFR 1.513-3 - Qualified convention and trade show activity.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... segment thereof) of the members of the qualifying organization; and (iii) The show is designed to achieve...— (i) Activities designed to attract to the show members of the sponsoring organization, members of an... interest in, and demand for such products or services; (ii) Activities designed to educate persons in...

  15. 26 CFR 1.513-3 - Qualified convention and trade show activity.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... segment thereof) of the members of the qualifying organization; and (iii) The show is designed to achieve...— (i) Activities designed to attract to the show members of the sponsoring organization, members of an... interest in, and demand for such products or services; (ii) Activities designed to educate persons in...

  16. 26 CFR 1.513-3 - Qualified convention and trade show activity.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... segment thereof) of the members of the qualifying organization; and (iii) The show is designed to achieve...— (i) Activities designed to attract to the show members of the sponsoring organization, members of an... interest in, and demand for such products or services; (ii) Activities designed to educate persons in...

  17. 26 CFR 1.513-3 - Qualified convention and trade show activity.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... segment thereof) of the members of the qualifying organization; and (iii) The show is designed to achieve...— (i) Activities designed to attract to the show members of the sponsoring organization, members of an... interest in, and demand for such products or services; (ii) Activities designed to educate persons in...

  18. 26 CFR 1.513-3 - Qualified convention and trade show activity.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... segment thereof) of the members of the qualifying organization; and (iii) The show is designed to achieve...— (i) Activities designed to attract to the show members of the sponsoring organization, members of an... interest in, and demand for such products or services; (ii) Activities designed to educate persons in...

  19. Tellurium in active volcanic environments: Preliminary results

    NASA Astrophysics Data System (ADS)

    Milazzo, Silvia; Calabrese, Sergio; D'Alessandro, Walter; Brusca, Lorenzo; Bellomo, Sergio; Parello, Francesco

    2014-05-01

    Tellurium is a toxic metalloid and, according to the Goldschmidt classification, a chalcophile element. In the last years its commercial importance has considerably increased because of its wide use in solar cells, thermoelectric and electronic devices of the last generation. Despite such large use, scientific knowledge about volcanogenic tellurium is very poor. Few previous authors report result of tellurium concentrations in volcanic plume, among with other trace metals. They recognize this element as volatile, concluding that volcanic gases and sulfur deposits are usually enriched with tellurium. Here, we present some results on tellurium concentrations in volcanic emissions (plume, fumaroles, ash leachates) and in environmental matrices (soils and plants) affected by volcanic emissions and/or deposition. Samples were collected at Etna and Vulcano (Italy), Turrialba (Costa Rica), Miyakejima, Aso, Asama (Japan), Mutnovsky (Kamchatka) at the crater rims by using common filtration techniques for aerosols (polytetrafluoroethylene filters). Filters were both eluted with Millipore water and acid microwave digested, and analyzed by inductively coupled plasma mass spectrometry (ICP-MS). Volcanic ashes emitted during explosive events on Etna and Copahue (Argentina) were analyzed for tellurium bulk composition and after leaching experiments to evaluate the soluble fraction of tellurium. Soils and leaves of vegetation were also sampled close to active volcanic vents (Etna, Vulcano, Nisyros, Nyiragongo, Turrialba, Gorely and Masaya) and investigated for tellurium contents. Preliminary results showed very high enrichments of tellurium in volcanic emissions comparing with other volatile elements like mercury, arsenic, thallium and bismuth. This suggests a primary transport in the volatile phase, probably in gaseous form (as also suggested by recent studies) and/or as soluble salts (halides and/or sulfates) adsorbed on the surface of particulate particles and ashes. First

  20. Arctigenin blocks the unfolded protein response and shows therapeutic antitumor activity.

    PubMed

    Kim, Ju-Young; Hwang, Ji-Hwan; Cha, Mi-Ran; Yoon, Mi-Young; Son, Eun-Soon; Tomida, Akihiro; Ko, Bosung; Song, Si-Whan; Shin-ya, Kazuo; Hwang, Yong-il; Park, Hae-Ryong

    2010-07-01

    Cancer cells in poorly vascularized solid tumors are constantly or intermittently exposed to stressful microenvironments, including glucose deprivation, hypoxia, and other forms of nutrient starvation. These tumor-specific conditions, especially glucose deprivation, activate a signaling pathway called the unfolded protein response (UPR), which enhances cell survival by induction of the stress proteins. We have established a screening method to discover anticancer agents that could preferentially inhibit tumor cell viability under glucose-deprived conditions. Here we identify arctigenin (ARC-G) as an active compound that shows selective cytotoxicity and inhibits the UPR during glucose deprivation. Indeed, ARC-G blocked expression of UPR target genes such as phosphorylated-PERK, ATF4, CHOP, and GRP78, which was accompanied by enhanced phosphorylation of eIF2 alpha during glucose deprivation. The UPR inhibition led to apoptosis involving a mitochondrial pathway by activation of caspase-9 and -3. Furthermore, ARC-G suppressed tumor growth of colon cancer HT-29 xenografts. Our results demonstrate that ARC-G can be served as a novel type of antitumor agent targeting the UPR in glucose-deprived solid tumors.

  1. Tobacco-expressed Brassica juncea chitinase BjCHI1 shows antifungal activity in vitro.

    PubMed

    Fung, King-Leung; Zhao, Kai-Jun; He, Zhu-Mei; Chye, Mee-Len

    2002-09-01

    We have previously isolated a Brassica juncea cDNA encoding BjCHI1, a novel chitinase with two chitin-binding domains, and have shown that its mRNA is induced by wounding and methyl jasmonate treatment (K.-J. Zhao and M.-L. Chye, Plant Mol. Biol. 40 (1999) 1009-1018). By the presence of two chitin-binding domains, BjCHI1 resembles the precursor of UDA (Urtica dioica agglutinin) but, unlike UDA, BjCHI1 retains its chitinase catalytic domain after post-translational processing. Here, we indicate the role of BjCHI1 in plant defense by demonstrating its mRNA induction upon Aspergillus niger infection or caterpillar Pieris rapae (L.) feeding. To further investigate the biological properties of BjCHI1, we transformed tobacco with a construct expressing the BjCHI1 cDNA from the CaMV 35S promoter. Subsequently, we purified BjCHI1 from the resultant transgenic Ro plants using a regenerated chitin column followed by fast protein liquid chromatography (FPLC). Also, the significance of the second chitin-binding domain in BjCHI1 was investigated by raising transgenic tobacco plants expressing BjCHI2, a deletion derivative of BjCHI1 lacking one chitin-binding domain. Colorimetric chitinase assays at 25 degrees C, pH 5, showed no significant differences between the activities of BjCHI1 and BjCHI2, suggesting that chitinase activity, due to the catalytic domain, is not enhanced by the presence of a second chitin-binding domain. Both BjCHI1 and BjCHI2 show in vitro anti-fungal activity toward Trichoderma viride, causing reductions in hyphal diameter, hyphal branching and conidia size. PMID:12175020

  2. Piper betle shows antioxidant activities, inhibits MCF-7 cell proliferation and increases activities of catalase and superoxide dismutase

    PubMed Central

    2012-01-01

    Background Breast cancer is the most common form of cancer and the focus on finding chemotherapeutic agents have recently shifted to natural products. Piper betle is a medicinal plant with various biological activities. However, not much data is available on the anti-cancer effects of P. betle on breast cancer. Due to the current interest in the potential effects of antioxidants from natural products in breast cancer treatment, we investigated the antioxidant activities of the leaves of P. betle and its inhibitory effect on the proliferation of the breast cancer cell line, MCF-7. Methods The leaves of P. betle were extracted with solvents of varying polarities (water, methanol, ethyl acetate and hexane) and their phenolic and flavonoid content were determined using colorimetric assays. Phenolic composition was characterized using HPLC. Antioxidant activities were measured using FRAP, DPPH, superoxide anion, nitric oxide and hyroxyl radical scavenging assays. Biological activities of the extracts were analysed using MTT assay and antioxidant enzyme (catalase, superoxide dismutase, glutathione peroxidase) assays in MCF-7 cells. Results Overall, the ethyl acetate extract showed the highest ferric reducing activity and radical scavenging activities against DPPH, superoxide anion and nitric oxide radicals. This extract also contained the highest phenolic content implying the potential contribution of phenolics towards the antioxidant activities. HPLC analyses revealed the presence of catechin, morin and quercetin in the leaves. The ethyl acetate extract also showed the highest inhibitory effect against the proliferation of MCF-7 cells (IC50=65 μg/ml). Treatment of MCF-7 cells with the plant extract increased activities of catalase and superoxide dismutase. Conclusions Ethyl acetate is the optimal solvent for the extraction of compounds with antioxidant and anti-proliferative activities. The increased activities of catalase and superoxide dismutase in the treated cells

  3. Polyethylenimine-cyclodextrin-tegafur conjugate shows anti-cancer activity and a potential for gene delivery*

    PubMed Central

    Hu, Qi-da; Fan, Hui; Lou, Wei-jian; Wang, Qing-qing; Tang, Gu-ping

    2011-01-01

    Polyethylenimine-cyclodextrin-tegafur (PEI-CyD-tegafur) conjugate was synthesized as a novel multifunctional prodrug of tegafur for co-delivery of chemotherapeutic agent tegafur and enhanced green fluorescent protein (EGFP) reporter plasmid DNA. Conjugation of tegafur to PEI-CyD via chemical linkage was characterized by 1H NMR spectrometry and ultraviolet (UV) spectrometry. PEI-CyD-tegafur was able to condense plasmid DNA into complexes of around 150 nm with positive charge at the N/P ratio of 25, in accordance with electron microscopy observation of compact and monodisperse nanoparticles. The results of in vitro experiments showed enhanced cytotoxicity and considerable transfection efficiency in B16F10 cell line. Therefore, PEI-CyD-tegafur may have great potential as a co-delivery system with anti-cancer activity and potential for gene delivery. PMID:21887847

  4. 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

  5. Transgenic tobacco expressing a foreign calmodulin gene shows an enhanced production of active oxygen species.

    PubMed Central

    Harding, S A; Oh, S H; Roberts, D M

    1997-01-01

    A strategy for elucidating specific molecular targets of calcium and calmodulin in plant defense responses has been developed. We have used a dominant-acting calmodulin mutant (VU-3, Lys to Arg115) to investigate the oxidative burst and nicotinamide co-enzyme fluxes after various stimuli (cellulase, harpin, incompatible bacteria, osmotic and mechanical) that elicit plant defense responses in transgenic tobacco cell cultures. VU-3 calmodulin differs from endogenous plant calmodulin in that it cannot be methylated post-translationally, and as a result it hyperactivates calmodulin-dependent NAD kinase. Cells expressing VU-3 calmodulin exhibited a stronger active oxygen burst that occurred more rapidly than in normal control cells challenged with the same stimuli. Increases in NADPH level were also greater in VU-3 cells and coincided both in timing and magnitude with development of the active oxygen species (AOS) burst. These data show that calmodulin is a target of calcium fluxes in response to elicitor or environmental stress, and provide the first evidence that plant NAD kinase may be a downstream target which potentiates AOS production by altering NAD(H)/NADP(H) homeostasis. PMID:9135130

  6. The Reverse Transcription Inhibitor Abacavir Shows Anticancer Activity in Prostate Cancer Cell Lines

    PubMed Central

    Molinari, Agnese; Parisi, Chiara; Bozzuto, Giuseppina; Toccacieli, Laura; Formisano, Giuseppe; De Orsi, Daniela; Paradisi, Silvia; Grober, OlÌ Maria Victoria; Ravo, Maria; Weisz, Alessandro; Arcieri, Romano; Vella, Stefano; Gaudi, Simona

    2010-01-01

    Background Transposable Elements (TEs) comprise nearly 45% of the entire genome and are part of sophisticated regulatory network systems that control developmental processes in normal and pathological conditions. The retroviral/retrotransposon gene machinery consists mainly of Long Interspersed Nuclear Elements (LINEs-1) and Human Endogenous Retroviruses (HERVs) that code for their own endogenous reverse transcriptase (RT). Interestingly, RT is typically expressed at high levels in cancer cells. Recent studies report that RT inhibition by non-nucleoside reverse transcriptase inhibitors (NNRTIs) induces growth arrest and cell differentiation in vitro and antagonizes growth of human tumors in animal model. In the present study we analyze the anticancer activity of Abacavir (ABC), a nucleoside reverse transcription inhibitor (NRTI), on PC3 and LNCaP prostate cancer cell lines. Principal Findings ABC significantly reduces cell growth, migration and invasion processes, considerably slows S phase progression, induces senescence and cell death in prostate cancer cells. Consistent with these observations, microarray analysis on PC3 cells shows that ABC induces specific and dose-dependent changes in gene expression, involving multiple cellular pathways. Notably, by quantitative Real-Time PCR we found that LINE-1 ORF1 and ORF2 mRNA levels were significantly up-regulated by ABC treatment. Conclusions Our results demonstrate the potential of ABC as anticancer agent able to induce antiproliferative activity and trigger senescence in prostate cancer cells. Noteworthy, we show that ABC elicits up-regulation of LINE-1 expression, suggesting the involvement of these elements in the observed cellular modifications. PMID:21151977

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

    PubMed

    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

    2015-10-01

    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

  8. 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

  9. 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.

  10. A piperidine amide extracted from Piper longum L. fruit shows activity against Aedes aegypti mosquito larvae.

    PubMed

    Yang, Young-Cheol; Lee, Sang-Guei; Lee, Hee-Kwon; Kim, Moo-Key; Lee, Sang-Hyun; Lee, Hoi-Seon

    2002-06-19

    Mosquito larvicidal activity of Piper longum fruit-derived materials against the fourth-instar larvae of Aedes aegypti was examined. A crude methanol extract of P. longum fruits was found to be active against the larvae, and the hexane fraction of the methanol extract showed a strong larvicidal activity of 100% mortality. The biologically active component of P. longum fruits was characterized as pipernonaline by spectroscopic analyses. The LC(50) value of pipernonaline was 0.25 mg/L. The toxicity of pipernonaline is comparable to that of pirimiphos-methyl as a mosquito larvicide. In tests with available components derived from P. longum, no activity was observed with piperettine, piperine, or piperlongumine.

  11. 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

  12. 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.

  13. 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…

  14. Lunar maria - result of mantle plume activity?

    NASA Astrophysics Data System (ADS)

    Sharkov, E.

    It is generally accepted that lunar maria are the result of catastrophic impact events. However, comparative studying of the Earth's and the Moon's tectonomagmatic evolution could evidence about another way of these specific structures origin. Such studies showed that the both planetary bodies evolved on the close scenario: their geological development began after solidification of global magmatic oceans which led to appearance of their primordial crusts: granitic on the Earth and anorthositic - on the Moon. The further evolution of the both bodies occurred in two stages. For their first stages, lasted ˜2.5 mlrd. years on the Earth and ˜1.5 mlrd. years on the Moon, were typical melts, generated in depleted mantle (Bogatikov et al., 2000). However, at the boundary 2.2-2.0 Ga ago on the Earth and 3.9-3.8 Ga on the Moon another type of magmas appeared: geochemical enriched Fe-Ti picrites and basalts, characteristic for the terrestrial Phanerozoic plume-related situations, and basaltic mare magmatism with high-Ti varieties on the Moon. It suggests that evolution of the Earth's magmatism was linked with ascending of mantle plumes (superplumes) of two generation: (1) generated in the mantle, depleted during solidification of magmatic ocean and Archean magmatic activity, and (2) generated at the core-mantle boundary (CMB). The latter were enriched in the mantle fluid components (Fe, Ti, alkalies, etc); this lighter material could ascend to shallower depths, leading to change of tectonic processes, in particular, to appearance of plate tectonics as the major type of tectonomagmatic activity till now (Bogatikov et al., 2000). By analogy to the Earth, magmatism of the Moon was also linked with ascending of mantle plumes: (1) generated in the depleted mantle (magnesian suite) and (2) generated at the lunar CMB with liquid at that time metallic core (mare basalt and picrites with high-Ti varieties). Like on the Earth, these plumes were lighter than the older plumes, and

  15. 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.

  16. 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.

  17. Male-to-female transsexuals show sex-atypical hypothalamus activation when smelling odorous steroids.

    PubMed

    Berglund, H; Lindström, P; Dhejne-Helmy, C; Savic, I

    2008-08-01

    One working hypothesis behind transsexuality is that the normal sex differentiation of certain hypothalamic networks is altered. We tested this hypothesis by investigating the pattern of cerebral activation in 12 nonhomosexual male-to-female transsexuals (MFTRs) when smelling 4,16-androstadien-3-one (AND) and estra-1,3,5(10),16-tetraen-3-ol (EST). These steroids are reported to activate the hypothalamic networks in a sex-differentiated way. Like in female controls the hypothalamus in MFTRs activated with AND, whereas smelling of EST engaged the amygdala and piriform cortex. Male controls, on the other hand, activated the hypothalamus with EST. However, when restricting the volume of interest to the hypothalamus activation was detected in MFTR also with EST, and explorative conjunctional analysis revealed that MFTR shared a hypothalamic cluster with women when smelling AND, and with men when smelling EST. Because the EST effect was limited, MFTR differed significantly only from male controls, and only for EST-AIR and EST-AND. These data suggest a pattern of activation away from the biological sex, occupying an intermediate position with predominantly female-like features. Because our MFTRs were nonhomosexual, the results are unlikely to be an effect of sexual practice. Instead, the data implicate that transsexuality may be associated with sex-atypical physiological responses in specific hypothalamic circuits, possibly as a consequence of a variant neuronal differentiation.

  18. 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

  19. [Results of 2 years of activity].

    PubMed

    Panigazzi, M

    2010-01-01

    Work-related injuries and occupational diseases are a scourge of modern, western societies, which, although technologically advanced, have difficulty in preventing, treating and rehabilitating victims with speed and efficiency. The current hospital neuromotor rehabilitation centres, whether public or accredited private structures, have notable difficulty in meeting the demand, which despite annual fluctuations and variable needs, does not, overall, seem to be decreasing. We present the results of an organization model developed at the "Fondazione Maugeri" Scientific Institute (Pavia, Italy), the criteria used for the activity, the technological innovations employed to determine ability, and the prospects for further development. This model is effective from a health care-rehabilitative point of view, also in the light of the new legislative scenarios, and is sustainable from an economic points of view; overall it is, therefore, efficient. PMID:21438253

  20. Triterpenoids of sour jujube show pronounced inhibitory effect on human tumor cells and antioxidant activity.

    PubMed

    Qiao, Aimin; Wang, Yihai; Xiang, Limin; Zhang, Zhenxue; He, Xiangjiu

    2014-10-01

    Sour jujube is a common fruit and traditional medicine in China. Bioactivity-guided fractionation of sour jujube was used to determine the chemical identity of potent antiproliferative and antioxidant constituents. Four novel ursane-type triterpenoids, together with 8 known were isolated and identified. The new triterpenoids were elucidated to be 2α,3β,13β,23-tetrahydroxy-urs-11-en-28-oic acid (3), 2α,3β-dihydroxy-urs-20(30)-en-28-oic acid (9), 2α,3β,28-trihydroxy-urs-20(30)-ene (10), and 3β,12β,13β-trihydroxy-ursan-28-oic acid (11). Among the triterpenoids isolated, 2α,3β,19α-trihydroxy-urs-12-en-28-oic acid (7), 9 and 10 showed high potent inhibitory activity toward the proliferation of HepG2 cells, which the IC50 values were lower than 5 μM. Compounds 9 and 10 also exhibited pronounced activity against MCF-7 cells, with IC50 value of 0.8 ± 0.03 and 1.5 ± 0.1 μM, respectively. Compound 10 showed high antioxidant activity with an EC50 of 0.8 ± 0.02 μM, which was 18.9 times higher than ascorbic acid in antioxidant capacity.

  1. The novel AKT inhibitor afuresertib shows favorable safety, pharmacokinetics, and clinical activity in multiple myeloma

    PubMed Central

    Spencer, Andrew; Yoon, Sung-Soo; Harrison, Simon J.; Morris, Shannon R.; Smith, Deborah A.; Brigandi, Richard A.; Gauvin, Jennifer; Kumar, Rakesh; Opalinska, Joanna B.

    2014-01-01

    The PI3K/AKT pathway is constitutively active in hematologic malignancies, providing proliferative and antiapoptotic signals and possibly contributing to drug resistance. We conducted an open-label phase 1 study to evaluate the maximum tolerated dose (MTD), safety, pharmacokinetics, and clinical activity of afuresertib—an oral AKT inhibitor—in patients with advanced hematologic malignancies. Seventy-three patients were treated at doses ranging from 25 to 150 mg per day. The MTD was established at 125 mg per day because of 2 dose-limiting toxicities in the 150-mg cohort (liver function test abnormalities). The most frequent adverse events were nausea (35.6%), diarrhea (32.9%), and dyspepsia (24.7%). Maximum plasma concentrations and area under the plasma concentration-time curves from time 0 to 24 hours were generally dose proportional at >75-mg doses; the median time to peak plasma concentrations was 1.5 to 2.5 hours post dose, with a half-life of approximately 1.7 days. Three multiple myeloma patients attained partial responses; an additional 3 attained minimal responses. Clinical activity was also observed in non-Hodgkin lymphoma, Langerhan's cell histiocytosis, and Hodgkin disease. Single-agent afuresertib showed a favorable safety profile and demonstrated clinical activity against hematologic malignancies, including multiple myeloma. This trial was registered at www.clinicaltrials.gov as #NCT00881946. PMID:25075128

  2. 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. PMID:27454593

  3. Honey, pollen, and propolis extracts show potent inhibitory activity against the zinc metalloenzyme carbonic anhydrase.

    PubMed

    Sahin, H; Aliyazicioglu, R; Yildiz, O; Kolayli, S; Innocenti, A; Supuran, C T

    2011-06-01

    Three different honey extracts from the endemic plant in the Black Sea region Rhododendron ponticum, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1), more precisely the human (h) isoforms hCA I and hCA II. Hexane, methanol, ethanol, and water solid-phase extractions (SPEs) showed inhibitory activity towards the two CA isozymes which were related to the total phenolic content. The highest inhibitory effects (0.036-0.039 mg/mL) were those of propolis methanolic extract. Among the three different samples investigated here, the aqueous extracts showed lower inhibitory effects compared to the organic solvent SPE extracts (in the range of 1.150- 5.144 mg/mL). The studied honey extracts constitute an interesting source of phenolic derivatives that might serve to identify lead compounds, targeting the physiologically relevant enzymes CA I and CA II.

  4. Youth at risk for obesity show greater activation of striatal and somatosensory regions to food.

    PubMed

    Stice, Eric; Yokum, Sonja; Burger, Kyle S; Epstein, Leonard H; Small, Dana M

    2011-03-23

    Obese humans, compared with normal-weight humans, have less striatal D2 receptors and striatal response to food intake; weaker striatal response to food predicts weight gain for individuals at genetic risk for reduced dopamine (DA) signaling, consistent with the reward-deficit theory of obesity. Yet these may not be initial vulnerability factors, as overeating reduces D2 receptor density, D2 sensitivity, reward sensitivity, and striatal response to food. Obese humans also show greater striatal, amygdalar, orbitofrontal cortex, and somatosensory region response to food images than normal-weight humans do, which predicts weight gain for those not at genetic risk for compromised dopamine signaling, consonant with the reward-surfeit theory of obesity. However, after pairings of palatable food intake and predictive cues, DA signaling increases in response to the cues, implying that eating palatable food contributes to increased responsivity. Using fMRI, we tested whether normal-weight adolescents at high- versus low-risk for obesity showed aberrant activation of reward circuitry in response to receipt and anticipated receipt of palatable food and monetary reward. High-risk youth showed greater activation in the caudate, parietal operculum, and frontal operculum in response to food intake and in the caudate, putamen, insula, thalamus, and orbitofrontal cortex in response to monetary reward. No differences emerged in response to anticipated food or monetary reward. Data indicate that youth at risk for obesity show elevated reward circuitry responsivity in general, coupled with elevated somatosensory region responsivity to food, which may lead to overeating that produces blunted dopamine signaling and elevated responsivity to food cues.

  5. Youth at Risk for Obesity Show Greater Activation of Striatal and Somatosensory Regions to Food

    PubMed Central

    Stice, E; Yokum, S; Burger, KS; Epstein, LH; Small, DM

    2011-01-01

    Obese versus normal-weight humans have less striatal D2 receptors and striatal response to food intake, and weaker striatal response to food predicts weight gain for individuals at genetic risk for reduced dopamine (DA) signaling, consistent with the reward deficit theory of obesity. Yet these may not be initial vulnerability factors, as overeating reduces D2 receptor density, D2 sensitivity, reward sensitivity, and striatal response to food. Obese versus normal-weight humans also show greater striatal, amygdalar, orbitofrontal cortex, and somatosensory region response to food images, which predicts weight gain for those not at genetic risk for compromised dopamine signaling, consonant with the reward surfeit theory of obesity. However, after pairings of palatable food intake and predictive cues, DA signaling increases in response to the cues, implying that eating palatable food contributes to increased responsivity. We tested whether normal-weight adolescents at high- versus low-risk for obesity showed aberrant activation of reward circuitry in response to receipt and anticipated receipt of palatable food and monetary reward using fMRI. High-risk youth showed greater activation in the caudate, parietal operculum, and frontal operculum in response to food intake and in the caudate, putamen, insula, thalamus, and orbitofrontal cortex in response to monetary reward. No differences emerged in response to anticipated food or monetary reward. Data indicate that youth at risk for obesity show elevated reward circuitry responsivity in general coupled with elevated somatosensory region responsivity to food, which may lead to overeating that produces blunted dopamine signaling and elevated responsivity to food cues. PMID:21430137

  6. Youth at risk for obesity show greater activation of striatal and somatosensory regions to food.

    PubMed

    Stice, Eric; Yokum, Sonja; Burger, Kyle S; Epstein, Leonard H; Small, Dana M

    2011-03-23

    Obese humans, compared with normal-weight humans, have less striatal D2 receptors and striatal response to food intake; weaker striatal response to food predicts weight gain for individuals at genetic risk for reduced dopamine (DA) signaling, consistent with the reward-deficit theory of obesity. Yet these may not be initial vulnerability factors, as overeating reduces D2 receptor density, D2 sensitivity, reward sensitivity, and striatal response to food. Obese humans also show greater striatal, amygdalar, orbitofrontal cortex, and somatosensory region response to food images than normal-weight humans do, which predicts weight gain for those not at genetic risk for compromised dopamine signaling, consonant with the reward-surfeit theory of obesity. However, after pairings of palatable food intake and predictive cues, DA signaling increases in response to the cues, implying that eating palatable food contributes to increased responsivity. Using fMRI, we tested whether normal-weight adolescents at high- versus low-risk for obesity showed aberrant activation of reward circuitry in response to receipt and anticipated receipt of palatable food and monetary reward. High-risk youth showed greater activation in the caudate, parietal operculum, and frontal operculum in response to food intake and in the caudate, putamen, insula, thalamus, and orbitofrontal cortex in response to monetary reward. No differences emerged in response to anticipated food or monetary reward. Data indicate that youth at risk for obesity show elevated reward circuitry responsivity in general, coupled with elevated somatosensory region responsivity to food, which may lead to overeating that produces blunted dopamine signaling and elevated responsivity to food cues. PMID:21430137

  7. 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

  8. Isolation of natural compounds from Phlomis stewartii showing α-glucosidase inhibitory activity.

    PubMed

    Jabeen, Bushra; Riaz, Naheed; Saleem, Muhammad; Naveed, Muhammad Akram; Ashraf, Muhammad; Alam, Umber; Rafiq, Hafiza Mehwish; Tareen, Rasool Bakhsh; Jabbar, Abdul

    2013-12-01

    Stewartiiside (1), a phenylethanoid glycoside and three 28-nortriterpenoids: stewertiisins A-C [(17R)-19(18→17)-abeo-3α,18β,23,24-tetrahydroxy-28-norolean-12-ene, 2; (17R)-19(18→17)-abeo-2α,16β,18β,23,24-pentahydroxy-28-norolean-12-en-3-one, 3; (17R)-19(18→17)-abeo-2α,3α,23,24-tetrahydroxy-28-noroleane-11,13-diene, 4] together with eight known compounds: lunariifolioside (5), notohamosin A (6), phlomispentanol (7), isorhamnetin 3-(6-p-coumaroyl)-β-D-glucopyranoside (8), tiliroside (9), caffeic acid (10), p-hydrxybenzoic acid (11) and oleanolic acid (12) were isolated from the ethyl acetate soluble fraction of the methanolic extract of whole plant of Phlomis stewartii. The structures of these isolates (1-12) were elucidated by the combination of 1D ((1)H and (13)C NMR), 2D (HMQC, HMBC COSY, NOESY) NMR spectroscopy and mass spectrometry (EIMS, HREIMS, FABMS, HRFABMS) and in comparison with literature data of related compounds. All the isolates (1-12) showed α-glucosidase inhibitory activity with IC50 values ranging between 14.5 and 355.4 μM, whereas, compounds 1, 5, 9 and 10 showed promising α-glucosidase inhibitory activity with IC50 values below 30 μM.

  9. 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. PMID:23142503

  10. 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.

  11. Apratoxin A Shows Novel Pancreas-Targeting Activity through the Binding of Sec 61.

    PubMed

    Huang, Kuan-Chun; Chen, Zhihong; Jiang, Yimin; Akare, Sandeep; Kolber-Simonds, Donna; Condon, Krista; Agoulnik, Sergei; Tendyke, Karen; Shen, Yongchun; Wu, Kuo-Ming; Mathieu, Steven; Choi, Hyeong-Wook; Zhu, Xiaojie; Shimizu, Hajime; Kotake, Yoshihiko; Gerwick, William H; Uenaka, Toshimitsu; Woodall-Jappe, Mary; Nomoto, Kenichi

    2016-06-01

    Apratoxin A is a natural product with potent antiproliferative activity against many human cancer cell lines. However, we and other investigators observed that it has a narrow therapeutic window in vivo Previous mechanistic studies have suggested its involvement in the secretory pathway as well as the process of chaperone-mediated autophagy. Still the link between the biologic activities of apratoxin A and its in vivo toxicity has remained largely unknown. A better understanding of this relationship is critically important for any further development of apratoxin A as an anticancer drug. Here, we describe a detailed pathologic analysis that revealed a specific pancreas-targeting activity of apratoxin A, such that severe pancreatic atrophy was observed in apratoxin A-treated animals. Follow-up tissue distribution studies further uncovered a unique drug distribution profile for apratoxin A, showing high drug exposure in pancreas and salivary gland. It has been shown previously that apratoxin A inhibits the protein secretory pathway by preventing cotranslational translocation. However, the molecule targeted by apratoxin A in this pathway has not been well defined. By using a (3)H-labeled apratoxin A probe and specific Sec 61α/β antibodies, we identified that the Sec 61 complex is the molecular target of apratoxin A. We conclude that apratoxin A in vivo toxicity is likely caused by pancreas atrophy due to high apratoxin A exposure. Mol Cancer Ther; 15(6); 1208-16. ©2016 AACR.

  12. Intervention to increase physical activity in irritable bowel syndrome shows long-term positive effects

    PubMed Central

    Johannesson, Elisabet; Ringström, Gisela; Abrahamsson, Hasse; Sadik, Riadh

    2015-01-01

    AIM: To assess the long-term effects of physical activity on irritable bowel syndrome (IBS) symptoms and on quality of life, fatigue, depression and anxiety. METHODS: Seventy-six patients from a previous randomized controlled interventional study on increased physical activity in IBS were asked to participate in this long-term follow-up study. The included patients attended one visit in which they filled out questionnaires and they underwent a submaximal cycle ergometer test. The primary end point was the change in the IBS Severity Scoring System (IBS-SSS) at baseline, i.e., before the intervention and at follow-up. The secondary endpoints were changes in quality of life, fatigue, depression and anxiety. RESULTS: A total of 39 [32 women, median age 45 (28-61) years] patients were included in this follow-up. Median follow-up time was 5.2 (range: 3.8-6.2) years. The IBS symptoms were improved compared with baseline [IBS-SSS: 276 (169-360) vs 218 (82-328), P = 0.001]. This was also true for the majority of the dimensions of psychological symptoms such as disease specific quality of life, fatigue, depression and anxiety. The reported time of physical activity during the week before the visit had increased from 3.2 (0.0-10.0) h at baseline to 5.2 (0.0-15.0) h at follow-up, P = 0.019. The most common activities reported were walking, aerobics and cycling. There was no significant difference in the oxygen uptake 31.8 (19.7-45.8) mL per min per kg at baseline vs 34.6 (19.0-54.6) mL/min per kg at follow-up. CONCLUSION: An intervention to increase physical activity has positive long-term effects on IBS symptoms and psychological symptoms. PMID:25593485

  13. AHTN and HHCB show weak estrogenic--but no uterotrophic activity.

    PubMed

    Seinen, W; Lemmen, J G; Pieters, R H; Verbruggen, E M; van der Burg, B

    1999-12-20

    .E., Giesy, J.P., Van den Berg, M., 1999. In vitro vitellogenin production by carp (Cyprimus carpio) hepatocytes as a screening method for determining (anti-) estrogenic activity of xenobiotics. Toxicol. Appl. Pharmacol., 157, 68-76). Therefore it is concluded that these compounds have very weak estrogenic potency, too weak to induce estrogenic effects in wildlife species or humans at the current levels of exposure. These results give further support to the promiscuity of estrogen receptors.

  14. Nonlinear analysis of motor activity shows differences between schizophrenia and depression: a study using Fourier analysis and sample entropy.

    PubMed

    Hauge, Erik R; Berle, Jan Øystein; Oedegaard, Ketil J; Holsten, Fred; Fasmer, Ole Bernt

    2011-01-28

    The purpose of this study has been to describe motor activity data obtained by using wrist-worn actigraphs in patients with schizophrenia and major depression by the use of linear and non-linear methods of analysis. Different time frames were investigated, i.e., activity counts measured every minute for up to five hours and activity counts made hourly for up to two weeks. The results show that motor activity was lower in the schizophrenic patients and in patients with major depression, compared to controls. Using one minute intervals the depressed patients had a higher standard deviation (SD) compared to both the schizophrenic patients and the controls. The ratio between the root mean square successive differences (RMSSD) and SD was higher in the schizophrenic patients compared to controls. The Fourier analysis of the activity counts measured every minute showed that the relation between variance in the low and the high frequency range was lower in the schizophrenic patients compared to the controls. The sample entropy was higher in the schizophrenic patients compared to controls in the time series from the activity counts made every minute. The main conclusions of the study are that schizophrenic and depressive patients have distinctly different profiles of motor activity and that the results differ according to period length analysed.

  15. 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.

  16. 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.

  17. Novel nuclear targeting coiled-coil protein of Helicobacter pylori showing Ca(2+)-independent, Mg(2+)-dependent DNase I activity.

    PubMed

    Kwon, Young Chul; Kim, Sinil; Lee, Yong Seok; Lee, Je Chul; Cho, Myung-Je; Lee, Woo-Kon; Kang, Hyung-Lyun; Song, Jae-Young; Baik, Seung Chul; Ro, Hyeon Su

    2016-05-01

    HP0059, an uncharacterized gene of Helicobacter pylori, encodes a 284-aa-long protein containing a nuclear localization sequence (NLS) and multiple leucine-rich heptad repeats. Effects of HP0059 proteins in human stomach cells were assessed by incubation of recombinant HP0059 proteins with the AGS human gastric carcinoma cell line. Wild-type HP0059 proteins showed cytotoxicity in AGS cells in a concentration-dependent manner, whereas NLS mutant protein showed no effect, suggesting that the cytotoxicity is attributed to host nuclear localization. AGS cells transfected with pEGFP-HP0059 plasmid showed strong GFP signal merged to the chromosomal DNA region. The chromosome was fragmented into multiple distinct dots merged with the GFP signal after 12 h of incubation. The chromosome fragmentation was further explored by incubation of AGS chromosomal DNA with recombinant HP0059 proteins, which leaded to complete degradation of the chromosomal DNA. HP0059 protein also degraded circular plasmid DNA without consensus, being an indication of DNase I activity. The DNase was activated by MgCl2, but not by CaCl2. The activity was completely blocked by EDTA. The optimal pH and temperature for DNase activity were 7.0-8.0 and 55°C, respectively. These results indicate that HP0059 possesses a novel DNase I activity along with a role in the genomic instability of human gastric cells, which may result in the transformation of gastric cells. PMID:27095458

  18. 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.

  19. 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

  20. 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

  1. Volar locking distal radius plates show better short-term results than other treatment options: A prospective randomised controlled trial

    PubMed Central

    Drobetz, Herwig; Koval, Lidia; Weninger, Patrick; Luscombe, Ruth; Jeffries, Paula; Ehrendorfer, Stefan; Heal, Clare

    2016-01-01

    AIM To compare the outcomes of displaced distal radius fractures treated with volar locking plates and with immediate postoperative mobilisation with the outcomes of these fractures treated with modalities that necessitate 6 wk wrist immobilisation. METHODS A prospective, randomised controlled single-centre trial was conducted with 56 patients who had a displaced radius fracture were randomised to treatment either with a volar locking plate (n = 29), or another treatment modality (n = 27; cast immobilisation with or without wires or external fixator). Outcomes were measured at 12 wk. Functional outcome scores measured were the Patient-Rated Wrist Evaluation (PRWE) Score; Disabilities of the Arm, Shoulder and Hand and activities of daily living (ADLs). Clinical outcomes were wrist range of motion and grip strength. Radiographic parameters were volar inclination and ulnar variance. RESULTS Patients in the volar locking plate group had significantly better PRWE scores, ADL scores, grip strength and range of extension at three months compared with the control group. All radiological parameters were significantly better in the volar locking plate group at 3 mo. CONCLUSION The present study suggests that volar locking plates produced significantly better functional and clinical outcomes at 3 mo compared with other treatment modalities. Anatomical reduction was significantly more likely to be preserved in the plating group. Level of evidence: II. PMID:27795951

  2. Hydroxyeicosapentaenoic acids from the Pacific krill show high ligand activities for PPARs[S

    PubMed Central

    Yamada, Hidetoshi; Oshiro, Eriko; Kikuchi, Sayaka; Hakozaki, Mayuka; Takahashi, Hideyuki; Kimura, Ken-ichi

    2014-01-01

    PPARs regulate the expression of genes for energy metabolism in a ligand-dependent manner. PPARs can influence fatty acid oxidation, the level of circulating triglycerides, glucose uptake and insulin sensitivity. Here, we demonstrate that 5-hydroxyeicosapentaenoic acid (HEPE), 8-HEPE, 9-HEPE, 12-HEPE and 18-HEPE (hydroxylation products of EPA) obtained from methanol extracts of Pacific krill (Euphausia pacifica) can act as PPAR ligands. Two of these products, 8-HEPE and 9-HEPE, enhanced the transcription levels of GAL4-PPARs to a significantly greater extent than 5-HEPE, 12-HEPE, 18-HEPE, EPA, and EPA ethyl-ester. 8-HEPE also activated significantly higher transcription of GAL4-PPARα, GAL4-PPARγ, and GAL4-PPARδ than EPA at concentrations greater than 4, 64, and 64 μM, respectively. We also demonstrated that 8-HEPE increased the expression levels of genes regulated by PPARs in FaO, 3T3-F442A, and C2C12 cells. Furthermore, 8-HEPE enhanced adipogenesis and glucose uptake. By contrast, at the same concentrations, EPA showed weak or little effect, indicating that 8-HEPE was the more potent inducer of physiological effects. PMID:24668940

  3. Downscaling CMIP5 climate models shows increased tropical cyclone activity over the 21st century

    PubMed Central

    Emanuel, Kerry A.

    2013-01-01

    A recently developed technique for simulating large [O(104)] numbers of tropical cyclones in climate states described by global gridded data is applied to simulations of historical and future climate states simulated by six Coupled Model Intercomparison Project 5 (CMIP5) global climate models. Tropical cyclones downscaled from the climate of the period 1950–2005 are compared with those of the 21st century in simulations that stipulate that the radiative forcing from greenhouse gases increases by over preindustrial values. In contrast to storms that appear explicitly in most global models, the frequency of downscaled tropical cyclones increases during the 21st century in most locations. The intensity of such storms, as measured by their maximum wind speeds, also increases, in agreement with previous results. Increases in tropical cyclone activity are most prominent in the western North Pacific, but are evident in other regions except for the southwestern Pacific. The increased frequency of events is consistent with increases in a genesis potential index based on monthly mean global model output. These results are compared and contrasted with other inferences concerning the effect of global warming on tropical cyclones. PMID:23836646

  4. Downscaling CMIP5 climate models shows increased tropical cyclone activity over the 21st century.

    PubMed

    Emanuel, Kerry A

    2013-07-23

    A recently developed technique for simulating large [O(10(4))] numbers of tropical cyclones in climate states described by global gridded data is applied to simulations of historical and future climate states simulated by six Coupled Model Intercomparison Project 5 (CMIP5) global climate models. Tropical cyclones downscaled from the climate of the period 1950-2005 are compared with those of the 21st century in simulations that stipulate that the radiative forcing from greenhouse gases increases by over preindustrial values. In contrast to storms that appear explicitly in most global models, the frequency of downscaled tropical cyclones increases during the 21st century in most locations. The intensity of such storms, as measured by their maximum wind speeds, also increases, in agreement with previous results. Increases in tropical cyclone activity are most prominent in the western North Pacific, but are evident in other regions except for the southwestern Pacific. The increased frequency of events is consistent with increases in a genesis potential index based on monthly mean global model output. These results are compared and contrasted with other inferences concerning the effect of global warming on tropical cyclones.

  5. 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.

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

    PubMed

    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 (23gkg(-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. PMID:25528132

  7. Active tectonics west of New Zealand's Alpine Fault: South Westland Fault Zone activity shows Australian Plate instability

    NASA Astrophysics Data System (ADS)

    De Pascale, Gregory P.; Chandler-Yates, Nicholas; Dela Pena, Federico; Wilson, Pam; May, Elijah; Twiss, Amber; Cheng, Che

    2016-04-01

    The 300 km long South Westland Fault Zone (SWFZ) is within the footwall of the Central Alpine Fault (<20 km away) and has 3500 m of dip-slip displacement, but it has been unknown if the fault is active. Here the first evidence for SWFZ thrust faulting in the "stable" Australian Plate is shown with cumulative dip-slip displacements up to 5.9 m (with 3 m throw) on Pleistocene and Holocene sediments and gentle hanging wall anticlinal folding. Cone penetration test (CPT) stratigraphy shows repeated sequences within the fault scarp (consistent with thrusting). Optically stimulated luminescence (OSL) dating constrains the most recent rupture post-12.1 ± 1.7 ka with evidence for three to four events during earthquakes of at least Mw 6.8. This study shows significant deformation is accommodated on poorly characterized Australian Plate structures northwest of the Alpine Fault and demonstrates that major active and seismogenic structures remain uncharacterized in densely forested regions on Earth.

  8. A chimeric protein of aluminum-activated malate transporter generated from wheat and Arabidopsis shows enhanced response to trivalent cations.

    PubMed

    Sasaki, Takayuki; Tsuchiya, Yoshiyuki; Ariyoshi, Michiyo; Ryan, Peter R; Yamamoto, Yoko

    2016-07-01

    TaALMT1 from wheat (Triticum aestivum) and AtALMT1 from Arabidopsis thaliana encode aluminum (Al)-activated malate transporters, which confer acid-soil tolerance by releasing malate from roots. Chimeric proteins from TaALMT1 and AtALMT1 (Ta::At, At::Ta) were previously analyzed in Xenopus laevis oocytes. Those studies showed that Al could activate malate efflux from the Ta::At chimera but not from At::Ta. Here, functions of TaALMT1, AtALMT1 and the chimeric protein Ta::At were compared in cultured tobacco BY-2 cells. We focused on the sensitivity and specificity of their activation by trivalent cations. The activation of malate efflux by Al was at least two-fold greater in the chimera than the native proteins. All proteins were also activated by lanthanides (erbium, ytterbium, gadolinium, and lanthanum), but the chimera again released more malate than TaALMT1 or AtALMT1. In Xenopus oocytes, Al, ytterbium, and erbium activated inward currents from the native TaALMT1 and the chimeric protein, but gadolinium only activated currents from the chimera. Lanthanum inhibited currents from both proteins. These results demonstrated that function of the chimera protein was altered compared to the native proteins and was more responsive to a range of trivalent cations when expressed in plant cells. PMID:27039280

  9. Genomic and Enzymatic Results Show Bacillus cellulosilyticus Uses a Novel Set of LPXTA Carbohydrases to Hydrolyze Polysaccharides

    PubMed Central

    Mead, David; Drinkwater, Colleen; Brumm, Phillip J.

    2013-01-01

    Background Alkaliphilic Bacillus species are intrinsically interesting due to the bioenergetic problems posed by growth at high pH and high salt. Three alkaline cellulases have been cloned, sequenced and expressed from Bacillus cellulosilyticus N-4 (Bcell) making it an excellent target for genomic sequencing and mining of biomass-degrading enzymes. Methodology/Principal Findings The genome of Bcell is a single chromosome of 4.7 Mb with no plasmids present and three large phage insertions. The most unusual feature of the genome is the presence of 23 LPXTA membrane anchor proteins; 17 of these are annotated as involved in polysaccharide degradation. These two values are significantly higher than seen in any other Bacillus species. This high number of membrane anchor proteins is seen only in pathogenic Gram-positive organisms such as Listeria monocytogenes or Staphylococcus aureus. Bcell also possesses four sortase D subfamily 4 enzymes that incorporate LPXTA-bearing proteins into the cell wall; three of these are closely related to each other and unique to Bcell. Cell fractionation and enzymatic assay of Bcell cultures show that the majority of polysaccharide degradation is associated with the cell wall LPXTA-enzymes, an unusual feature in Gram-positive aerobes. Genomic analysis and growth studies both strongly argue against Bcell being a truly cellulolytic organism, in spite of its name. Preliminary results suggest that fungal mycelia may be the natural substrate for this organism. Conclusions/Significance Bacillus cellulosilyticus N-4, in spite of its name, does not possess any of the genes necessary for crystalline cellulose degradation, demonstrating the risk of classifying microorganisms without the benefit of genomic analysis. Bcell is the first Gram-positive aerobic organism shown to use predominantly cell-bound, non-cellulosomal enzymes for polysaccharide degradation. The LPXTA-sortase system utilized by Bcell may have applications both in anchoring

  10. A specific cathepsin-L-like protease purified from an insect midgut shows antibacterial activity against gut symbiotic bacteria.

    PubMed

    Byeon, Jin Hee; Seo, Eun Sil; Lee, Jun Beom; Lee, Min Ja; Kim, Jiyeun Kate; Yoo, Jin Wook; Jung, Yunjin; Lee, Bok Luel

    2015-11-01

    Because gut symbiotic bacteria affect host biology, host insects are expected to evolve some mechanisms for regulating symbiont population. The bean bug, Riptortus pedestris, harbors the Burkholderia genus as a gut symbiont in the midgut organ, designated as the M4 region. Recently, we demonstrated that the lysate of M4B, the region adjacent to M4, harbors potent antibacterial activity against symbiotic Burkholderia but not to cultured Burkholderia. However, the bona fide substance responsible for observed antibacterial activity was not identified in the previous study. Here, we report that cathepsin-L-like protease purified from the lysate of M4B showed strong antibacterial activity against symbiotic Burkholderia but not the cultured Burkholderia. To further confirm this activity, recombinant cathepsin-L-like protease expressed in Escherichia coli also showed antibacterial activity against symbiotic Burkholderia. These results suggest that cathepsin-L-like protease purified from the M4B region plays a critical role in controlling the population of the Burkholderia gut symbiont.

  11. 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.

  12. 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

  13. 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. PMID:26579205

  14. Physical activity across the curriculum: year one process evaluation results

    PubMed Central

    Gibson, Cheryl A; Smith, Bryan K; DuBose, Katrina D; Greene, J Leon; Bailey, Bruce W; Williams, Shannon L; Ryan, Joseph J; Schmelzle, Kristin H; Washburn, Richard A; Sullivan, Debra K; Mayo, Matthew S; Donnelly, Joseph E

    2008-01-01

    Background Physical Activity Across the Curriculum (PAAC) is a 3-year elementary school-based intervention to determine if increased amounts of moderate intensity physical activity performed in the classroom will diminish gains in body mass index (BMI). It is a cluster-randomized, controlled trial, involving 4905 children (2505 intervention, 2400 control). Methods We collected both qualitative and quantitative process evaluation data from 24 schools (14 intervention and 10 control), which included tracking teacher training issues, challenges and barriers to effective implementation of PAAC lessons, initial and continual use of program specified activities, and potential competing factors, which might contaminate or lessen program effects. Results Overall teacher attendance at training sessions showed exceptional reach. Teachers incorporated active lessons on most days, resulting in significantly greater student physical activity levels compared to controls (p < 0.0001). Enjoyment ratings for classroom-based lessons were also higher for intervention students. Competing factors, which might influence program results, were not carried out at intervention or control schools or were judged to be minimal. Conclusion In the first year of the PAAC intervention, process evaluation results were instrumental in identifying successes and challenges faced by teachers when trying to modify existing academic lessons to incorporate physical activity. PMID:18606013

  15. Regional brain activation during meditation shows time and practice effects: an exploratory FMRI study.

    PubMed

    Baron Short, E; Kose, Samet; Mu, Qiwen; Borckardt, Jeffery; Newberg, Andrew; George, Mark S; Kozel, F Andrew

    2010-03-01

    Meditation involves attentional regulation and may lead to increased activity in brain regions associated with attention such as dorsal lateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). Using functional magnetic resonance imaging, we examined whether DLPFC and ACC were activated during meditation. Subjects who meditate were recruited and scanned on a 3.0 Tesla scanner. Subjects meditated for four sessions of 12 min and performed four sessions of a 6 min control task. Individual and group t-maps were generated of overall meditation response versus control response and late meditation response versus early meditation response for each subject and time courses were plotted. For the overall group (n = 13), and using an overall brain analysis, there were no statistically significant regional activations of interest using conservative thresholds. A region of interest analysis of the entire group time courses of DLPFC and ACC were statistically more active throughout meditation in comparison to the control task. Moreover, dividing the cohort into short (n = 8) and long-term (n = 5) practitioners (>10 years) revealed that the time courses of long-term practitioners had significantly more consistent and sustained activation in the DLPFC and the ACC during meditation versus control in comparison to short-term practitioners. The regional brain activations in the more practised subjects may correlate with better sustained attention and attentional error monitoring. In summary, brain regions associated with attention vary over the time of a meditation session and may differ between long- and short-term meditation practitioners.

  16. 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.

  17. A transgenic apple callus showing reduced polyphenol oxidase activity and lower browning potential.

    PubMed

    Murata, M; Nishimura, M; Murai, N; Haruta, M; Homma, S; Itoh, Y

    2001-02-01

    Polyphenol oxidase (PPO) is responsible for enzymatic browning of apples. Apples lacking PPO activity might be useful not only for the food industry but also for studies of the metabolism of polyphenols and the function of PPO. Transgenic apple calli were prepared by using Agrobacterium tumefaciens carrying the kanamycin (KM) resistant gene and antisense PPO gene. Four KM-resistant callus lines were obtained from 356 leaf explants. Among these transgenic calli, three calli grew on the medium containing KM at the same rate as non-transgenic callus on the medium without KM. One callus line had an antisense PPO gene, in which the amount and activity of PPO were reduced to half the amount and activity in non-transgenic callus. The browning potential of this line, which was estimated by adding chlorogenic acid, was also half the browning potential of non-transgenic callus.

  18. Isolation and analysis of polysaccharide showing high hyaluronidase inhibitory activity in Nostochopsis lobatus MAC0804NAN.

    PubMed

    Yamaguchi, Yuji; Koketsu, Mamoru

    2016-03-01

    An active substance with high hyaluronidase inhibitory effect was isolated from the edible cyanobacterium Nostochopsis lobatus MAC0804NAN strain and characterized. The active component in the hot water extract was purified by anion exchange and gel filtration chromatography and was found to be a polysaccharide. The IC(50) against hyaluronidase of the purified polysaccharide was 7.18 μg/ml whose inhibitory activity is 14.5 times stronger than that of disodium cromoglycate (DSCG), an anti-allergy medication. The carbohydrate composition which was analyzed by GC-MS and NMR was found to be composed mainly of glucose, glucuronic acid, fucose, 2-O-methylfucose, mannose, galactose and xylose.

  19. 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…

  20. Cerato-platanin shows expansin-like activity on cellulosic materials.

    PubMed

    Baccelli, Ivan; Luti, Simone; Bernardi, Rodolfo; Scala, Aniello; Pazzagli, Luigia

    2014-01-01

    Cerato-platanin (CP) is a non-catalytic protein with a double ψβ-barrel fold located in the cell wall of the phytopathogenic fungus Ceratocystis platani. CP is released during growth and induces defence-related responses in plants. CP is also the first member of the "cerato-platanin family" (CPF) (Pfam PF07249). In the CPF, the molecular mechanism of action on plants and above all the biological role in fungal life are little-known aspects. However, an expansin-like function has recently been suggested concerning CP. Expansin-like proteins have the ability to act non-hydrolytically on cellulose. In the present work, the expansin-like activity of CP and Pop1, a CP family member, was investigated. Like expansins, CP and Pop1 were able to weaken filter paper in a concentration-dependent manner and without the production of reducing sugars. A metal-dependent polysaccharide monooxygenase-like activity was excluded. The optimum of activity was pH5.0, 38 °C. CP was also able to cause fragmentation of the crystalline cellulose Avicel and the breakage and defibration of cotton fibres. However, the interaction did not involve a stable bond with the substrates and CP did not significantly enhance the hydrolytic activity of cellulase. On the other hand, CP and Pop1 bound quickly to chitin. We consider CP as a novel one-domain expansin-like protein. We propose a structural role for CP in the fungal cell wall due to the ability to bind chitin, and hypothesize a functional role in the interaction of the fungus with the plant for the weakening activity shown on cellulose.

  1. Electricity in Volcanic Clouds: Investigations show that lightning can result from charge-separation processes in a volcanic crater.

    PubMed

    Anderson, R; Gathman, S; Hughes, J; Björnsson, S; Jónasson, S; Blanchard, D C; Moore, C B; Survilas, H J; Vonnegut, B

    1965-05-28

    In November of 1963 an oceanic volcano produced an island, Surtsey, just off the southern coast of Iceland. The volcanic crater was often flooded with sea water. Vigorous eruptions of steam and tephra were accompanied by an enhancement of the normal fine-weather potential gradient, and lightning was often observed. Measurements of atmospheric electricity and visual and photographic observations lead us to believe that the electrical activity is caused by the ejection from the volcano into the atmosphere of material carrying a large positive charge. The concentration of charge in the eruption plume as it issued from the orifice of the volcano is estimated to be of the order of 10(5) or 10(6) elementary charges per cubic centimeter.

  2. Electricity in Volcanic Clouds: Investigations show that lightning can result from charge-separation processes in a volcanic crater.

    PubMed

    Anderson, R; Gathman, S; Hughes, J; Björnsson, S; Jónasson, S; Blanchard, D C; Moore, C B; Survilas, H J; Vonnegut, B

    1965-05-28

    In November of 1963 an oceanic volcano produced an island, Surtsey, just off the southern coast of Iceland. The volcanic crater was often flooded with sea water. Vigorous eruptions of steam and tephra were accompanied by an enhancement of the normal fine-weather potential gradient, and lightning was often observed. Measurements of atmospheric electricity and visual and photographic observations lead us to believe that the electrical activity is caused by the ejection from the volcano into the atmosphere of material carrying a large positive charge. The concentration of charge in the eruption plume as it issued from the orifice of the volcano is estimated to be of the order of 10(5) or 10(6) elementary charges per cubic centimeter. PMID:17748113

  3. 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.

  4. Echinomycin, a potential binder of FKBP12, shows minor effect on calcineurin activity.

    PubMed

    Singh, Vikramjeet; Nand, Amita; Chen, Caixia; Li, ZhiPeng; Li, Sheng-Jie; Wang, Songbai; Yang, Mo; Merino, Alejandro; Zhang, Lixin; Zhu, Jingsong

    2014-10-01

    Echinomycin, a member of the quinoxaline family of antibiotics, is known to be a small-molecule inhibitor of hypoxia inducible factor-1 (HIF-1) DNA binding activity. Recently, it has been shown to suppress mammalian target of rapamycin (mTOR) signaling and growth in leukemia cell lines. In this study, we investigated whether echinomycin interacts with the FKBP12 protein. Molecular docking was used, and the predicted binding energy was -10.61 kcal/mol. Moreover, surface plasmon resonance imaging and fluorescence quenching techniques were used to validate this interaction. Echinomycin binds to FKBP12 with a strong binding affinity comparable with rapamycin. Furthermore, the echinomycin-FKBP12 complex has been shown to affect calcineurin activity when tested in a calcineurin phosphatase inhibition assay. All of these studies have shown that echinomycin may have a double impact on HIF signaling by direct inhibition and through mTOR.

  5. 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. PMID:27030628

  6. 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.

  7. 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.

  8. 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. PMID:25110971

  9. Rosmarinic acid from eelgrass shows nematicidal and antibacterial activities against pine wood nematode and its carrying bacteria.

    PubMed

    Wang, Jingyu; Pan, Xueru; Han, Yi; Guo, Daosen; Guo, Qunqun; Li, Ronggui

    2012-12-01

    Pine wilt disease (PWD), a destructive disease for pine trees, is caused by the pine wood nematode (PWN), Bursaphelenchus xylophilus and additional bacteria. In this study, extracts of Zostera marina showed a high nematicidal activity against PWN and some of the bacteria that it carries. Light yellow crystals were obtained from extracts of Z. marina through solvent extraction, followed by chromatography on AB-8 resin and crystallization. The NMR and HPLC analysis showed that the isolated compound was rosmarinic acid (RosA). RosA showed effective nematicidal activity, of which the LC₅₀ (50% lethal concentration) to PWN at 24 h, 48 h and 72 h was 1.18 mg/g, 1.05 mg/g and 0.95 mg/g, respectively. To get a high yield rate of RosA from Z. marina, single factor experiments and an L₉ (3⁴) orthogonal experiment were performed. This extraction process involved 70% ethanol for 3 h at 40 °C. The extraction dosage was 1:50 (w/v). The highest yield of RosA from Zostera was 3.13 mg/g DW (dried weight). The crude extracts of Zostera marina (10 mg/mL) and RosA (1 mg/mL) also showed inhibitory effects to some bacterial strains carried by PWN: Klebsiella sp., Stenotrophomonas maltophilia, Streptomyces sp. and Pantoea agglomerans. The results of these studies provide clues for preparing pesticide to control PWD from Z. marina. PMID:23201594

  10. Rosmarinic acid from eelgrass shows nematicidal and antibacterial activities against pine wood nematode and its carrying bacteria.

    PubMed

    Wang, Jingyu; Pan, Xueru; Han, Yi; Guo, Daosen; Guo, Qunqun; Li, Ronggui

    2012-12-01

    Pine wilt disease (PWD), a destructive disease for pine trees, is caused by the pine wood nematode (PWN), Bursaphelenchus xylophilus and additional bacteria. In this study, extracts of Zostera marina showed a high nematicidal activity against PWN and some of the bacteria that it carries. Light yellow crystals were obtained from extracts of Z. marina through solvent extraction, followed by chromatography on AB-8 resin and crystallization. The NMR and HPLC analysis showed that the isolated compound was rosmarinic acid (RosA). RosA showed effective nematicidal activity, of which the LC₅₀ (50% lethal concentration) to PWN at 24 h, 48 h and 72 h was 1.18 mg/g, 1.05 mg/g and 0.95 mg/g, respectively. To get a high yield rate of RosA from Z. marina, single factor experiments and an L₉ (3⁴) orthogonal experiment were performed. This extraction process involved 70% ethanol for 3 h at 40 °C. The extraction dosage was 1:50 (w/v). The highest yield of RosA from Zostera was 3.13 mg/g DW (dried weight). The crude extracts of Zostera marina (10 mg/mL) and RosA (1 mg/mL) also showed inhibitory effects to some bacterial strains carried by PWN: Klebsiella sp., Stenotrophomonas maltophilia, Streptomyces sp. and Pantoea agglomerans. The results of these studies provide clues for preparing pesticide to control PWD from Z. marina.

  11. A collaborative accountable care model in three practices showed promising early results on costs and quality of care.

    PubMed

    Salmon, Richard B; Sanderson, Mark I; Walters, Barbara A; Kennedy, Karen; Flores, Robert C; Muney, Alan M

    2012-11-01

    Cigna's Collaborative Accountable Care initiative provides financial incentives to physician groups and integrated delivery systems to improve the quality and efficiency of care for patients in commercial open-access benefit plans. Registered nurses who serve as care coordinators employed by participating practices are a central feature of the initiative. They use patient-specific reports and practice performance reports provided by Cigna to improve care coordination, identify and close care gaps, and address other opportunities for quality improvement. We report interim quality and cost results for three geographically and structurally diverse provider practices in Arizona, New Hampshire, and Texas. Although not statistically significant, these early results revealed favorable trends in total medical costs and quality of care, suggesting that a shared-savings accountable care model and collaborative support from the payer can enable practices to take meaningful steps toward full accountability for care quality and efficiency.

  12. 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

  13. 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.

  14. The diverse members of the mammalian HSP70 machine show distinct chaperone-like activities.

    PubMed

    Hageman, Jurre; van Waarde, Maria A W H; Zylicz, Alicja; Walerych, Dawid; Kampinga, Harm H

    2011-04-01

    Humans contain many HSP (heat-shock protein) 70/HSPA- and HSP40/DNAJ-encoding genes and most of the corresponding proteins are localized in the cytosol. To test for possible functional differences and/or substrate specificity, we assessed the effect of overexpression of each of these HSPs on refolding of heat-denatured luciferase and on the suppression of aggregation of a non-foldable polyQ (polyglutamine)-expanded Huntingtin fragment. Overexpressed chaperones that suppressed polyQ aggregation were found not to be able to stimulate luciferase refolding. Inversely, chaperones that supported luciferase refolding were poor suppressors of polyQ aggregation. This was not related to client specificity itself, as the polyQ aggregation inhibitors often also suppressed heat-induced aggregation of luciferase. Surprisingly, the exclusively heat-inducible HSPA6 lacks both luciferase refolding and polyQ aggregation-suppressing activities. Furthermore, whereas overexpression of HSPA1A protected cells from heat-induced cell death, overexpression of HSPA6 did not. Inversely, siRNA (small interfering RNA)-mediated blocking of HSPA6 did not impair the development of heat-induced thermotolerance. Yet, HSPA6 has a functional substrate-binding domain and possesses intrinsic ATPase activity that is as high as that of the canonical HSPA1A when stimulated by J-proteins. In vitro data suggest that this may be relevant to substrate specificity, as purified HSPA6 could not chaperone heat-unfolded luciferase but was able to assist in reactivation of heat-unfolded p53. So, even within the highly sequence-conserved HSPA family, functional differentiation is larger than expected, with HSPA6 being an extreme example that may have evolved to maintain specific critical functions under conditions of severe stress.

  15. Presentation Showing Results of a Hydrogeochemical Investigation of the Standard Mine Vicinity, Upper Elk Creek Basin, Colorado

    USGS Publications Warehouse

    Manning, Andrew H.; Verplanck, Philip L.; Mast, M. Alisa; Wanty, Richard B.

    2008-01-01

    PREFACE This Open-File Report consists of a presentation given in Crested Butte, Colorado on December 13, 2007 to the Standard Mine Advisory Group. The presentation was paired with another presentation given by the Colorado Division of Reclamation, Mining, and Safety on the physical features and geology of the Standard Mine. The presentation in this Open-File Report summarizes the results and conclusions of a hydrogeochemical investigation of the Standard Mine performed by the U.S. Geological Survey (Manning and others, in press). The purpose of the investigation was to aid the U.S. Environmental Protection Agency in evaluating remediation options for the Standard Mine site. Additional details and supporting data related to the information in this presentation can be found in Manning and others (in press).

  16. One novel quinoxaline derivative as a potent human cyclophilin A inhibitor shows highly inhibitory activity against mouse spleen cell proliferation.

    PubMed

    Li, Jian; Chen, Jing; Zhang, Li; Wang, Feng; Gui, Chunshan; Zhang, Li; Qin, Yu; Xu, Qiang; Liu, Hong; Nan, Fajun; Shen, Jingkang; Bai, Donglu; Chen, Kaixian; Shen, Xu; Jiang, Hualiang

    2006-08-15

    Cyclophilin A (CypA) is a ubiquitous cellular enzyme playing critical roles in many biological processes, and its inhibitor has been reported to have potential immunosuppressive activity. In this work, we reported a novel quinoxaline derivative, 2,3-di(furan-2-yl)-6-(3-N,N-diethylcarbamoyl-piperidino)carbonylamino quinoxaline (DC838, 3), which was confirmed to be a potent inhibitor against human CypA. By using the surface plasmon resonance (SPR) and fluorescence titration techniques, the kinetic analysis of CypA/DC838 interaction was quantitatively performed. CypA peptidyl prolyl cis-trans isomerase (PPIase) activity inhibition assay showed that DC838 demonstrated highly CypA PPIase inhibitory activity. In vivo assay results showed that DC838 could inhibit mouse spleen cell proliferation induced by concanavalin A (Con A). Molecular docking simulation further elucidated the specific DC838 binding to CypA at the atomic level. The current work should provide useful information in the discovery of immunosuppressor based on CypA inhibitor.

  17. Low-frequency ac electroporation shows strong frequency dependence and yields comparable transfection results to dc electroporation.

    PubMed

    Zhan, Yihong; Cao, Zhenning; Bao, Ning; Li, Jianbo; Wang, Jun; Geng, Tao; Lin, Hao; Lu, Chang

    2012-06-28

    Conventional electroporation has been conducted by employing short direct current (dc) pulses for delivery of macromolecules such as DNA into cells. The use of alternating current (ac) field for electroporation has mostly been explored in the frequency range of 10kHz-1MHz. Based on Schwan equation, it was thought that with low ac frequencies (10Hz-10kHz), the transmembrane potential does not vary with the frequency. In this report, we utilized a flow-through electroporation technique that employed continuous 10Hz-10kHz ac field (based on either sine waves or square waves) for electroporation of cells with defined duration and intensity. Our results reveal that electropermeabilization becomes weaker with increased frequency in this range. In contrast, transfection efficiency with DNA reaches its maximum at medium frequencies (100-1000Hz) in the range. We postulate that the relationship between the transfection efficiency and the ac frequency is determined by combined effects from electrophoretic movement of DNA in the ac field, dependence of the DNA/membrane interaction on the ac frequency, and variation of transfection under different electropermeabilization intensities. The fact that ac electroporation in this frequency range yields high efficiency for transfection (up to ~71% for Chinese hamster ovary cells) and permeabilization suggests its potential for gene delivery.

  18. High affinity and covalent-binding microtubule stabilizing agents show activity in chemotherapy-resistant acute myeloid leukemia cells

    PubMed Central

    Pera, Benet; Calvo-Vidal, M. Nieves; Ambati, Srikanth; Jordi, Michel; Kahn, Alissa; Díaz, J. Fernando; Fang, Weishuo; Altmann, Karl-Heinz; Cerchietti, Leandro; Moore, Malcolm A.S.

    2016-01-01

    Treatment failure in acute myeloid leukemia (AML) is frequently due to the persistence of a cell population resistant to chemotherapy through different mechanisms, in which drug efflux via ATP-binding cassette (ABC) proteins, specifically P-glycoprotein, is one of the most recognized. However, disappointing results from clinical trials employing inhibitors for these transporters have demonstrated the need to adopt different strategies. We hypothesized that microtubule targeting compounds presenting high affinity or covalent binding could overcome the effect of ABC transporters. We therefore evaluated the activity of the high-affinity paclitaxel analog CTX-40 as well as the covalent binder zampanolide (ZMP) in AML cells. Both molecules were active in chemosensitive as well as in chemoresistant cell lines overexpressing P-glycoprotein. Moreover, ZMP or CTX-40 in combination with daunorubicin showed synergistic killing without increased in vitro hematopoietic toxicity. In a primary AML sample, we further demonstrated that ZMP and CTX-40 are active in progenitor and differentiated leukemia cell populations. In sum, our data indicate that high affinity and covalent-binding anti-microtubule agents are active in AML cells otherwise chemotherapy resistant. PMID:26277539

  19. Selection Indices and Multivariate Analysis Show Similar Results in the Evaluation of Growth and Carcass Traits in Beef Cattle

    PubMed Central

    Brito Lopes, Fernando; da Silva, Marcelo Corrêa; Magnabosco, Cláudio Ulhôa; Goncalves Narciso, Marcelo; Sainz, Roberto Daniel

    2016-01-01

    This research evaluated a multivariate approach as an alternative tool for the purpose of selection regarding expected progeny differences (EPDs). Data were fitted using a multi-trait model and consisted of growth traits (birth weight and weights at 120, 210, 365 and 450 days of age) and carcass traits (longissimus muscle area (LMA), back-fat thickness (BF), and rump fat thickness (RF)), registered over 21 years in extensive breeding systems of Polled Nellore cattle in Brazil. Multivariate analyses were performed using standardized (zero mean and unit variance) EPDs. The k mean method revealed that the best fit of data occurred using three clusters (k = 3) (P < 0.001). Estimates of genetic correlation among growth and carcass traits and the estimates of heritability were moderate to high, suggesting that a correlated response approach is suitable for practical decision making. Estimates of correlation between selection indices and the multivariate index (LD1) were moderate to high, ranging from 0.48 to 0.97. This reveals that both types of indices give similar results and that the multivariate approach is reliable for the purpose of selection. The alternative tool seems very handy when economic weights are not available or in cases where more rapid identification of the best animals is desired. Interestingly, multivariate analysis allowed forecasting information based on the relationships among breeding values (EPDs). Also, it enabled fine discrimination, rapid data summarization after genetic evaluation, and permitted accounting for maternal ability and the genetic direct potential of the animals. In addition, we recommend the use of longissimus muscle area and subcutaneous fat thickness as selection criteria, to allow estimation of breeding values before the first mating season in order to accelerate the response to individual selection. PMID:26789008

  20. Why DA and DB white dwarfs do not show coronal activity and p-mode oscillations

    SciTech Connect

    Musielak, Z.E.; Fontenla, J.M. )

    1989-11-01

    The problems of nonradiative heating of outer atmospheric layers and p-mode oscillations in white dwarfs caused by acoustic waves generated in convective zones are discussed. These effects have been studied by calculating the cutoff periods for adiabatic and isothermal waves propagating in atmospheres of DA and DB stars with Teff greater than or equal 20,000 K and log g = 6-9. The obtained cutoff periods are approximately bounded by 0.01 and 40 sec for high- and low-gravity white dwarfs, respectively. Expected amplitudes of p-mode oscillations corresponding to trapped acoustic waves with small angular wave numbers are estimated, indicating that the amplitudes could be observed as Doppler shifts of spectral lines which might be detectable if adequate spectral resolution were available. The luminosity variations corresponding to these amplitudes are unlikely to be observable when all damping processes are accounted for. Results also indicate that the present theory of convection predicts some irregularities in the behavior of physical parameters. 34 refs.

  1. Why DA and DB white dwarfs do not show coronal activity and p-mode oscillations

    NASA Technical Reports Server (NTRS)

    Musielak, Z. E.; Fontenla, J. M.

    1989-01-01

    The problems of nonradiative heating of outer atmospheric layers and p-mode oscillations in white dwarfs caused by acoustic waves generated in convective zones are discussed. These effects have been studied by calculating the cutoff periods for adiabatic and isothermal waves propagating in atmospheres of DA and DB stars with Teff greater than or equal 20,000 K and log g = 6-9. The obtained cutoff periods are approximately bounded by 0.01 and 40 sec for high- and low-gravity white dwarfs, respectively. Expected amplitudes of p-mode oscillations corresponding to trapped acoustic waves with small angular wave numbers are estimated, indicating that the amplitudes could be observed as Doppler shifts of spectral lines which might be detectable if adequate spectral resolution were available. The luminosity variations corresponding to these amplitudes are unlikely to be observable when all damping processes are accounted for. Results also indicate that the present theory of convection predicts some irregularities in the behavior of physical parameters.

  2. Do different implant surfaces exposed in the oral cavity of humans show different biofilm compositions and activities?

    PubMed

    Groessner-Schreiber, Birte; Hannig, Matthias; Dück, Alexander; Griepentrog, Michael; Wenderoth, Dirk F

    2004-12-01

    Osseointegrated dental implants play an important role in restorative dentistry. However, plaque accumulation may cause inflammatory reactions around the implants, sometimes leading to implant failure. In this in vivo study the influence of two physical hard coatings on bacterial adhesion was examined in comparison with a pure titanium surface. Thin glass sheets coated with titanium nitride (TiN), zirconium nitride (ZrN) or pure titanium were mounted on removable intraoral splints in two adults. After 60 h of intraoral exposure, the biofilms were analyzed to determine the number of bacteria, the types of bacteria [by applying single-strand conformation polymorphism (SSCP analysis) of 16S rRNA genes], and whether or not the bacteria were active (by SSCP analysis of 16S rRNA). The results showed that bacterial cell counts were higher on the pure titanium-coated glass sheets than on the glass sheets coated with TiN or ZrN. The lowest number of bacterial cells was present on theZrN-coated glass. However, the metabolic activity (RNA fingerprints) of bacteria on TiN- and ZrN-coated glass sheets seemed to be lower than the activity of bacteria on the titanium-coated surfaces, whereas SSCP fingerprints based on 16S rDNA revealed that the major 16S bands are common to all of the fingerprints, independently of the surface coating. PMID:15560835

  3. Sequential treatment with betulinic acid followed by 5-fluorouracil shows synergistic cytotoxic activity in ovarian cancer cells.

    PubMed

    Wang, Ying-Jian; Liu, Jun-Bao; Dou, Yu-Chang

    2015-01-01

    Betulinic acid selectively inhibits the growth of ovarian carcinoma cell lines without affecting the normal cells. In the present study, the effect of 5-fluorouracil (5-FU) and betulinic acid (BA) combination on ovarian carcinoma cells was studied. The results demonstrated that ovarian carcinoma cells on concurrent or 5-FU followed by BA treatment show increased Sub-G1 cell population, increased rate of cell apoptosis and morphological changes in mitochondrial membrane. In OVCAR 432 cells treatment with sequential combination of 5-FU and BA increased the Sub-G1 cell population to 51.3% and growth inhibition rate of > 72%. However, exposure to BA before 5-FU treatment caused a decrease in rate of inhibition to < 35%. Treatment with combination of 5 μM of 5-FU and 1 μM of BA for 48 h, led to an induction of apoptosis in 79.7% and induced morphological changes in OVCAR 432 cells. The Western blot results showed high concentration of cytochrome c in the cell cytosol after 24 h of 5-FU and BA combination treatment. Treatment of BA-responsive RMS-13 cells with 5-FU and BA combination resulted in inhibition of GLI1, GLI2, PTCH1, and IGF2 genes. In addition, we found a significant reduction in hedgehog activity of RMS-13 cells after 5-FU and BA combination treatment by means of a hedgehog-responsive reporter assay. Therefore, 5-FU and BA combination can be a promising regimen for the treatment of ovarian carcinoma. PMID:25755712

  4. The human interferon-regulated ISG95 protein interacts with RNA polymerase II and shows methyltransferase activity

    SciTech Connect

    Haline-Vaz, Thais; Lima Silva, Tereza Cristina; Zanchin, Nilson I.T.

    2008-08-08

    A major mechanism of cellular resistance to viral invasion involves genes from the interferon signaling pathway, called ISGs (interferon stimulated genes). Global transcriptional profiling studies have linked increased expression of ISG95 (KIAA0082) to response to interferon treatment and viral infection, suggesting that it may be part of the cellular defense against viral replication. In this work, we show that the ISG95 promoter can drive interferon-induced transcription of a reporter gene in Vero cells. Recombinant ISG95 shows RNA- and S-adenosyl-methionine binding and protein methyltransferase activity in vitro. ISG95 interacts with the C-terminal domain of RNA polymerase II, which is consistent with its nuclear localization and with the predicted function of the WW domain found in the C-terminal region of ISG95. The results presented in this work indicate that ISG95 is part of the interferon response pathway and functions in the pre-mRNA processing events mediated by the C-terminal domain of the RNA polymerase II.

  5. Fungal α-arabinofuranosidases of glycosyl hydrolase families 51 and 54 show a dual arabinofuranosyl- and galactofuranosyl-hydrolyzing activity.

    PubMed

    Tefsen, Boris; Lagendijk, Ellen L; Park, Joohae; Akeroyd, Michiel; Schachtschabel, Doreen; Winkler, Robert; van Die, Irma; Ram, Arthur F J

    2012-08-01

    Aspergillus niger possesses a galactofuranosidase activity, however, the corresponding enzyme or gene encoding this enzyme has never been identified. As evidence is mounting that enzymes exist with affinity for both arabinofuranose and galactofuranose, we investigated the possibility that α-L-arabinofuranosidases, encoded by the abfA and abfB genes, are responsible for the galactofuranosidase activity of A. niger. Characterization of the recombinant AbfA and AbfB proteins revealed that both enzymes do not only hydrolyze p-nitrophenyl-α-L-arabinofuranoside (pNp-α-Araf) but are also capable of hydrolyzing p-nitrophenyl-β-D-galactofuranoside (pNp-β-Galf). Molecular modeling of the AbfB protein with pNp-β-Galf confirmed the possibility for AbfB to interact with this substrate, similarly as with pNp-α-Araf. We also show that galactomannan, a cell wall compound of A. niger, containing β-linked terminal and internal galactofuranosyl moieties, can be degraded by an enzyme activity that is present in the supernatant of inulin-grown A. niger. Interestingly, purified AbfA and AbfB did not show this hydrolyzing activity toward A. nigergalactomannan. In summary, our studies demonstrate that AbfA and AbfB, α-L-arabinofuranosidases from different families, both contain a galactofuranose (Galf)-hydrolyzing activity. In addition, our data support the presence of a Galf-hydrolase activity expressed by A. niger that is capable of degrading fungal galactomannan.

  6. Individuals at risk for Alzheimer’s disease show differential patterns of ERP brain activation during odor identification

    PubMed Central

    2012-01-01

    Background Studies suggest that older adults at risk of developing Alzheimer’s disease may show olfactory processing deficits before other signs of dementia appear. Methods We studied 60 healthy non-demented individuals, half of whom were positive for the genetic risk factor the Apolipoprotein E ɛ4 allele, in three different age groups. Event-related potentials to visual and olfactory identification tasks were recorded and analyzed for latency and amplitude differences, and plotted via topographical maps. Results Varying patterns of brain activation were observed over the post-stimulus epoch for ɛ4- versus ɛ4+ individuals on topographical maps. Individuals with the ɛ4 allele demonstrated different ERP peak latencies during identification of olfactory but not visual stimuli. High correct ApoE classification rates were obtained utilizing the olfactory ERP. Conclusions Olfactory ERPs demonstrate functional decline in individuals at risk for Alzheimer’s disease at much earlier ages than previously observed, suggesting the potential for pre-clinical detection of AD at very early stages. PMID:22849610

  7. Voluntary and involuntary running in the rat show different patterns of theta rhythm, physical activity, and heart rate.

    PubMed

    Li, Jia-Yi; Kuo, Terry B J; Yen, Jiin-Cherng; Tsai, Shih-Chih; Yang, Cheryl C H

    2014-05-01

    Involuntarily exercising rats undergo more physical and mental stress than voluntarily exercising rats; however, these findings still lack electrophysiological evidence. Many studies have reported that theta rhythm appears when there is mental stress and that it is affected by emotional status. Thus we hypothesized that the differences between voluntary and involuntary movement should also exist in the hippocampal theta rhythm. Using the wheel and treadmill exercise models as voluntary and involuntary exercise models, respectively, this study wirelessly recorded the hippocampal electroencephalogram, electrocardiogram, and three-dimensional accelerations of young male rats. Treadmill and wheel exercise produced different theta patterns in the rats before and during running. Even though the waking baselines for the two exercise types were recorded in different environments, there did not exist any significant difference after distinguishing the rats' sleep/wake status. When the same movement-related parameters are considered, the treadmill running group showed more changes in their theta frequency (4-12 Hz), in their theta power between 9.5-12 Hz, and in their heart rate than the wheel running group. A positive correlation between the changes in high-frequency (9.5-12 Hz) theta power and heart rate was identified. Our results reveal various voluntary and involuntary changes in hippocampal theta rhythm as well as divergences in heart rate and high-frequency theta activity that may represent the effects of an additional emotional state or the sensory interaction during involuntary running by rats. PMID:24623507

  8. 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.

  9. 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. PMID:26077893

  10. Lung Adenocarcinomas and Lung Cancer Cell Lines Show Association of MMP-1 Expression With STAT3 Activation.

    PubMed

    Schütz, Alexander; Röser, Katrin; Klitzsch, Jana; Lieder, Franziska; Aberger, Fritz; Gruber, Wolfgang; Mueller, Kristina M; Pupyshev, Alexander; Moriggl, Richard; Friedrich, Karlheinz

    2015-04-01

    Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in the majority of lung cancer. This study aims at defining connections between STAT3 function and the malignant properties of non-small cell lung carcinoma (NSCLC) cells. To address possible mechanisms by which STAT3 influences invasiveness, the expression of matrix metalloproteinase-1 (MMP-1) was analyzed and correlated with the STAT3 activity status. Studies on both surgical biopsies and on lung cancer cell lines revealed a coincidence of STAT3 activation and strong expression of MMP-1. MMP-1 and tyrosine-phosphorylated activated STAT3 were found co-localized in cancer tissues, most pronounced in tumor fronts, and in particular in adenocarcinomas. STAT3 activity was constitutive, although to different degrees, in the lung cancer cell lines investigated. Three cell lines (BEN, KNS62, and A549) were identified in which STAT3 activitation was inducible by Interleukin-6 (IL-6). In A549 cells, STAT3 activity enhanced the level of MMP-1 mRNA and stimulated transcription from the MMP-1 promoter in IL-6-stimulated A549 cells. STAT3 specificity of this effect was confirmed by STAT3 knockdown through RNA interference. Our results link aberrant activity of STAT3 in lung cancer cells to malignant tumor progression through up-regulation of expression of invasiveness-associated MMPs.

  11. Autistic adolescents show atypical activation of the brain's mentalizing system even without a prior history of mentalizing problems.

    PubMed

    White, Sarah J; Frith, Uta; Rellecke, Julian; Al-Noor, Zainab; Gilbert, Sam J

    2014-04-01

    Some autistic children pass classic Theory of Mind (ToM) tasks that others fail, but the significance of this finding is at present unclear. We identified two such groups of primary school age (labelled ToM+ and ToM-) and a matched comparison group of typically developing children (TD). Five years later we tested these participants again on a ToM test battery appropriate for adolescents and conducted an fMRI study with a story based ToM task. We also assessed autistic core symptoms at these two time points. At both times the ToM- group showed more severe social communication impairments than the ToM+ group, and while showing an improvement in mentalizing performance, they continued to show a significant impairment compared to the NT group. Two independent ROI analyses of the BOLD signal showed activation of the mentalizing network including medial prefrontal cortex, posterior cingulate and lateral temporal cortices. Strikingly, both ToM+ and ToM- groups showed very similar patterns of heightened activation in comparison with the NT group. No differences in other brain regions were apparent. Thus, autistic adolescents who do not have a history of mentalizing problems according to our ToM battery showed the same atypical neurophysiological response during mentalizing as children who did have such a history. This finding indicates that heterogeneity at the behavioural level may nevertheless map onto a similar phenotype at the neuro-cognitive level.

  12. Chemical modification of xylanase from Trichosporon cutaneum shows the presence of carboxyl groups and cysteine residues essential for enzyme activity.

    PubMed

    Wen, L; Miao, Z W; Qing, W D

    1999-08-01

    The endo-beta-1,4-xylanase (EC 3.2.1.8) from Trichosporon cutaneum was chemically modified using amino acid-specific reagents. The enzyme does not bear arginines essential for activity, since 1,2-cyclohexanedione and 2,3-butanedione, although they modify the enzyme (after chromatographic analysis), have no effect on its activity. Reaction of the enzyme with tetranitromethane and N-acetylimidazole did not result in a significant activity loss as a result of modification of tyrosine residues. The water-soluble carbodiimide 1-[3-(dimethylamino) propyl]-3-ethylcarbodiimide inactivated the xylanase rapidly and completely in a pseudo-first-order process, and kinetic analysis indicated that at least one molecule of carbodiimide binds to the enzyme for inactivation. A mixture of neutral xylooligomers provided significant protection of the enzyme against this carbodiimide inactivation. Reaction of the xylanase with 2,4,6-trinitrobenzene sulfonic acid did not result in a significant activity loss as a result of modification of lysine residues. Titration of the enzyme with 5,5'-dithiobis-(2-nitrobenzoic acid) and treatment with iodoacetamide and p-chloromercuribenzoate indicated the presence of a free/active thiol group. Xylan completely protected the enzyme from inactivation by p-hydroxymercuribenzoate, suggesting the presence of cysteine at the substrate-binding site. Inactivation of xylanase by p-hydroxymercuribenzoate could be restored by cysteine. PMID:10609644

  13. Some Attenuated Variants of Vesicular Stomatitis Virus Show Enhanced Oncolytic Activity against Human Glioblastoma Cells relative to Normal Brain Cells▿

    PubMed Central

    Wollmann, Guido; Rogulin, Vitaliy; Simon, Ian; Rose, John K.; van den Pol, Anthony N.

    2010-01-01

    Vesicular stomatitis virus (VSV) has been shown in laboratory studies to be effective against a variety of tumors, including malignant brain tumors. However, attenuation of VSV may be necessary to balance the potential toxicity toward normal cells, particularly when targeting brain tumors. Here we compared 10 recombinant VSV variants resulting from different attenuation strategies. Attenuations included gene shifting (VSV-p1-GFP/RFP), M protein mutation (VSV-M51), G protein cytoplasmic tail truncations (VSV-CT1/CT9), G protein deletions (VSV-dG-GFP/RFP), and combinations thereof (VSV-CT9-M51). Using in vitro viability and replication assays, the VSV variants were grouped into three categories, based on their antitumor activity and non-tumor-cell attenuation. In the first group, wild-type-based VSV-G/GFP, tumor-adapted VSV-rp30, and VSV-CT9 showed a strong antitumor profile but also retained some toxicity toward noncancer control cells. The second group, VSV-CT1, VSV-dG-GFP, and VSV-dG-RFP, had significantly diminished toxicity toward normal cells but showed little oncolytic action. The third group displayed a desired combination of diminished general toxicity and effective antitumor action; this group included VSV-M51, VSV-CT9-M51, VSV-p1-GFP, and VSV-p1-RFP. A member of the last group, VSV-p1-GFP, was then compared in vivo against wild-type-based VSV-G/GFP. Intranasal inoculation of young, postnatal day 16 mice with VSV-p1-GFP showed no adverse neurological effects, whereas VSV-G/GFP was associated with high lethality (80%). Using an intracranial tumor xenograft model, we further demonstrated that attenuated VSV-p1-GFP targets and kills human U87 glioblastoma cells after systemic application. We concluded that some, but not all, attenuated VSV mutants display a favorable oncolytic profile and merit further investigation. PMID:19906910

  14. 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.

  15. Planarity of heteroaryldithiocarbazic acid derivatives showing tuberculostatic activity. III. Mono- and diesters of 3-(pyrazin-2-ylcarbonyl)dithiocarbazic acid.

    PubMed

    Szczesio, Małgorzata; Olczak, Andrzej; Gołka, Jolanta; Gobis, Katarzyna; Foks, Henryk; Główka, Marek L

    2011-07-01

    Methyl 2-(pyrazin-2-ylcarbonyl)hydrazinecarbodithioate, C(7)H(8)N(4)OS(2), (E1), N'-[bis(methylsulfanyl)methylidene]pyrazine-2-carbohydrazide, C(8)H(10)N(4)OS(2), (F1), N'-[bis(methylsulfanyl)methylidene]-6-methoxypyrazine-2-carbohydrazide, C(9)H(12)N(4)O(2)S(2), (F2), and methyl 1-methyl-2-(pyrazin-2-ylcarbonyl)hydrazinecarbodithioate, C(8)H(10)N(4)OS(2), (G1), can be considered as derivatives of classical (thio)amide-type tuberculostatics, and all are moderately active against Mycobacterium tuberculosis. This study was undertaken in a search for relationships between activity and specific intramolecular interactions, especially conjugations and hydrogen-bond contacts, and the molecular structures were compared with respective amine analogues, also active against the pathogen. Despite the differences between the amine and carbonyl groups with opposite functions in the hydrogen bond, the two types of structure show a surprisingly similar planar geometry, mostly due to the conjugations aided by the bifurcated intramolecular hydrogen-bond contact between the N-H group of the central hydrazide group as donor and a pyrazine N atom and an S atom of the dithio function as acceptors. Planarity was suggested to be crucial for the tuberculostatic activity of these compounds. The N-methylated derivative (G1) showed a significant twist at the N-N bond [torsion angle = -121.9 (3)°] due to the methyl substitution, which precludes an intramolecular N-H···S contact and the planarity of the whole molecule. Nonetheless, the compound shows moderate tuberculostatic activity.

  16. In Vitro Analysis of Albendazole Sulfoxide Enantiomers Shows that (+)-(R)-Albendazole Sulfoxide Is the Active Enantiomer against Taenia solium

    PubMed Central

    Paredes, Adriana; de Campos Lourenço, Tiago; Marzal, Miguel; Rivera, Andrea; Dorny, Pierre; Mahanty, Siddhartha; Guerra-Giraldez, Cristina; García, Hector H.; Cass, Quezia B.

    2013-01-01

    Albendazole is an anthelmintic drug widely used in the treatment of neurocysticercosis (NCC), an infection of the brain with Taenia solium cysts. However, drug levels of its active metabolite, albendazole sulfoxide (ABZSO), are erratic, likely resulting in decreased efficacy and suboptimal cure rates in NCC. Racemic albendazole sulfoxide is composed of ABZSO (+)-(R)- and (−)-(S) enantiomers that have been shown to differ in pharmacokinetics and activity against other helminths. The antiparasitic activities of racemic ABZSO and its (+)-(R)- and (−)-(S) enantiomers against T. solium cysts were evaluated in vitro. Parasites were collected from naturally infected pigs, cultured, and exposed to the racemic mixture or to each enantiomer (range, 10 to 500 ng/ml) or to praziquantel as a reference drug. The activity of each compound against cysts was assayed by measuring the ability to evaginate and inhibition of alkaline phosphatase (AP) and parasite antigen release. (+)-(R)-ABZSO was significantly more active than (−)-(S)-ABZSO in suppressing the release of AP and antigen into the supernatant in a dose- and time-dependent manner, indicating that most of the activity of ABZSO resides in the (+)-(R) enantiomer. Use of this enantiomer alone may lead to increased efficacy and/or less toxicity compared to albendazole. PMID:23229490

  17. In vitro analysis of albendazole sulfoxide enantiomers shows that (+)-(R)-albendazole sulfoxide is the active enantiomer against Taenia solium.

    PubMed

    Paredes, Adriana; de Campos Lourenço, Tiago; Marzal, Miguel; Rivera, Andrea; Dorny, Pierre; Mahanty, Siddhartha; Guerra-Giraldez, Cristina; García, Hector H; Nash, Theodore E; Cass, Quezia B

    2013-02-01

    Albendazole is an anthelmintic drug widely used in the treatment of neurocysticercosis (NCC), an infection of the brain with Taenia solium cysts. However, drug levels of its active metabolite, albendazole sulfoxide (ABZSO), are erratic, likely resulting in decreased efficacy and suboptimal cure rates in NCC. Racemic albendazole sulfoxide is composed of ABZSO (+)-(R)- and (-)-(S) enantiomers that have been shown to differ in pharmacokinetics and activity against other helminths. The antiparasitic activities of racemic ABZSO and its (+)-(R)- and (-)-(S) enantiomers against T. solium cysts were evaluated in vitro. Parasites were collected from naturally infected pigs, cultured, and exposed to the racemic mixture or to each enantiomer (range, 10 to 500 ng/ml) or to praziquantel as a reference drug. The activity of each compound against cysts was assayed by measuring the ability to evaginate and inhibition of alkaline phosphatase (AP) and parasite antigen release. (+)-(R)-ABZSO was significantly more active than (-)-(S)-ABZSO in suppressing the release of AP and antigen into the supernatant in a dose- and time-dependent manner, indicating that most of the activity of ABZSO resides in the (+)-(R) enantiomer. Use of this enantiomer alone may lead to increased efficacy and/or less toxicity compared to albendazole.

  18. 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

  19. Saraca indica bark extract shows in vitro antioxidant, antibreast cancer activity and does not exhibit toxicological effects.

    PubMed

    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.

  20. 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.

  1. Doxifluridine-conjugated 2-5A analog shows strong RNase L activation ability and tumor suppressive effect.

    PubMed

    Kitamura, Yoshiaki; Kito, Seiya; Nakashima, Remi; Tanaka, Katsuki; Nagaoka, Kumi; Kitade, Yukio

    2016-08-15

    RNase L is activated by 2',5'-oligoadenylates (2-5A) at subnanomolar levels to cleave single-stranded RNA. We previously reported the hypothesis that the introduction of an 8-methyladenosine residue at the 2'-terminus of the 2-5A tetramer shifts the 2-5A binding site of RNase L. In this study, we synthesized various 5'-modified 2-5A analogs with 8-methyladenosine at the 2'-terminus. The doxifluridine-conjugated 8-methyladenosine-substituted 2-5A analog was significantly more effective as an activator of RNase L than the parent 5'-monophophorylated 2-5A tetramer and showed a tumor suppressive effect against human cervical cancer cells. PMID:27364610

  2. 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.

  3. 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. PMID:27454594

  4. Hellenic Amateur Astronomy Association's activities: Preliminary results on Perseids 2010

    NASA Astrophysics Data System (ADS)

    Maravelias, G.

    2011-01-01

    Preliminary results on the Perseids 2010 are presented. Visual and video observations were obtained by the author and a first reduction of the visual data shows that a maximum of ZHR ~120 was reached during the night 12-13 of August 2010. Moreover, a video setup was tested (DMK camera and UFO Capture v2) and the results show that, under some limitations, valuable data can be obtained.

  5. 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

    2015-12-01

    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.

  6. 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

  7. Origanum vulgare subsp. hirtum essential oil prevented biofilm formation and showed antibacterial activity against planktonic and sessile bacterial cells.

    PubMed

    Schillaci, Domenico; Napoli, Edoardo Marco; Cusimano, Maria Grazia; Vitale, Maria; Ruberto, Andgiuseppe

    2013-10-01

    Essential oils from six different populations of Origanum vulgare subsp. hirtum were compared for their antibiofilm properties. The six essential oils (A to F) were characterized by a combination of gas chromatography with flame ionization detector and gas chromatography with mass spectrometer detector analyses. All oils showed weak activity against the planktonic form of a group of Staphylococcus aureus strains and against a Pseudomonas aeruginosa ATCC 15442 reference strain. The ability to inhibit biofilm formation was investigated at sub-MIC levels of 200, 100, and 50 m g/ml by staining sessile cells with safranin. Sample E showed the highest average effectiveness against all tested strains at 50 m g/ml and had inhibition percentages ranging from 30 to 52%. In the screening that used preformed biofilm from the reference strain P. aeruginosa, essential oils A through E were inactive at 200 m g/ml; F was active with a percentage of inhibition equal to 53.2%. Oregano essential oil can inhibit the formation of biofilms of various food pathogens and food spoilage organisms. PMID:24112575

  8. 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

    2016-01-01

    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

  9. Origanum vulgare subsp. hirtum essential oil prevented biofilm formation and showed antibacterial activity against planktonic and sessile bacterial cells.

    PubMed

    Schillaci, Domenico; Napoli, Edoardo Marco; Cusimano, Maria Grazia; Vitale, Maria; Ruberto, Andgiuseppe

    2013-10-01

    Essential oils from six different populations of Origanum vulgare subsp. hirtum were compared for their antibiofilm properties. The six essential oils (A to F) were characterized by a combination of gas chromatography with flame ionization detector and gas chromatography with mass spectrometer detector analyses. All oils showed weak activity against the planktonic form of a group of Staphylococcus aureus strains and against a Pseudomonas aeruginosa ATCC 15442 reference strain. The ability to inhibit biofilm formation was investigated at sub-MIC levels of 200, 100, and 50 m g/ml by staining sessile cells with safranin. Sample E showed the highest average effectiveness against all tested strains at 50 m g/ml and had inhibition percentages ranging from 30 to 52%. In the screening that used preformed biofilm from the reference strain P. aeruginosa, essential oils A through E were inactive at 200 m g/ml; F was active with a percentage of inhibition equal to 53.2%. Oregano essential oil can inhibit the formation of biofilms of various food pathogens and food spoilage organisms.

  10. Trans Fatty Acid Derived Phospholipids Show Increased Membrane Cholesterol and Reduced Receptor Activation as Compared to Their Cis Analogs

    PubMed Central

    Niu, Shui-Lin; Mitchell, Drake C.; Litman, Burton J.

    2005-01-01

    The consumption of trans fatty acid (TFA) is linked to the elevation of LDL cholesterol and is considered to be a major health risk factor for coronary heart disease. Despite several decades of extensive research on this subject, the underlying mechanism of how TFA modulates serum cholesterol levels remains elusive. In this study, we examined the molecular interaction of TFA-derived phospholipid with cholesterol and the membrane receptor rhodopsin in model membranes. Rhodopsin is a prototypical member of the G-protein coupled receptor family. It has a well-characterized structure and function and serves as a model membrane receptor in this study. Phospholipid–cholesterol affinity was quantified by measuring cholesterol partition coefficients. Phospholipid–receptor interactions were probed by measuring the level of rhodopsin activation. Our study shows that phospholipid derived from TFA had a higher membrane cholesterol affinity than their cis analogues. TFA phospholipid membranes also exhibited a higher acyl chain packing order, which was indicated by the lower acyl chain packing free volume as determined by DPH fluorescence and the higher transition temperature for rhodopsin thermal denaturation. The level of rhodopsin activation was diminished in TFA phospholipids. Since membrane cholesterol level and membrane receptors are involved in the regulation of cholesterol homeostasis, the combination of higher cholesterol content and reduced receptor activation associated with the presence of TFA–phospholipid could be factors contributing to the elevation of LDL cholesterol. PMID:15766276

  11. CPU-12, a novel synthesized oxazolo[5,4-d]pyrimidine derivative, showed superior anti-angiogenic activity.

    PubMed

    Liu, Jiping; Deng, Ya-Hui; Yang, Ling; Chen, Yijuan; Lawali, Manzo; Sun, Li-Ping; Liu, Yu

    2015-09-01

    Angiogenesis is a crucial requirement for malignant tumor growth, progression and metastasis. Tumor-derived factors stimulate formation of new blood vessels which actively support tumor growth and spread. Various of drugs have been applied to inhibit tumor angiogenesis. CPU-12, 4-chloro-N-(4-((2-(4-methoxyphenyl)-5-methyloxazolo[5,4-d] pyrimidin-7-yl)amino)phenyl)benzamide, is a novel oxazolo[5,4-d]pyrimidine derivative that showed potent activity in inhibiting VEGF-induced angiogenesis in vitro and ex-vivo. In cell toxicity experiments, CPU-12 significantly inhibited the human umbilical vein endothelial cell (HUVEC) proliferation in a dose-dependent manner with a low IC50 value at 9.30 ± 1.24 μM. In vitro, CPU-12 remarkably inhibited HUVEC's migration, chemotactic invasion and capillary-like tube formation in a dose-dependent manner. In ex-vivo, CPU-12 effectively inhibited new microvessels sprouting from the rat aortic ring. In addition, the downstream signalings of vascular endothelial growth factor receptor-2 (VEGFR-2), including the phosphorylation of PI3K, ERK1/2 and p38 MAPK, were effectively down-regulated by CPU-12. These evidences suggested that angiogenic response via the induction of VEGFR through distinct signal transduction pathways regulating proliferation, migration and tube formation of endothelial cells was significantly inhibited by the novel small molecule compound CPU-12 in vitro and ex-vivo. In conclusion, CPU-12 showed superior anti-angiogenic activity in vitro.

  12. Thionin Thi2.1 from Arabidopsis thaliana expressed in endothelial cells shows antibacterial, antifungal and cytotoxic activity.

    PubMed

    Loeza-Angeles, Heber; Sagrero-Cisneros, Eduardo; Lara-Zárate, Leticia; Villagómez-Gómez, Erik; López-Meza, Joel E; Ochoa-Zarzosa, Alejandra

    2008-10-01

    Thionins are plant antimicrobial peptides with antibacterial and antifungal activities. Thionin Thi2.1 cDNA from Arabidopsis thaliana was expressed in BVE-E6E7 bovine endothelial cell line and its activity was evaluated against Escherichia coli, Staphylococcus aureus, Candida albicans and different mammal cell lines. Total protein (2.5 microg) from conditioned medium (CM) of clone EC-Thi2.1 inhibited the growth of E. coli, S. aureus (>90%) and C. albicans strains (>80%) in relation to the CM from control cells. Also, CM of EC-Thi2.1 inhibited the viability of several transformed and normal mammal cell lines (38-95%). These results suggest that thionin Thi2.1 is an antimicrobial peptide that could be use in the treatment of mammalian infectious diseases. PMID:18563581

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

    PubMed

    Keum, Dongil; Kruse, Martin; Kim, Dong-Il; Hille, Bertil; Suh, Byung-Chang

    2016-06-28

    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

  14. 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.

  15. 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. PMID:27482096

  16. 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.

  17. Active Aging Promotion: Results from the Vital Aging Program

    PubMed Central

    Caprara, Mariagiovanna; Molina, María Ángeles; Schettini, Rocío; Santacreu, Marta; Orosa, Teresa; Mendoza-Núñez, Víctor Manuel; Rojas, Macarena; Fernández-Ballesteros, Rocío

    2013-01-01

    Active aging is one of the terms in the semantic network of aging well, together with others such as successful, productive, competent aging. All allude to the new paradigm in gerontology, whereby aging is considered from a positive perspective. Most authors in the field agree active aging is a multidimensional concept, embracing health, physical and cognitive fitness, positive affect and control, social relationships and engagement. This paper describes Vital Aging, an individual active aging promotion program implemented through three modalities: Life, Multimedia, and e-Learning. The program was developed on the basis of extensive evidence about individual determinants of active aging. The different versions of Vital Aging are described, and four evaluation studies (both formative and summative) are reported. Formative evaluation reflected participants' satisfaction and expected changes; summative evaluations yielded some quite encouraging results using quasi-experimental designs: those who took part in the programs increased their physical exercise, significantly improved their diet, reported better memory, had better emotional balance, and enjoyed more cultural, intellectual, affective, and social activities than they did before the course, thus increasing their social relationships. These results are discussed in the context of the common literature within the field and, also, taking into account the limitations of the evaluations accomplished. PMID:23476644

  18. 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

  19. The Nucleoside Analog BMS-986001 Shows Greater In Vitro Activity against HIV-2 than against HIV-1.

    PubMed

    Smith, Robert A; Raugi, Dana N; Wu, Vincent H; Leong, Sally S; Parker, Kate M; Oakes, Mariah K; Sow, Papa Salif; Ba, Selly; Seydi, Moussa; Gottlieb, Geoffrey S

    2015-12-01

    Treatment options for individuals infected with human immunodeficiency virus type 2 (HIV-2) are restricted by the intrinsic resistance of the virus to nonnucleoside reverse transcriptase inhibitors (NNRTIs) and the reduced susceptibility of HIV-2 to several protease inhibitors (PIs) used in antiretroviral therapy (ART). In an effort to identify new antiretrovirals for HIV-2 treatment, we evaluated the in vitro activity of the investigational nucleoside analog BMS-986001 (2',3'-didehydro-3'-deoxy-4'-ethynylthymidine; also known as censavudine, festinavir, OBP-601, 4'-ethynyl stavudine, or 4'-ethynyl-d4T). In single-cycle assays, BMS-986001 inhibited HIV-2 isolates from treatment-naive individuals, with 50% effective concentrations (EC50s) ranging from 30 to 81 nM. In contrast, EC50s for group M and O isolates of HIV-1 ranged from 450 to 890 nM. Across all isolates tested, the average EC50 for HIV-2 was 9.5-fold lower than that for HIV-1 (64 ± 18 nM versus 610 ± 200 nM, respectively; mean ± standard deviation). BMS-986001 also exhibited full activity against HIV-2 variants whose genomes encoded the single amino acid changes K65R and Q151M in reverse transcriptase, whereas the M184V mutant was 15-fold more resistant to the drug than the parental HIV-2ROD9 strain. Taken together, our findings show that BMS-986001 is an effective inhibitor of HIV-2 replication. To our knowledge, BMS-986001 is the first nucleoside analog that, when tested against a diverse collection of HIV-1 and HIV-2 isolates, exhibits more potent activity against HIV-2 than against HIV-1 in culture. PMID:26392486

  20. The Nucleoside Analog BMS-986001 Shows Greater In Vitro Activity against HIV-2 than against HIV-1

    PubMed Central

    Raugi, Dana N.; Wu, Vincent H.; Leong, Sally S.; Parker, Kate M.; Oakes, Mariah K.; Sow, Papa Salif; Ba, Selly; Seydi, Moussa; Gottlieb, Geoffrey S.

    2015-01-01

    Treatment options for individuals infected with human immunodeficiency virus type 2 (HIV-2) are restricted by the intrinsic resistance of the virus to nonnucleoside reverse transcriptase inhibitors (NNRTIs) and the reduced susceptibility of HIV-2 to several protease inhibitors (PIs) used in antiretroviral therapy (ART). In an effort to identify new antiretrovirals for HIV-2 treatment, we evaluated the in vitro activity of the investigational nucleoside analog BMS-986001 (2′,3′-didehydro-3′-deoxy-4′-ethynylthymidine; also known as censavudine, festinavir, OBP-601, 4′-ethynyl stavudine, or 4′-ethynyl-d4T). In single-cycle assays, BMS-986001 inhibited HIV-2 isolates from treatment-naive individuals, with 50% effective concentrations (EC50s) ranging from 30 to 81 nM. In contrast, EC50s for group M and O isolates of HIV-1 ranged from 450 to 890 nM. Across all isolates tested, the average EC50 for HIV-2 was 9.5-fold lower than that for HIV-1 (64 ± 18 nM versus 610 ± 200 nM, respectively; mean ± standard deviation). BMS-986001 also exhibited full activity against HIV-2 variants whose genomes encoded the single amino acid changes K65R and Q151M in reverse transcriptase, whereas the M184V mutant was 15-fold more resistant to the drug than the parental HIV-2ROD9 strain. Taken together, our findings show that BMS-986001 is an effective inhibitor of HIV-2 replication. To our knowledge, BMS-986001 is the first nucleoside analog that, when tested against a diverse collection of HIV-1 and HIV-2 isolates, exhibits more potent activity against HIV-2 than against HIV-1 in culture. PMID:26392486

  1. The Nucleoside Analog BMS-986001 Shows Greater In Vitro Activity against HIV-2 than against HIV-1.

    PubMed

    Smith, Robert A; Raugi, Dana N; Wu, Vincent H; Leong, Sally S; Parker, Kate M; Oakes, Mariah K; Sow, Papa Salif; Ba, Selly; Seydi, Moussa; Gottlieb, Geoffrey S

    2015-12-01

    Treatment options for individuals infected with human immunodeficiency virus type 2 (HIV-2) are restricted by the intrinsic resistance of the virus to nonnucleoside reverse transcriptase inhibitors (NNRTIs) and the reduced susceptibility of HIV-2 to several protease inhibitors (PIs) used in antiretroviral therapy (ART). In an effort to identify new antiretrovirals for HIV-2 treatment, we evaluated the in vitro activity of the investigational nucleoside analog BMS-986001 (2',3'-didehydro-3'-deoxy-4'-ethynylthymidine; also known as censavudine, festinavir, OBP-601, 4'-ethynyl stavudine, or 4'-ethynyl-d4T). In single-cycle assays, BMS-986001 inhibited HIV-2 isolates from treatment-naive individuals, with 50% effective concentrations (EC50s) ranging from 30 to 81 nM. In contrast, EC50s for group M and O isolates of HIV-1 ranged from 450 to 890 nM. Across all isolates tested, the average EC50 for HIV-2 was 9.5-fold lower than that for HIV-1 (64 ± 18 nM versus 610 ± 200 nM, respectively; mean ± standard deviation). BMS-986001 also exhibited full activity against HIV-2 variants whose genomes encoded the single amino acid changes K65R and Q151M in reverse transcriptase, whereas the M184V mutant was 15-fold more resistant to the drug than the parental HIV-2ROD9 strain. Taken together, our findings show that BMS-986001 is an effective inhibitor of HIV-2 replication. To our knowledge, BMS-986001 is the first nucleoside analog that, when tested against a diverse collection of HIV-1 and HIV-2 isolates, exhibits more potent activity against HIV-2 than against HIV-1 in culture.

  2. "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 state's best…

  3. Bovine natural killer cells are present in Escherichia coli infected mammary gland tissue and show antimicrobial activity in vitro.

    PubMed

    Sipka, Anja; Pomeroy, Brianna; Klaessig, Suzanne; Schukken, Ynte

    2016-10-01

    Natural killer (NK) cells are early responders in bacterial infections but their role in bovine mastitis has not been characterized. For the first time, we show the presence of NK cells (NKp46(+)/CD3(-)) in bovine mammary gland tissue after an intramammary challenge with Escherichia (E.) coli. A small number of NK cells was detected in milk from quarters before and during an E. coli challenge. In vitro cultures of primary bovine mammary gland epithelial cells stimulated with UV irradiated E. coli induced significant migration of peripheral blood NK cells (pbNK) within 2h. Furthermore, pbNK cells significantly reduced counts of live E. coli in vitro within 2h of culture. The results show that bovine NK cells have the capacity to migrate to the site of infection and produce antibacterial mediators. These findings introduce NK cells as a leukocyte population in the mammary gland with potential functions in the innate immune response in bovine mastitis. PMID:27638120

  4. First Results of the TIGRE Chromospheric Activity Survey

    NASA Astrophysics Data System (ADS)

    Mittag, M.; Hempelmann, A.; Gonzalez-Perez, J. N.; Schmitt, J. H. M. M.

    2015-01-01

    We present the first results of the stellar activity survey with TIGRE (Telescopio Internacional de Guanajuato, Robótico-Espectroscópico). This long term program was started in August 2013 with the monitoring of a larger number of stars. We aim at measuring the short- and long-term variability of stellar activity for stars of different spectral types and luminosity classes, using indicators of different spectral lines (mainly Ca II S-Index, Ca II IR triplet, H_α and sodium D). A transformation equation of the TIGRE S-Index into the Mount Wilson S-index was derived in order to compare our results to the vast body of existing S-index measurements. Furthermore, the correlation between the S-index and the lines of the Ca II IR triplet has been studied, based on strictly simultaneous observations.

  5. Human Ebola virus infection results in substantial immune activation.

    PubMed

    McElroy, Anita K; Akondy, Rama S; Davis, Carl W; Ellebedy, Ali H; Mehta, Aneesh K; Kraft, Colleen S; Lyon, G Marshall; Ribner, Bruce S; Varkey, Jay; Sidney, John; Sette, Alessandro; Campbell, Shelley; Ströher, Ute; Damon, Inger; Nichol, Stuart T; Spiropoulou, Christina F; Ahmed, Rafi

    2015-04-14

    Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10-50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1-2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients' discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus. PMID:25775592

  6. Human Ebola virus infection results in substantial immune activation.

    PubMed

    McElroy, Anita K; Akondy, Rama S; Davis, Carl W; Ellebedy, Ali H; Mehta, Aneesh K; Kraft, Colleen S; Lyon, G Marshall; Ribner, Bruce S; Varkey, Jay; Sidney, John; Sette, Alessandro; Campbell, Shelley; Ströher, Ute; Damon, Inger; Nichol, Stuart T; Spiropoulou, Christina F; Ahmed, Rafi

    2015-04-14

    Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10-50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1-2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients' discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.

  7. The polysaccharide isolated from Pleurotus nebrodensis (PN-S) shows immune-stimulating activity in RAW264.7 macrophages.

    PubMed

    Cui, Hai-Yan; Wang, Chang-Lu; Wang, Yu-Rong; Li, Zhen-Jing; Zhang, Ya-Nan

    2015-05-01

    A novel Pleurotus nebrodensis polysaccharide (PN-S) was purified and characterized, and its immune-stimulating activity was evaluated in RAW264.7 macrophages. PN-S induced the proliferation of RAW264.7 cells in a dose-dependent manner, as determined by the MTT assay. After exposure to PN-S, the phagocytosis of the macrophages was significantly improved, with remarkable changes in morphology being observed. Flow cytometric analysis demonstrated that PN-S promoted RAW264.7 cells to progress through S and G2/M phases. PN-S treatment enhanced the productions of interleukin-6 (IL-6), nitric oxide (NO), interferon gamma (INF-γ), and tumor necrosis factor-α (TNF-α) in the macrophages, with up-regulation of mRNA expressions of interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), interferon gamma(INF-γ) and tumor necrosis factor-α (TNF-α) being observed in a dose-dependent manner, as measured by qRT-PCR. In conclusion, these results suggest that the purified PN-S can improve immunity by activating macrophages.

  8. Recombinant murine toxin from Yersinia pestis shows high toxicity and β-adrenergic blocking activity in mice.

    PubMed

    Fan, Yanxiao; Zhou, Yazhou; Feng, Na; Wang, Qiong; Tian, Guang; Wu, Xiaohong; Liu, Zizhong; Bi, Yujing; Yang, Ruifu; Wang, Xiaoyi

    2016-05-01

    Yersinia pestis murine toxin (Ymt) encoded on pMT1 is a 61-kDa protein, a member of the phospholipase D superfamily, which is found in all the domains of life. It is considered to be an intracellular protein required for the survival of Y. pestis in the midgut of the flea, but the exact role of Ymt in the pathogenesis of Y. pestis has not been clarified. Purified Ymt is highly toxic to mice and rats, but the exact mechanism of the animals' death is unclear. Here, we prepared a recombinant Ymt in Escherichia coli BL21 cells, and determined its toxicity and activity. We demonstrated that recombinant Ymt was as toxic to mice as the native protein when administered via the intraperitoneal or intravenous route, and inhibited the elevation of blood sugar caused by adrenaline. We also demonstrated that recombinant Ymt was highly toxic to mice when administered via the muscular or subcutaneous route. We also show that the multiple organ congestion or hemorrhage caused by Ymt poisoning may explain the death of the mice. PMID:26774329

  9. A preorganized metalloreceptor for alkaline earth ions showing calcium versus magnesium selectivity in water: biological activity of selected metal complexes.

    PubMed

    Amatori, Stefano; Ambrosi, Gianluca; Fanelli, Mirco; Formica, Mauro; Fusi, Vieri; Giorgi, Luca; Macedi, Eleonora; Micheloni, Mauro; Paoli, Paola; Rossi, Patrizia

    2014-08-25

    The N,N'-bis[(3-hydroxy-4-pyron-2-yl)methyl]-N,N'-dimethylethylendiamine (Malten = L) forms the highly stable [CuH(-2)L] species in water, in which the converging maltol oxygen atoms form an electron-rich area able to host hard metal ions. When considering the alkaline earth series (AE), the [Cu(H(-2)L)] species binds all metal ions, with the exception of Mg(2+), exhibiting the relevant property to discriminate Ca(2+) versus Mg(2+) at physiological pH 7.4; the binding of the AE metal is visible to the naked eye. The stability constant values of the trinuclear [AE{Cu(H(-2)L)}2](2+) species formed reach the maximum for Ca(2+) (log K=7.7). Ca(2+) also forms a tetranuclear [Ca{Cu(H(-2)L)}]2(4+) species at a high Ca(2+) concentration. Tri- and tetranuclear calcium complexes show blue- and pink-colored crystals, respectively. [Cu(H(-2)L)] is the most active species in inducing DNA alterations. The DNA damages are compatible with its hydrolytic cleavages.

  10. 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.

  11. 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. PMID:27229725

  12. Inactivated ORF virus shows antifibrotic activity and inhibits human hepatitis B virus (HBV) and hepatitis C virus (HCV) replication in preclinical models.

    PubMed

    Paulsen, Daniela; Urban, Andreas; Knorr, Andreas; Hirth-Dietrich, Claudia; Siegling, Angela; Volk, Hans-Dieter; Mercer, Andrew A; Limmer, Andreas; Schumak, Beatrix; Knolle, Percy; Ruebsamen-Schaeff, Helga; Weber, Olaf

    2013-01-01

    Inactivated orf virus (iORFV), strain D1701, is a potent immune modulator in various animal species. We recently demonstrated that iORFV induces strong antiviral activity in animal models of acute and chronic viral infections. In addition, we found D1701-mediated antifibrotic effects in different rat models of liver fibrosis. In the present study, we compare iORFV derived from two different strains of ORFV, D1701 and NZ2, respectively, with respect to their antifibrotic potential as well as their potential to induce an antiviral response controlling infections with the hepatotropic pathogens hepatitis C virus (HCV) and hepatitis B virus (HBV). Both strains of ORFV showed anti-viral activity against HCV in vitro and against HBV in a transgenic mouse model without signs of necro-inflammation in vivo. Our experiments suggest that the absence of liver damage is potentially mediated by iORFV-induced downregulation of antigen cross-presentation in liver sinus endothelial cells. Furthermore, both strains showed significant anti-fibrotic activity in rat models of liver fibrosis. iORFV strain NZ2 appeared more potent compared to strain D1701 with respect to both its antiviral and antifibrotic activity on the basis of dosages estimated by titration of active virus. These results show a potential therapeutic approach against two important human liver pathogens HBV and HCV that independently addresses concomitant liver fibrosis. Further studies are required to characterize the details of the mechanisms involved in this novel therapeutic principle.

  13. Summary of the Results of STIS SMOV4 Calibration Activities

    NASA Astrophysics Data System (ADS)

    Proffitt, Charles R.; Aloisi, Alessandra; Bohlin, Ralph; Cox, Colin, Goudfrooij, Paul; Gull, Thodore, R.; Kaiser, Mary Beth; Lallo, Matt; Lennon, Daniel J.; Lindler, Don J.; Makidon, Russ; Niemi, Sami-Matias; Serrano, Beverly; Wheeler, Thomas; Wolfe, Michael E.; Serrano, Beverly; Woodgate, Bruce; Zheng, Wei

    2014-01-01

    After HST Servicing Mission 4 (SM4), there was a period of Science Mission Observatory Verification (SMOV4), to check out the new and repaired instruments. Here we summarize the execution and results of the Space Telescope Imaging Spectrograph (STIS) SMOV 4 activities undertaken to ensure that the repaired STIS instrument was ready to carry out its scheduled science program after a nearly five year hiatus in operation. The results of the initial aliveness and functional tests are reviewed, anomalies that aff ected the execution of the STIS SMOV plan are discussed, and the results of each STIS SMOV activity executed are summarized. In most respects the performance of STIS after the SM4 repair is very similar to that seen prior to the 2004 failure. Notable chang es include a significant and unexpected enhancement of the NUV MAMA dark rate that has been declining only very slowly, and continued degradation of the CCD performance due to radiation damage. Post - repair throughputs of most modes are close to expectation s based on extrapolation of previous trends.

  14. 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.

  15. Connexin30-deficient mice show increased emotionality and decreased rearing activity in the open-field along with neurochemical changes.

    PubMed

    Dere, E; De Souza-Silva, M A; Frisch, C; Teubner, B; Söhl, G; Willecke, K; Huston, J P

    2003-08-01

    Gap-junction channels in the brain, formed by connexin (Cx) proteins with a distinct regional/cell-type distribution, allow intercellular electrical and metabolic communication. In astrocytes, mainly the connexins 43, 26 and 30 are expressed. In addition, connexin30 is expressed in ependymal and leptomeningeal cells, as well as in skin and cochlea. The functional implications of the astrocytic gap-junctional network are not well understood and evidence regarding their behavioural relevance is lacking. Thus, we have tested groups of Cx30-/-, Cx30+/-, and Cx30+/+ mice in the open-field, an object exploration task, in the graded anxiety test and on the rotarod. The Cx30-/- mice showed reduced exploratory activity in terms of rearings but not locomotion in the open-field and object exploration task. Furthermore, Cx30-/- mice exhibited anxiogenic behaviour as shown by higher open-field centre avoidance and corner preference. Graded anxiety test and rotarod performance was similar across groups. The Cx30-/- mice had elevated choline levels in the ventral striatum, possibly related to their aberrant behavioural phenotypes. The Cx30+/- mice had lower dopamine and metabolite levels in the amygdala and ventral striatum and lower hippocampal 5-hydroxyindole acid (5-HIAA) concentrations relative to Cx30+/+ mice. Furthermore, the Cx30+/- mice had lower acetylcholine concentrations in the ventral striatum and higher choline levels in the neostriatum, relative to Cx30+/+ mice. Our data suggest that the elimination of connexin30 can alter the reactivity to novel environments, pointing to the importance of gap-junctional signalling in behavioural processes.

  16. The selective VEGFR1-3 inhibitor axitinib (AG-013736) shows antitumor activity in human neuroblastoma xenografts.

    PubMed

    Rössler, Jochen; Monnet, Yann; Farace, Francoise; Opolon, Paule; Daudigeos-Dubus, Estelle; Bourredjem, Abderrahmane; Vassal, Gilles; Geoerger, Birgit

    2011-06-01

    Tumor angiogenesis in childhood neuroblastoma is an important prognostic factor suggesting a potential role for antiangiogenic agents in the treatment of high-risk disease. Within the KidsCancerKinome project, we evaluated the new oral selective pan-VEGFR tyrosine kinase inhibitor axitinib (AG-013736) against neuroblastoma cell lines and the subcutaneous and orthotopic xenograft model IGR-N91 derived from a primary bone marrow metastasis. Axitinib reduced cell proliferation in a dose-dependent manner with IC(50) doses between 274 and >10,000 nmol/l. Oral treatment with 30 mg/kg BID for 2 weeks in advanced tumors yielded significant tumor growth delay, with a median time to reach five times initial tumor volume of 11.4 days compared to controls (p = 0.0006) and resulted in significant reduction in bioluminescence. Simultaneous inhibition of VEGFR downstream effector mTOR using rapamycin 20 mg/kg q2d×5 did not statistically enhance tumor growth delay compared to single agent activities. Axitinib downregulated VEGFR-2 phosphorylation resulting in significantly decreased microvessel density (MVD) and overall surface fraction of tumor vessels (OSFV) in all xenografts as measured by CD34 immunohistochemical staining (mean MVD ± SD and OSFV at 14 days 21.27 ± 10.03 in treated tumors vs. 48.79 ± 17.27 in controls and 0.56% vs. 1.29%; p = 0.0006, respectively). We further explored the effects of axitinib on circulating mature endothelial cells (CECs) and endothelial progenitor cells (CEPs) measured by flow cytometry. While only transient modification was observed for CECs, CEP counts were significantly reduced during and up to 14 days after end of treatment. Axitinib has potent antiangiogenic properties that may warrant further evaluation in neuroblastoma. PMID:20715103

  17. 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. PMID:26615488

  18. 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.

  19. 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

  20. Rapakinin, Arg-Ile-Tyr, derived from rapeseed napin, shows anti-opioid activity via the prostaglandin IP receptor followed by the cholecystokinin CCK(2) receptor in mice.

    PubMed

    Yamada, Yuko; Ohinata, Kousaku; Lipkowski, Andrzej W; Yoshikawa, Masaaki

    2011-02-01

    Rapakinin, Arg-Ile-Tyr, is a vasorelaxing, anti-hypertensive and anorexigenic peptide derived from rapeseed napin. In this study, we found that rapakinin intracerebroventricularly administered to mice inhibited the analgesic effect of morphine, evaluated by the tail-pinch test. The anti-opioid activity of rapakinin was blocked by LY225910, an antagonist of the cholecystokinin (CCK) CCK(2) receptor, but not by lorglumide, an antagonist of the CCK(1) receptor. The anti-opioid activity of rapakinin was also blocked by CAY10441, an antagonist of the prostaglandin (PG) IP receptor. These results suggest that the anti-opioid activity of rapakinin is mediated by the CCK(2) and IP receptors. The anti-opioid activity induced by ciprostene, an IP receptor agonist, was blocked by LY225910, while that of CCK-8 was not blocked by CAY10441. Thus, it is demonstrated that the CCK-CCK(2) system was activated downstream of the PGI(2)-IP receptor system. Taken together, rapakinin shows anti-opioid activity via the activation of the PGI(2)-IP receptor system followed by the CCK-CCK(2) receptor system.

  1. 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…

  2. 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…

  3. Combination of glycosphingosomes and liposomal doxorubicin shows increased activity against dimethyl-α-benzanthracene-induced fibrosarcoma in mice

    PubMed Central

    Khan, Masood A; Aljarbou, Ahmed N; Aldebasi, Yousef H; Alorainy, Mohammed S; Khan, Arif

    2015-01-01

    The present study aimed to assess the antitumor effect of glycosphingolipid-incorporated liposomes (glycosphingosomes) in combination with liposomal doxorubicin (Lip-Dox) in a mouse model of fibrosarcoma. Glycosphingosomes were prepared by incorporating glycosphingolipids isolated from Sphingomonas paucimobilis into the liposomes of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, cholesterol, and cardiolipin. Tumors were induced by administering dimethyl-α-benzanthracene, and tumor-bearing mice were treated with various formulations of Dox, including free Dox, Lip-Dox, or glycosphingosomes + Lip-Dox. Mice were observed for 90 days to monitor their survival and tumor size. Free Dox, but not Lip-Dox or a combination of glycosphingosomes and Lip-Dox, caused the substantial depletion of leukocytes and significantly increased the levels of lactate dehydrogenase and creatinine kinase in mice. Tumor-bearing mice treated with a combination of glycosphingosomes and Lip-Dox showed restricted tumor growth and increased survival when compared to those treated with free Dox or Lip-Dox. The results of the present study suggest that a combination of glycosphingosomes and Lip-Dox may prove to be very effective in the treatment of tumors. PMID:26504383

  4. Analysis of conservative tracer measurement results using the Frechet distribution at planted horizontal subsurface flow constructed wetlands filled with coarse gravel and showing the effect of clogging processes.

    PubMed

    Dittrich, Ernő; Klincsik, Mihály

    2015-11-01

    A mathematical process, developed in Maple environment, has been successful in decreasing the error of measurement results and in the precise calculation of the moments of corrected tracer functions. It was proved that with this process, the measured tracer results of horizontal subsurface flow constructed wetlands filled with coarse gravel (HSFCW-C) can be fitted more accurately than with the conventionally used distribution functions (Gaussian, Lognormal, Fick (Inverse Gaussian) and Gamma). This statement is true only for the planted HSFCW-Cs. The analysis of unplanted HSFCW-Cs needs more research. The result of the analysis shows that the conventional solutions (completely stirred series tank reactor (CSTR) model and convection-dispersion transport (CDT) model) cannot describe these types of transport processes with sufficient accuracy. These outcomes can help in developing better process descriptions of very difficult transport processes in HSFCW-Cs. Furthermore, a new mathematical process can be developed for the calculation of real hydraulic residence time (HRT) and dispersion coefficient values. The presented method can be generalized to other kinds of hydraulic environments.

  5. Candida tropicalis from veterinary and human sources shows similar in vitro hemolytic activity, antifungal biofilm susceptibility and pathogenesis against Caenorhabditis elegans.

    PubMed

    Brilhante, Raimunda Sâmia Nogueira; Oliveira, Jonathas Sales de; Evangelista, Antônio José de Jesus; Serpa, Rosana; Silva, Aline Lobão da; Aguiar, Felipe Rodrigues Magalhães de; Pereira, Vandbergue Santos; Castelo-Branco, Débora de Souza Collares Maia; Pereira-Neto, Waldemiro Aquino; Cordeiro, Rossana de Aguiar; Sidrim, José Júlio Costa; Rocha, Marcos Fábio Gadelha

    2016-08-30

    The aim of this study was to evaluate the in vitro hemolytic activity and biofilm antifungal susceptibility of veterinary and human Candida tropicalis strains, as well as their pathogenesis against Caenorhabditis elegans. Twenty veterinary isolates and 20 human clinical isolates of C. tropicalis were used. The strains were evaluated for their hemolytic activity and biofilm production. Biofilm susceptibility to itraconazole, fluconazole, voriconazole, amphotericin B and caspofungin was assessed using broth microdilution assay. The in vivo evaluation of strain pathogenicity was investigated using the nematode C. elegans. Hemolytic factor was observed in 95% of the strains and 97.5% of the isolates showed ability to form biofilm. Caspofungin and amphotericin B showed better results than azole antifungals against mature biofilms. Paradoxical effect on mature biofilm metabolic activity was observed at elevated concentrations of caspofungin (8-64μg/mL). Azole antifungals were not able to inhibit mature C. tropicalis biofilms, even at the higher tested concentrations. High mortality rates of C. elegans were observed when the worms were exposed to with C. tropicalis strains, reaching up to 96%, 96h after exposure of the worms to C. tropicalis strains. These results reinforce the high pathogenicity of C. tropicalis from veterinary and human sources and show the effectiveness of caspofungin and amphotericin B against mature biofilms of this species. PMID:27527785

  6. Cues Resulting in Desire for Sexual Activity in Women

    PubMed Central

    McCall, Katie; Meston, Cindy

    2010-01-01

    Introduction A number of questionnaires have been created to assess levels of sexual desire in women, but to our knowledge, there are currently no validated measures for assessing cues that result in sexual desire. A questionnaire of this nature could be useful for both clinicians and researchers, because it considers the contextual nature of sexual desire and it draws attention to individual differences in factors that can contribute to sexual desire. Aim The aim of the present study was to create a multidimensional assessment tool of cues for sexual desire in women that is validated in women with and without hypoactive sexual desire disorder (HSDD). Methods Factor analyses conducted on both an initial sample (N = 874) and a community sample (N = 138) resulted in the Cues for Sexual Desire Scale (CSDS) which included four factors: (i) Emotional Bonding Cues; (ii) Erotic/ Explicit Cues; (iii) Visual/Proximity Cues; and (iv) Implicit/Romantic Cues. Main Outcome Measures Scale construction of cues associated with sexual desire and differences between women with and without sexual dysfunction. Results The CSDS demonstrated good reliability and validity and was able to detect significant differences between women with and without HSDD. Results from regression analyses indicated that both marital status and level of sexual functioning predicted scores on the CSDS. The CSDS provided predictive validity for the Female Sexual Function Index desire and arousal domain scores, and increased cues were related to a higher reported frequency of sexual activity in women. Conclusions The findings from the present study provide valuable information regarding both internal and external triggers that can result in sexual desire for women. We believe that the CSDS could be beneficial in therapeutic settings to help identify cues that do and do not facilitate sexual desire in women with clinically diagnosed desire difficulties. PMID:16942529

  7. Test results of an active magnetic regenerative refrigerator

    NASA Astrophysics Data System (ADS)

    Degregoria, A. J.; Feuling, L. J.; Laatsch, J. F.; Rowe, J. R.; Trueblood, J. R.; Wang, A. A.

    The principle of the Active Magnetic Regenerator (AMR) is tested with an experimental refrigerator designed to operate within the temperature range of about 4 to 80 K. Applications, including helium and hydrogen liquefaction and hydrogen slush generation, are envisioned. The device uses a single moveable superconducting solenoidal magnet in persistent mode to alternately charge and discharge two in-line beds of magnetic material. Between magnet motions, a double-acting piston displacer moves heat transfer fluid in the form of helium gas through the beds, absorbing heat at the cold heat exchanger and rejecting heat at the hot heat exchanger. A description of the refrigerator and performance results are presented. Comparisons to a detailed AMR model are shown.

  8. How often do German children and adolescents show signs of common mental health problems? Results from different methodological approaches – a cross-sectional study

    PubMed Central

    2014-01-01

    Background Child and adolescent mental health problems are ubiquitous and burdensome. Their impact on functional disability, the high rates of accompanying medical illnesses and the potential to last until adulthood make them a major public health issue. While methodological factors cause variability of the results from epidemiological studies, there is a lack of prevalence rates of mental health problems in children and adolescents according to ICD-10 criteria from nationally representative samples. International findings suggest only a small proportion of children with function impairing mental health problems receive treatment, but information about the health care situation of children and adolescents is scarce. The aim of this epidemiological study was a) to classify symptoms of common mental health problems according to ICD-10 criteria in order to compare the statistical and clinical case definition strategies using a single set of data and b) to report ICD-10 codes from health insurance claims data. Methods a) Based on a clinical expert rating, questionnaire items were mapped on ICD-10 criteria; data from the Mental Health Module (BELLA study) were analyzed for relevant ICD-10 and cut-off criteria; b) Claims data were analyzed for relevant ICD-10 codes. Results According to parent report 7.5% (n = 208) met the ICD-10 criteria of a mild depressive episode and 11% (n = 305) showed symptoms of depression according to cut-off score; Anxiety is reported in 5.6% (n = 156) and 11.6% (n = 323), conduct disorder in 15.2% (n = 373) and 14.6% (n = 357). Self-reported symptoms in 11 to 17 year olds resulted in 15% (n = 279) reporting signs of a mild depression according to ICD-10 criteria (vs. 16.7% (n = 307) based on cut-off) and 10.9% (n = 201) reported symptoms of anxiety (vs. 15.4% (n = 283)). Results from routine data identify 0.9% (n = 1,196) with a depression diagnosis, 3.1% (n = 6,729) with anxiety and 1.4% (n

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

    PubMed

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

    2015-10-01

    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

  10. Transgene silencing of the Hutchinson-Gilford progeria syndrome mutation results in a reversible bone phenotype, whereas resveratrol treatment does not show overall beneficial effects.

    PubMed

    Strandgren, Charlotte; Nasser, Hasina Abdul; McKenna, Tomás; Koskela, Antti; Tuukkanen, Juha; Ohlsson, Claes; Rozell, Björn; Eriksson, Maria

    2015-08-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disorder that is most commonly caused by a de novo point mutation in exon 11 of the LMNA gene, c.1824C>T, which results in an increased production of a truncated form of lamin A known as progerin. In this study, we used a mouse model to study the possibility of recovering from HGPS bone disease upon silencing of the HGPS mutation, and the potential benefits from treatment with resveratrol. We show that complete silencing of the transgenic expression of progerin normalized bone morphology and mineralization already after 7 weeks. The improvements included lower frequencies of rib fractures and callus formation, an increased number of osteocytes in remodeled bone, and normalized dentinogenesis. The beneficial effects from resveratrol treatment were less significant and to a large extent similar to mice treated with sucrose alone. However, the reversal of the dental phenotype of overgrown and laterally displaced lower incisors in HGPS mice could be attributed to resveratrol. Our results indicate that the HGPS bone defects were reversible upon suppressed transgenic expression and suggest that treatments targeting aberrant progerin splicing give hope to patients who are affected by HGPS.

  11. Magnetic Sphincter Augmentation for Gastroesophageal Reflux at 5 Years: Final Results of a Pilot Study Show Long-Term Acid Reduction and Symptom Improvement

    PubMed Central

    Saino, Greta; Bonavina, Luigi; Lipham, John C.; Dunn, Daniel

    2015-01-01

    Abstract Background: As previously reported, the magnetic sphincter augmentation device (MSAD) preserves gastric anatomy and results in less severe side effects than traditional antireflux surgery. The final 5-year results of a pilot study are reported here. Patients and Methods: A prospective, multicenter study evaluated safety and efficacy of the MSAD for 5 years. Prior to MSAD placement, patients had abnormal esophageal acid and symptoms poorly controlled by proton pump inhibitors (PPIs). Patients served as their own control, which allowed comparison between baseline and postoperative measurements to determine individual treatment effect. At 5 years, gastroesophageal reflux disease (GERD)-Health Related Quality of Life (HRQL) questionnaire score, esophageal pH, PPI use, and complications were evaluated. Results: Between February 2007 and October 2008, 44 patients (26 males) had an MSAD implanted by laparoscopy, and 33 patients were followed up at 5 years. Mean total percentage of time with pH <4 was 11.9% at baseline and 4.6% at 5 years (P < .001), with 85% of patients achieving pH normalization or at least a 50% reduction. Mean total GERD-HRQL score improved significantly from 25.7 to 2.9 (P < .001) when comparing baseline and 5 years, and 93.9% of patients had at least a 50% reduction in total score compared with baseline. Complete discontinuation of PPIs was achieved by 87.8% of patients. No complications occurred in the long term, including no device erosions or migrations at any point. Conclusions: Based on long-term reduction in esophageal acid, symptom improvement, and no late complications, this study shows the relative safety and efficacy of magnetic sphincter augmentation for GERD. PMID:26437027

  12. Optimal active vibration absorber: Design and experimental results

    NASA Technical Reports Server (NTRS)

    Lee-Glauser, Gina; Juang, Jer-Nan; Sulla, Jeffrey L.

    1992-01-01

    An optimal active vibration absorber can provide guaranteed closed-loop stability and control for large flexible space structures with collocated sensors/actuators. The active vibration absorber is a second-order dynamic system which is designed to suppress any unwanted structural vibration. This can be designed with minimum knowledge of the controlled system. Two methods for optimizing the active vibration absorber parameters are illustrated: minimum resonant amplitude and frequency matched active controllers. The Controls-Structures Interaction Phase-1 Evolutionary Model at NASA LaRC is used to demonstrate the effectiveness of the active vibration absorber for vibration suppression. Performance is compared numerically and experimentally using acceleration feedback.

  13. Preliminary results and future activities at the GARFIELD apparatus

    NASA Astrophysics Data System (ADS)

    Gramegna, F.; Mastinu, P. F.; Vannucci, L.; Bruno, M.; D'Agostino, M.; Fiandri, L.; Lanchais, A.; Vannini, G.; Casini, G.; Chiari, M.; Nannini, A.; Bonasera, A.; Cavallaro, S.; Cosmano, A.; Moroni, A.; Ordine, A.; Abbondanno, U.; Milazzo, P. M.; Margagliotti, G. M.

    2002-01-01

    A new apparatus has been designed and built to study reaction mechanisms in the energy regime of the ALPI linear accelerator of the Laboratori Nazionali di Legnaro (E/A = 5 - 20 MeV). In this paper the importance of studying these mechanisms will be underlined, no more as a problem limited to a narrow energy range or a single process, but as a continuous trend from low to high energies and from the physics of stable nuclei to that one regarding instabilities. With this remarks in mind, a first experiment has been performed studying the reaction 32S+58Ni at 11AMeV. Preliminary results show that important information can be derived on multi-body emission, which can contribute to renew the interest in this energy regime.

  14. 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.

  15. 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. PMID:23712090

  16. Solar activity variations of ionosonde measurements and modeling results

    NASA Astrophysics Data System (ADS)

    Altadill, D.; Arrazola, D.; Blanch, E.; Buresova, D.

    2008-08-01

    The time series of hourly electron density profiles N(h) obtained at several mid-latitude stations in Europe have been used to obtain N(h) profiles on a monthly basis and to extract both the expected bottomside parameters and a proxy of the ionospheric variability as functions of time and height. With these data we present advances on a “Local Model” technique for the parameters B0 and B1, its applicability to other ionospheric stations, to other bottomside ionospheric parameters, and to modeling the time/height variability of the profile. The Local Model (LM) is an empirical model based on the experimental results of the solar activity dependence of the daily and seasonal behavior of the above parameters. The LM improves the IRI-2001 prediction of the B0 and B1 by factor of two at mid-latitudes. Moreover, the LM can be used to simulate other ionospheric parameters and to build mean N(h) profiles and the deviations from them. The modeling of both the average N(h) profiles and their deviations is an useful tool for ionospheric model users who want to know both the expected patterns and their deviations.

  17. New approaches to enhance active steering system functionalities: preliminary results

    NASA Astrophysics Data System (ADS)

    Serarslan, Benan

    2014-09-01

    An important development of the steering systems in general is active steering systems like active front steering and steer-by-wire systems. In this paper the current functional possibilities in application of active steering systems are explored. A new approach and additional functionalities are presented that can be implemented to the active steering systems without additional hardware such as new sensors and electronic control units. Commercial active steering systems are controlling the steering angle depending on the driving situation only. This paper introduce methods for enhancing active steering system functionalities depending not only on the driving situation but also vehicle parameters like vehicle mass, tyre and road condition. In this regard, adaptation of the steering ratio as a function of above mentioned vehicle parameters is presented with examples. With some selected vehicle parameter changes, the reduction of the undesired influences on vehicle dynamics of these parameter changes has been demonstrated theoretically with simulations and with real-time driving measurements.

  18. Germ Line Variants of Human N-Methylpurine DNA Glycosylase Show Impaired DNA Repair Activity and Facilitate 1,N6-Ethenoadenine-induced Mutations*

    PubMed Central

    Adhikari, Sanjay; Chetram, Mahandranauth A.; Woodrick, Jordan; Mitra, Partha S.; Manthena, Praveen V.; Khatkar, Pooja; Dakshanamurthy, Sivanesan; Dixon, Monica; Karmahapatra, Soumendra K.; Nuthalapati, Nikhil K.; Gupta, Suhani; Narasimhan, Ganga; Mazumder, Raja; Loffredo, Christopher A.; Üren, Aykut; Roy, Rabindra

    2015-01-01

    Human N-methylpurine DNA glycosylase (hMPG) initiates base excision repair of a number of structurally diverse purine bases including 1,N6-ethenoadenine, hypoxanthine, and alkylation adducts in DNA. Genetic studies discovered at least eight validated non-synonymous single nucleotide polymorphisms (nsSNPs) of the hMPG gene in human populations that result in specific single amino acid substitutions. In this study, we tested the functional consequences of these nsSNPs of hMPG. Our results showed that two specific arginine residues, Arg-141 and Arg-120, are important for the activity of hMPG as the germ line variants R120C and R141Q had reduced enzymatic activity in vitro as well as in mammalian cells. Expression of these two variants in mammalian cells lacking endogenous MPG also showed an increase in mutations and sensitivity to an alkylating agent compared with the WT hMPG. Real time binding experiments by surface plasmon resonance spectroscopy suggested that these variants have substantial reduction in the equilibrium dissociation constant of binding (KD) of hMPG toward 1,N6-ethenoadenine-containing oligonucleotide (ϵA-DNA). Pre-steady-state kinetic studies showed that the substitutions at arginine residues affected the turnover of the enzyme significantly under multiple turnover condition. Surface plasmon resonance spectroscopy further showed that both variants had significantly decreased nonspecific (undamaged) DNA binding. Molecular modeling suggested that R141Q substitution may have resulted in a direct loss of the salt bridge between ϵA-DNA and hMPG, whereas R120C substitution redistributed, at a distance, the interactions among residues in the catalytic pocket. Together our results suggest that individuals carrying R120C and R141Q MPG variants may be at risk for genomic instability and associated diseases as a consequence. PMID:25538240

  19. 5-epi-Torrubiellutin C shows antiproliferative activity on DU145 prostate cancer cells through inactivation of the AKT/mTOR pathway.

    PubMed

    Singh, Ashita; Mahipal, Bodugam; Chandrasekhar, Srivari; Ummanni, Ramesh

    2014-04-01

    Cell-based assays for evaluation of the anticancer potential of a focused small molecule library have identified a few potential hit molecules. Among the hits identified, Torrubiellutins (3a) showed good anticancer potential across the cells used in screening assays. Torrubiellutins are isolated from fungal insects Torrubiella luteorostrata and diverse pharmacological effects for these have been reported. However, it is not known as to how Torrubiellutins act through signaling pathways inhibiting the growth of eukaryotic cells. The current study aimed to determine the anticancer potential of Torrubiellutins by defining the molecular mechanism of cytotoxicity using DU145 cells. The results showed that the inhibition of prostate cancer cell growth by 3a was associated with inhibition of anchorage-independent growth, cell migration, and, to a small extent, apoptosis-mediated cell death by caspase activation. The growth-inhibitory effects of 3a are supported by inactivation of prosurvival pathways. Immunoblot analysis showed that the treatment of DU145 cells with 3a resulted in specific downregulation of AKT/mammalian target of rapamycin (mTOR) and its downstream effector proteins p70S6K, GSK3β, and STAT3. On the basis of these findings, we propose that the changes observed in the AKT/mTOR signaling axis are new targets of 3a that are involved in its inhibitory activity on the proliferation of prostate cancer cells, suggesting its potential for further investigation as a promising anticancer agent. PMID:24445589

  20. Differential and Active Charging Results from the ATS Spacecraft.

    NASA Astrophysics Data System (ADS)

    Olsen, Richard Christopher

    1980-12-01

    This study of spacecraft charging concentrates on the differential charging and artificial particle emission experiments on ATS-5 and ATS-6. It was found that differential charging of spacecraft surfaces generated large electrostatic barriers to spacecraft generated electrons, from photoemission, secondary emission, and thermal emitters. The electrostatic barrier is a potential minimum outside the charged spacecraft which causes low energy electrons to be trapped near the spacecraft. The large dish antenna on ATS-6 was identified as the source of the electrostatic barrier around the Environmental Measurements Experiment package. Daylight charging on ATS-6 was shown to have behavior suggesting the dominance of differential charging on the absolute potential of the mainframe. Electron emission experiments on ATS-5 in eclipse charging environments showed that the electron emitter could partially or totally discharge the satellite, but the mainframe recharged negatively in a few 10's of seconds. The equilibrium emitter current was found to be .3 microamps, substantially below the milliamp capability of the emitter. The limiting of the current and the time dependence seen in the ATS-5 potential during these operations were explained as the result of differential charging of the insulating surfaces on the spacecraft, and the creation of an electrostatic barrier by the differential potential. This barrier limited the artificially generated electron current to the point that the net flux to the spacecraft was again negative. Both the daylight charging events of ATS-6 and the eclipse electron emission experiments of ATS-5 were further analyzed with a simple time dependent model which showed that the barrier height quickly reached an equilibrium value which limited but did not completely stop electron emission. Average and differential potentials developed in time subject to the constraint that the barrier height remain constant. Ion engine operations and plasma emission

  1. Rapamycin and Chloroquine: The In Vitro and In Vivo Effects of Autophagy-Modifying Drugs Show Promising Results in Valosin Containing Protein Multisystem Proteinopathy

    PubMed Central

    Nalbandian, Angèle; Llewellyn, Katrina J.; Nguyen, Christopher; Yazdi, Puya G.; Kimonis, Virginia E.

    2015-01-01

    Mutations in the valosin containing protein (VCP) gene cause hereditary Inclusion body myopathy (hIBM) associated with Paget disease of bone (PDB), frontotemporal dementia (FTD), more recently termed multisystem proteinopathy (MSP). Affected individuals exhibit scapular winging and die from progressive muscle weakness, and cardiac and respiratory failure, typically in their 40s to 50s. Histologically, patients show the presence of rimmed vacuoles and TAR DNA-binding protein 43 (TDP-43)-positive large ubiquitinated inclusion bodies in the muscles. We have generated a VCPR155H/+ mouse model which recapitulates the disease phenotype and impaired autophagy typically observed in patients with VCP disease. Autophagy-modifying agents, such as rapamycin and chloroquine, at pharmacological doses have previously shown to alter the autophagic flux. Herein, we report results of administration of rapamycin, a specific inhibitor of the mechanistic target of rapamycin (mTOR) signaling pathway, and chloroquine, a lysosomal inhibitor which reverses autophagy by accumulating in lysosomes, responsible for blocking autophagy in 20-month old VCPR155H/+ mice. Rapamycin-treated mice demonstrated significant improvement in muscle performance, quadriceps histological analysis, and rescue of ubiquitin, and TDP-43 pathology and defective autophagy as indicated by decreased protein expression levels of LC3-I/II, p62/SQSTM1, optineurin and inhibiting the mTORC1 substrates. Conversely, chloroquine-treated VCPR155H/+ mice revealed progressive muscle weakness, cytoplasmic accumulation of TDP-43, ubiquitin-positive inclusion bodies and increased LC3-I/II, p62/SQSTM1, and optineurin expression levels. Our in vitro patient myoblasts studies treated with rapamycin demonstrated an overall improvement in the autophagy markers. Targeting the mTOR pathway ameliorates an increasing list of disorders, and these findings suggest that VCP disease and related neurodegenerative multisystem proteinopathies can

  2. Biosynthesis of fatty acid derived aldehydes is induced upon mechanical wounding and its products show fungicidal activities in cucumber.

    PubMed

    Matsui, Kenji; Minami, Akari; Hornung, Ellen; Shibata, Hidetoshi; Kishimoto, Kyutaro; Ahnert, Volker; Kindl, Helmut; Kajiwara, Tadahiko; Feussner, Ivo

    2006-04-01

    Fatty acid 9/13-hydroperoxide lyase (9/13-HPL) in cucumber is an enzyme that can cleave either 9- or 13-hydroperoxides of polyunsaturated fatty acids to form C9- or C6-aldehydes, respectively, as products. In order to reveal the physiological function of 9/13-HPL, its expression profiles were analyzed, and it was found that 9/13-HPL expression was developmentally regulated and high in the hypocotyls, female flowers and mature fruits. However, its transcript as well as its activity was only induced by mechanical wounding in mature leaves. To analyze the biosynthesis of HPL-derived aldehydes in more detail we isolated and characterized the yet missing 9-lipoxygenase (LOX) that is mainly expressed in hypocotyls, cotyledons and flowers and that may provide HPL with fatty acid 9-hydroperoxides as substrates. As in the case with C6-aldehydes in most plant species, C9-aldehydes were also formed rapidly after disruption of the tissues. C9-aldehydes had fungicidal activities against fungal pathogens, Botrytis cinerea and Fusarium oxysporum. Because the concentration needed to cause toxic effect on the pathogens was almost equivalent to that found in disrupted tissues, the C9-aldehydes thus formed could be helpful to sterilize the wounds since they are less volatile in comparison to C6-aldehydes. PMID:16497344

  3. 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

  4. Monounsaturated fatty acid ether oligomers formed during heating of virgin olive oil show agglutination activity against human red blood cells.

    PubMed

    Patrikios, Ioannis S; Mavromoustakos, Thomas M

    2014-01-29

    The present work focuses on the characterization of molecules formed when virgin olive oil is heated at 130 °C for 24 h open in air, which are found to be strong agglutinins. The hemagglutinating activity of the newly formed molecule isolated from the heated virgin olive oil sample was estimated against human red blood cells (RBCs). Dimers and polymers (high molecular weight molecules) were identified through thin layer chromatography (TLC) of the oil mixture. (1)H and (13)C nuclear magnetic resonance (NMR) and gas chromatography-mass spectroscopy (GC-MS) were the methods used for structural characterization. Among others, oligomerization of at least two monounsaturated fatty acids (FA) by an ether linkage between the hydrocarbon chains is involved. Light microscopy was used to characterize and visualize the agglutination process. Agglutination without fusion or lysis was observed. It was concluded that the heating of virgin olive oil open in air, among other effects, produces oligomerization as well as polymerization of unsaturated FA, possibly of monohydroxy, monounsaturated FA that is associated with strong hemagglutinating activity against human RBCs. The nutritional value and the effects on human health of such oligomers are not discussed in the literature and remain to be investigated. PMID:24410166

  5. 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.

  6. 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. PMID:25142179

  7. 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.

  8. 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

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

    PubMed Central

    Webster, J Christopher; Francis, Michael M; Porter, Julia K; Robinson, Gillian; Stokes, Clare; Horenstein, Ben; Papke, Roger L

    1999-01-01

    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. PMID:10455283

  10. Modeling upward brine migration through faults as a result of CO2 storage in the Northeast German Basin shows negligible salinization in shallow aquifers

    NASA Astrophysics Data System (ADS)

    Kuehn, M.; Tillner, E.; Kempka, T.; Nakaten, B.

    2012-12-01

    The geological storage of CO2 in deep saline formations may cause salinization of shallower freshwater resources by upward flow of displaced brine from the storage formation into potable groundwater. In this regard, permeable faults or fractures can serve as potential leakage pathways for upward brine migration. The present study uses a regional-scale 3D model based on real structural data of a prospective CO2 storage site in Northeastern Germany to determine the impact of compartmentalization and fault permeability on upward brine migration as a result of pressure elevation by CO2 injection. To evaluate the degree of salinization in the shallower aquifers, different fault leakage scenarios were carried out using a newly developed workflow in which the model grid from the software package Petrel applied for pre-processing is transferred to the reservoir simulator TOUGH2-MP/ECO2N. A discrete fault description is achieved by using virtual elements. A static 3D geological model of the CO2 storage site with an a real size of 40 km x 40 km and a thickness of 766 m was implemented. Subsequently, large-scale numerical multi-phase multi-component (CO2, NaCl, H2O) flow simulations were carried out on a high performance computing system. The prospective storage site, located in the Northeast German Basin is part of an anticline structure characterized by a saline multi-layer aquifer system. The NE and SW boundaries of the study area are confined by the Fuerstenwalde Gubener and the Lausitzer Abbruch fault zones represented by four discrete faults in the model. Two formations of the Middle Bunter were chosen to assess brine migration through faults triggered by an annual injection rate of 1.7 Mt CO2 into the lowermost formation over a time span of 20 years. In addition to varying fault permeabilities, different boundary conditions were applied to evaluate the effects of reservoir compartmentalization. Simulation results show that the highest pressurization within the storage

  11. 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

  12. A solution NMR study showing that active site ligands and nucleotides directly perturb the allosteric equilibrium in aspartate transcarbamoylase.

    PubMed

    Velyvis, Algirdas; Yang, Ying R; Schachman, Howard K; Kay, Lewis E

    2007-05-22

    The 306-kDa aspartate transcarbamoylase is a well studied regulatory enzyme, and it has emerged as a paradigm for understanding allostery and cooperative binding processes. Although there is a consensus that the cooperative binding of active site ligands follows the Monod-Wyman-Changeux (MWC) model of allostery, there is some debate about the binding of effectors such as ATP and CTP and how they influence the allosteric equilibrium between R and T states of the enzyme. In this article, the binding of substrates, substrate analogues, and nucleotides is studied, along with their effect on the R-T equilibrium by using highly deuterated, (1)H,(13)C-methyl-labeled protein in concert with methyl-transverse relaxation optimized spectroscopy (TROSY) NMR. Although only the T state of the enzyme can be observed in spectra of wild-type unliganded aspartate transcarbamoylase, binding of active-site substrates shift the equilibrium so that correlations from the R state become visible, allowing the equilibrium constant (L') between ligand-saturated R and T forms of the enzyme to be measured quantitatively. The equilibrium constant between unliganded R and T forms (L) also is obtained, despite the fact that the R state is "invisible" in spectra, by means of an indirect process that makes use of relations that emerge from the fact that ligand binding and the R-T equilibrium are linked. Titrations with MgATP unequivocally establish that its binding directly perturbs the R-T equilibrium, consistent with the Monod-Wyman-Changeux model. This study emphasizes the utility of modern solution NMR spectroscopy in understanding protein function, even for systems with aggregate molecular masses in the hundreds of kilodaltons.

  13. 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

  14. 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.

  15. A dual mTORC1 and mTORC2 inhibitor shows antitumor activity in esophageal squamous cell carcinoma cells and sensitizes them to cisplatin.

    PubMed

    Huang, Yu; Xi, Qingsong; Chen, Yu; Wang, Jing; Peng, Ping; Xia, Shu; Yu, Shiying

    2013-10-01

    The mammalian target of rapamycin (mTOR) signaling pathway is critical for the growth and proliferation of various malignant tumors, including esophageal squamous cell carcinoma (ESCC). Therefore, targeting of mTOR protein is a promising strategy for therapy in this disease. In the present study, we examined the antitumor effects of a specific mTOR kinase inhibitor, PP242, which blocks both mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) pathways, in two ESCC cell lines: Eca-109 and TE-1. We showed that PP242, but not rapamycin, attenuated the activities of both mTORC1 and mTORC2 signaling in ESCC. PP242 inhibited 4E-binding protein-1 phosphorylation and abrogated mTORC1-dependent PI3K/Akt feedback activation. Significantly, PP242 effectively suppressed ESCC cell proliferation, induced apoptosis, and arrested the cell cycle. Furthermore, PP242 promoted cisplatin-induced apoptosis and enhanced the antitumor efficacy of cisplatin in ESCC cells, which was likely to be associated with inhibition of Akt activity. Our results show that simultaneous targeting of both mTORC1 and mTORC2 pathways leads to effective antitumor actions in ESCC, and strongly suggest that dual mTORC1/2 inhibitors should be developed as potential agents for the treatment of ESCC.

  16. Stellar activity and coronal heating: an overview of recent results.

    PubMed

    Testa, Paola; Saar, Steven H; Drake, Jeremy J

    2015-05-28

    Observations of the coronae of the Sun and of solar-like stars provide complementary information to advance our understanding of stellar magnetic activity, and of the processes leading to the heating of their outer atmospheres. While solar observations allow us to study the corona at high spatial and temporal resolution, the study of stellar coronae allows us to probe stellar activity over a wide range of ages and stellar parameters. Stellar studies therefore provide us with additional tools for understanding coronal heating processes, as well as the long-term evolution of solar X-ray activity. We discuss how recent studies of stellar magnetic fields and coronae contribute to our understanding of the phenomenon of activity and coronal heating in late-type stars. PMID:25897087

  17. Stellar activity and coronal heating: an overview of recent results

    PubMed Central

    Testa, Paola; Saar, Steven H.; Drake, Jeremy J.

    2015-01-01

    Observations of the coronae of the Sun and of solar-like stars provide complementary information to advance our understanding of stellar magnetic activity, and of the processes leading to the heating of their outer atmospheres. While solar observations allow us to study the corona at high spatial and temporal resolution, the study of stellar coronae allows us to probe stellar activity over a wide range of ages and stellar parameters. Stellar studies therefore provide us with additional tools for understanding coronal heating processes, as well as the long-term evolution of solar X-ray activity. We discuss how recent studies of stellar magnetic fields and coronae contribute to our understanding of the phenomenon of activity and coronal heating in late-type stars. PMID:25897087

  18. Stellar activity and coronal heating: an overview of recent results.

    PubMed

    Testa, Paola; Saar, Steven H; Drake, Jeremy J

    2015-05-28

    Observations of the coronae of the Sun and of solar-like stars provide complementary information to advance our understanding of stellar magnetic activity, and of the processes leading to the heating of their outer atmospheres. While solar observations allow us to study the corona at high spatial and temporal resolution, the study of stellar coronae allows us to probe stellar activity over a wide range of ages and stellar parameters. Stellar studies therefore provide us with additional tools for understanding coronal heating processes, as well as the long-term evolution of solar X-ray activity. We discuss how recent studies of stellar magnetic fields and coronae contribute to our understanding of the phenomenon of activity and coronal heating in late-type stars.

  19. 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

  20. A G-quadruplex-binding compound showing anti-tumour activity in an in vivo model for pancreatic cancer

    PubMed Central

    Ohnmacht, Stephan A; Marchetti, Chiara; Gunaratnam, Mekala; Besser, Rachael J; Haider, Shozeb M; Di Vita, Gloria; Lowe, Helen L; Mellinas-Gomez, Maria; Diocou, Seckou; Robson, Mathew; Šponer, Jiri; Islam, Barira; Barbara Pedley, R; Hartley, John A; Neidle, Stephen

    2015-01-01

    We report here that a tetra-substituted naphthalene-diimide derivative (MM41) has significant in vivo anti-tumour activity against the MIA PaCa-2 pancreatic cancer xenograft model. IV administration with a twice-weekly 15 mg/kg dose produces ca 80% tumour growth decrease in a group of tumour-bearing animals. Two animals survived tumour-free after 279 days. High levels of MM41 are rapidly transported into cell nuclei and were found to accumulate in the tumour. MM41 is a quadruplex-interactive compound which binds strongly to the quadruplexes encoded in the promoter sequences of the BCL-2 and k-RAS genes, both of which are dis-regulated in many human pancreatic cancers. Levels of BCL-2 were reduced by ca 40% in tumours from MM41-treated animals relative to controls, consistent with BCL-2 being a target for MM41. Molecular modelling suggests that MM41 binds to a BCL-2 quadruplex in a manner resembling that previously observed in co-crystal structures with human telomeric quadruplexes. This supports the concept that MM41 (and by implication other quadruplex-targeting small molecules) can bind to quadruplex-forming promoter regions in a number of genes and down-regulate their transcription. We suggest that quadruplexes within those master genes that are up-regulated drivers for particular cancers, may be selective targets for compounds such as MM41. PMID:26077929

  1. 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. PMID:27596418

  2. A G-quadruplex-binding compound showing anti-tumour activity in an in vivo model for pancreatic cancer.

    PubMed

    Ohnmacht, Stephan A; Marchetti, Chiara; Gunaratnam, Mekala; Besser, Rachael J; Haider, Shozeb M; Di Vita, Gloria; Lowe, Helen L; Mellinas-Gomez, Maria; Diocou, Seckou; Robson, Mathew; Šponer, Jiri; Islam, Barira; Pedley, R Barbara; Hartley, John A; Neidle, Stephen

    2015-01-01

    We report here that a tetra-substituted naphthalene-diimide derivative (MM41) has significant in vivo anti-tumour activity against the MIA PaCa-2 pancreatic cancer xenograft model. IV administration with a twice-weekly 15 mg/kg dose produces ca 80% tumour growth decrease in a group of tumour-bearing animals. Two animals survived tumour-free after 279 days. High levels of MM41 are rapidly transported into cell nuclei and were found to accumulate in the tumour. MM41 is a quadruplex-interactive compound which binds strongly to the quadruplexes encoded in the promoter sequences of the BCL-2 and k-RAS genes, both of which are dis-regulated in many human pancreatic cancers. Levels of BCL-2 were reduced by ca 40% in tumours from MM41-treated animals relative to controls, consistent with BCL-2 being a target for MM41. Molecular modelling suggests that MM41 binds to a BCL-2 quadruplex in a manner resembling that previously observed in co-crystal structures with human telomeric quadruplexes. This supports the concept that MM41 (and by implication other quadruplex-targeting small molecules) can bind to quadruplex-forming promoter regions in a number of genes and down-regulate their transcription. We suggest that quadruplexes within those master genes that are up-regulated drivers for particular cancers, may be selective targets for compounds such as MM41. PMID:26077929

  3. Benchmarking Evaluation Results for Prototype Extravehicular Activity Gloves

    NASA Technical Reports Server (NTRS)

    Aitchison, Lindsay; McFarland, Shane

    2012-01-01

    The Space Suit Assembly (SSA) Development Team at NASA Johnson Space Center has invested heavily in the advancement of rear-entry planetary exploration suit design but largely deferred development of extravehicular activity (EVA) glove designs, and accepted the risk of using the current flight gloves, Phase VI, for unique mission scenarios outside the Space Shuttle and International Space Station (ISS) Program realm of experience. However, as design reference missions mature, the risks of using heritage hardware have highlighted the need for developing robust new glove technologies. To address the technology gap, the NASA Game-Changing Technology group provided start-up funding for the High Performance EVA Glove (HPEG) Project in the spring of 2012. The overarching goal of the HPEG Project is to develop a robust glove design that increases human performance during EVA and creates pathway for future implementation of emergent technologies, with specific aims of increasing pressurized mobility to 60% of barehanded capability, increasing the durability by 100%, and decreasing the potential of gloves to cause injury during use. The HPEG Project focused initial efforts on identifying potential new technologies and benchmarking the performance of current state of the art gloves to identify trends in design and fit leading to establish standards and metrics against which emerging technologies can be assessed at both the component and assembly levels. The first of the benchmarking tests evaluated the quantitative mobility performance and subjective fit of four prototype gloves developed by Flagsuit LLC, Final Frontier Designs, LLC Dover, and David Clark Company as compared to the Phase VI. All of the companies were asked to design and fabricate gloves to the same set of NASA provided hand measurements (which corresponded to a single size of Phase Vi glove) and focus their efforts on improving mobility in the metacarpal phalangeal and carpometacarpal joints. Four test

  4. The Aminosteroid Derivative RM-133 Shows In Vitro and In Vivo Antitumor Activity in Human Ovarian and Pancreatic Cancers

    PubMed Central

    Kenmogne, Lucie Carolle; Ayan, Diana; Roy, Jenny; Maltais, René; Poirier, Donald

    2015-01-01

    Ovarian and pancreatic cancers are two of the most aggressive and lethal cancers, whose management faces only limited therapeutic options. Typically, these tumors spread insidiously accompanied first with atypical symptoms, and usually shift to a drug resistance phenotype with the current pharmaceutical armamentarium. Thus, the development of new drugs acting via a different mechanism of action represents a clear priority. Herein, we are reporting for the first time that the aminosteroid derivative RM-133, developed in our laboratory, displays promising activity on two models of aggressive cancers, namely ovarian (OVCAR-3) and pancreatic (PANC-1) cancers. The IC50 value of RM-133 was 0.8 μM and 0.3 μM for OVCAR-3 and PANC-1 cell lines in culture, respectively. Based on pharmacokinetic studies on RM-133 using 11 different vehicles, we selected two main vehicles: aqueous 0.4% methylcellulose:ethanol (92:8) and sunflower oil:ethanol (92:8) for in vivo studies. Using subcutaneous injection of RM-133 with the methylcellulose-based vehicle, growth of PANC-1 tumors xenografted to nude mice was inhibited by 63%. Quite interestingly, RM-133 injected subcutaneously with the methylcellulose-based or sunflower-based vehicles reduced OVCAR-3 xenograft growth by 122% and 100%, respectively. After the end of RM-133 treatment using the methylcellulose-based vehicle, OVCAR-3 tumor growth inhibition was maintained for ≥ 1 week. RM-133 was also well tolerated in the whole animal, no apparent sign of toxicity having been detected in the xenograft studies. PMID:26660672

  5. 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

  6. Rats with congenital learned helplessness respond less to sucrose but show no deficits in activity or learning.

    PubMed

    Vollmayr, Barbara; Bachteler, Daniel; Vengeliene, Valentina; Gass, Peter; Spanagel, Rainer; Henn, Fritz

    2004-04-01

    Inbred rat strains for congenital learned helplessness (cLH) and for congenital resistance to learned helplessness (cNLH) were investigated as a model to study genetic predisposition to major depression. Congenitally helpless rats respond less to sucrose under a progressive ratio schedule. This is not confounded by locomotor hypoactivity: in contrast, cLH rats show a slight hyperactivity during the first 5 min of an open field test. cLH rats acquire operant responding to sucrose as readily as cNLH rats and exhibit normal memory acquisition and retrieval in the Morris water maze, thus ruling out general learning deficits as the cause of the decreased response to sucrose. Reduced total responses and reduced breaking points for sucrose in the cLH strain argue for anhedonia, which is an analogue to loss of pleasure essential for the diagnosis of major depressive episodes, and thus confirm the validity of congenitally learned helpless rats as a model of major depression.

  7. Functional Characterization of Three Concomitant MtDNA LHON Mutations Shows No Synergistic Effect on Mitochondrial Activity.

    PubMed

    Cruz-Bermúdez, Alberto; Vicente-Blanco, Ramiro J; Hernández-Sierra, Rosana; Montero, Mayte; Alvarez, Javier; González Manrique, Mar; Blázquez, Alberto; Martín, Miguel Angel; Ayuso, Carmen; Garesse, Rafael; Fernández-Moreno, Miguel A

    2016-01-01

    The presence of more than one non-severe pathogenic mutation in the same mitochondrial DNA (mtDNA) molecule is very rare. Moreover, it is unclear whether their co-occurrence results in an additive impact on mitochondrial function relative to single mutation effects. Here we describe the first example of a mtDNA molecule harboring three Leber's hereditary optic neuropathy (LHON)-associated mutations (m.11778G>A, m.14484T>C, m.11253T>C) and the analysis of its genetic, biochemical and molecular characterization in transmitochondrial cells (cybrids). Extensive characterization of cybrid cell lines harboring either the 3 mutations or the single classic m.11778G>A and m.14484T>C mutations revealed no differences in mitochondrial function, demonstrating the absence of a synergistic effect in this model system. These molecular results are in agreement with the ophthalmological characteristics found in the triple mutant patient, which were similar to those carrying single mtDNA LHON mutations.

  8. Functional Characterization of Three Concomitant MtDNA LHON Mutations Shows No Synergistic Effect on Mitochondrial Activity

    PubMed Central

    Cruz-Bermúdez, Alberto; Vicente-Blanco, Ramiro J.; Hernández-Sierra, Rosana; Montero, Mayte; Alvarez, Javier; González Manrique, Mar; Blázquez, Alberto; Martín, Miguel Angel; Ayuso, Carmen; Garesse, Rafael; Fernández-Moreno, Miguel A.

    2016-01-01

    The presence of more than one non-severe pathogenic mutation in the same mitochondrial DNA (mtDNA) molecule is very rare. Moreover, it is unclear whether their co-occurrence results in an additive impact on mitochondrial function relative to single mutation effects. Here we describe the first example of a mtDNA molecule harboring three Leber's hereditary optic neuropathy (LHON)-associated mutations (m.11778G>A, m.14484T>C, m.11253T>C) and the analysis of its genetic, biochemical and molecular characterization in transmitochondrial cells (cybrids). Extensive characterization of cybrid cell lines harboring either the 3 mutations or the single classic m.11778G>A and m.14484T>C mutations revealed no differences in mitochondrial function, demonstrating the absence of a synergistic effect in this model system. These molecular results are in agreement with the ophthalmological characteristics found in the triple mutant patient, which were similar to those carrying single mtDNA LHON mutations. PMID:26784702

  9. Storytelling Slide Shows to Improve Diabetes and High Blood Pressure Knowledge and Self-Efficacy: Three-Year Results among Community Dwelling Older African Americans

    ERIC Educational Resources Information Center

    Bertera, Elizabeth M.

    2014-01-01

    This study combined the African American tradition of oral storytelling with the Hispanic medium of "Fotonovelas." A staggered pretest posttest control group design was used to evaluate four Storytelling Slide Shows on health that featured community members. A total of 212 participants were recruited for the intervention and 217 for the…

  10. 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.

  11. Ferrocene/fullerene hybrids showing large second-order nonlinear optical activities: impact of the cage unit size.

    PubMed

    Wang, Wen-Yong; Wang, Li; Ma, Na-Na; Zhu, Chang-Li; Qiu, Yong-Qing

    2015-06-01

    The electron donor-acceptor complexes, which undergo intramolecular charge transfer under external stimulus, are an emerging class of materials showing important application in nonlinear optics. Synthesizing ferrocene/fullerene complexes through face-to-face fusion would enjoy the merits of both ferrocene and fullerene due to their strong donor-acceptor interactions. Four ferrocene/fullerene hybrid complexes with the gradual extension of fullerene cage size, including CpFe(C60H5), CpFe(C66H5), CpFe(C70H5), and CpFe(C80H5) (Cp is cyclopentadienyl), have been investigated by density functional theory. These hybrid molecules give eclipsed and staggered isomers. The main reason that the eclipsed isomer is stable is that the eclipsed structure possesses large CpFefullerene bonding energy. The CpFefullerene interaction is smaller than that of CpFefullerene, which must come from two different interfaces. The presence of covalent bond character between CpFe and fullerene is supported by the localized orbital locator, deformation of electron density distribution and energy decomposition analysis. Significantly, the absorption bands and first hyperpolarizabilities of these hybrid complexes are strongly sensitive to the fullerene cage size, which is ascribed to a change in the charge transfer pattern, especially for CpFe(C80H5), which displays reverse π → π* charge transfer from bottom to top cage, leading to notable hyperpolarizability. Investigation of the structure-property relationship at the molecular level can benefit the design and preparation of such hybrid complexes in chemistry and materials science.

  12. 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. PMID:26202846

  13. Soil Moisture Active Passive Satellite Status and Recent Validation Results

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Soil Moisture Active Passive (SMAP) mission was launched in January, 2015 and began its calibration and validation (cal/val) phase in May, 2015. Cal/Val will begin with a focus on instrument measurements, brightness temperature and backscatter, and evolve to the geophysical products that include...

  14. Active commuting and physical activity in adolescents from Europe: results from the HELENA study.

    PubMed

    Chillón, Palma; Ortega, Francisco B; Ruiz, Jonatan R; De Bourdeaudhuij, Ilse; Martínez-Gómez, David; Vicente-Rodriguez, Germán; Widhalm, Kurt; Molnar, Dénes; Gottrand, Frédéric; González-Gross, Marcela; Ward, Dianne S; Moreno, Luis A; Castillo, Manuel J; Sjöström, Michael

    2011-05-01

    We assessed commuting patterns in adolescents from 10 European cities and examined associations with physical activity (PA). A total of 3112 adolescents were included. PA was objectively measured with accelerometry. Commuting patterns and overall PA were self-reported using questions from the International Physical Activity Questionnaire modified for adolescents (IPAQ-A). Adolescents reported to spend 30 min (15,60) [expressed as median (25th, 75th percentiles)] walking. In boys, associations between active commuting (walking and biking) and PA levels were observed for moderate, moderate-to-vigorous and overall PA. In girls, these associations were observed for moderate and moderate-to-vigorous PA (walking). Similar results were found with the IPAQ-A. We observed positive associations between overall commuting and PA levels in European adolescents, yet due to the cross-sectional study design we cannot state the direction of these. Future studies should address the causation between active commuting and PA levels.

  15. The Arabidopsis homologs of CCR4-associated factor 1 show mRNA deadenylation activity and play a role in plant defence responses.

    PubMed

    Liang, Wenxing; Li, Changbao; Liu, Fang; Jiang, Hongling; Li, Shuyu; Sun, Jiaqiang; Wu, Xiaoyan; Li, Chuanyou

    2009-03-01

    Messenger RNA (mRNA) turnover in eukaryotic cells begins with shortening of the poly (A) tail at the 3' end, a process called deadenylation. In yeast, the deadenylation reaction is predominantly mediated by CCR4 and CCR4-associated factor 1 (CAF1), two components of the well-characterised protein complex named CCR4-NOT. We report here that AtCAF1a and AtCAF1b, putative Arabidopsis homologs of the yeast CAF1 gene, partially complement the growth defect of the yeast caf1 mutant in the presence of caffeine or at high temperatures. The expression of AtCAF1a and AtCAF1b is induced by multiple stress-related hormones and stimuli. Both AtCAF1a and AtCAF1b show deadenylation activity in vitro and point mutations in the predicted active sites disrupt this activity. T-DNA insertion mutants disrupting the expression of AtCAF1a and/or AtCAF1b are defective in deadenylation of stress-related mRNAs, indicating that the two AtCAF1 proteins are involved in regulated mRNA deadenylation in vivo. Interestingly, the single and double mutants of AtCAF1a and AtCAF1b show reduced expression of pathogenesis-related (PR) genes PR1 and PR2 and are more susceptible to Pseudomonas syringae pv tomato DC3000 (Pst DC3000) infection, whereas transgenic plants over-expressing AtCAF1a show elevated expression of PR1 and PR2 and increased resistance to the same pathogen. Our results suggest roles of the AtCAF1 proteins in regulated mRNA deadenylation and defence responses to pathogen infections.

  16. Annoyance resulting from intrusion of aircraft sounds upon various activities

    NASA Technical Reports Server (NTRS)

    Gunn, W. J.; Shepherd, W. T.; Fletcher, J. L.

    1975-01-01

    An experiment was conducted in which subjects were engaged in TV viewing, telephone listening, or reverie (no activity) for a 1/2-hour session. During the session, they were exposed to a series of recorded aircraft sounds at the rate of one flight every 2 minutes. Within each session, four levels of flyover noise, separated by dB increments, were presented several times in a Latin Square balanced sequence. The peak level of the noisiest flyover in any session was fixed at 95, 90, 85, 75, or 70 dBA. At the end of the test session, subjects recorded their responses to the aircraft sounds, using a bipolar scale which covered the range from very pleasant to extremely annoying. Responses to aircraft noises were found to be significantly affected by the particular activity in which the subjects were engaged. Not all subjects found the aircraft sounds to be annoying.

  17. Active X-ray mirror development at UCL: preliminary results

    NASA Astrophysics Data System (ADS)

    Atkins, Carolyn; Doel, Peter; Yao, Jun; Brooks, David; Thompson, Samantha; Willingale, Richard; Feldman, Charlotte; Button, Tim; Zhang, Dou; James, Ady

    2007-12-01

    The Smart X-ray Optics project is a UK based consortium consisting of several institutions to investigate the application of active/adaptive optics upon both small and large scale grazing incidence x-ray optics. The work done at University College London (UCL) focuses on the application of piezoelectric materials to large scale optics in order to actively deform the mirror's surface. These optics are geared towards the next generation of x-ray telescopes and it is hoped that the project will be able to achieve a resolution greater than that currently available by Chandra (0.5"). One of the aims of the consortium is to produce a working prototype. The initial design is based on a thin nickel ellipsoid segment with an x-ray reflective coating, on the back of which will be bonded a series of piezoelectric actuators. Investigation into the specification of the design of an active x-ray optic prototype and suitable support test structure has been undertaken. The dimensions and constraints upon the prototype, and the manufacturing process to produce a nickel shell are discussed. Finite element analysis (FEA) of the physical characteristics of piezoelectric materials has shown the ability to deform the nickel surface to correct for errors of several microns. FEA has also been utilised in the specification of the prototype's support structure to ensure that gravitational sag upon the optic is kept to a minimum. Laboratory experiments have tested a series of materials, different actuators and bonding methods, which could then be applied to the prototype.

  18. Towards active capsular endoscopy: preliminary results on a legged platform.

    PubMed

    Menciassi, Arianna; Stefanini, Cesare; Orlandi, Giovanni; Quirini, Marco; Dario, Paolo

    2006-01-01

    This paper illustrates the problem of active locomotion in the gastrointestinal tract for endoscopic capsules. Authors analyze the problem of locomotion in unstructured, flexible and tubular environments and explain the reasons leading to the selection of a legged system. They present a theoretical simulation of legged capsule locomotion, which is used to define the optimal parameters for capsule design and gait selection. Finally, a legged capsule--about 3 cm3 in volume--is presented; it consists of 4 back legs whose actuation is achieved thanks to a miniaturized DC brushless motor. In vitro tests demonstrate good performance in terms of achievable speed (92 mm/min).

  19. Experimental results using active control of traveling wave power flow

    NASA Technical Reports Server (NTRS)

    Miller, David W.; Hall, Steven R.

    1991-01-01

    Active structural control experiments conducted on a 24-ft pinned-free beam derived feedback compensators on the basis of a traveling-wave approach. A compensator is thus obtained which eliminates resonant behavior by absorbing all impinging power. A causal solution is derived for this noncausal compensator which mimics its behavior in a given frequency range, using the Wiener-Hopf. This optimal Wiener-Hopf compensator's structure-damping performance is found to exceed any obtainable by means of rate feedback. Performance limitations encompassed the discovery of frequencies above which the sensor and actuator were no longer dual and an inadvertent coupling of the control hardware to unmodeled structure torsion modes.

  20. CHP REGIONAL APPLICATION CENTERS: ACTIVITIES AND SELECTED RESULTS

    SciTech Connect

    Schweitzer, Martin

    2010-08-01

    Between 2001 and 2005, the U.S. Department of Energy (DOE) created a set of eight Regional Application Centers (RACs) to facilitate the development and deployment of Combined Heat and Power (CHP) technologies. By utilizing the thermal energy that is normally wasted when electricity is produced at central generating stations, Combined Heat and Power installations can save substantial amounts of energy compared to more traditional technologies. In addition, the location of CHP facilities at or near the point of consumption greatly reduces or eliminates electric transmission and distribution losses. The regional nature of the RACs allows each one to design and provide services that are most relevant to the specific economic and market conditions in its particular geographic area. Between them, the eight RACs provide services to all 50 states and the District of Columbia. Through the end of the federal 2009 fiscal year (FY 2009), the primary focus of the RACs was on providing CHP-related information to targeted markets, encouraging the creation and adoption of public policies and incentives favorable to CHP, and providing CHP users and prospective users with technical assistance and support on specific projects. Beginning with the 2010 fiscal year, the focus of the regional centers broadened to include district energy and waste heat recovery and these entities became formally known as Clean Energy Application Centers, as required by the Energy Independence and Security Act (EISA) of 2007. In 2007, ORNL led a cooperative effort to establish metrics to quantify the RACs accomplishments. That effort began with the development of a detailed logic model describing RAC operations and outcomes, which provided a basis for identifying important activities and accomplishments to track. A data collection spreadsheet soliciting information on those activities for FY 2008 and all previous years of RAC operations was developed and sent to the RACs in the summer of 2008. This

  1. Benchmark Active Controls Technology (BACT) Wing CFD Results

    NASA Technical Reports Server (NTRS)

    Schuster, David M.; Bartels, Robert E.

    2000-01-01

    The Benchmark Active Controls Technology (BACT) wing test (see chapter 8E) provides data for the validation of aerodynamic, aeroelastic, and active aeroelastic control simulation codes. These data provide a rich database for development and validation of computational aeroelastic and aeroservoelastic methods. In this vein, high-level viscous CFD analyses of the BACT wing have been performed for a subset of the test conditions available in the dataset. The computations presented in this section investigate the aerodynamic characteristics of the rigid clean wing configuration as well as simulations of the wing with a static and oscillating aileron and spoiler deflection. Two computational aeroelasticity codes extensively used at NASA Langley Research Center are implemented in this simulation. They are the ENS3DAE and CFL3DAE computational aeroelasticity programs. Both of these methods solve the three-dimensional compressible Navier-Stokes equations for both rigid and flexible vehicles, but they use significantly different approaches to the solution 6f the aerodynamic equations of motion. Detailed descriptions of both methods are presented in the following section.

  2. Mathematical modelling in Matlab of the experimental results shows the electrochemical potential difference - temperature of the WC coatings immersed in a NaCl solution

    NASA Astrophysics Data System (ADS)

    Benea, M. L.; Benea, O. D.

    2016-02-01

    The method used for purchasing the corrosion behaviour the WC coatings deposited by plasma spraying, on a martensitic stainless steel substrate consists in measuring the electrochemical potential of the coating, respectively that of the substrate, immersed in a NaCl solution as corrosive agent. The mathematical processing of the obtained experimental results in Matlab allowed us to make some correlations between the electrochemical potential of the coating and the solution temperature is very well described by some curves having equations obtained by interpolation order 4.

  3. Transitioning from preclinical to clinical chemopreventive assessments of lyophilized black raspberries: interim results show berries modulate markers of oxidative stress in Barrett's esophagus patients.

    PubMed

    Kresty, Laura A; Frankel, Wendy L; Hammond, Cynthia D; Baird, Maureen E; Mele, Jennifer M; Stoner, Gary D; Fromkes, John J

    2006-01-01

    Increased fruit and vegetable consumption is associated with decreased risk of a number of cancers of epithelial origin, including esophageal cancer. Dietary administration of lyophilized black raspberries (LBRs) has significantly inhibited chemically induced oral, esophageal, and colon carcinogenesis in animal models. Likewise, berry extracts added to cell cultures significantly inhibited cancer-associated processes. Positive results in preclinical studies have supported further investigation of berries and berry extracts in high-risk human cohorts, including patients with existing premalignancy or patients at risk for cancer recurrence. We are currently conducting a 6-mo chemopreventive pilot study administering 32 or 45 g (female and male, respectively) of LBRs to patients with Barrett's esophagus (BE), a premalignant esophageal condition in which the normal stratified squamous epithelium changes to a metaplastic columnar-lined epithelium. BE's importance lies in the fact that it confers a 30- to 40-fold increased risk for the development of esophageal adenocarcinoma, a rapidly increasing and extremely deadly malignancy. This is a report on interim findings from 10 patients. To date, the results support that daily consumption of LBRs promotes reductions in the urinary excretion of two markers of oxidative stress, 8-epi-prostaglandin F2alpha (8-Iso-PGF2) and, to a lesser more-variable extent, 8-hydroxy-2'-deoxyguanosine (8-OHdG), among patients with BE.

  4. Do Media Use and Physical Activity Compete in Adolescents? Results of the MoMo Study

    PubMed Central

    Spengler, Sarah; Mess, Filip; Woll, Alexander

    2015-01-01

    Purpose The displacement hypothesis predicts that physical activity and media use compete in adolescents; however, findings are inconsistent. A more differentiated approach at determining the co-occurrence of physical activity and media use behaviors within subjects may be warranted. The aim of this study was to determine the co-occurrence of physical activity and media use by identifying clusters of adolescents with specific behavior patterns including physical activity in various settings (school, sports club, leisure time) and different types of media use (watching TV, playing console games, using PC / Internet). Methods Cross-sectional data of 2,083 adolescents (11–17 years) from all over Germany were collected between 2009 and 2012 in the Motorik-Modul Study. Physical activity and media use were self-reported. Cluster analyses (Ward’s method and K-means analysis) were used to identify behavior patterns of boys and girls separately. Results Eight clusters were identified for boys and seven for girls. The clusters demonstrated that a high proportion of boys (33%) as well as girls (42%) show low engagement in both physical activity and media use, irrespective of setting or type of media. Other adolescents are engaged in both behaviors, but either physical activity (35% of boys, 27% of girls) or media use (31% of boys and girls) predominates. These adolescents belong to different clusters, whereat in most clusters either one specific setting of physical activity or a specific combination of different types of media predominates. Conclusion The results of this study support to some extent the hypothesis that media use and physical activity compete: Very high media use occurred with low physical activity behavior, but very high activity levels co-occurred with considerable amounts of time using any media. There was no evidence that type of used media was related to physical activity levels, neither setting of physical activity was related to amount of media use

  5. Intraepithelial and lamina propria lymphocytes show distinct patterns of apoptosis whereas both populations are active in Fas based cytotoxicity in coeliac disease

    PubMed Central

    Di, S; Ciccocioppo, R; D'Alo, S; Parroni, R; Millimaggi, D; Cifone, M; Corazza, G

    2001-01-01

    BACKGROUND—Lamina propria (LPLs) and intraepithelial (IELs) lymphocytes are markedly increased in coeliac mucosa, and are thought to play a crucial role in the generation of villous atrophy in coeliac disease (CD). However, the mechanisms by which they mediate the killing of enterocytes in this condition are still poorly characterised.
AIM—We investigated Fas mediated cytotoxicity and apoptosis of both LPLs and IELs, isolated from 10 untreated coeliac patients, 10 coeliac patients on a gluten free diet, and 10 biopsied controls.
METHODS—Fas and Fas ligand expression were assessed by flow cytometry and immunocytochemistry. Lymphocyte cytotoxicity against Fas expressing Jurkat cells was determined by the Jam test. The effect of the antagonist ZB4 anti-Fas antibody on apoptotic activity exerted by coeliac lymphocytes against enterocytes was analysed. Lymphocyte apoptosis was assessed by oligonucleosome ELISA.
RESULTS—LPLs and IELs showed increased apoptotic activity and higher levels of Fas ligand expression in untreated CD compared with treated CD patients and controls. Enterocyte apoptosis observed after coculturing coeliac lymphocytes and enterocytes in the presence of ZB4 antibody was reduced. In active CD, LPLs manifested increased apoptosis whereas IELs showed decreased apoptosis.
CONCLUSIONS—Our results support the involvement of the Fas/Fas ligand system in CD associated enterocyte apoptosis. Increased LPL apoptosis is likely to downregulate mucosal inflammation whereas decreased IEL apoptosis could be responsible for autoimmune and malignant complications of CD.


Keywords: apoptosis; coeliac disease; cytotoxicity assay; Fas/Fas ligand system; intraepithelial lymphocytes; lamina propria lymphocytes PMID:11511560

  6. Show What You Know

    ERIC Educational Resources Information Center

    Eccleston, Jeff

    2007-01-01

    Big things come in small packages. This saying came to the mind of the author after he created a simple math review activity for his fourth grade students. Though simple, it has proven to be extremely advantageous in reinforcing math concepts. He uses this activity, which he calls "Show What You Know," often. This activity provides the perfect…

  7. Summary of FY15 results of benchmark modeling activities

    SciTech Connect

    Arguello, J. Guadalupe

    2015-08-01

    Sandia is participating in the third phase of an is a contributing partner to a U.S.-German "Joint Project" entitled "Comparison of current constitutive models and simulation procedures on the basis of model calculations of the thermo-mechanical behavior and healing of rock salt." The first goal of the project is to check the ability of numerical modeling tools to correctly describe the relevant deformation phenomena in rock salt under various influences. Achieving this goal will lead to increased confidence in the results of numerical simulations related to the secure storage of radioactive wastes in rock salt, thereby enhancing the acceptance of the results. These results may ultimately be used to make various assertions regarding both the stability analysis of an underground repository in salt, during the operating phase, and the long-term integrity of the geological barrier against the release of harmful substances into the biosphere, in the post-operating phase.

  8. Results of Skylab medical experiment M171: Metabolic activity

    NASA Technical Reports Server (NTRS)

    Michel, E. L.; Rummel, J. A.; Sawin, C. F.; Buderer, M. C.; Lem, J. D.

    1974-01-01

    The experiment was conducted to establish whether man's ability to perform mechanical work would be progressively altered as a result of exposure to the weightless environment of space flight. The Skylab crewmen exercised on a bicycle ergometer at workloads approximating 25, 50, and 75 percent of their maximum aerobic capacity. The physiological parameters monitored were respiratory gas exchange, blood pressure, and vectorcardiogram/heart rate. The results of these tests indicate that the crewmen had no significant decrement in their responses to exercise during their exposure to zero gravity. The results of the third manned Skylab mission (Skylab 4) are presented and a comparison is made of the overall results obtained from the three successively longer Skylab manned missions. The Skylab 4 crewmembers' 84-day in-flight responses to exercise were no worse and were probably better than the responses of the crewmen on the first two Skylab missions. Indications that exercise was an important contributing factor in maintaining this response are discussed.

  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. 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.

  11. European activities in exobiology in earth orbit: results and perspectives

    NASA Astrophysics Data System (ADS)

    Horneck, G.

    1999-01-01

    A large portion of European activities in Earth orbit have concentrated on studies of the responses of resistant microbes to the harsh environment of space with the aim of providing experimental evidence testing the hypothesis that interplanetary transfer of life is possible. Various types of microorganisms, such as bacterial or fungal spores, as well as viruses and biomolecules, such as DNA, amino acids and liposomes, have been exposed to selected and combined space conditions outside the Earth's magnetic field (Apollo 16) or in low Earth orbit (Spacelab 1, Spacelab D2, ERA on EURECA, LDEF, BIOPAN on FOTON). Space parameters, such as high vacuum, intense solar ultraviolet radiation, different components of the cosmic radiation field and temperature extremes affected the genetic stability of the organisms in space, leading to increased mutation rates, DNA damage and inactivation. Extraterrestrial solar UV radiation was the most lethal factor. If shielded against the influx of solar UV, spores of Bacillus subtilis survived for more than 5 years in space. Future research will be directed towards long-term studies of microbes in artificial meteorites, as well as of microbial communities from special ecological niches, such as endolithic and endoevaporitic ecosystems. For these studies, the European Space Agency will provide the facility EXPOSE to be accommodated on the External Platform of the International Space Station during the Early Utilization Phase.

  12. The uses and results of active tetanus immunization

    PubMed Central

    Scheibel, Inga

    1955-01-01

    Both in animal experiments and in the course of two world wars active immunization has proved a safe method of protection against tetanus, and a method superior to passive serum prophylaxis. The three types of vaccine—plain, combined, and precipitated or adsorbed—all have their advantages and disadvantages, and the choice between them must be left to individual national health authorities. They should, however, be administered in two or three doses to confer basic immunity. What amount of circulating antitoxin is necessary to give full protection has not been accurately determined, but it is clear that one recall dose should be given about a year after the first injections as part of the routine course of injections. This seems enough to provide a long-lasting immunity, but a dose of vaccine should also be given at the time of injury. General immunization of the population is not practicable, but children, who are among the groups most at risk, can be immunized relatively simply by combined diphtheria and tetanus vaccine; in many countries, indeed, this is being done on an ever-increasing scale. PMID:13270078

  13. High Fc Density Particles Result in Binary Complement Activation but Tunable Macrophage Phagocytosis

    NASA Astrophysics Data System (ADS)

    Sulchek, Todd; Pacheco, Patricia; White, David

    2014-03-01

    Macrophage phagocytosis and complement system activation represent two key components of the immune system and both can be activated through the presentation of multiple Fc domains of IgG antibodies. We have created functionalized micro- and nanoparticles with various densities of Fc domains to understand the modulation of the immune system for eventual use as a novel immunomodulation platform. Phagocytosis assays were carried out by adding functionalized particles to macrophage cells and quantitatively determined using fluorescent microscopy and flow cytometry. Complement system activation by the functionalized particles in human serum was quantified with an enzyme immunoassay. Our phagocytosis assay revealed a strong dependence on particle size and Fc density. For small particles, as the Fc density increased, the number of particles phagocytosed also increased. Large particles were phagocytosed at significantly lower levels and showed no dependency on Fc density. Complement was successfully activated at levels comparable to positive controls for small particles at high Fc densities. However at low Fc densities, there is a significant decrease in complement activation. This result suggests a binary response for complement system activation with a threshold density for successful activation. Therefore, varying the Fc density on micro/nanoparticles resulted in a tunable response in macrophage phagocytosis while a more binary response for complement activation.

  14. Current Results and Proposed Activities in Microgravity Fluid Dynamics

    NASA Technical Reports Server (NTRS)

    Polezhaev, V. I.

    1996-01-01

    The Institute for Problems in Mechanics' Laboratory work in mathematical and physical modelling of fluid mechanics develops models, methods, and software for analysis of fluid flow, instability analysis, direct numerical modelling and semi-empirical models of turbulence, as well as experimental research and verification of these models and their applications in technological fluid dynamics, microgravity fluid mechanics, geophysics, and a number of engineering problems. This paper presents an overview of the results in microgravity fluid dynamics research during the last two years. Nonlinear problems of weakly compressible and compressible fluid flows are discussed.

  15. United States radiological health activities: inspection results of mammography facilities

    PubMed Central

    Spelic, DC; Kaczmarek, RV; Hilohi, M; Belella, S

    2007-01-01

    Purpose: The Mammography Quality Standards Act (MQSA) was enacted in 1992 to set national standards for high-quality mammography, including standards for mammographic X-ray equipment, patient dose, clinical image quality, and related technical parameters. The MQSA also requires minimum qualifications for radiologic technologists, interpreting physicians and medical physicists, mandates acceptable practices for quality-control, quality-assurance, and requires processes to audit medical outcomes. This paper presents the findings of MQSA inspections of facilities, which characterize significant factors affecting mammography quality in the United States. Materials and Methods: Trained inspectors collected data regarding X-ray technical factors, made exposure measurements for the determination of mean glandular dose (MGD), evaluated image quality, and inspected the quality of the film-processing environment. The average annual facility and total U.S. screening exam workloads were computed using workload data reported by facilities. Results: Mammography facilities have made technical improvements as evidenced by a narrower distribution of doses, higher phantom-film background optical densities associated with higher phantom image-quality scores, and better film processing. It is estimated that approximately 36 million screening mammography exams were conducted in 2006, a rate that is almost triple the exam volume estimated for 1997. Digital mammography (DM) is now in use at approximately 14% (1,191 of 8,834) of MQSA-certified mammography facilities. The results indicate that DM can offer lower dose to the patient while providing comparable or better image quality. PMID:21614276

  16. Activation of AMP-activated protein kinase in response to temperature elevation shows seasonal variation in the zebra mussel, Dreissena polymorpha.

    PubMed

    Jost, Jennifer A; Keshwani, Sarah S; Abou-Hanna, Jacob J

    2015-04-01

    Global climate change is affecting ectothermic species, and a variety of studies are needed on thermal tolerances, especially from cellular and physiological perspectives. This study utilized AMP-activated protein kinase (AMPK), a key regulator of cellular energy levels, to examine the effects of high water temperatures on zebra mussel (Dreissena polymorpha) physiology. During heating, AMPK activity increased as water temperature increased to a point, and maximum AMPK activity was detected at high, but sublethal, water temperatures. This pattern varied with season, suggesting that cellular mechanisms of seasonal thermal acclimatization affect basic metabolic processes during sublethal heat stress. There was a greater seasonal variation in the water temperature at which maximum AMPK activity was measured than in lethal water temperature. Furthermore, baseline AMPK activity varied significantly across seasons, most likely reflecting altered metabolic states during times of growth and reproduction. In addition, when summer-collected mussels were lab-acclimated to winter and spring water temperatures, patterns of heat stress mirrored those of field-collected animals. These data suggest that water temperature is the main driver of the seasonal variation in physiology. This study concluded that AMPK activity, which reflects changes in energy supply and demand during heat stress, can serve as a sensitive and early indicator of temperature stress in mussels.

  17. Activation of AMP-activated protein kinase in response to temperature elevation shows seasonal variation in the zebra mussel, Dreissena polymorpha.

    PubMed

    Jost, Jennifer A; Keshwani, Sarah S; Abou-Hanna, Jacob J

    2015-04-01

    Global climate change is affecting ectothermic species, and a variety of studies are needed on thermal tolerances, especially from cellular and physiological perspectives. This study utilized AMP-activated protein kinase (AMPK), a key regulator of cellular energy levels, to examine the effects of high water temperatures on zebra mussel (Dreissena polymorpha) physiology. During heating, AMPK activity increased as water temperature increased to a point, and maximum AMPK activity was detected at high, but sublethal, water temperatures. This pattern varied with season, suggesting that cellular mechanisms of seasonal thermal acclimatization affect basic metabolic processes during sublethal heat stress. There was a greater seasonal variation in the water temperature at which maximum AMPK activity was measured than in lethal water temperature. Furthermore, baseline AMPK activity varied significantly across seasons, most likely reflecting altered metabolic states during times of growth and reproduction. In addition, when summer-collected mussels were lab-acclimated to winter and spring water temperatures, patterns of heat stress mirrored those of field-collected animals. These data suggest that water temperature is the main driver of the seasonal variation in physiology. This study concluded that AMPK activity, which reflects changes in energy supply and demand during heat stress, can serve as a sensitive and early indicator of temperature stress in mussels. PMID:25498351

  18. 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

  19. Results of mobile gamma scanning activities in St. Louis, Missouri

    SciTech Connect

    Rodriguez, R E; Witt, D A; Cottrell, W D; Carrier, R F

    1991-06-01

    From 1942 through approximately 1966, the Mallinckrodt Chemical Works operated four plants in St. Louis, Missouri, for the Manhattan Engineer District and the Atomic Energy Commission. A variety of production processes using uranium- and radium-bearing ore materials were performed at the plants. It is the policy of the DOE to verify that radiological conditions at such sites or facilities comply with current DOE guidelines. Guidelines for release and use of such sites have become more stringent as research has provided more information since previous cleanups. The Formerly Utilized Sites Remedial Action Program (FUSRAP) was established as part of that effort to confirm the closeout status of facilities under contract to agencies preceding DOE during early nuclear energy development. Under the FUSRAP program, the Mallinckrodt properties have been previously investigated to determine the extent of on-site radiological contamination. At the request of DOE, Oak Ridge National Laboratory (ORNL) conducted a survey in May 1990, of public roadways and suspected haul routes between the Mallinckrodt plant and storage sites in St. Louis to ensure that no residual radioactive materials were conveyed off-site. A mobile gamma scanning van with an on-board computer system was used to identify possible anomalies. Suspect areas are those displaying measurements deviating from gamma exposure rates identified as typical for radiologically unenhanced areas in the vicinity of the areas of interest. The instrumentation highlighted three anomaly locations each of which measured less than 1m{sup 2} in size. None of the slightly elevated radiation levels originated from material associated with former AEC-related processing operations in the area. The anomalies resulted from elevated concentrations of radionuclides present in phosphate fertilizers, increased thorium in road-base gravel, and emanations from the radioactive storage site near the Latty Avenue airport. 9 refs., 3 figs.

  20. Report of a successful ongoing pregnancy as a result of IMSI with assisted oocyte activation.

    PubMed

    Doroftei, Bogdan; Zlei, Mihaela; Simionescu, Gabriela; Maftei, Radu; Cumpata, Simona; Emerson, Geraldine

    2015-05-03

    We report a successful ongoing pregnancy obtained in a case of total globozoospermia after intracytoplasmic morphologically selected sperm injection (IMSI) with oocyte activation. The first semen analysis on investigation showed partial globozoospermia. However, under high magnification assessment at oocyte retrieval only round headed sperm were observed. Considering the high risk of a complete failure to fertilize from IMSI the couple gave written informed consent to the use of oocyte activation media post IMSI. One embryo fertilized, developed to a hatching blastocyst and was transferred resulting in an ongoing pregnancy. This successful outcome shows the use of IMSI is useful in the evaluation of total globozooozpermia and therefore aids in the justification of the use of oocyte activation media.

  1. 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

  2. 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 Central

    Currie, Richard A.; Peffer, Richard C.; Goetz, Amber K.; Omiecinski, Curtis J.; Goodman, Jay I.

    2014-01-01

    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. PMID:24675475

  3. 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

    2014-07-01

    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.

  4. 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.

  5. Early activation of caspases during T lymphocyte stimulation results in selective substrate cleavage in nonapoptotic cells.

    PubMed

    Alam, A; Cohen, L Y; Aouad, S; Sékaly, R P

    1999-12-20

    Apoptosis induced by T cell receptor (TCR) triggering in T lymphocytes involves activation of cysteine proteases of the caspase family through their proteolytic processing. Caspase-3 cleavage was also reported during T cell stimulation in the absence of apoptosis, although the physiological relevance of this response remains unclear. We show here that the caspase inhibitor benzyloxycarbonyl (Cbz)-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD) blocks proliferation, major histocompatibility complex class II expression, and blastic transformation during stimulation of peripheral blood lymphocytes. Moreover, T cell activation triggers the selective processing and activation of downstream caspases (caspase-3, -6, and -7), but not caspase-1, -2, or -4, as demonstrated even in intact cells using a cell-permeable fluorescent substrate. Caspase-3 processing occurs in different T cell subsets (CD4(+), CD8(+), CD45RA(+), and CD45RO(+)), and in activated B lymphocytes. The pathway leading to caspase activation involves death receptors and caspase-8, which is also processed after TCR triggering, but not caspase-9, which remains as a proenzyme. Most importantly, caspase activity results in a selective substrate specificity, since poly(ADP-ribose) polymerase (PARP), lamin B, and Wee1 kinase, but not DNA fragmentation factor (DFF45) or replication factor C (RFC140), are processed. Caspase and substrate processing occur in nonapoptotic lymphocytes. Thus, caspase activation is an early and physiological response in viable, stimulated lymphocytes, and appears to be involved in early steps of lymphocyte activation. PMID:10601362

  6. 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.

  7. Brain activation patterns resulting from learning letter forms through active self-production and passive observation in young children

    PubMed Central

    Kersey, Alyssa J.; James, Karin H.

    2013-01-01

    Although previous literature suggests that writing practice facilitates neural specialization for letters, it is unclear if this facilitation is driven by the perceptual feedback from the act of writing or the actual execution of the motor act. The present study addresses this issue by measuring the change in BOLD signal in response to hand-printed letters, unlearned cursive letters, and cursive letters that 7-year-old children learned actively, by writing, and passively, by observing an experimenter write. Brain activation was assessed using fMRI while perceiving letters—in both cursive and manuscript forms. Results showed that active training led to increased recruitment of the sensori-motor network associated with letter perception as well as the insula and claustrum, but passive observation did not. This suggests that perceptual networks for newly learned cursive letters are driven by motor execution rather than by perceptual feedback. PMID:24069007

  8. Brain activation patterns resulting from learning letter forms through active self-production and passive observation in young children.

    PubMed

    Kersey, Alyssa J; James, Karin H

    2013-01-01

    Although previous literature suggests that writing practice facilitates neural specialization for letters, it is unclear if this facilitation is driven by the perceptual feedback from the act of writing or the actual execution of the motor act. The present study addresses this issue by measuring the change in BOLD signal in response to hand-printed letters, unlearned cursive letters, and cursive letters that 7-year-old children learned actively, by writing, and passively, by observing an experimenter write. Brain activation was assessed using fMRI while perceiving letters-in both cursive and manuscript forms. Results showed that active training led to increased recruitment of the sensori-motor network associated with letter perception as well as the insula and claustrum, but passive observation did not. This suggests that perceptual networks for newly learned cursive letters are driven by motor execution rather than by perceptual feedback.

  9. 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

  10. 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. PMID:26097095

  11. 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.

  12. Results.

    ERIC Educational Resources Information Center

    Zemsky, Robert; Shaman, Susan; Shapiro, Daniel B.

    2001-01-01

    Describes the Collegiate Results Instrument (CRI), which measures a range of collegiate outcomes for alumni 6 years after graduation. The CRI was designed to target alumni from institutions across market segments and assess their values, abilities, work skills, occupations, and pursuit of lifelong learning. (EV)

  13. Hyperthermostable Thermotoga maritima xylanase XYN10B shows high activity at high temperatures in the presence of biomass-dissolving hydrophilic ionic liquids.

    PubMed

    Yu, Tianyi; Anbarasan, Sasikala; Wang, Yawei; Telli, Kübra; Aslan, Aşkın Sevinç; Su, Zhengding; Zhou, Yin; Zhang, Li; Iivonen, Piia; Havukainen, Sami; Mentunen, Tero; Hummel, Michael; Sixta, Herbert; Binay, Baris; Turunen, Ossi; Xiong, Hairong

    2016-07-01

    The gene of Thermotoga maritima GH10 xylanase (TmXYN10B) was synthesised to study the extreme limits of this hyperthermostable enzyme at high temperatures in the presence of biomass-dissolving hydrophilic ionic liquids (ILs). TmXYN10B expressed from Pichia pastoris showed maximal activity at 100 °C and retained 92 % of maximal activity at 105 °C in a 30-min assay. Although the temperature optimum of activity was lowered by 1-ethyl-3-methylimidazolium acetate ([EMIM]OAc), TmXYN10B retained partial activity in 15-35 % hydrophilic ILs, even at 75-90 °C. TmXYN10B retained over 80 % of its activity at 90 °C in 15 % [EMIM]OAc and 15-25 % 1-ethyl-3-methylimidazolium dimethylphosphate ([EMIM]DMP) during 22-h reactions. [EMIM]OAc may rigidify the enzyme and lower V max. However, only minor changes in kinetic parameter K m showed that competitive inhibition by [EMIM]OAc of TmXYN10B is minimal. In conclusion, when extended enzymatic reactions under extreme conditions are required, TmXYN10B shows extraordinary potential. PMID:27240671

  14. Neutralization of feline infectious peritonitis virus: preparation of monoclonal antibody that shows cell tropism in neutralizing activity after viral absorption into the cells.

    PubMed

    Kida, K; Hohdatsu, T; Kashimoto-Tokunaga, J; Koyama, H

    2000-01-01

    Feline infectious peritonitis virus (FIPV) infection of feline macro-phages is enhanced by mouse anti-FIPV monoclonal antibody (MAb). This anti-body-dependent enhancement (ADE) of FIPV infection is dependent on mouse MAb subclass, and MAb of IgG2a subclass has a strong ADE activity. Furthermore, MAb showing strong neutralizing activity in Felis catus whole fetus (fcwf-4) cells and Crandell feline kidney (CrFK) cells shows strong enhancing activity in feline macrophages, indicating that the neutralizing epitope and the enhancing epitope are closely related. In this study, we prepared MAb FK50-4 that showed a strong neutralizing activity in feline macrophages, despite the fact that the MAb belonged to the IgG2a subclass. However, MAb FK50-4 did not exhibit neutralizing activity in CrFK cells or fcwf-4 cells, thus showing a very unusual property. MAb FK50-4 recognized FIPV small integral membrane glycoprotein (M protein). Even when feline macrophages were pretreated with MAb FK50-4 prior to FIPV inoculation, this antibody prevented FIPV infection. This reaction disappeared after treatment of FK50-4 with protein A. The neutralizing activity of FK50-4 was also effective on feline macrophages after the cells were inoculated with FIPV. These findings indicated that the FIPV replication mechanism differs between feline macrophages and CrFK/fcwf-4 cells and that a neutralizing epitope that can prevent FIPV infection of feline macrophages after viral absorption is present on M protein.

  15. Incorporation of Cobalt‐Cyclen Complexes into Templated Nanogels Results in Enhanced Activity

    PubMed Central

    Jorge, Ana Rita; Chernobryva, Mariya; Rigby, Stephen E. J.

    2015-01-01

    Abstract Recent advances in nanomaterials have identified nanogels as an excellent matrix for novel biomimetic catalysts using the molecular imprinting approach. Polymerisable Co‐cyclen complexes with phosphonate and carbonate templates have been prepared, fully characterised and used to obtain nanogels that show high activity and turnover with low catalytic load, compared to the free complex, in the hydrolysis of 4‐nitrophenyl phosphate, a nerve agent simulant. This work demonstrates that the chemical structure of the template has an impact on the coordination geometry and oxidation state of the metal centre in the polymerisable complex resulting in very significant changes in the catalytic properties of the polymeric matrix. Both pseudo‐octahedral cobalt(III) and trigonal‐bipyramidal cobalt(II) structures have been used for the synthesis of imprinted nanogels, and the catalytic data demonstrate that: i) the imprinted nanogels can be used in 15 % load and show turnover; ii) the structural differences in the polymeric matrices resulting from the imprinting approach with different templates are responsible for the molecular recognition capabilities and the catalytic activity. Nanogel P1, imprinted with the carbonate template, shows >50 % higher catalytic activity than P2 imprinted with the phosphonate. PMID:26661923

  16. 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

  17. [Physical activity: results of the German Health Interview and Examination Survey for Adults (DEGS1)].

    PubMed

    Krug, S; Jordan, S; Mensink, G B M; Müters, S; Finger, J; Lampert, T

    2013-05-01

    Regular physical activity can have a positive effect on health at any age. Today's lifestyles, however, can often be characterised as sedentary. Therefore, the promotion of physical activity and sports has become an integral part of public health measures. The representative data of adults aged 18 to 79 years in Germany obtained from the "German Health Interview and Examination Survey for Adults" (DEGS1) provide an overview of self-estimated current physical activity behaviour. The results show that one third of the adult population claims to pay close attention to reaching a sufficient level of physical activity and one fourth participates in sports for at least 2 h/week on a regular basis. Thus, the percentage of adults regularly engaged in sports has increased compared to the previous "German National Health Interview and Examination Survey 1998". Still, four out of five adults do not achieve at least 2.5 h/week of moderate-intensity physical activity as recommended by the World Health Organisation. Consequently, future individual-level and population-level interventions should focus on target group-specific measures while continuing to promote regular physical activity in all segments of the population. An English full-text version of this article is available at SpringerLink as supplemental.

  18. 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

  19. 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

  20. Ethanolic extracts of Tinospora cordifolia and Alstonia scholaris show antimicrobial activity towards clinical isolates of methicillin-resistant and carbapenemase-producing bacteria.

    PubMed

    Bonvicini, Francesca; Mandrone, Manuela; Antognoni, Fabiana; Poli, Ferruccio; Gentilomi, Giovanna Angela

    2014-01-01

    The aim of this study was to determine the in vitro antimicrobial activity of crude extracts of three plants from Ayurveda tradition (Tinospora cordifolia, Alstonia scholaris, Crataeva nurvala) against reference microbial strains and clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and carbapenemase-producing Klebsiella pneumoniae. IC50 values were obtained by micro-dilution methods meeting the requirements of the NCCLS standard. The cytotoxicity of the extracts was also investigated on a mammalian cell line. Extracts displayed a variable degree of antimicrobial activity and did not interfere with mammalian cell proliferation. T. cordifolia and A. scholaris exhibited a higher inhibitory activity against clinical isolates of MRSA and carbapenemase-producing K. pneumoniae compared with reference strains, while C. nurvala exhibited a different behaviour. An antifungal activity towards Candida albicans was observed for A. scholaris extract. Results indicate that constituents from T. cordifolia and A. scholaris may be a potential source of new therapeutic strategies for infectious diseases. PMID:24749692

  1. Nobiletin, a polymethoxylated flavonoid from citrus, shows anti-angiogenic activity in a zebrafish in vivo model and HUVEC in vitro model.

    PubMed

    Lam, Kai Heng; Alex, Deepa; Lam, In Kei; Tsui, Stephen Kwok Wing; Yang, Zi Feng; Lee, Simon Ming Yuen

    2011-11-01

    Traditional Chinese medicinal herbs are a rich source of compounds with reported anti-inflammatory and anti-carcinogenic effects. Growing evidence shows the codependence of chronic inflammation and angiogenesis, and the potential benefits of targeting angiogenesis in the treatment of chronic inflammation and targeting inflammation in the treatment of diseases with impaired angiogenesis. We hypothesized that the anti-inflammatory activity of the natural compounds may owe at least some of its efficacy to their anti-angiogenic activity and hence we investigated the anti-angiogenic activity of these compounds in vivo in zebrafish embryos and in vitro in human umbilical vein endothelial cells (HUVECs). Nobiletin, a polymethoxylated flavonoid from citrus fruits, showed anti-angiogenic activity in both assays. Nobiletin inhibited the formation of intersegmental vessels (ISVs) in live transgenic zebrafish embryos expressing green fluorescent protein (GFP) in the vasculature. Cell cycle analysis of dissociated zebrafish embryo cells showed that nobiletin induced G0/G1 phase accumulation in a dose-dependent manner in GFP-positive endothelial cells. Nobiletin also dose-dependently induced VEGF-A mRNA expression. In HUVECs, nobiletin inhibited endothelial cell proliferation and, to a greater extent, tube formation in a dose-dependent manner. As in the in vivo study, nobiletin induced G0/G1 cell cycle arrest in HUVECs. However, this arrest was not accompanied by an increase in apoptosis, indicating a cytostatic effect of nobiletin. This study, for the first time, identifies nobiletin as having potent anti-angiogenic activity and suggests that nobiletin has a great potential for future research and development as a cytostatic anti-proliferative agent.

  2. Subconjunctival Sirolimus for the Treatment of Chronic Active Anterior Uveitis: Results of a Pilot Trial

    PubMed Central

    Sen, H. Nida; Larson, Theresa A.; Meleth, Annal D.; Smith, Wendy M.; Nussenblatt, Robert B.

    2012-01-01

    Purpose To evaluate the safety and possible efficacy of subconjunctival sirolimus for the treatment of chronic active anterior uveitis Design Prospective, non-randomized, open-label clinical trial. Methods This single-center pilot trial enrolled 5 patients with chronic active anterior uveitis. The study drug was administered as single subconjunctival injection of 30μL (1,320μg) sirolimus in the study eye at the baseline visit. Study visits were performed at baseline, 2 weeks, 4 weeks and monthly until 4 months, and included a complete ophthalmic exam, review of systems, adverse event assessment at each visit, physical exam and ancillary ophthalmic testing at some visits. The primary outcome measure was a 2-step reduction in the anterior chamber inflammation within 4 weeks of injection of the study drug. Results There were 3 females and 2 males; 4 patients had idiopathic anterior uveitis and one had psoriatic arthritis-associated anterior uveitis. Three of the five patients met the primary outcome criteria by showing at least a 2-step decrease in inflammation within 4 weeks, 2 patients showed a 1-step decrease in inflammation within the same time frame. No recurrence was encountered during a 4 month follow-up. There were no serious adverse events. Conclusions Subconjunctival sirolimus appears to be well tolerated in this pilot trial and shows promise as a treatment for active inflammation in patients with chronic anterior uveitis. Larger studies are needed to assess its usefulness in uveitis. PMID:22465364

  3. 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.

  4. Identification of novel Saccharomyces cerevisiae proteins with nuclear export activity: cell cycle-regulated transcription factor ace2p shows cell cycle-independent nucleocytoplasmic shuttling.

    PubMed

    Jensen, T H; Neville, M; Rain, J C; McCarthy, T; Legrain, P; Rosbash, M

    2000-11-01

    Nuclear export of proteins containing leucine-rich nuclear export signals (NESs) is mediated by the NES receptor CRM1/Crm1p. We have carried out a yeast two-hybrid screen with Crm1p as a bait. The Crm1p-interacting clones were subscreened for nuclear export activity in a visual assay utilizing the Crm1p-inhibitor leptomycin B (LMB). This approach identified three Saccharomyces cerevisiae proteins not previously known to have nuclear export activity. These proteins are the 5' RNA triphosphatase Ctl1p, the cell cycle-regulated transcription factor Ace2p, and a protein encoded by the previously uncharacterized open reading frame YDR499W. Mutagenesis analysis show that YDR499Wp contains an NES that conforms to the consensus sequence for leucine-rich NESs. Mutagenesis of Ctl1p and Ace2p were unable to identify specific NES residues. However, a 29-amino-acid region of Ace2p, rich in hydrophobic residues, contains nuclear export activity. Ace2p accumulates in the nucleus at the end of mitosis and activates early-G(1)-specific genes. We now provide evidence that Ace2p is nuclear not only in late M-early G(1) but also during other stages of the cell cycle. This feature of Ace2p localization explains its ability to activate genes such as CUP1, which are not expressed in a cell cycle-dependent manner.

  5. 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)

  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. 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…

  8. National level promotion of physical activity: results from England's ACTIVE for LIFE campaign

    PubMed Central

    Hillsdon, M; Cavill, N; Nanchahal, K; Diamond, A; White, I

    2001-01-01

    STUDY OBJECTIVE—To assess the impact of a national campaign on awareness of the campaign, change in knowledge of physical activity recommendations and self reported physical activity.
DESIGN—three year prospective longitudinal survey using a multi-stage, cluster random probability design to select participants.
SETTING—England.
PARTICIPANTS—A nationally representative sample of 3189 adults aged 16-74 years.
MAIN OUTCOME MEASURES—Awareness of the advertising element of the campaign, changes in knowledge of physical activity recommendations for health and self reported physical activity.
RESULTS—38% of participants were aware of the main advertising images, assessed six to eight months after the main television advertisement. The proportion of participants knowledgeable about moderate physical activity recommendations increased by 3.0% (95% CI: 1.4%, 4.5%) between waves 1 and 2 and 3.7% (95% CI: 2.1%, 5.3%) between waves 1 and 3. The change in proportion of active people between baseline and waves 1 and 2 was
−0.02 (95% CI: −2.0 to +1.7) and between waves 1 and 3 was −9.8 (−7.9 to −11.7).
CONCLUSION—The proportion of participants who were knowledgeable about the new recommendations, increased significantly after the campaign. There was however, no significant difference in knowledge by awareness of the main campaign advertisement. There is no evidence that ACTIVE for LIFE improved physical activity, either overall or in any subgroup.


Keywords: exercise; mass media; follow up studies; health promotion; physical activity PMID:11553661

  9. Eupafolin and Ethyl Acetate Fraction of Kalanchoe gracilis Stem Extract Show Potent Antiviral Activities against Enterovirus 71 and Coxsackievirus A16

    PubMed Central

    Wang, Ching-Ying; Huang, Shun-Chueh; Lai, Zhen-Rung; Ho, Yu-Ling; Jou, Yu-Jen; Kung, Szu-Hao; Zhang, Yongjun; Chang, Yuan-Shiun; Lin, Cheng-Wen

    2013-01-01

    Enterovirus 71 (EV71) and coxsackievirus A16 (CoxA16) are main pathogens of hand-foot-and-mouth disease, occasionally causing aseptic meningitis and encephalitis in tropical and subtropical regions. Kalanchoe gracilis, Da-Huan-Hun, is a Chinese folk medicine for treating pain and inflammation, exhibiting antioxidant and anti-inflammatory activities. Our prior report (2012) cited K. gracilis leaf extract as moderately active against EV71 and CoxA16. This study further rates antienteroviral potential of K. gracilis stem (KGS) extract to identify potent antiviral fractions and components. The extract moderately inhibits viral cytopathicity and virus yield, as well as in vitro replication of EV71 (IC50 = 75.18 μg/mL) and CoxA16 (IC50 = 81.41 μg/mL). Ethyl acetate (EA) fraction of KGS extract showed greater antiviral activity than that of n-butanol or aqueous fraction: IC50 values of 4.21 μg/mL against EV71 and 9.08 μg/mL against CoxA16. HPLC analysis, UV-Vis absorption spectroscopy, and plaque reduction assay indicate that eupafolin is a vital component of EA fraction showing potent activity against EV71 (IC50 = 1.39 μM) and CoxA16 (IC50 = 5.24 μM). Eupafolin specifically lessened virus-induced upregulation of IL-6 and RANTES by inhibiting virus-induced ERK1/2, AP-1, and STAT3 signals. Anti-enteroviral potency of KGS EA fraction and eupafolin shows the clinical potential against EV71 and CoxA16 infection. PMID:24078828

  10. Novel antiviral characteristics of nanosized copper(I) iodide particles showing inactivation activity against 2009 pandemic H1N1 influenza virus.

    PubMed

    Fujimori, Yoshie; Sato, Tetsuya; Hayata, Taishi; Nagao, Tomokazu; Nakayama, Mikio; Nakayama, Tsuruo; Sugamata, Ryuichi; Suzuki, Kazuo

    2012-02-01

    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.

  11. 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

  12. Beta-catenin-activated hepatocellular adenoma showing hyperintensity on hepatobiliary-phase gadoxetic-enhanced magnetic resonance imaging and overexpression of OATP8.

    PubMed

    Yoneda, Norihide; Matsui, Osamu; Kitao, Azusa; Kozaka, Kazuto; Gabata, Toshifumi; Sasaki, Motoko; Nakanuma, Yasuni; Murata, Kiyoshi; Tani, Toru

    2012-11-01

    We report a male case of beta-catenin-activated hepatocellular adenoma (HCA) focusing on findings of gadoxetic-acid-enhanced magnetic resonance imaging (EOB-MRI) and discussing the molecular background and possible clinical significance. The patient was a 31-year-old man in whom computed tomography (CT) showed a large nodule of 14 cm in diameter in the right liver lobe. On dynamic contrast-enhanced CT, heterogeneous and slight to moderate enhancement was observed during the early phase, with washout in the late phase. Focal fat deposits and a scar-like portion in the lesion were also seen. Most of the lesion was slightly hyperintense compared with the background liver on the hepatobiliary phase of EOB-MRI. After operation, this patient was confirmed pathologically as having beta-catenin-activated HCA with a portion suggestive of malignant transformation. In addition, intense organic anion transporter polypeptide 8 expression was observed throughout the tumor by immunohistochemical staining.

  13. Acylated oleanane-type triterpene saponins from the flowers of Bellis perennis show anti-proliferative activities against human digestive tract carcinoma cell lines.

    PubMed

    Ninomiya, Kiyofumi; Motai, Chiaki; Nishida, Eriko; Kitagawa, Niichiro; Yoshihara, Kazuya; Hayakawa, Takao; Muraoka, Osamu; Li, Xuezheng; Nakamura, Seikou; Yoshikawa, Masayuki; Matsuda, Hisashi; Morikawa, Toshio

    2016-07-01

    Seven oleanane-type triterpene saponin bisdesmosides, perennisaponins N-T (1-7), were newly isolated from a methanol extract of daisy, the flowers of Bellis perennis L. (Asteraceae). The structures were determined based on chemical and physicochemical data and confirmed using previously isolated related compounds as references. The isolates, including 13 previously reported perennisaponins A-M (8-20), exhibited anti-proliferative activities against human digestive tract carcinoma HSC-2, HSC-4, and MKN-45 cells. Among them, perennisaponin O (2, IC50 = 11.2, 14.3, and 6.9 μM, respectively) showed relatively strong activities. The mechanism of action of 2 against HSC-2 was found to involve apoptotic cell death. PMID:27178360

  14. A novel, selective inhibitor of fibroblast growth factor receptors that shows a potent broad spectrum of antitumor activity in several tumor xenograft models.

    PubMed

    Zhao, Genshi; Li, Wei-Ying; Chen, Daohong; Henry, James R; Li, Hong-Yu; Chen, Zhaogen; Zia-Ebrahimi, Mohammad; Bloem, Laura; Zhai, Yan; Huss, Karen; Peng, Sheng-Bin; McCann, Denis J

    2011-11-01

    The fibroblast growth factor receptors (FGFR) are tyrosine kinases that are present in many types of endothelial and tumor cells and play an important role in tumor cell growth, survival, and migration as well as in maintaining tumor angiogenesis. Overexpression of FGFRs or aberrant regulation of their activities has been implicated in many forms of human malignancies. Therefore, targeting FGFRs represents an attractive strategy for development of cancer treatment options by simultaneously inhibiting tumor cell growth, survival, and migration as well as tumor angiogenesis. Here, we describe a potent, selective, small-molecule FGFR inhibitor, (R)-(E)-2-(4-(2-(5-(1-(3,5-Dichloropyridin-4-yl)ethoxy)-1H-indazol-3yl)vinyl)-1H-pyrazol-1-yl)ethanol, designated as LY2874455. This molecule is active against all 4 FGFRs, with a similar potency in biochemical assays. It exhibits a potent activity against FGF/FGFR-mediated signaling in several cancer cell lines and shows an excellent broad spectrum of antitumor activity in several tumor xenograft models representing the major FGF/FGFR relevant tumor histologies including lung, gastric, and bladder cancers and multiple myeloma, and with a well-defined pharmacokinetic/pharmacodynamic relationship. LY2874455 also exhibits a 6- to 9-fold in vitro and in vivo selectivity on inhibition of FGF- over VEGF-mediated target signaling in mice. Furthermore, LY2874455 did not show VEGF receptor 2-mediated toxicities such as hypertension at efficacious doses. Currently, this molecule is being evaluated for its potential use in the clinic.

  15. Activation of Benznidazole by Trypanosomal Type I Nitroreductases Results in Glyoxal Formation

    PubMed Central

    Hall, Belinda S.

    2012-01-01

    Benznidazole, a 2-nitroimidazole, is the front-line treatment used against American trypanosomiasis, a parasitic infection caused by Trypanosoma cruzi. Despite nearly 40 years of use, the trypanocidal activity of this prodrug is not fully understood. It has been proposed that benznidazole activation leads to the formation of reductive metabolites that can cause a series of deleterious effects, including DNA damage and thiol depletion. Here, we show that the key step in benznidazole activation involves an NADH-dependent trypanosomal type I nitroreductase. This catalyzes an oxygen-insensitive reaction with the interaction of enzyme, reductant, and prodrug occurring through a ping-pong mechanism. Liquid chromatography/mass spectrometry (LC/MS) analysis of the resultant metabolites identified 4,5-dihydro-4,5-dihydroxyimidazole as the major product of a reductive pathway proceeding through hydroxylamine and hydroxy intermediates. The breakdown of this product released the reactive dialdehyde glyoxal, which, in the presence of guanosine, generated guanosine-glyoxal adducts. These experiments indicate that the reduction of benznidazole by type I nitroreductase activity leads to the formation of highly reactive metabolites and that the expression of this enzyme is key to the trypanocidal properties displayed by the prodrug. PMID:22037852

  16. Changes in electrical activity in muscles resulting from chiropractic adjustment: a pilot study.

    PubMed

    Shambaugh, P

    1987-12-01

    This study examines the effects of chiropractic adjustment on the muscles of the back. Vertebrae that are hypomobile may be held in that state by the erector spinae muscle group; adjusting such vertebrae should result in less muscle tension. By measuring the change in electrical activity, such relaxation can be observed. Hypomobile vertebrae were found by motion palpation. The patient was then placed prone and surface electrodes were placed over the upper trapezius, upper erector spinae (T3-T5), and lumbar erector spinae (L1-L3) muscle groups on both sides of the body. The patient was adjusted using full spine toggle recoil thrusts, and postadjustment readings were taken. Results from this study show that significant changes in muscle electrical activity occur as a consequence of adjusting. On average, a 25% reduction in muscle activity was observed across the 20 subjects tested, while no significant reductions were observed with the control group of 14 subjects. Significant reductions in side-to-side imbalances were also observed.

  17. A 'Propagating' Active Across-Arc Normal Fault Shows Rupture Process of the Basement: the Case of the Southwestern Ryukyu Arc

    NASA Astrophysics Data System (ADS)

    Matsumoto, T.; Shinjo, R.; Nakamura, M.; Kubo, A.; Doi, A.; Tamanaha, S.

    2011-12-01

    Ryukyu Arc is located on the southwestern extension of Japanese Island-arc towards the east of Taiwan Island along the margin of the Asian continent off China. The island-arc forms an arcuate trench-arc-backarc system. A NW-ward subduction of the Philippine Sea Plate (PSP)at a rate of 6-8 cm/y relative to the Eurasian Plate (EP) causes frequent earthquakes. The PSP is subducting almost normally in the north-central area and more obliquely around the southwestern area. Behind the arc-trench system, the Okinawa Trough (OT) was formed by back-arc rifting, where active hydrothermal vent systems have been discovered. Several across-arc submarine faults are located in the central and southern Ryukyu Arc. The East Ishigaki Fault (EIF) is one of the across-arc normal faults located in the southwestern Ryukyu Arc, ranging by 44km and extending from SE to NW. This fault was surveyed by SEABAT8160 multibeam echo sounder and by ROV Hyper-Dolphin in 2005 and 2008. The result shows that the main fault consists of five fault segments. A branched segment from the main fault was also observed. The southernmost segment is most mature (oldest but still active) and the northernmost one is most nascent. This suggests the north-westward propagation of the fault rupture corresponding to the rifting of the southwestern OT and the southward retreat of the arc-trench system. Considering that the fault is segmented and in some part branched, propagation might take place episodically rather than continuously from SE to NW. The ROV survey also revealed the rupture process of the limestone basement along this fault from the nascent stage to the mature stage. Most of the rock samples collected from the basement outcrop were limestone blocks (or calcareous sedimentary rocks). Limestone basement was observed to the west on the hanging wall far away from the main fault scarp. Then fine-grained sand with ripple marks was observed towards the main scarp. Limestone basement was observed on the main

  18. The Great Cometary Show

    NASA Astrophysics Data System (ADS)

    2007-01-01

    The ESO Very Large Telescope Interferometer, which allows astronomers to scrutinise objects with a precision equivalent to that of a 130-m telescope, is proving itself an unequalled success every day. One of the latest instruments installed, AMBER, has led to a flurry of scientific results, an anthology of which is being published this week as special features in the research journal Astronomy & Astrophysics. ESO PR Photo 06a/07 ESO PR Photo 06a/07 The AMBER Instrument "With its unique capabilities, the VLT Interferometer (VLTI) has created itself a niche in which it provide answers to many astronomical questions, from the shape of stars, to discs around stars, to the surroundings of the supermassive black holes in active galaxies," says Jorge Melnick (ESO), the VLT Project Scientist. The VLTI has led to 55 scientific papers already and is in fact producing more than half of the interferometric results worldwide. "With the capability of AMBER to combine up to three of the 8.2-m VLT Unit Telescopes, we can really achieve what nobody else can do," added Fabien Malbet, from the LAOG (France) and the AMBER Project Scientist. Eleven articles will appear this week in Astronomy & Astrophysics' special AMBER section. Three of them describe the unique instrument, while the other eight reveal completely new results about the early and late stages in the life of stars. ESO PR Photo 06b/07 ESO PR Photo 06b/07 The Inner Winds of Eta Carinae The first results presented in this issue cover various fields of stellar and circumstellar physics. Two papers deal with very young solar-like stars, offering new information about the geometry of the surrounding discs and associated outflowing winds. Other articles are devoted to the study of hot active stars of particular interest: Alpha Arae, Kappa Canis Majoris, and CPD -57o2874. They provide new, precise information about their rotating gas envelopes. An important new result concerns the enigmatic object Eta Carinae. Using AMBER with

  19. 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).

  20. Identification of a new cyathane diterpene that induces mitochondrial and autophagy-dependent apoptosis and shows a potent in vivo anti-colorectal cancer activity.

    PubMed

    He, Luwei; Han, Junjie; Li, Baowei; Huang, Li; Ma, Ke; Chen, Quan; Liu, Xinzhong; Bao, Li; Liu, Hongwei

    2016-03-23

    Diterpenes has been reported to possess multiple bioactivities consisting of anti-microbial and anti-inflammatory properties. This study reveals a new cyathane-type diterpene (cyathin Q) from the culture of the fungus Cyathus africanus by bioactivity-guided separation. The structure of cyathin Q was determined based on spectroscopic measurements (NMR and MS). The bioactivity evaluation shows that cyathin Q has a strong anticancer activity against HCT116 cells and Bax-deficient HCT116 in vitro and in vivo. This compound induced hallmarks of apoptotic events in HCT116 cells, including caspase activation, cytochrome c release, poly (ADP-ribose) polymerase (PARP) cleavage, and depolarization of the mitochondrial inner transmembrane potential. This process is accompanied with the increased mitochondrial ROS, down-regulation of Bcl-2 protein, and up-regulation of Bim protein. We also observed the cleavage of autophagy-related protein ATG5 in cyathin Q-induced apoptosis. Taken together, our study identified a new fungal diterpene that exhibited anticancer activity via induction of mitochondria and autophagy-dependent apoptosis in HCT116 cells.

  1. 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.

  2. Activity of the Novel Peptide Arminin against Multiresistant Human Pathogens Shows the Considerable Potential of Phylogenetically Ancient Organisms as Drug Sources▿

    PubMed Central

    Augustin, René; Anton-Erxleben, Friederike; Jungnickel, Stephanie; Hemmrich, Georg; Spudy, Björn; Podschun, Rainer; Bosch, Thomas C. G.

    2009-01-01

    The emergence of multidrug-resistant bacteria highlights the need for new antibacterial agents. Arminin 1a is a novel antimicrobial peptide discovered during investigations of the epithelial defense of the ancient metazoan Hydra. Following proteolytic processing, the 31-amino-acid-long positively charged C-terminal part of arminin 1a exhibits potent and broad-spectrum activity against bacteria, including multiresistant human pathogenic strains, such as methicillin-resistant Staphylococcus aureus (MRSA) strains (minimal bactericidal concentration, 0.4 μM to 0.8 μM). Ultrastructural observations indicate that bacteria are killed by disruption of the bacterial cell wall. Remarkably, the antibacterial activity of arminin 1a is not affected under the physiological salt conditions of human blood. In addition, arminin 1a is a selective antibacterial agent that does not affect human erythrocyte membranes. Arminin 1a shows no sequence homology to any known antimicrobial peptide. Because of its high level of activity against multiresistant bacterial strains pathogenic for humans, the peptide arminin 1a is a promising template for a new class of antibiotics. Our data suggest that ancient metazoan organisms such as Hydra hold promise for the detection of novel antimicrobial molecules and the treatment of infections caused by multiresistant bacteria. PMID:19770277

  3. A Novel Eg5 Inhibitor (LY2523355) Causes Mitotic Arrest and Apoptosis in Cancer Cells and Shows Potent Antitumor Activity in Xenograft Tumor Models.

    PubMed

    Ye, Xiang S; Fan, Li; Van Horn, Robert D; Nakai, Ryuichiro; Ohta, Yoshihisa; Akinaga, Shiro; Murakata, Chikara; Yamashita, Yoshinori; Yin, Tinggui; Credille, Kelly M; Donoho, Gregory P; Merzoug, Farhana F; Li, Heng; Aggarwal, Amit; Blanchard, Kerry; Westin, Eric H

    2015-11-01

    Intervention of cancer cell mitosis by antitubulin drugs is among the most effective cancer chemotherapies. However, antitubulin drugs have dose-limiting side effects due to important functions of microtubules in resting normal cells and are often rendered ineffective by rapid emergence of resistance. Antimitotic agents with different mechanisms of action and improved safety profiles are needed as new treatment options. Mitosis-specific kinesin Eg5 represents an attractive anticancer target for discovering such new antimitotic agents, because Eg5 is essential only in mitotic progression and has no roles in resting, nondividing cells. Here, we show that a novel selective Eg5 inhibitor, LY2523355, has broad target-mediated anticancer activity in vitro and in vivo. LY2523355 arrests cancer cells at mitosis and causes rapid cell death that requires sustained spindle-assembly checkpoint (SAC) activation with a required threshold concentration. In vivo efficacy of LY2523355 is highly dose/schedule-dependent, achieving complete remission in a number of xenograft tumor models, including patient-derived xenograft (PDX) tumor models. We further establish that histone-H3 phosphorylation of tumor and proliferating skin cells is a promising pharmacodynamic biomarker for in vivo anticancer activity of LY2523355. PMID:26304237

  4. 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.

  5. Hedgehog signaling pathway is active in GBM with GLI1 mRNA expression showing a single continuous distribution rather than discrete high/low clusters.

    PubMed

    Chandra, Vikas; Das, Tapojyoti; Gulati, Puneet; 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. Improving Hiroshima Air-Over-Ground Thermal/Epithermal Activation Calculations Using a MUSH Model to Show the Importance of Local Shielding

    SciTech Connect

    Pace, J.V.

    2002-02-14

    Achieving agreement between measured and calculated neutron activation data resulting from Hiroshima and Nagasaki A-bomb detonations has been a major problem since the early 1980's. This has been particularly true for the materials that are activated by thermal and epithermal neutrons. Since thermal and epithermal neutrons are not transported very far from the weapon, the local shielding environment around the measurement location can be very important. A set of calculations incorporating an average density local-environment material (mush) has been made to demonstrate that the local environment plays an important role in the calculation-measurement agreement process. The optimum solution would be to include the local environment in all thermal neutron response calculations.

  7. Process evaluation methods, implementation fidelity results and relationship to physical activity and healthy eating in the Faith, Activity, and Nutrition (FAN) study.

    PubMed

    Saunders, Ruth P; Wilcox, Sara; Baruth, Meghan; Dowda, Marsha

    2014-04-01

    Faith, Activity and Nutrition (FAN), a community-based participatory research project in African American churches, aimed to increase congregant physical activity and healthy eating. The Health-Promoting Church framework, developed collaboratively with faith-based partners, guided the intervention and a comprehensive process evaluation. The Health-Promoting Church components related to healthy eating and physical activity were getting the message out, opportunities, pastor support, and organizational policy. There was no evidence for sequential mediation for any of the healthy eating components. These results illustrate the complexity of systems change within organizational settings and the importance of conducting process evaluation. The FAN intervention resulted in increased implementation for all physical activity and most healthy eating components. Mediation analyses revealed no direct association between implementation and increased physical activity; rather, sequential mediation analysis showed that implementation of physical activity messages was associated with improved self-efficacy at the church level, which was associated with increased physical activity.

  8. Gender, body mass index and rheumatoid arthritis disease activity: results from the QUEST-RA study

    PubMed Central

    Jawaheer, Damini; Olsen, Jørn; Lahiff, Maureen; Forsberg, Sinikka; Lähteenmäki, Jukka; Silveira, Ines Guimaraes da; Rocha, Francisco Airton; Laurindo, Ieda Maria Magalhães; Mota, Licia Maria Henrique da; Drosos, Alexandros A.; Murphy, Eithne; Sheehy, Claire; Quirke, Edel; Cutolo, Maurizio; Rexhepi, Sylejman; Dadoniene, Jolanta; Verstappen, Suzan M.M.; Sokka, Tuulikki

    2010-01-01

    Objective To investigate whether body mass index (BMI), as a proxy for body fat, influences rheumatoid arthritis (RA) disease activity in a gender-specific manner. Methods Consecutive patients with RA were enrolled from 25 countries into the QUEST-RA program between 2005 and 2008. Clinical and demographic data were collected by treating rheumatologists and by patient self-report. Distributions of Disease Activity Scores (DAS28), BMI, age, and disease duration were assessed for each country and for the entire dataset; mean values between genders were compared using Student’s t-tests. An association between BMI and DAS28 was investigated using linear regression, adjusting for age, disease duration and country. Results A total of 5,161 RA patients (4,082 women and 1,079 men) were included in the analyses. Overall, women were younger, had longer disease duration, and higher DAS28 scores than men, but BMI was similar between genders. The mean DAS28 scores increased with increasing BMI from normal to overweight and obese, among women, whereas the opposite trend was observed among men. Regression results showed BMI (continuous or categorical) to be associated with DAS28. Compared to the normal BMI range, being obese was associated with a larger difference in mean DAS28 (0.23, 95% CI: 0.11, 0.34) than being overweight (0.12, 95% CI: 0.03, 0.21); being underweight was not associated with disease activity. These associations were more pronounced among women, and were not explained by any single component of the DAS28. Conclusion BMI appears to be associated with RA disease activity in women, but not in men. PMID:20810033

  9. Missense mutation in immunodeficient patients shows the multifunctional roles of coiled-coil domain 3 (CC3) in STIM1 activation

    PubMed Central

    Maus, Mate; Jairaman, Amit; Stathopulos, Peter B.; Muik, Martin; Fahrner, Marc; Weidinger, Carl; Benson, Melina; Fuchs, Sebastian; Ehl, Stephan; Romanin, Christoph; Ikura, Mitsuhiko; Prakriya, Murali; Feske, Stefan

    2015-01-01

    Store-operated Ca2+ entry (SOCE) is a universal Ca2+ influx pathway that is important for the function of many cell types. SOCE occurs upon depletion of endoplasmic reticulum (ER) Ca2+ stores and relies on a complex molecular interplay between the plasma membrane (PM) Ca2+ channel ORAI1 and the ER Ca2+ sensor stromal interaction molecule (STIM) 1. Patients with null mutations in ORAI1 or STIM1 genes present with severe combined immunodeficiency (SCID)-like disease. Here, we describe the molecular mechanisms by which a loss-of-function STIM1 mutation (R429C) in human patients abolishes SOCE. R429 is located in the third coiled-coil (CC3) domain of the cytoplasmic C terminus of STIM1. Mutation of R429 destabilizes the CC3 structure and alters the conformation of the STIM1 C terminus, thereby releasing a polybasic domain that promotes STIM1 recruitment to ER–PM junctions. However, the mutation also impairs cytoplasmic STIM1 oligomerization and abolishes STIM1–ORAI1 interactions. Thus, despite its constitutive localization at ER–PM junctions, mutant STIM1 fails to activate SOCE. Our results demonstrate multifunctional roles of the CC3 domain in regulating intra- and intermolecular STIM1 interactions that control (i) transition of STIM1 from a quiescent to an active conformational state, (ii) cytoplasmic STIM1 oligomerization, and (iii) STIM1–ORAI1 binding required for ORAI1 activation. PMID:25918394

  10. 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.

  11. Two Proteins with Ornithine Acetyltransferase Activity Show Different Functions in Streptomyces clavuligerus: Oat2 Modulates Clavulanic Acid Biosynthesis in Response to Arginine

    PubMed Central

    de la Fuente, A.; Martín, J. F.; Rodríguez-García, A.; Liras, P.

    2004-01-01

    The oat2 gene, located in the clavulanic acid gene cluster in Streptomyces clavuligerus, is similar to argJ, which encodes N-acetylornithine:glutamic acid acetyltransferase activity. Purified proteins obtained by expression in Escherichia coli of the argJ and oat2 genes of S. clavuligerus posses N-acetyltransferase activity. The kinetics and substrate specificities of both proteins are very similar. Deletion of the oat2 gene did not affect the total N-acetylornithine transferase activity and slightly reduced the formation of clavulanic acid under standard culture conditions. However, the oat2 mutant produced more clavulanic acid than the parental strain in cultures supplemented with high levels (above 1 mM) of arginine. The purified S. clavuligerus ArgR protein bound the arginine box in the oat2 promoter, and the expression of oat2 was higher in mutants with a disruption in argR (arginine-deregulated), confirming that the Arg boxes of oat2 are functional in vivo. Our results suggest that the Oat2 protein or one of its reaction products has a regulatory role that modulates clavulanic acid biosynthesis in response to high arginine concentrations. PMID:15375131

  12. Active behavior of abdominal wall muscles: Experimental results and numerical model formulation.

    PubMed

    Grasa, J; Sierra, M; Lauzeral, N; Muñoz, M J; Miana-Mena, F J; Calvo, B

    2016-08-01

    In the present study a computational finite element technique is proposed to simulate the mechanical response of muscles in the abdominal wall. This technique considers the active behavior of the tissue taking into account both collagen and muscle fiber directions. In an attempt to obtain the computational response as close as possible to real muscles, the parameters needed to adjust the mathematical formulation were determined from in vitro experimental tests. Experiments were conducted on male New Zealand White rabbits (2047±34g) and the active properties of three different muscles: Rectus Abdominis, External Oblique and multi-layered samples formed by three muscles (External Oblique, Internal Oblique, and Transversus Abdominis) were characterized. The parameters obtained for each muscle were incorporated into a finite strain formulation to simulate active behavior of muscles incorporating the anisotropy of the tissue. The results show the potential of the model to predict the anisotropic behavior of the tissue associated to fibers and how this influences on the strain, stress and generated force during an isometric contraction. PMID:27111629

  13. Active behavior of abdominal wall muscles: Experimental results and numerical model formulation.

    PubMed

    Grasa, J; Sierra, M; Lauzeral, N; Muñoz, M J; Miana-Mena, F J; Calvo, B

    2016-08-01

    In the present study a computational finite element technique is proposed to simulate the mechanical response of muscles in the abdominal wall. This technique considers the active behavior of the tissue taking into account both collagen and muscle fiber directions. In an attempt to obtain the computational response as close as possible to real muscles, the parameters needed to adjust the mathematical formulation were determined from in vitro experimental tests. Experiments were conducted on male New Zealand White rabbits (2047±34g) and the active properties of three different muscles: Rectus Abdominis, External Oblique and multi-layered samples formed by three muscles (External Oblique, Internal Oblique, and Transversus Abdominis) were characterized. The parameters obtained for each muscle were incorporated into a finite strain formulation to simulate active behavior of muscles incorporating the anisotropy of the tissue. The results show the potential of the model to predict the anisotropic behavior of the tissue associated to fibers and how this influences on the strain, stress and generated force during an isometric contraction.

  14. 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

  15. 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.

  16. Chronic ethanol consumption by mice results in activated splenic T cells.

    PubMed

    Song, Kejing; Coleman, Ruth A; Zhu, Xiaoyan; Alber, Carol; Ballas, Zuhair K; Waldschmidt, Thomas J; Cook, Robert T

    2002-12-01

    Previous studies have shown that T cells from human alcoholics overexpress activation or memory markers such as human leukocyte antigen-DR, CD45RO, CD57, and CD11b and may have reduced levels of CD62L. In those studies, we demonstrated that the increased CD57(+) T cell population rapidly produces interferon-gamma (IFN-gamma) and tumor necrosis factor alpha, independent of a second signal requirement, consistent with an increased effector T cell population. In contrast to the length of alcohol abuse by human alcoholics, most work with mice has involved 2-week ethanol exposures or less, which result in decreased IFN-gamma responses. In the present work, we have evaluated C57Bl/6 or BALB/c mice, which were administered 20% w/v ethanol in water for 3-13 weeks. In these mice, rapid cytoplasmic IFN-gamma expression by T cells after stimulation through the T cell receptor was significantly increased versus normals. Studies of surface-activation markers showed that T cells from chronically ethanol-fed mice had reduced CD62L expression and an increased percentage of CD44(hi) T cells. The CD44(hi) subset was largely second signal-independent for secreted IFN-gamma and interleukin (IL)-4 production at early times after stimulation. The enriched T cells of chronic ethanol mice secreted more IFN-gamma and IL-4 than controls and equivalent IL-2 at early times after stimulation (6-24 h). The overall results support the concept that in humans and mice, chronic alcohol exposure of sufficient duration results in T cell activation or sensitization in vivo and an increased percentage of the effector/memory subset.

  17. Inactivated E. coli transformed with plasmids that produce dsRNA against infectious salmon anemia virus hemagglutinin show antiviral activity when added to infected ASK cells

    PubMed Central

    García, Katherine; Ramírez-Araya, Sebastián; Díaz, Álvaro; Reyes-Cerpa, Sebastián; Espejo, Romilio T.; Higuera, Gastón; Romero, Jaime

    2015-01-01

    Infectious salmon anemia virus (ISAV) has caused great losses to the Chilean salmon industry, and the success of prevention and treatment strategies is uncertain. The use of RNA interference (RNAi) is a promising approach because during the replication cycle, the ISAV genome must be transcribed to mRNA in the cytoplasm. We explored the capacity of E. coli transformed with plasmids that produce double-stranded RNA (dsRNA) to induce antiviral activity when added to infected ASK cells. We transformed the non-pathogenic Escherichia coli HT115 (DE3) with plasmids that expressed highly conserved regions of the ISAV genes encoding the nucleoprotein (NP), fusion (F), hemagglutinin (HE), and matrix (M) proteins as dsRNA, which is the precursor of the RNAi mechanism. The inactivated transformed bacteria carrying dsRNA were tested for their capacity to silence the target ISAV genes, and the dsRNA that were able to inhibit gene expression were subsequently tested for their ability to attenuate the cytopathic effect (CPE) and reduce the viral load. Of the four target genes tested, inactivated E. coli transformed with plasmids producing dsRNA targeting HE showed antiviral activity when added to infected ASK cells. PMID:25932022

  18. Inactivated E. coli transformed with plasmids that produce dsRNA against infectious salmon anemia virus hemagglutinin show antiviral activity when added to infected ASK cells.

    PubMed

    García, Katherine; Ramírez-Araya, Sebastián; Díaz, Álvaro; Reyes-Cerpa, Sebastián; Espejo, Romilio T; Higuera, Gastón; Romero, Jaime

    2015-01-01

    Infectious salmon anemia virus (ISAV) has caused great losses to the Chilean salmon industry, and the success of prevention and treatment strategies is uncertain. The use of RNA interference (RNAi) is a promising approach because during the replication cycle, the ISAV genome must be transcribed to mRNA in the cytoplasm. We explored the capacity of E. coli transformed with plasmids that produce double-stranded RNA (dsRNA) to induce antiviral activity when added to infected ASK cells. We transformed the non-pathogenic Escherichia coli HT115 (DE3) with plasmids that expressed highly conserved regions of the ISAV genes encoding the nucleoprotein (NP), fusion (F), hemagglutinin (HE), and matrix (M) proteins as dsRNA, which is the precursor of the RNAi mechanism. The inactivated transformed bacteria carrying dsRNA were tested for their capacity to silence the target ISAV genes, and the dsRNA that were able to inhibit gene expression were subsequently tested for their ability to attenuate the cytopathic effect (CPE) and reduce the viral load. Of the four target genes tested, inactivated E. coli transformed with plasmids producing dsRNA targeting HE showed antiviral activity when added to infected ASK cells.

  19. Characterization of the Trypanosoma cruzi ortholog of the SBDS protein reveals an intrinsically disordered extended C-terminal region showing RNA-interacting activity.

    PubMed

    de Oliveira, Juliana Ferreira; Castilho, Beatriz A; Sforça, Mauricio L; Krieger, Marco Aurélio; Zeri, Ana Carolina; Guimarães, Beatriz G; Zanchin, Nilson I T

    2009-04-01

    The human SBDS gene and its yeast ortholog SDO1 encode essential proteins that are involved in ribosome biosynthesis. SDO1 has been implicated in recycling of the ribosomal biogenesis factor Tif6p from pre-66S particles as well as in translation activation of 60S ribosomes. The SBDS protein is highly conserved, containing approximately 250 amino acid residues in animals, fungi and Archaea, while SBDS orthologs of plants and a group of protists contain an extended C-terminal region. In this work, we describe the characterization of the Trypanosoma cruzi SBDS ortholog (TcSBDS). TcSBDS co-fractionates with polysomes in sucrose density gradients, which is consistent with a role in ribosome biosynthesis. We show that TcSBDS contains a C-terminal extension of 200 amino acids that displays the features of intrinsically disordered proteins as determined by proteolytic, circular dichroism and NMR analyses. Interestingly, the C-terminal extension is responsible for TcSBDS-RNA interaction activity in electrophoretic mobility shift assays. This finding suggests that Trypanosomatidae and possibly also other organisms containing SBDS with extended C-terminal regions have evolved an additional function for SBDS in ribosome biogenesis.

  20. A highly sensitive telomerase activity assay that eliminates false-negative results caused by PCR inhibitors.

    PubMed

    Yaku, Hidenobu; Murashima, Takashi; Miyoshi, Daisuke; Sugimoto, Naoki

    2013-01-01

    An assay for telomerase activity based on asymmetric polymerase chain reaction (A-PCR) on magnetic beads (MBs) and subsequent application of cycling probe technology (CPT) is described. In this assay, the telomerase reaction products are immobilized on MBs, which are then washed to remove PCR inhibitors that are commonly found in clinical samples. The guanine-rich sequences (5'-(TTAGGG)n-3') of the telomerase reaction products are then preferentially amplified by A-PCR, and the amplified products are subsequently detected via CPT, where a probe RNA with a fluorophore at the 5' end and a quencher at the 3' end is hydrolyzed by RNase H in the presence of the target DNA. The catalyst-mediated cleavage of the probe RNA enhances fluorescence from the 5' end of the probe. The assay allowed us to successfully detect HeLa cells selectively over normal human dermal fibroblast (NHDF) cells. Importantly, this selectivity produced identical results with regard to detection of HeLa cells in the absence and presence of excess NHDF cells; therefore, this assay can be used for practical clinical applications. The lower limit of detection for HeLa cells was 50 cells, which is lower than that achieved with a conventional telomeric repeat amplification protocol assay. Our assay also eliminated false-negative results caused by PCR inhibitors. Furthermore, we show that this assay is appropriate for screening among G-quadruplex ligands to find those that inhibit telomerase activity.

  1. A highly sensitive telomerase activity assay that eliminates false-negative results caused by PCR inhibitors.

    PubMed

    Yaku, Hidenobu; Murashima, Takashi; Miyoshi, Daisuke; Sugimoto, Naoki

    2013-01-01

    An assay for telomerase activity based on asymmetric polymerase chain reaction (A-PCR) on magnetic beads (MBs) and subsequent application of cycling probe technology (CPT) is described. In this assay, the telomerase reaction products are immobilized on MBs, which are then washed to remove PCR inhibitors that are commonly found in clinical samples. The guanine-rich sequences (5'-(TTAGGG)n-3') of the telomerase reaction products are then preferentially amplified by A-PCR, and the amplified products are subsequently detected via CPT, where a probe RNA with a fluorophore at the 5' end and a quencher at the 3' end is hydrolyzed by RNase H in the presence of the target DNA. The catalyst-mediated cleavage of the probe RNA enhances fluorescence from the 5' end of the probe. The assay allowed us to successfully detect HeLa cells selectively over normal human dermal fibroblast (NHDF) cells. Importantly, this selectivity produced identical results with regard to detection of HeLa cells in the absence and presence of excess NHDF cells; therefore, this assay can be used for practical clinical applications. The lower limit of detection for HeLa cells was 50 cells, which is lower than that achieved with a conventional telomeric repeat amplification protocol assay. Our assay also eliminated false-negative results caused by PCR inhibitors. Furthermore, we show that this assay is appropriate for screening among G-quadruplex ligands to find those that inhibit telomerase activity. PMID:24071983

  2. Regulatory Implications of Non-Trivial Splicing: Isoform 3 of Rab1A Shows Enhanced Basal Activity and Is Not Controlled by Accessory Proteins.

    PubMed

    Schöppner, Patricia; Csaba, Gergely; Braun, Tatjana; Daake, Marina; Richter, Bettina; Lange, Oliver F; Zacharias, Martin; Zimmer, Ralf; Haslbeck, Martin

    2016-04-24

    Alternative splicing often affects structured and highly conserved regions of proteins, generating so called non-trivial splicing variants of unknown structure and cellular function. The human small G-protein Rab1A is involved in the regulation of the vesicle transfer from the ER to Golgi. A conserved non-trivial splice variant lacks nearly 40% of the sequence of the native Rab1A, including most of the regulatory interaction sites. We show that this variant of Rab1A represents a stable and folded protein, which is still able to bind nucleotides and co-localizes with membranes. Nevertheless, it should be mentioned that compared to other wild-typeRabGTPases, the measured nucleotide binding affinities are dramatically reduced in the variant studied. Furthermore, the Rab1A variant forms hetero-dimers with wild-type Rab1A and its presence in the cell enhances the efficiency of alkaline phosphatase secretion. However, this variant shows no specificity for GXP nucleotides, a constantly enhanced GTP hydrolysis activity and is no longer controlled by GEF or GAP proteins, indicating a new regulatory mechanism for the Rab1A cycle via alternative non-trivial splicing. PMID:26953259

  3. Next-generation sequencing with a myeloid gene panel in core-binding factor AML showed KIT activation loop and TET2 mutations predictive of outcome

    PubMed Central

    Cher, C Y; Leung, G M K; Au, C H; Chan, T L; Ma, E S K; Sim, J P Y; Gill, H; Lie, A K W; Liang, R; Wong, K F; Siu, L L P; Tsui, C S P; So, C C; Wong, H W W; Yip, S F; Lee, H K K; Liu, H S Y; Lau, J S M; Luk, T H; Lau, C K; Lin, S Y; Kwong, Y L; Leung, A Y H

    2016-01-01

    Clinical outcome and mutations of 96 core-binding factor acute myeloid leukemia (AML) patients 18–60 years old were examined. Complete remission (CR) after induction was 94.6%. There was no significant difference in CR, leukemia-free-survival (LFS) and overall survival (OS) between t(8;21) (N=67) and inv(16) patients (N=29). Univariate analysis showed hematopoietic stem cell transplantation at CR1 as the only clinical parameter associated with superior LFS. Next-generation sequencing based on a myeloid gene panel was performed in 72 patients. Mutations in genes involved in cell signaling were associated with inferior LFS and OS, whereas those in genes involved in DNA methylation were associated with inferior LFS. KIT activation loop (AL) mutations occurred in 25 patients, and were associated with inferior LFS (P=0.003) and OS (P=0.001). TET2 mutations occurred in 8 patients, and were associated with significantly shorter LFS (P=0.015) but not OS. Patients negative for KIT-AL and TET2 mutations (N=41) had significantly better LFS (P<0.001) and OS (P=0.012) than those positive for both or either mutation. Multivariate analysis showed that KIT-AL and TET2 mutations were associated with inferior LFS, whereas age ⩾40 years and marrow blast ⩾70% were associated with inferior OS. These observations provide new insights that may guide better treatment for this AML subtype. PMID:27391574

  4. Tetraploidization of diploid Dioscorea results in activation of the antioxidant defense system and increased heat tolerance.

    PubMed

    Zhang, Xiao-Yi; Hu, Chun-Gen; Yao, Jia-Ling

    2010-01-15

    Polyploidy is reported to show increased tolerance to environmental stress. In this work, tetraploid plants of Dioscorea zingiberensis were obtained by colchicine treatment of shoots propagated in vitro. The highest tetraploid induction rate was achieved by treatment with 0.15% colchicine for 24h. Diploid and tetraploid plants were exposed to normal (28 degrees C) and high temperature (42 degrees C) for 5d during which physiological indices were measured. Compared with diploid plants, relative electrolyte leakage and contents of malondialdehyde, superoxide anions and hydrogen peroxide were lower in tetraploids, while activities of antioxidant enzymes, such as superoxide dismutase, peroxidase, catalase, ascorbate peroxidase and glutathione reductase, were stimulated and antioxidants (ascorbic acid and glutathione) were maintained at high concentrations. These results indicate that tetraploid plants possess a stronger antioxidant defense system and increased heat tolerance. PMID:19692145

  5. New Activity of Chiron: Results from 5 Years of Photometric Monitoring

    NASA Astrophysics Data System (ADS)

    Duffard, René; Lazzaro, Daniela; Pinto, Sandro; Carvano, Jorge; Angeli, Claudia; Alvarez-Candal, Alvaro; Fernández, Silvia

    2002-11-01

    The results of photometric observations of Centaur object Chiron carried out at the Observatório do Pico dos Dias (OPD, Brazil), the Estación Astrofı´sica de Bosque Alegre (EABA, Argentina), and Complejo Astronómico El Leoncito (CASLEO, Argentina) from 1997 to 2001 are presented here. The analysis of the photometric data shows that the brightness of Chiron reached a minimum value in 1999 and began increasing again in 2000. The absolute magnitude, HV, varied from 7.26 in June 1999 to 5.78 in April 2001. The data tend to indicate that Chiron is starting a new outburst of activity which is compatible with a sporadic cometary behavior not related to heliocentric distance.

  6. Loss of succinate dehydrogenase activity results in dependency on pyruvate carboxylation for cellular anabolism.

    PubMed

    Lussey-Lepoutre, Charlotte; Hollinshead, Kate E R; Ludwig, Christian; Menara, Mélanie; Morin, Aurélie; Castro-Vega, Luis-Jaime; Parker, Seth J; Janin, Maxime; Martinelli, Cosimo; Ottolenghi, Chris; Metallo, Christian; Gimenez-Roqueplo, Anne-Paule; Favier, Judith; Tennant, Daniel A

    2015-11-02

    The tricarboxylic acid (TCA) cycle is a central metabolic pathway responsible for supplying reducing potential for oxidative phosphorylation and anabolic substrates for cell growth, repair and proliferation. As such it thought to be essential for cell proliferation and tissue homeostasis. However, since the initial report of an inactivating mutation in the TCA cycle enzyme complex, succinate dehydrogenase (SDH) in paraganglioma (PGL), it has become clear that some cells and tissues are not only able to survive with a truncated TCA cycle, but that they are also able of supporting proliferative phenotype observed in tumours. Here, we show that loss of SDH activity leads to changes in the metabolism of non-essential amino acids. In particular, we demonstrate that pyruvate carboxylase is essential to re-supply the depleted pool of aspartate in SDH-deficient cells. Our results demonstrate that the loss of SDH reduces the metabolic plasticity of cells, suggesting vulnerabilities that can be targeted therapeutically.

  7. Convolvulus galaticus, Crocus antalyensis, and Lilium candidum extracts show their antitumor activity through induction of p53-mediated apoptosis on human breast cancer cell line MCF-7 cells.

    PubMed

    Tokgun, Onur; Akca, Hakan; Mammadov, Ramazan; Aykurt, Candan; Deniz, Gökhan

    2012-11-01

    Conventional and newly emerging treatment procedures such as chemotherapy, catalytic therapy, photodynamic therapy, and radiotherapy have not succeeded in reversing the outcome of cancer diseases to any drastic extent, which has led researchers to investigate alternative treatment options. The extensive repertoire of traditional medicinal knowledge systems from various parts of the world are being re-investigated for their healing properties. It has been reported that several members of the Convolvulaceae, Iridaceae, and Liliaceae families have antitumor activity against some tumor cell lines. Here we first report that Convolvulus galaticus, Crocus antalyensis, and Lilium candidum species have cytotoxic activity on human breast cancer cell line MCF-7 cells. Plant samples were collected and identified, and their cytotoxic effects on the MCF-7 cell line were examined at different concentrations of methanol extracts. We found that all three plants have cytotoxic effects on MCF-7 cells but that C. galaticus has the strongest cytotoxic effect even in the lowest extract concentration tested (0.32 μg/mL). Our results indicate that these plant extracts have cytotoxic effects on human breast carcinoma cell line MCF-7 cells and that this cytotoxic effect comes from p53-mediated stimulation of apoptosis.

  8. Active-Site Engineering of Benzaldehyde Lyase Shows That a Point Mutation Can Confer Both New Reactivity and Susceptibility to Mechanism-Based Inhibition

    SciTech Connect

    Brandt, Gabriel S.; Kneen, Malea M.; Petsko, Gregory A.; Ringe, Dagmar; McLeish, Michael J.

    2010-02-11

    Benzaldehyde lyase (BAL) from Pseudomonas putida is a thiamin diphosphate (ThDP)-dependent enzyme that catalyzes the breakdown of (R)-benzoin. Here we report that a point mutant, BAL A28S, not only catalyzes the decarboxylation of benzoylformate but, like benzoylformate decarboxylase (BFDC), is also inactivated by the benzoylformate analogues methyl benzoylphosphonate (MBP) and benzoylphosphonate (BP). The latter has no effect on wild-type BAL, and the inactivation of the A28S variant is shown to result from phosphorylation of the newly introduced serine residue. This lends support to the proposal that an appropriately placed nucleophile facilitates the expulsion of carbon dioxide from the active site in many ThDP-dependent decarboxylases.

  9. A membrane-associated movement protein of Pelargonium flower break virus shows RNA-binding activity and contains a biologically relevant leucine zipper-like motif.

    PubMed

    Martínez-Turiño, Sandra; Hernández, Carmen

    2011-05-10

    Two small viral proteins (DGBp1 and DGBp2) have been proposed to act in a concerted manner to aid intra- and intercellular trafficking of carmoviruses though the distribution of functions and mode of action of each protein partner are not yet clear. Here we have confirmed the requirement of the DGBps of Pelargonium flower break virus (PFBV), p7 and p12, for pathogen movement. Studies focused on p12 have shown that it associates to cellular membranes, which is in accordance to its hydrophobic profile and to that reported for several homologs. However, peculiarities that distinguish p12 from other DGBps2 have been found. Firstly, it contains a leucine zipper-like motif which is essential for virus infectivity in plants. Secondly, it has an unusually long and basic N-terminal region that confers RNA binding activity. The results suggest that PFBV p12 may differ mechanistically from related proteins and possible roles of PFBV DGBps are discussed.

  10. Pseudoephedrine/ephedrine shows potent anti-inflammatory activity against TNF-α-mediated acute liver failure induced by lipopolysaccharide/D-galactosamine.

    PubMed

    Wu, Zhongping; Kong, Xiangliang; Zhang, Tong; Ye, Jin; Fang, Zhaoqin; Yang, Xuejun

    2014-02-01

    The anti-inflammatory effects of pseudoephedrine/ephedrine were investigated using the experimental model of lipopolysaccharide (LPS)-induced acute liver failure in D-galactosamine (D-GalN)-sensitised male rats in order to elucidate effects other than sympathomimetic effects. Rats were intraperitoneally injected with D-GalN (400 mg/kg) and LPS (40 μg/kg) to induce acute liver failure. The treatment groups were then intraperitoneally administered pseudoephedrine/ephedrine at 0 h and 4 h after induction and the activation induced by treatment with pseudoephedrine and/or LPS on the primary Kupffer cells (KCs) was monitored. Compared with controls induced by GalN/LPS alone, pseudoephedrine dramatically reduced the infiltration of inflammatory cells and bile ductular hyperplasia and hepatic necrosis observed in liver sections. It inhibited both hepatocellular apoptosis and the expression of monocyte chemotactic protein-1. It lowered the production of tumour necrosis factor-α (TNF-α) in the beginning of acute liver failure induced by D-GalN/LPS. Correspondingly, levels of alanine aminotransferase (ALT), total bilirubin (TBIL) and malondialdehyde were attenuated. Ephedrine demonstrated all these identical protective effects as well. In addition, pseudoephedrine significantly suppressed the production of p-IκB-α, reducing the degradation of sequestered nuclear factor kappa B (NF-κB) in the cytoplasm, and inhibited the translocation of NF-κB/p65 to the nucleus, the transcription of TNF-α mRNA and the production of TNF-α in primary KCs. These results suggest that pseudoephedrine and ephedrine have a potent anti-inflammatory activity against D-GalN/LPS-induced acute liver failure in rats, and this comprehensive anti-inflammatory effect may result from the inhibition of TNF-α production. PMID:24365491

  11. Pseudoephedrine/ephedrine shows potent anti-inflammatory activity against TNF-α-mediated acute liver failure induced by lipopolysaccharide/D-galactosamine.

    PubMed

    Wu, Zhongping; Kong, Xiangliang; Zhang, Tong; Ye, Jin; Fang, Zhaoqin; Yang, Xuejun

    2014-02-01

    The anti-inflammatory effects of pseudoephedrine/ephedrine were investigated using the experimental model of lipopolysaccharide (LPS)-induced acute liver failure in D-galactosamine (D-GalN)-sensitised male rats in order to elucidate effects other than sympathomimetic effects. Rats were intraperitoneally injected with D-GalN (400 mg/kg) and LPS (40 μg/kg) to induce acute liver failure. The treatment groups were then intraperitoneally administered pseudoephedrine/ephedrine at 0 h and 4 h after induction and the activation induced by treatment with pseudoephedrine and/or LPS on the primary Kupffer cells (KCs) was monitored. Compared with controls induced by GalN/LPS alone, pseudoephedrine dramatically reduced the infiltration of inflammatory cells and bile ductular hyperplasia and hepatic necrosis observed in liver sections. It inhibited both hepatocellular apoptosis and the expression of monocyte chemotactic protein-1. It lowered the production of tumour necrosis factor-α (TNF-α) in the beginning of acute liver failure induced by D-GalN/LPS. Correspondingly, levels of alanine aminotransferase (ALT), total bilirubin (TBIL) and malondialdehyde were attenuated. Ephedrine demonstrated all these identical protective effects as well. In addition, pseudoephedrine significantly suppressed the production of p-IκB-α, reducing the degradation of sequestered nuclear factor kappa B (NF-κB) in the cytoplasm, and inhibited the translocation of NF-κB/p65 to the nucleus, the transcription of TNF-α mRNA and the production of TNF-α in primary KCs. These results suggest that pseudoephedrine and ephedrine have a potent anti-inflammatory activity against D-GalN/LPS-induced acute liver failure in rats, and this comprehensive anti-inflammatory effect may result from the inhibition of TNF-α production.

  12. 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

  13. 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

  14. 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. PMID:25972878

  15. 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.

  16. Sonic hedgehog shedding results in functional activation of the solubilized protein.

    PubMed

    Ohlig, Stefanie; Farshi, Pershang; Pickhinke, Ute; van den Boom, Johannes; Höing, Susanne; Jakuschev, Stanislav; Hoffmann, Daniel; Dreier, Rita; Schöler, Hans R; Dierker, Tabea; Bordych, Christian; Grobe, Kay

    2011-06-14

    All Hedgehog (Hh) proteins are released from producing cells despite being synthesized as N- and C-terminally lipidated, membrane-tethered molecules. Thus, a cellular mechanism is needed for Hh solubilization. We previously suggested that a disintegrin and metalloprotease (ADAM)-mediated shedding of Sonic hedgehog (ShhNp) from its lipidated N and C termini results in protein solubilization. This finding, however, seemed at odds with the established role of N-terminal palmitoylation for ShhNp signaling activity. We now resolve this paradox by showing that N-palmitoylation of ShhNp N-terminal peptides is required for their proteolytic removal during solubilization. These peptides otherwise block ShhNp zinc coordination sites required for ShhNp binding to its receptor Patched (Ptc), explaining the essential yet indirect role of N-palmitoylation for ShhNp function. We suggest a functional model in which membrane-tethered multimeric ShhNp is at least partially autoinhibited in trans but is processed into fully active, soluble multimers upon palmitoylation-dependent cleavage of inhibitory N-terminal peptides. PMID:21664575

  17. Employment of a promoter-swapping technique shows that PhoU modulates the activity of the PstSCAB2 ABC transporter in Escherichia coli.

    PubMed

    Rice, Christopher D; Pollard, Jacob E; Lewis, Zachery T; McCleary, William R

    2009-02-01

    Expression of the Pho regulon in Escherichia coli is induced in response to low levels of environmental phosphate (P(i)). Under these conditions, the high-affinity PstSCAB(2) protein (i.e., with two PstB proteins) is the primary P(i) transporter. Expression from the pstSCAB-phoU operon is regulated by the PhoB/PhoR two-component regulatory system. PhoU is a negative regulator of the Pho regulon; however, the mechanism by which PhoU accomplishes this is currently unknown. Genetic studies of phoU have proven to be difficult because deletion of the phoU gene leads to a severe growth defect and creates strong selection for compensatory mutations resulting in confounding data. To overcome the instability of phoU deletions, we employed a promoter-swapping technique that places expression of the phoBR two-component system under control of the P(tac) promoter and the lacO(ID) regulatory module. This technique may be generally applicable for controlling expression of other chromosomal genes in E. coli. Here we utilized P(phoB)::P(tac) and P(pstS)::P(tac) strains to characterize phenotypes resulting from various DeltaphoU mutations. Our results indicate that PhoU controls the activity of the PstSCAB(2) transporter, as well as its abundance within the cell. In addition, we used the P(phoB)::P(tac) DeltaphoU strain as a platform to begin characterizing new phoU mutations in plasmids.

  18. Physical activity in solid organ transplant recipients: organizational aspects and preliminary results of the Italian project.

    PubMed

    Roi, G S; Stefoni, S; Mosconi, G; Brugin, E; Burra, P; Ermolao, A; Granito, M; Macini, P; Mastrosimone, S; Nacchia, F; Pegoraro, C; Rigotti, P; Sella, G; Sgarzi, S; Tamè, M R; Totti, V; Trerotola, M; Tripi, F; Nanni Costa, A

    2014-09-01

    Most of the difficulties when trying to realize the proposal to prescribe physical activity for transplantation patients come from patient attitudes and cultural beliefs that ignore the benefits of exercise, but there also are organizational aspects arising from the difficulties that these patients face in accessing supervised exercise facilities. To address these difficulties, the Italian study project "Transplant … and Now Sport" was developed based on a model of cooperation among transplantation specialists, sports physicians, and exercise specialists organized as a team combining their specific skills to effectively actuate the physical exercise programs. This preliminary report is based on 26 patients (16 male, 10 female; 47.8±10.0 years old; 21 kidney and 5 liver transplantations; time from transplantation 2.3±1.4 years) who performed prescribed and supervised exercises consisting of 3 sessions per week of aerobic and strengthening exercises for 1 year. Preliminary results show a significant decrease in body mass index (t=1.966; P<.05) and a significant increase in peak aerobic power (t=4.535; P<.01) and maximum workload (t=4.665; P<.01) on the incremental cycling test. Also maximum strength of knee extensors (t=2.933; P<.05) and elbow flexors (t=2.450; P<.05) and countermovement jump performance (t=2.303; P<.05) significantly increased. Creatinine and proteinuria tended to decrease, but the differences were not significant. In health-related quality of life assessed by the SF-36 questionnaire, the Bodily Pain, General Health, Vitality, Social Functioning, and Role Emotional scale scores showed a significant improvement (P<.05). Preliminary results of the study protocol "Transplant…and Now Sport" show the positive effects of the model based on cooperation among transplantation centers, sports medicine centers, and gyms in the administration of a supervised exercise prescription. These data should be considered a contribution to developing and promoting

  19. Antimicrobial activity of human α-defensin 5 and its linear analogs: N-terminal fatty acylation results in enhanced antimicrobial activity of the linear analogs.

    PubMed

    Mathew, Basil; Nagaraj, Ramakrishnan

    2015-09-01

    Human α-defensin 5 (HD5) exhibits broad spectrum antimicrobial activity and plays an important role in mucosal immunity of the small intestine. Although there have been several studies, the structural requirements for activity and mechanism of bacterial killing is yet to be established unequivocally. In this study, we have investigated the antimicrobial activity of HD5 and linear analogs. Cysteine deletions attenuated the antibacterial activity considerably. Candidacidal activity was affected to a lesser extent. Fatty acid conjugated linear analogs showed antimicrobial activity comparable activity to HD5. Effective surface charge neutralization of bacteria was observed for HD5 as compared to the non-fatty acylated linear analogs. Our results show that HD5 and non-fatty acylated linear analogs enter the bacterial cytoplasm without causing damage to the bacterial inner membrane. Although fatty acylated peptides exhibited antimicrobial activity comparable to HD5, their mechanism of action involved permeabilization of the Escherichia coli inner membrane. HD5 and analogs had the ability to bind plasmid DNA. HD5 had greater binding affinity to plasmid DNA as compared to the analogs. The three dimensional structure of HD5 favors greater interaction with the bacterial cell surface and also with DNA. Antibacterial activity of HD5 involves entry into bacterial cytoplasm and binding to DNA which would result in shut down of the bacterial metabolism leading to cell death. We show how a moderately active linear peptide derived from the α-defensin HD5 can be engineered to enhance antimicrobial activity almost comparable to the native peptide. PMID:26206286

  20. Mouse gastric tumor models with prostaglandin E2 pathway activation show similar gene expression profiles to intestinal-type human gastric cancer

    PubMed Central

    2009-01-01

    Background Gastric cancers are generally classified into better differentiated intestinal-type tumor and poorly differentiated diffuse-type one according to Lauren's histological categorization. Although induction of prostaglandin E2 pathway promotes gastric tumors in mice in cooperation with deregulated Wnt or BMP signalings, it has remained unresolved whether the gastric tumor mouse models recapitulate either of human gastric cancer type. This study assessed the similarity in expression profiling between gastric tumors of transgenic mice and various tissues of human cancers to find best-fit human tumors for the transgenic mice models. Results Global expression profiling initially found gastric tumors from COX-2/mPGES-1 (C2mE)-related transgenic mice (K19-C2mE, K19-Wnt1/C2mE, and K19-Nog/C2mE) resembled gastric cancers among the several tissues of human cancers including colon, breast, lung and gastric tumors. Next, classification of the C2mE-related transgenic mice by a gene signature to distinguish human intestinal- and diffuse-type tumors showed C2mE-related transgenic mice were more similar to intestinal-type compared with diffuse one. We finally revealed that induction of Wnt pathway cooperating with the prostaglandin E2 pathway in mice (K19-Wnt1/C2mE mice) further reproduce features of human gastric intestinal-type tumors. Conclusion We demonstrated that C2mE-related transgenic mice show significant similarity to intestinal-type gastric cancer when analyzed by global expression profiling. These results suggest that the C2mE-related transgenic mice, especially K19-Wnt1/C2mE mice, serve as a best-fit model to study molecular mechanism underlying the tumorigenesis of human gastric intestinal-type cancers. PMID:20015407

  1. Low dose cadmium poisoning results in sustained ERK phosphorylation and caspase activation

    SciTech Connect

    Martin, Patrick . E-mail: pmartin@unice.fr; Poggi, Marie Christine . E-mail: poggi@unice.fr; Chambard, Jean Claude . E-mail: chambard@unice.fr; Boulukos, Kim E. . E-mail: boulukos@unice.fr; Pognonec, Philippe . E-mail: pognonec@unice.fr

    2006-11-24

    Cadmium poisoning has been known to result in a wide variety of cellular responses, including oxidative stress and kinase activation. It has been reported that ERK is activated following acute cadmium exposure, and this response is commonly seen as a classical ERK survival mechanism. Here, we analyzed different cell types for their responses to low concentrations of cadmium poisoning. We found that there is an association between cell susceptibility to cadmium toxicity and ERK activation. This activation is atypical, since it consists of a sustained ERK phosphorylation, that lasts up to 6 days post stimulation. This activation is associated with the appearance of cleaved caspases 8 and 3, processed PARP, and irreversible damage. Pharmacological inhibition of ERK phosphorylation results in the ability of cells to resist cadmium poisoning. Our data indicate that low cadmium concentrations result in an unconventional ERK sustained phosphorylation, which in turn leads to death signaling.

  2. Oscillatory phase modulates the timing of neuronal activations and resulting behavior.

    PubMed

    Coon, W G; Gunduz, A; Brunner, P; Ritaccio, A L; Pesaran, B; Schalk, G

    2016-06-01

    Human behavioral response timing is highly variable from trial to trial. While it is generally understood that behavioral variability must be due to trial-by-trial variations in brain function, it is still largely unknown which physiological mechanisms govern the timing of neural activity as it travels through networks of neuronal populations, and how variations in the timing of neural activity relate to variations in the timing of behavior. In our study, we submitted recordings from the cortical surface to novel analytic techniques to chart the trajectory of neuronal population activity across the human cortex in single trials, and found joint modulation of the timing of this activity and of consequent behavior by neuronal oscillations in the alpha band (8-12Hz). Specifically, we established that the onset of population activity tends to occur during the trough of oscillatory activity, and that deviations from this preferred relationship are related to changes in the timing of population activity and the speed of the resulting behavioral response. These results indicate that neuronal activity incurs variable delays as it propagates across neuronal populations, and that the duration of each delay is a function of the instantaneous phase of oscillatory activity. We conclude that the results presented in this paper are supportive of a general model for variability in the effective speed of information transmission in the human brain and for variability in the timing of human behavior. PMID:26975551

  3. Activities Contributing to Total Energy Expenditure in the United States: Results from the NHAPS Study

    PubMed Central

    Dong, Linda; Block, Gladys; Mandel, Shelly

    2004-01-01

    Background Physical activity is increasingly recognized as an important factor influencing health and disease status. Total energy expenditure, both low-intensity and high-intensity, contributes to maintenance of healthy body weight. This paper presents the results of a quantitative approach to determining the activities that contribute to total energy expenditure in the United States. Methods Data from the National Human Activity Pattern Survey (NHAPS) were used. In 1992–1994 the NHAPS sampled 4,185 females and 3,330 males, aged 18 years and over, weighted to be representative of the 48 contiguous United States. A detailed report of each activity performed in the previous 24 hours was obtained. A score was created for each activity, by multiplying duration and intensity for each individual and summing across individuals. This score was then used to rank each activity according to its contribution to total population energy expenditure, for the total sample and separately for each gender, race, age, region, and season. Results This analysis reveals our society to be primarily sedentary; leisure time physical activity contributed only approximately 5% of the population's total energy expenditure. Not counting sleeping, the largest contributor to energy expenditure was "Driving a car", followed by "Office work" and "Watching TV". Household activities accounted for 20.1% and 33.3% of energy expenditure for males and females respectively. Conclusion The information presented in this paper may be useful in identifying common activities that could be appropriate targets for behavioral interventions to increase physical activity. PMID:15169563

  4. Active Learning in Large Classes: Can Small Interventions Produce Greater Results than Are Statistically Predictable?

    ERIC Educational Resources Information Center

    Adrian, Lynne M.

    2010-01-01

    Six online postings and six one-minute papers were added to an introductory first-year class, forming 5 percent of the final grade, but represented significant intervention in class functioning and amount of active learning. Active learning produced results in student performance beyond the percentage of the final grade it constituted. (Contains 1…

  5. Does Pedometer Goal Setting Improve Physical Activity among Native Elders? Results from a Randomized Pilot Study

    ERIC Educational Resources Information Center

    Sawchuk, Craig N.; Russo, Joan E.; Charles, Steve; Goldberg, Jack; Forquera, Ralph; Roy-Byrne, Peter; Buchwald, Dedra

    2011-01-01

    We examined if step-count goal setting resulted in increases in physical activity and walking compared to only monitoring step counts with pedometers among American Indian/Alaska Native elders. Outcomes included step counts, self-reported physical activity and well-being, and performance on the 6-minute walk test. Although no significant…

  6. Soil hydrological and soil property changes resulting from termite activity on agricultural fields in Burkina Faso

    NASA Astrophysics Data System (ADS)

    Mettrop, I.; Cammeraat, L. H.; Verbeeten, E.

    2009-04-01

    Termites are important ecosystem-engineers in subtropical and tropical regions. The effect of termite activity affecting soil infiltration is well documented in the Sahelian region. Most studies find increased infiltration rates on surfaces that are affected by termite activity in comparison to crusted areas showing non-termite presence. Crusted agricultural fields in the Sanmatenga region in Burkina Faso with clear termite activity were compared to control fields without visual ground dwelling termite activity. Fine scale rainfall simulations were carried out on crusted termite affected and control sites. Furthermore soil moisture change, bulk density, soil organic matter as well as general soil characteristics were studied. The top soils in the study area were strongly crusted (structural crust) after the summer rainfall and harvest of millet. They have a loamy sand texture underlain by a shallow sandy loam Bt horizon. The initial soil moisture conditions were significantly higher on the termite plots when compared to control sites. It was found that the amount of runoff produced on the termite plots was significantly higher, and also the volumetric soil moisture content after the experiments was significantly lower if compared to the control plots. Bulk density showed no difference whereas soil organic matter was significantly higher under termite affected areas, in comparison to the control plots. Lab tests showed no significant difference in hydrophobic behavior of the topsoil and crust material. Micro and macro-structural properties of the topsoil did not differ significantly between the termite sites and the control sites. The texture of the top 5 cm of the soil was also found to be not significantly different. The infiltration results are contradictory to the general literature, which reports increased infiltration rates after prolonged termite activity although mostly under different initial conditions. The number of nest entrances was clearly higher in

  7. Agaricus bisporus and Agaricus brasiliensis (1→6)-β-D-glucans show immunostimulatory activity on human THP-1 derived macrophages.

    PubMed

    Smiderle, Fhernanda R; Alquini, Giovana; Tadra-Sfeir, Michelle Z; Iacomini, Marcello; Wichers, Harry J; Van Griensven, Leo J L D

    2013-04-15

    The (1→6)-β-D-glucans from Agaricus bisporus and Agaricus brasiliensis were purified to evaluate their effects on the innate immune system. THP-1 macrophages were used to investigate the induction of the expression of TNF-α, IL1β, and COX-2 by RT-PCR. The purification of the polysaccharides gave rise to fractions containing 96-98% of glucose. The samples were analyzed by GC-MS, HPSEC and (13)C NMR, which confirmed the presence of homogeneous (1→6)-β-D-glucans. The β-glucans were incubated with THP-1 derived macrophages, for 3 h and 6 h to evaluate their effects on the expression of pro-inflammatory genes. Both β-glucans stimulated the expression of such genes as much as the pro-inflammatory control (LPS). When the cells were incubated with LPS+β-glucan, a significant inhibition of the expression of IL-1β and COX-2 was observed for both treatments after 3 h of incubation. By the results, we conclude that the (1→6)-β-D-glucans present an immunostimulatory activity when administered to THP-1 derived macrophages.

  8. Disruption of PPARγ signaling results in mouse prostatic intraepithelial neoplasia involving active autophagy

    PubMed Central

    Jiang, Ming; Fernandez, Suzanne; Jerome, W. Gray; He, Yue; Yu, Xiuping; Cai, Hui; Boone, Braden; Yi, Yajun; Magnuson, Mark A.; Roy-Burman, Pradip; Matusik, Robert J.; Shappell, Scott B.; Hayward, Simon W.

    2009-01-01

    Peroxisome proliferator-activated receptor-gamma (PPARγ) regulates the interface between cellular lipid metabolism, redox status and organelle differentiation. Conditional prostatic epithelial knockout of PPARγ in mice resulted in focal hyperplasia which developed into mouse prostatic intraepithelial neoplasia (mPIN). The grade of PIN became more severe with time. Electron microscopy (EM) showed accumulated secondary lysosomes containing cellular organelles and debris suggestive of autophagy. Consistent with this analysis the autophagy marker LC3 was found to be upregulated in areas of PIN in PPARγ KO tissues. We selectively knocked down PPARγ2 isoform in wild-type mouse prostatic epithelial cells and examined the consequences of this in a tissue recombination model. Histopathologically grafted tissues resembled the conditional PPARγ KO mouse prostates. EM studies of PPARγ- and PPARγ2-deficient epithelial cells in vitro were suggestive of autophagy, consistent with the prostatic tissue analysis. This was confirmed by examining expression of beclin-1 and LC3. Gene expression profiling in PPARγ-/γ2-deficient cells indicated a major dysregulation of cell cycle control and metabolic signaling networks related to peroxisomal and lysosomal maturation, lipid oxidation and degradation. The putative autophagic phenotypes of PPARγ-deficient cells could be rescued by re-expression of either γ1 or γ2 isoform. We conclude that disruption of PPARγ signaling results in autophagy and oxidative stress during mPIN pathogenesis. PMID:19834493

  9. Upper Pleistocene - Holocene activity of the Carrascoy Fault (Murcia, SE Spain): preliminary results from paleoseismological research.

    NASA Astrophysics Data System (ADS)

    Martin-Banda, Raquel; Garcia-Mayordomo, Julian; Insua-Arevalo, Juan M.; Salazar, Angel; Rodriguez-Escudero, Emilio; Alvarez-Gomez, Jose A.; Martinez-Diaz, Jose J.; Herrero, Maria J.; Medialdea, Alicia

    2014-05-01

    The Carrascoy Fault is located in the Internal Zones of the Betic Cordillera (Southern Spain). In particular, the Carrascoy Fault is one of the major faults forming the Eastern Betic Shear Zone, the main structure accommodating the convergence between Nubian and Eurasian plates in the westernmost Mediterranean. So far, the Carrascoy Fault has been defined as a left-lateral strike-slip fault. It extends for at least 31 km in a NE-SW trend from the village of Zeneta (Murcia) at its northeastern tip, to the Cañaricos village, controlling the northern edge of the Carrascoy Range and its linkage to the Guadalentin Depression towards the southwest. This is an area of moderate seismic activity, but densely populated, the capital of the region, Murcia, being settled very close to the fault. Hence, the knowledge of the structure and kinematics of the Carrascoy Fault is essential for assessing reliably the seismic hazard of the region. We present a detailed-scale geological and geomorphological map along the fault zone created from a LIDAR DEM combined with fieldwork, and geological and geophysical information. Furthermore, a number of trenches have been dug across the fault at different locations providing insights in the fault most recent activity as well as paleoseismic data. Preliminary results suggest that the Cararscoy Fault has recently changed its kinematic showing a near pure reverse motion. According to this, the fault can be divided into two distinct segments, the eastern one: Zeneta - Fuensanta, and the western one: Fuensanta - Cañaricos, each one having its own characteristic style and geodynamics. Some new active strands of the fault locate at the foot of the very first relief towards the North of the older strand, forming the current southern border of the Guadalentin Depression. These new faults show an increasingly reverse component westwards, so that the Fuensanta - Cañaricos segment is constituted by thrusts, which are blind at its western end

  10. Active shield technology for space craft protection revisited in new laboratory results and analysis

    NASA Astrophysics Data System (ADS)

    Bamford, R.; Gibson, K. J.; Thornton, A. T.; Bradford, J.; Bingham, R.; Gargate, L.; Silva, L. O.; Fonseca, R. A.; Hapgood, M.; Norberg, C.; Todd, T.; Stamper, R.

    2009-04-01

    Energetic ions in the solar wind plasma are a known hazard to both spacecraft electronics and to astronaut's health. Of primary concern is the exposure to keV--MeV protons on manned space flights to the Moon and Mars that extend over long periods of time. Attempts to protect the spacecraft include active shields that are reminiscent of Star Trek "deflector" shields. Here we describe a new experiment to test the shielding concept of a dipole-like magnetic field and plasma, surrounding the spacecraft forming a "mini magnetosphere". Initial laboratory experiments have been conducted to determine the effectiveness of a magnetized plasma barrier to be able to expel an impacting, low beta, supersonic flowing energetic plasma representing the Solar Wind. Optical and Langmuir probe data of the plasma density, the plasma flow velocity, and the intensity of the dipole field clearly show the creation of a narrow transport barrier region and diamagnetic cavity virtually devoid of energetic plasma particles. This demonstrates the potential viability of being able to create a small "hole" in a Solar Wind plasma, of the order of the ion Larmor orbit width, in which an inhabited spacecraft could reside in relative safety. The experimental results have been quantitatively compared to a 3D particle-in-cell ‘hybrid' code simulation that uses kinetic ions and fluid electrons, showing good qualitative agreement and excellent quantitative agreement. Together the results demonstrate the pivotal role of particle kinetics in determining generic plasma transport barriers. [1] [1] R Bamford et al., "The interaction of a flowing plasma with a dipole magnetic field: measurements and modelling of a diamagnetic cavity relevant to spacecraft protection." 2008 Plasma Phys. Control. Fusion 50 124025 (11pp) doi: 10.1088/0741-3335/50/12/124025

  11. 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…

  12. Dust loading in Gusev crater, Mars: Results from two active dust devil seasons

    NASA Astrophysics Data System (ADS)

    Waller, D. A.; Greeley, R.; Neakrase, L. D.; Landis, G. A.; Whelley, P.; Thompson, S. D.

    2009-12-01

    Dust devils dominate the volcanic plains at the Mars Exploration Rover (MER) landing site within the Low Albedo Zone (LAZ) in Gusev Crater. Previous studies indicate that the inferred pressure drop within the dust devil core allows the vortex to lift large amounts of unconsolidated dust high into the atmosphere which contributes to the atmospheric haze. Previous laboratory results indicate that dust devils are efficient in lifting very fine-grained (<10 μm) material, even when boundary layer winds do not exceed previously predicted threshold wind speeds (~30-35 m/s at 1.5 m above the surface for Mars conditions). Since landing in Gusev crater in January 2004, MER Spirit has obtained data for two dust devil seasons (defined as the period of time when the first and last dust devils were imaged), with a third season currently being analyzed. These seasons typically correspond to southern spring and summer, when winds capable of lifting sediment are determined to be most frequent. All observations for Season One were taken as Spirit neared the summit of Husband Hill. During Season Two Spirit imaged dust devils in the plains as it traversed within the Inner Basin, a low-lying area in the Columbia Hills complex. All results were extrapolated so that they are representative of the entire LAZ. Season One lasted 270 sols (March 2005 to December 2005 corresponding to Ls 173.2 to 339.5 degrees), whereas Season Two lasted 153 sols (January 2007 to June 2007 corresponding to Ls 171.2 to 266.7 degrees) and ended suddenly on sol 1240 just after the dust devil frequency peaked for the season. This abrupt drop in dust devil activity corresponded to atmospheric opacity levels that exceeded 1.0 and the onset of a global dust storm that originated in the southern hemisphere that engulfed Gusev within weeks. Results show a large contrast in activity between the two seasons. An 81% decrease in dust devil frequency across the plains was found in Season Two. 533 dust devils were imaged

  13. Preliminary results from a study of the impact of digital activity trackers on health risk status.

    PubMed

    Rowe-Roberts, Dinah; Cercos, Robert; Mueller, Florian 'Floyd'

    2014-01-01

    Digital activity trackers are becoming increasingly more widespread and affordable, providing new opportunities to support participatory e-health programs in which participants take an active role. However, there is limited knowledge of how to deploy these activity trackers within these programs. In response, we conducted a 7-month study with 212 employees using a wireless activity tracker to log step count. Our results suggest that these devices can support improving physical activity levels and consequently reduce diabetes risk factors. Furthermore, the intervention seems more effective for people with higher risk factors. With our work we aim to contribute to a better understanding of the issues and challenges involved in the design of participatory e-health programs that include activity trackers. PMID:25087541

  14. Subliminal psychodynamic activation: updated comprehensive list of experimental results and comments on previous lists.

    PubMed

    Fudin, R; Benjamin, C

    1992-06-01

    A comprehensive list of results from visual subliminal psychodynamic activation experiments is presented. This list includes results reported since the publication of the last comprehensive list by Weinberger and Hardaway in 1990 and several results not found on that list. On the present list, SPA results are categorized according to criteria that we contend are more objective than those used previously. In contrast to conclusions drawn from previous lists prepared by Silverman in 1980 and 1983, by Weinberger and Hardaway in 1990, and by Weinberger and Silverman in 1987, the present list indicates that the results of a majority of experiments do not clearly support hypotheses tested by the subliminal psychodynamic activation method. Aspects of Hardaway's meta-analyses from 1987 and 1990 for major areas of research on subliminal psychodynamic activation are discussed in terms of suggestions for further research. PMID:1608734

  15. Active Source Tomography of Stromboli Volcano (Italy): Results From the 2006 Seismic Experiment.

    NASA Astrophysics Data System (ADS)

    Zuccarello, L.; Patanè, D.; Cocina, O.; Castellano, M.; Sgroi, T.; Favali, P.; de Gori, P.

    2008-12-01

    Stromboli island, located in the Southern Tyrrhenian sea, is the emerged part (about 900 m a.s.l.) of a 3km-high strato-volcano. Its persistent Strombolian activity, documented for over 2000 years, is sometimes interrupted by lava effusions or major explosions. Despite the amount of recent published geophysical studies aimed to clarifying eruption dynamics, the spatial extend and geometrical characteristics of the plumbing system remain poorly understood. In fact, the knowledge of the inner structure and the zones of magma storage is limited to the upper few hundreds meters of the volcanic edifice and P- and S-waves velocity models are available only in restricted areas. In order to obtain a more suitable internal structural and velocity models of the volcano, from 25 November to 2 December 2006, a seismic tomography experiment through active seismics using air-gun sources was carried out and the final Vp model is here presented. The data has been inverted for the Vp structure by using the code Simulps13q, considering a 3D grid of nodes spaced 0.5 km down to 2 km depth, beneath the central part of volcano. The results show a relatively high velocity zones located both in the inner part of the volcanic structure, at about 1km b.s.l. and in the last 200-300 m a.s.l. in correspondence with the volcanic conduit. Slower zones were located around the summit craters in agreement with volcanological and petrological informations for the area. The relatively high velocity zones could suggest the presence of intrusive bodies related to the plumbing system.

  16. Active and passive cigarette smoking and breast cancer risk: results from the EPIC cohort.

    PubMed

    Dossus, Laure; Boutron-Ruault, Marie-Christine; Kaaks, Rudolf; Gram, Inger T; Vilier, Alice; Fervers, Béatrice; Manjer, Jonas; Tjonneland, Anne; Olsen, Anja; Overvad, Kim; Chang-Claude, Jenny; Boeing, Heiner; Steffen, Annika; Trichopoulou, Antonia; Lagiou, Pagona; Sarantopoulou, Maria; Palli, Domenico; Berrino, Franco; Tumino, Rosario; Vineis, Paolo; Mattiello, Amalia; Bueno-de-Mesquita, H Bas; van Duijnhoven, Franzel J B; Bakker, Marieke F; Peeters, Petra Hm; Weiderpass, Elisabete; Bjerkaas, Eivind; Braaten, Tonje; Menéndez, Virginia; Agudo, Antonio; Sanchez, Maria-Jose; Amiano, Pilar; Tormo, Maria-Jose; Barricarte, Aurelio; Butt, Salma; Khaw, Kay-Tee; Wareham, Nicholas; Key, Tim J; Travis, Ruth C; Rinaldi, Sabina; McCormack, Valerie; Romieu, Isabelle; Cox, David G; Norat, Teresa; Riboli, Elio; Clavel-Chapelon, Françoise

    2014-04-15

    Recent cohort studies suggest that increased breast cancer risks were associated with longer smoking duration, higher pack-years and a dose-response relationship with increasing pack-years of smoking between menarche and first full-term pregnancy (FFTP). Studies with comprehensive quantitative life-time measures of passive smoking suggest an association between passive smoking dose and breast cancer risk. We conducted a study within the European Prospective Investigation into Cancer and Nutrition to examine the association between passive and active smoking and risk of invasive breast cancer and possible effect modification by known breast cancer risk factors. Among the 322,988 women eligible for the study, 9,822 developed breast cancer (183,608 women with passive smoking information including 6,264 cases). When compared to women who never smoked and were not being exposed to passive smoking at home or work at the time of study registration, current, former and currently exposed passive smokers were at increased risk of breast cancer (hazard ratios (HR) [95% confidence interval (CI)] 1.16 [1.05-1.28], 1.14 [1.04-1.25] and 1.10 [1.01-1.20], respectively). Analyses exploring associations in different periods of life showed the most important increase in risk with pack-years from menarche to FFTP (1.73 [1.29-2.32] for every increase of 20 pack-years) while pack-years smoked after menopause were associated with a significant decrease in breast cancer risk (HR = 0.53, 95% CI: 0.34-0.82 for every increase of 20 pack-years). Our results provide an important replication, in the largest cohort to date, that smoking (passively or actively) increases breast cancer risk and that smoking between menarche and FFTP is particularly deleterious.

  17. Active and passive cigarette smoking and breast cancer risk: results from the EPIC cohort.

    PubMed

    Dossus, Laure; Boutron-Ruault, Marie-Christine; Kaaks, Rudolf; Gram, Inger T; Vilier, Alice; Fervers, Béatrice; Manjer, Jonas; Tjonneland, Anne; Olsen, Anja; Overvad, Kim; Chang-Claude, Jenny; Boeing, Heiner; Steffen, Annika; Trichopoulou, Antonia; Lagiou, Pagona; Sarantopoulou, Maria; Palli, Domenico; Berrino, Franco; Tumino, Rosario; Vineis, Paolo; Mattiello, Amalia; Bueno-de-Mesquita, H Bas; van Duijnhoven, Franzel J B; Bakker, Marieke F; Peeters, Petra Hm; Weiderpass, Elisabete; Bjerkaas, Eivind; Braaten, Tonje; Menéndez, Virginia; Agudo, Antonio; Sanchez, Maria-Jose; Amiano, Pilar; Tormo, Maria-Jose; Barricarte, Aurelio; Butt, Salma; Khaw, Kay-Tee; Wareham, Nicholas; Key, Tim J; Travis, Ruth C; Rinaldi, Sabina; McCormack, Valerie; Romieu, Isabelle; Cox, David G; Norat, Teresa; Riboli, Elio; Clavel-Chapelon, Françoise

    2014-04-15

    Recent cohort studies suggest that increased breast cancer risks were associated with longer smoking duration, higher pack-years and a dose-response relationship with increasing pack-years of smoking between menarche and first full-term pregnancy (FFTP). Studies with comprehensive quantitative life-time measures of passive smoking suggest an association between passive smoking dose and breast cancer risk. We conducted a study within the European Prospective Investigation into Cancer and Nutrition to examine the association between passive and active smoking and risk of invasive breast cancer and possible effect modification by known breast cancer risk factors. Among the 322,988 women eligible for the study, 9,822 developed breast cancer (183,608 women with passive smoking information including 6,264 cases). When compared to women who never smoked and were not being exposed to passive smoking at home or work at the time of study registration, current, former and currently exposed passive smokers were at increased risk of breast cancer (hazard ratios (HR) [95% confidence interval (CI)] 1.16 [1.05-1.28], 1.14 [1.04-1.25] and 1.10 [1.01-1.20], respectively). Analyses exploring associations in different periods of life showed the most important increase in risk with pack-years from menarche to FFTP (1.73 [1.29-2.32] for every increase of 20 pack-years) while pack-years smoked after menopause were associated with a significant decrease in breast cancer risk (HR = 0.53, 95% CI: 0.34-0.82 for every increase of 20 pack-years). Our results provide an important replication, in the largest cohort to date, that smoking (passively or actively) increases breast cancer risk and that smoking between menarche and FFTP is particularly deleterious. PMID:24590452

  18. β-Eliminative depolymerization of the fucosylated chondroitin sulfate and anticoagulant activities of resulting fragments.

    PubMed

    Gao, Na; Lu, Feng; Xiao, Chuang; Yang, Lian; Chen, Jun; Zhou, Kai; Wen, Dandan; Li, Zi; Wu, Mingyi; Jiang, Jianmin; Liu, Guangming; Zhao, Jinhua

    2015-01-01

    Fucosylated chondroitin sulfate (FCS) from sea cucumber with complex structure has potent anticoagulant activity by inhibition of intrinsic tenase; however, it could activate factor XII and platelet. To obtain FCS' fragments with selective inhibition on intrinsic tenase, a method for β-eliminative depolymerization of FCS was developed by treating FCS benzyl esters with alkaline in anhydrous solution. Our results demonstrated that the glycosidic linkages of GalNAc-β1, 4-GlcA were selectively cleaved and distinctive Δ(4,5) unsaturated hexuronic acid was formed at non-reducing end of resulting fragments, while the main structures were essentially stable during depolymerization. By this method, five depolymerized fragments (dFCSs) with various molecular sizes were prepared and their anticoagulant activities and activation activities of factor XII and platelet were compared. Overall, dFCSs with Mw 3.2-8.8 kDa reserved potent anticoagulant activities by inhibition of intrinsic tenase, and activation activities of factor XII or platelet could be diminished or eliminated.

  19. 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...

  20. Positive Control Mutations in the MyoD Basic Region Fail to Show Cooperative DNA Binding and Transcriptional Activation in vitro

    NASA Astrophysics Data System (ADS)

    Bengal, Eyal; Flores, Osvaldo; Rangarajan, Pundi N.; Chen, Amy; Weintraub, Harold; Verma, Inder M.

    1994-06-01

    An in vitro transcription system from HeLa cells has been established in which MyoD and E47 proteins activate transcription both as homodimers and heterodimers. However, heterodimers activate transcription more efficiently than homodimers, and function synergistically from multiple binding sites. Positive control mutants in the basic region of MyoD that have previously been shown to be defective in initiating the myogenic program, can bind DNA but have lost their ability to function as transcriptional activators in vitro. Additionally, positive control mutants, unlike wild-type MyoD, fail to bind cooperatively to DNA. We propose that binding of MyoD complexes to high affinity MyoD binding sites induces conformational changes that facilitate cooperative binding to multiple sites and promote transcriptional activation.

  1. Modification of Pulsed Electric Field Conditions Results in Distinct Activation Profiles of Platelet-Rich Plasma

    PubMed Central

    Frelinger, Andrew L.; Gerrits, Anja J.; Garner, Allen L.; Torres, Andrew S.; Caiafa, Antonio; Morton, Christine A.; Berny-Lang, Michelle A.; Carmichael, Sabrina L.; Neculaes, V. Bogdan; Michelson, Alan D.

    2016-01-01

    Background Activated autologous platelet-rich plasma (PRP) used in therapeutic wound healing applications is poorly characterized and standardized. Using pulsed electric fields (PEF) to activate platelets may reduce variability and eliminate complications associated with the use of bovine thrombin. We previously reported that exposing PRP to sub-microsecond duration, high electric field (SMHEF) pulses generates a greater number of platelet-derived microparticles, increased expression of prothrombotic platelet surfaces, and differential release of growth factors compared to thrombin. Moreover, the platelet releasate produced by SMHEF pulses induced greater cell proliferation than plasma. Aims To determine whether sub-microsecond duration, low electric field (SMLEF) bipolar pulses results in differential activation of PRP compared to SMHEF, with respect to profiles of activation markers, growth factor release, and cell proliferation capacity. Methods PRP activation by SMLEF bipolar pulses was compared to SMHEF pulses and bovine thrombin. PRP was prepared using the Harvest SmartPreP2 System from acid citrate dextrose anticoagulated healthy donor blood. PEF activation by either SMHEF or SMLEF pulses was performed using a standard electroporation cuvette preloaded with CaCl2 and a prototype instrument designed to take into account the electrical properties of PRP. Flow cytometry was used to assess platelet surface P-selectin expression, and annexin V binding. Platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), endothelial growth factor (EGF) and platelet factor 4 (PF4), and were measured by ELISA. The ability of supernatants to stimulate proliferation of human epithelial cells in culture was also evaluated. Controls included vehicle-treated, unactivated PRP and PRP with 10 mM CaCl2 activated with 1 U/mL bovine thrombin. Results PRP activated with SMLEF bipolar pulses or thrombin had similar light scatter profiles, consistent with the

  2. Post-Knowledge of Results Delay: Effects of Interpolated Activity on Learning and Performance.

    ERIC Educational Resources Information Center

    Benedetti, Carol; McCullagh, Penny

    1987-01-01

    Experimental evidence strongly supports the assumption that knowledge of results (KR) is necessary for learning to occur. This study compares the effects of KR or no-KR with the effects of an interpolated verbal activity on learning and performance of a timed motor task. Results are presented. (Author/MT)

  3. 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

  4. Pseudomonas aeruginosa cells adapted to benzalkonium chloride show resistance to other membrane-active agents but not to clinically relevant antibiotics.

    PubMed

    Loughlin, M F; Jones, M V; Lambert, P A

    2002-04-01

    Our objective was to determine whether strains of Pseudomonas aeruginosa can adapt to growth in increasing concentrations of the disinfectant benzalkonium chloride (BKC), and whether co-resistance to clinically relevant antimicrobial agents occurs. Attempts were made to determine what phenotypic alterations accompanied resistance and whether these explained the mechanism of resistance. Strains were serially passaged in increasing concentrations of BKC in static nutrient broth cultures. Serotyping and genotyping were used to determine purity of the cultures. Two strains were examined for cross-resistance to other disinfectants and antibiotics by broth dilution MIC determination. Alterations in outer membrane proteins and lipopolysaccharide (LPS) expressed were examined by SDS-PAGE. Cell surface hydrophobicity and charge, uptake of disinfectant and proportion of specific fatty acid content of outer and cytoplasmic membranes were determined. Two P. aeruginosa strains showed a stable increase in resistance to BKC. Co-resistance to other quaternary ammonium compounds was observed in both strains; chloramphenicol and polymyxin B resistance were observed in one and a reduction in resistance to tobramycin observed in the other. However, no increased resistance to other biocides (chlorhexidine, triclosan, thymol) or antibiotics (ceftazidime, imipenem, ciprofloxacin, tobramycin) was detected. Characteristics accompanying resistance included alterations in outer membrane proteins, uptake of BKC, cell surface charge and hydrophobicity, and fatty acid content of the cytoplasmic membrane, although no evidence was found for alterations in LPS. Each of the two strains had different alterations in phenotype, indicating that such adaptation is unique to each strain of P. aeruginosa and does not result from a single mechanism shared by the whole species. PMID:11909837

  5. Scanning L-Band Active Passive (SLAP) - Recent Results from an Airborne Simulator for SMAP

    NASA Technical Reports Server (NTRS)

    Kim, Edward

    2015-01-01

    Scanning L-band Active Passive (SLAP) is a recently-developed NASA airborne instrument specially tailored to simulate the new Soil Moisture Active Passive (SMAP) satellite instrument suite. SLAP conducted its first test flights in December, 2013 and participated in its first science campaign-the IPHEX ground validation campaign of the GPM mission-in May, 2014. This paper will present results from additional test flights and science observations scheduled for 2015.

  6. Brown Norway rats, a putative schizophrenia model, show increased electroencephalographic activity at rest and decreased event-related potential amplitude, power, and coherence in the auditory sensory gating paradigm.

    PubMed

    Tomimatsu, Yoshiro; Hibino, Ryosuke; Ohta, Hiroyuki

    2015-08-01

    In recent schizophrenia clinical research, electroencephalographic (EEG) oscillatory activities induced by a sensory stimulus or behavioral tasks have gained considerable interest as functional and pathophysiological biomarkers. The Brown Norway (BN) rat is a putative schizophrenia model that shows naturally low sensorimotor gating and deficits in cognitive performance, although other phenotypes have not been studied. The present study aimed to investigate the neurophysiological features of BN rats, particularly EEG/event-related potential (ERP). EEG activity was recorded at rest and during the auditory sensory gating paradigm under an awake, freely moving condition. Frequency and ERP analysis were performed along with time-frequency analysis of evoked power and intertrial coherence. Compared with Wistar-Kyoto rats, a well-documented control line, BN rats showed increased EEG power at rest, particularly in the theta and gamma ranges. In ERP analysis, BN rats showed reduced N40-P20 amplitude but normal sensory gating. The rats also showed reduced evoked power and intertrial coherence against auditory stimuli. These results suggest that BN rats show features of EEG/ERP measures clinically relevant to schizophrenia and may provide additional opportunities for translational research.

  7. Supplementation with Sodium Selenite and Selenium-Enriched Microalgae Biomass Show Varying Effects on Blood Enzymes Activities, Antioxidant Response, and Accumulation in Common Barbel (Barbus barbus)

    PubMed Central

    Kouba, Antonín; Velíšek, Josef; Stará, Alžběta; Masojídek, Jiří; Kozák, Pavel

    2014-01-01

    Yearling common barbel (Barbus barbus L.) were fed four purified casein-based diets for 6 weeks in outdoor cages. Besides control diet, these were supplemented with 0.3 mg kg−1 dw selenium (Se) from sodium selenite, or 0.3 and 1.0 mg kg−1 from Se-enriched microalgae biomass (Chlorella), a previously untested Se source for fish. Fish mortality, growth, Se accumulation in muscle and liver, and activity of selected enzymes in blood plasma, muscle, liver, and intestine were evaluated. There was no mortality, and no differences in fish growth, among groups. Se concentrations in muscle and liver, activity of alanine aminotransferase and creatine kinase in blood plasma, glutathione reductase (GR) in muscle, and GR and catalase in muscle and liver suggested that selenium from Se-enriched Chlorella is more readily accumulated and biologically active while being less toxic than sodium selenite. PMID:24772422

  8. Does pedometer goal setting improve physical activity among Native elders? Results from a randomized pilot study.

    PubMed

    Sawchuk, Craig N; Russo, Joan E; Charles, Steve; Goldberg, Jack; Forquera, Ralph; Roy-Byrne, Peter; Buchwald, Dedra

    2011-01-01

    We examined if step-count goal setting resulted in increases in physical activity and walking compared to only monitoring step counts with pedometers among American Indian/Alaska Native elders. Outcomes included step counts, self-reported physical activity and well-being, and performance on the 6-minute walk test. Although no significant between-group differences were found, within-group analyses indicated that elders significantly improved on the majority of step count, physical activity, health-related quality of life, and 6-minute walk outcomes.

  9. 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

    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.

  10. Preliminary Results from the iMUSH Active Source Seismic Experiment

    NASA Astrophysics Data System (ADS)

    Levander, Alan; Kiser, Eric; Palomeras, Imma; Zelt, Colin; Schmandt, Brandon; Hansen, Steve; Harder, Steven; Creagar, Kenneth; Vidale, John; Abers, Geoffrey

    2015-04-01

    iMUSH (imaging Magma Under Saint Helens) is a US NSF sponsored multi-disciplinary investigation of Mount Saint Helens (MSH), currently the most active volcano in the Cascades arc in the northwestern United States. The project consists of active and passive seismic experiments, extensive magnetotelluric sounding, and geological/geochemical studies involving scientists at 7 institutions in the U.S. and Europe. The long-term goal of the seismic project is to combine analysis of the active source data with that of data from the 70 element broadband seismograph operating from summer 2014 until 2016. Combining seismic and MT analyses with other data, we hope to image the MSH volcanic plumbing system from the surface to the subducting Juan de Fuca slab. Here we describe preliminary results of the iMUSH active source seismic experiment, conducted in July and August 2014. The active source experiment consisted of twenty-three 454 or 908 kg weight shots recorded by ~3500 seismographs deployed at ~6,000 locations. Of these instruments, ~900 Nodal Seismic instruments were deployed continuously for two weeks in an areal array within 10 km of the MSH summit. 2,500 PASSCAL Texan instruments were deployed twice for five days in 3 areal arrays and 2 dense orthogonal linear arrays that extended from MSH to distances > 80 km. Overall the data quality from the shots is excellent. The seismograph arrays also recorded dozens of micro-earthquakes beneath the MSH summit and along the MSH seismic zone, and numerous other local and regional earthquakes. In addition, at least one low frequency event beneath MSH was recorded during the experiment. At this point we have begun various types of analysis of the data set: We have determined an average 1D Vp structure from stacking short-term/long-term average ratios, we have determined the 2-D Vp structure from ray-trace inversions along the two orthogonal profiles (in the NW-SE and NE-SW directions), and we have made low-fold CMP stacks of the

  11. 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 not BSA. Its maximum activity is found at 37°C and pH 7.5, but it retained almost 70% activity at pH 10.0. It was shown to be a metalloprotease inhibited by Cu(2+), Ni(2+), Zn(2+), Hg(2+), Fe(2+), and Mg(2+), but induced by Mn(2+). After incubation at 100°C for 5min, the enzyme presented over 40% activity, but only 14 to 30% when submitted to milder heat treatments. This behavior may cause significant problems under conditions commonly used for the processing and storage of milk and dairy products, particularly UHT milk. A specific peptide sequenced by mass spectrometer analysis allowed the identification of gene that encodes this extracellular protease in the genome of Pseudomonas fluorescens 07A strain. The enzyme has 477 AA and highly conserved Ca(2+)- and Zn(2+)-binding domains, indicating that Ca(2+), the main ion in milk, is also a cofactor. This work contributes to the understanding of the biochemical aspects of enzyme activity and associates them with its sequence and structure. These findings are essential for the full understanding and control of these enzymes and the technological problems they cause in the dairy industry. PMID:27497896

  12. The surface geometry of inherited joint and fracture trace patterns resulting from active and passive deformation

    NASA Technical Reports Server (NTRS)

    Podwysocki, M. H.; Gold, D. P.

    1974-01-01

    Hypothetical models are considered for detecting subsurface structure from the fracture or joint pattern, which may be influenced by the structure and propagated to the surface. Various patterns of an initially orthogonal fracture grid are modeled according to active and passive deformation mechanisms. In the active periclinal structure with a vertical axis, fracture frequency increased both over the dome and basin, and remained constant with decreasing depth to the structure. For passive periclinal features such as a reef or sand body, fracture frequency is determined by the arc of curvature and showed a reduction over the reefmound and increased over the basin.

  13. Development of Visualizations and Loggable Activities for the Geosciences. Results from Recent TUES Sponsored Projects

    NASA Astrophysics Data System (ADS)

    De Paor, D. G.; Bailey, J. E.; Whitmeyer, S. J.

    2012-12-01

    Our TUES research centers on the role of digital data, visualizations, animations, and simulations in undergraduate geoscience education. Digital hardware (smartphones, tablets, GPSs, GigaPan robotic camera mounts, etc.) are revolutionizing field data collection. Software products (GIS, 3-D scanning and modeling programs, virtual globes, etc.) have truly transformed the way geoscientists teach, learn, and do research. Whilst Google-Earth-style visualizations are famously user-friend for the person browsing, they can be notoriously unfriendly for the content creator. Therefore, we developed tools to help educators create and share visualizations as easily as if posting on Facebook. Anyone whoIf you wish to display geological cross sections on Google Earth, go to digitalplanet.org, upload image files, position them on a line of section, and share with the world through our KMZ hosting service. Other tools facilitate screen overlay and 3-D map symbol generation. We advocate use of such technology to enable undergraduate students to 'publish' their first mapping efforts even while they are working in the field. A second outcome of our TUES projects merges Second-Life-style interaction with Google Earth. We created games in which students act as first responders for natural hazard mitigation, prospectors for natural resource explorations, and structural geologist for map-making. Students are represented by avatars and collaborate by exchange of text messages - the natural mode of communication for the current generation. Teachers view logs showing student movements as well as transcripts of text messages and can scaffold student learning and geofence students to prevent wandering. Early results of in-class testing show positive learning outcomes. The third aspect of our program emphasizes dissemination. Experience shows that great effort is required to overcome activation energy and ensure adoption of new technology into the curriculum. We organized a GSA Penrose

  14. Public medical shows.

    PubMed

    Walusinski, Olivier

    2014-01-01

    In the second half of the 19th century, Jean-Martin Charcot (1825-1893) became famous for the quality of his teaching and his innovative neurological discoveries, bringing many French and foreign students to Paris. A hunger for recognition, together with progressive and anticlerical ideals, led Charcot to invite writers, journalists, and politicians to his lessons, during which he presented the results of his work on hysteria. These events became public performances, for which physicians and patients were transformed into actors. Major newspapers ran accounts of these consultations, more like theatrical shows in some respects. The resultant enthusiasm prompted other physicians in Paris and throughout France to try and imitate them. We will compare the form and substance of Charcot's lessons with those given by Jules-Bernard Luys (1828-1897), Victor Dumontpallier (1826-1899), Ambroise-Auguste Liébault (1823-1904), Hippolyte Bernheim (1840-1919), Joseph Grasset (1849-1918), and Albert Pitres (1848-1928). We will also note their impact on contemporary cinema and theatre. PMID:25273491

  15. Ni(II), Cu(II), and Zn(II) Diethyldithiocarbamate Complexes Show Various Activities Against the Proteasome in Breast Cancer Cells

    PubMed Central

    Cvek, Boris; Milacic, Vesna; Taraba, Jan; Dou, Q. Ping

    2008-01-01

    A series of three complexes with diethyldithiocarbamate ligand and three different metals (Ni, Cu, Zn) was prepared, confirmed by X-ray crystallography, and tested in human breast cancer MDA-MB-231 cells. Zinc and copper complexes, but not nickel complex, were found to be more active against cellular 26S proteasome than against purified 20S proteasome core particle. One of the possible explanations is inhibition of JAMM domain in the 19S proteasome lid. PMID:18816109

  16. Return to sporting activity after Birmingham hip resurfacing arthroplasty: Mid term results

    PubMed Central

    Sandiford, Nemandra; Muirhead-Allwood, SK; Skinner, JA

    2015-01-01

    Background: Hip resurfacing arthroplasty (HRA) is primarily indicated for young, active patients with disabling coxarthrosis who wish to remain active and return to sports after surgery. Relatively few prospective studies have assessed return to sporting activity and impact of gender and age on this. Materials and Methods: Seventy-nine consecutive patients treated with HRA were included. Patients were reviewed clinically and radiologically. Function was assessed using the modified University of California Los Angeles (UCLA) activity score. The Oxford, Harris and WOMAC hip scores were calculated. Results: Average age at the time of surgery was 54.9 years (range 34.5–73.6 years). Average preoperative and postoperative UCLA scores were 4 and 7.6 respectively. Patients were involved in 2 (0–4) sporting activities preoperatively and 2 (0–5) postoperatively. Preoperative and postoperative Oxford Hip Scores, Harris Hip Score and WOMAC scores were 40, 46 and 51 and 16, 94 and 3 respectively (P < 0.0001). Patients returned to sports at an average of 3 months postoperatively. Conclusion: Patients were able to return to sports by 3 months and perform the same number of activities at preoperative intensity. Activity levels are maintained up to the medium term with few complications. PMID:26806965

  17. Deriving rules from activity diary data: A learning algorithm and results of computer experiments

    NASA Astrophysics Data System (ADS)

    Arentze, Theo A.; Hofman, Frank; Timmermans, Harry J. P.

    Activity-based models consider travel as a derived demand from the activities households need to conduct in space and time. Over the last 15 years, computational or rule-based models of activity scheduling have gained increasing interest in time-geography and transportation research. This paper argues that a lack of techniques for deriving rules from empirical data hinders the further development of rule-based systems in this area. To overcome this problem, this paper develops and tests an algorithm for inductively deriving rules from activity-diary data. The decision table formalism is used to exhaustively represent the theoretically possible decision rules that individuals may use in sequencing a given set of activities. Actual activity patterns of individuals are supplied to the system as examples. In an incremental learning process, the system progressively improves on the selection of rules used for reproducing the examples. Computer experiments based on simulated data are performed to fine-tune rule selection and rule value update functions. The results suggest that the system is effective and fairly robust for parameter settings. It is concluded, therefore, that the proposed approach opens up possibilities to derive empirically tested rule-based models of activity scheduling. Follow-up research will be concerned with testing the system on empirical data.

  18. Status of data, major results, and plans for geophysical activities, Yucca Mountain Project

    SciTech Connect

    Oliver, H.W.; Hardin, E.L.; Nelson, P.H.

    1990-07-01

    This report describes past and planned geophysical activities associated with the Yucca Mountain Project and is intended to serve as a starting point for integration of geophysical activities. This report relates past results to site characterization plans, as presented in the Yucca Mountain Site Characterization Plan (SCP). This report discusses seismic exploration, potential field methods, geoelectrical methods, teleseismic data collection and velocity structural modeling, and remote sensing. This report discusses surface-based, airborne, borehole, surface-to-borehole, crosshole, and Exploratory Shaft Facility-related activities. The data described in this paper, and the publications discussed, have been selected based on several considerations; location with respect to Yucca Mountain, whether the success or failure of geophysical data is important to future activities, elucidation of features of interest, and judgment as to the likelihood that the method will produce information that is important for site characterization. 65 refs., 19 figs., 12 tabs.

  19. Disease Mutations in Rab7 Result in Unregulated Nucleotide Exchange and Inappropriate Activation

    SciTech Connect

    B McCray; E Skordalakes; J Taylor

    2011-12-31

    Rab GTPases are molecular switches that orchestrate vesicular trafficking, maturation and fusion by cycling between an active, GTP-bound form, and an inactive, GDP-bound form. The activity cycle is coupled to GTP hydrolysis and is tightly controlled by regulatory proteins. Missense mutations of the GTPase Rab7 cause a dominantly inherited axonal degeneration known as Charcot-Marie-Tooth type 2B through an unknown mechanism. We present the 2.8 A crystal structure of GTP-bound L129F mutant Rab7 which reveals normal conformations of the effector binding regions and catalytic site, but an alteration to the nucleotide binding pocket that is predicted to alter GTP binding. Through extensive biochemical analysis, we demonstrate that disease-associated mutations in Rab7 do not lead to an intrinsic GTPase defect, but permit unregulated nucleotide exchange leading to both excessive activation and hydrolysis-independent inactivation. Consistent with augmented activity, mutant Rab7 shows significantly enhanced interaction with a subset of effector proteins. In addition, dynamic imaging demonstrates that mutant Rab7 is abnormally retained on target membranes. However, we show that the increased activation of mutant Rab7 is counterbalanced by unregulated, GTP hydrolysis-independent membrane cycling. Notably, disease mutations are able to rescue the membrane cycling of a GTPase-deficient mutant. Thus, we demonstrate that disease mutations uncouple Rab7 from the spatial and temporal control normally imposed by regulatory proteins and cause disease not by a gain of novel toxic function, but by misregulation of native Rab7 activity.

  20. Television Quiz Show Simulation

    ERIC Educational Resources Information Center

    Hill, Jonnie Lynn

    2007-01-01

    This article explores the simulation of four television quiz shows for students in China studying English as a foreign language (EFL). It discusses the adaptation and implementation of television quiz shows and how the students reacted to them.

  1. Depolymerization of Fucosylated Chondroitin Sulfate with a Modified Fenton-System and Anticoagulant Activity of the Resulting Fragments

    PubMed Central

    Li, Jun-hui; Li, Shan; Zhi, Zi-jian; Yan, Lu-feng; Ye, Xing-qian; Ding, Tian; Yan, Lei; Linhardt, Robert John; Chen, Shi-guo

    2016-01-01

    Fucosylated chondroitin sulfate (fCS) from sea cucumber Isostichopus badionotus (fCS-Ib) with a chondroitin sulfate type E (CSE) backbone and 2,4-O-sulfo fucose branches has shown excellent anticoagulant activity although has also show severe adverse effects. Depolymerization represents an effective method to diminish this polysaccharide’s side effects. The present study reports a modified controlled Fenton system for degradation of fCS-Ib and the anticoagulant activity of the resulting fragments. Monosaccharides and nuclear magnetic resonance (NMR) analysis of the resulting fragments indicate that no significant chemical changes in the backbone of fCS-Ib and no loss of sulfate groups take place during depolymerization. A reduction in the molecular weight of fCS-Ib should result in a dramatic decrease in prolonging activated partial thromboplastin time and thrombin time. A decrease in the inhibition of thrombin (FIIa) by antithromin III (AT III) and heparin cofactor II (HCII), and the slight decrease of the inhibition of factor X activity, results in a significant increase of anti-factor Xa (FXa)/anti-FIIa activity ratio. The modified free-radical depolymerization method enables preparation of glycosaminoglycan (GAG) oligosaccharides suitable for investigation of clinical anticoagulant application. PMID:27657094

  2. 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.

  3. "Exercise Dependence"--A Problem or Natural Result of High Activity?

    ERIC Educational Resources Information Center

    Phelan, Suzanne; Bond, Dale S.; Lang, Wei; Jordan, Dustin; Wing, Rena R.

    2011-01-01

    Objectives: To compare physical activity (PA) and exercise dependence (ED) in 267 weight-loss maintainers (WLM) and 213 normal-weight (NW) controls. Methods: PA and ED assessed via accelerometery and the Exercise Dependence Questionnaire. Results: WLM had higher PA levels and ED scores than those of NW (P less than 0.0001). WLM status (P = 0.006)…

  4. Expanding the family of heteroleptic oxidovanadium(IV) compounds with salicylaldehyde semicarbazones and polypyridyl ligands showing anti-Trypanosoma cruzi activity.

    PubMed

    Scalese, Gonzalo; Benítez, Julio; Rostán, Santiago; Correia, Isabel; Bradford, Lara; Vieites, Marisol; Minini, Lucía; Merlino, Alicia; Coitiño, E Laura; Birriel, Estefania; Varela, Javier; Cerecetto, Hugo; González, Mercedes; Pessoa, João Costa; Gambino, Dinorah

    2015-06-01

    Searching for prospective vanadium-based drugs for the treatment of Chagas disease, a new series of heteroleptic [V(IV)O(L-2H)(NN)] compounds was developed by including the lipophilic 3,4,7,8-tetramethyl-1,10-phenanthroline (tmp) NN ligand and seven tridentate salicylaldehyde semicarbazone derivatives (L1-L7). The compounds were characterized in the solid state and in solution. EPR spectroscopy suggests that the NN ligand is bidentate bound through both nitrogen donor atoms in an axial-equatorial mode. The EPR and (51)V-NMR spectra of aerated solutions at room temperature indicate that the compounds are stable to hydrolysis and that no significant oxidation of V(IV) to V(V) takes place at least in 24h. The complexes are more active in vitro against Trypanosoma cruzi, the parasite responsible for Chagas disease, than the reference drug Nifurtimox and most of them are more active than previously reported [V(IV)O(L-2H)(NN)] complexes of other NN co-ligands. Selectivity towards the parasite was analyzed using J-774 murine macrophages as mammalian cell model. Due to both, high activity and high selectivity, L2, L4, L5 and L7 complexes could be considered new hits for further drug development. Lipophilicity probably plays a relevant role in the bioactivity of the new compounds. The [V(IV)O(L-2H)(NN)] compounds were designed aiming DNA as potential molecular target. Therefore, the novel L1-L7 tmp complexes were screened by computational modeling, comparing their DNA-binding features with those of previously reported [V(IV)O(L-2H)(NN)] compounds with different NN co-ligands. Whereas all the complexes interact well with DNA, with binding modes and strength tuned in different extents by the NN and semicarbazone co-ligands, molecular docking suggests that the observed anti-T. cruzi activity cannot be explained upon DNA intercalation as the sole mechanism of action. PMID:25824466

  5. Ablation of PGC-1beta results in defective mitochondrial activity, thermogenesis, hepatic function, and cardiac performance.

    PubMed

    Lelliott, Christopher J; Medina-Gomez, Gema; Petrovic, Natasa; Kis, Adrienn; Feldmann, Helena M; Bjursell, Mikael; Parker, Nadeene; Curtis, Keira; Campbell, Mark; Hu, Ping; Zhang, Dongfang; Litwin, Sheldon E; Zaha, Vlad G; Fountain, Kimberly T; Boudina, Sihem; Jimenez-Linan, Mercedes; Blount, Margaret; Lopez, Miguel; Meirhaeghe, Aline; Bohlooly-Y, Mohammad; Storlien, Leonard; Strömstedt, Maria; Snaith, Michael; Oresic, Matej; Abel, E Dale; Cannon, Barbara; Vidal-Puig, Antonio

    2006-11-01

    The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1beta (PGC-1beta) has been implicated in important metabolic processes. A mouse lacking PGC-1beta (PGC1betaKO) was generated and phenotyped using physiological, molecular, and bioinformatic approaches. PGC1betaKO mice are generally viable and metabolically healthy. Using systems biology, we identified a general defect in the expression of genes involved in mitochondrial function and, specifically, the electron transport chain. This defect correlated with reduced mitochondrial volume fraction in soleus muscle and heart, but not brown adipose tissue (BAT). Under ambient temperature conditions, PGC-1beta ablation was partially compensated by up-regulation of PGC-1alpha in BAT and white adipose tissue (WAT) that lead to increased thermogenesis, reduced body weight, and reduced fat mass. Despite their decreased fat mass, PGC1betaKO mice had hypertrophic adipocytes in WAT. The thermogenic role of PGC-1beta was identified in thermoneutral and cold-adapted conditions by inadequate responses to norepinephrine injection. Furthermore, PGC1betaKO hearts showed a blunted chronotropic response to dobutamine stimulation, and isolated soleus muscle fibres from PGC1betaKO mice have impaired mitochondrial function. Lack of PGC-1beta also impaired hepatic lipid metabolism in response to acute high fat dietary loads, resulting in hepatic steatosis and reduced lipoprotein-associated triglyceride and cholesterol content. Altogether, our data suggest that PGC-1beta plays a general role in controlling basal mitochondrial function and also participates in tissue-specific adaptive responses during metabolic stress. PMID:17090215

  6. Ablation of PGC-1β Results in Defective Mitochondrial Activity, Thermogenesis, Hepatic Function, and Cardiac Performance

    PubMed Central

    Petrovic, Natasa; Kis, Adrienn; Feldmann, Helena M; Bjursell, Mikael; Parker, Nadeene; Curtis, Keira; Campbell, Mark; Hu, Ping; Zhang, Dongfang; Litwin, Sheldon E; Zaha, Vlad G; Fountain, Kimberly T; Boudina, Sihem; Jimenez-Linan, Mercedes; Blount, Margaret; Lopez, Miguel; Meirhaeghe, Aline; Bohlooly-Y, Mohammad; Storlien, Leonard; Strömstedt, Maria; Snaith, Michael; Orešič, Matej; Abel, E. Dale; Cannon, Barbara; Vidal-Puig, Antonio

    2006-01-01

    The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1β (PGC-1β) has been implicated in important metabolic processes. A mouse lacking PGC-1β (PGC1βKO) was generated and phenotyped using physiological, molecular, and bioinformatic approaches. PGC1βKO mice are generally viable and metabolically healthy. Using systems biology, we identified a general defect in the expression of genes involved in mitochondrial function and, specifically, the electron transport chain. This defect correlated with reduced mitochondrial volume fraction in soleus muscle and heart, but not brown adipose tissue (BAT). Under ambient temperature conditions, PGC-1β ablation was partially compensated by up-regulation of PGC-1α in BAT and white adipose tissue (WAT) that lead to increased thermogenesis, reduced body weight, and reduced fat mass. Despite their decreased fat mass, PGC1βKO mice had hypertrophic adipocytes in WAT. The thermogenic role of PGC-1β was identified in thermoneutral and cold-adapted conditions by inadequate responses to norepinephrine injection. Furthermore, PGC1βKO hearts showed a blunted chronotropic response to dobutamine stimulation, and isolated soleus muscle fibres from PGC1βKO mice have impaired mitochondrial function. Lack of PGC-1β also impaired hepatic lipid metabolism in response to acute high fat dietary loads, resulting in hepatic steatosis and reduced lipoprotein-associated triglyceride and cholesterol content. Altogether, our data suggest that PGC-1β plays a general role in controlling basal mitochondrial function and also participates in tissue-specific adaptive responses during metabolic stress. PMID:17090215

  7. Nanoparticle delivery of sterically hindered platinum(IV) prodrugs shows 100 times higher potency than that of cisplatin upon light activation.

    PubMed

    Song, Haiqin; Kang, Xiang; Sun, Jing; Jing, Xiabin; Wang, Zehua; Yan, Lesan; Qi, Ruogu; Zheng, Minhua

    2016-02-01

    The introduction of a sterically hindered pyridine ligand to a photosensitive platinum(iv) drug for drug delivery resulted in a >100 fold increase in effectiveness compared to the gold standard, cisplatin. PMID:26727577

  8. Heterologous Expression of MeLEA3: A 10 kDa Late Embryogenesis Abundant Protein of Cassava, Confers Tolerance to Abiotic Stress in Escherichia coli with Recombinant Protein Showing In Vitro Chaperone Activity.

    PubMed

    Barros, Nicolle L F; da Silva, Diehgo T; Marques, Deyvid N; de Brito, Fabiano M; dos Reis, Savio P; de Souza, Claudia R B

    2015-01-01

    Late embryogenesis abundant (LEA) proteins are small molecular weight proteins involved in acquisition of tolerance to drought, salinity, high temperature, cold, and freezing stress in many plants. Previous studies revealed a cDNA sequence coding for a 10 kDa atypical LEA protein, named MeLEA3, predicted to be located into mitochondria with potential role in salt stress response of cassava (Manihot esculenta Crantz). Here we aimed to produce the recombinant MeLEA3 protein by heterologous expression in Escherichia coli and evaluate the tolerance of bacteria expressing this protein under abiotic stress. Our result revealed that the recombinant MeLEA3 protein conferred a protective function against heat and salt stress in bacterial cells. Also, the recombinant MeLEA3 protein showed in vitro chaperone activity by protection of NdeI restriction enzyme activity under heat stress. PMID:25990084

  9. KSC Wildlife Show

    NASA Technical Reports Server (NTRS)

    1994-01-01

    This video highlights footage of the many forms of animal and plant life that inhabit the environs surrounding KSC. Shown are birds, alligators, butterflies, and plants as they react to shuttle launches and other activities eminating from KSC.

  10. 10 years of cloud droplet activation data from Pallas, Northern Finland - preliminary results

    NASA Astrophysics Data System (ADS)

    Kivekäs, Niku; Asmi, Eija; Brus, David; Komppula, Mika; Lihavainen, Heikki

    2016-04-01

    Activation of atmospheric aerosol particles into cloud droplets has been studied in situ at Pallas measurement station in Finnish Lapland from year 2005 to present day. The site is located on a hill top, about 300 m above the surrounding lowlands, and it is inside a cloud for 15 % of time. Here in-cloud periods are defined as periods when visibility was below 1000 m. There are two parallel Differential Mobility Particle Sizers (DMPS) at the site, measuring the number concentration and dry size distribution of atmospheric aerosol particles. One DMPS is connected to a PM2.5 inlet, the other to a total air inlet with no cut-off diameter. After each inlet the particles are dried to evaporate any water in them. This way it is possible to measure simultaneously the dry number-size-distribution of all particles, and that of particles with wet diameter smaller than 2.5 m. As the latter does not include cloud droplets, the difference between the two measurements represents the number concentration and size distribution of those particles that have activated into cloud droplets. The number concentration of particles at Pallas has a clear seasonal cycle, being highest during summer and lowest during winter. The monthly mean number concentration of particles with diameter larger than 100 nm varied from 38 cm-3 in November to 270 cm-3 in July. During in-cloud periods the monthly mean number concentration of activated particles of this same size class showed a similar pattern, varying from 23 cm-3 (November) to 110 cm-3 in April. The monthly mean D50 activation diameter (diameter at which 50 % of particles activate) varied from 85 nm (February) to 189 nm (July), showing an average 0.1 nm increase for each added particle with diameter > 100 nm. The activated fraction of particles in all sizes decreased sharply when visibility exceeded 1000 m. The highest activated fractions of particles were not observed during the periods of the thickest clouds, but during clouds with in

  11. Inappropriate Neural Activity during a Sensitive Period in Embryogenesis Results in Persistent Seizure-like Behavior

    PubMed Central

    Giachello, Carlo N.G.; Baines, Richard A.

    2015-01-01

    Summary Maturation of neural circuits requires activity-dependent processes that underpin the emergence of appropriate behavior in the adult. It has been proposed that disruption of these events, during specific critical periods when they exert maximal influence, may lead to neurodevelopmental diseases, including epilepsy [1, 2, 3]. However, complexity of neurocircuitry, coupled with the lack of information on network formation in mammals, makes it difficult to directly investigate this hypothesis. Alternative models, including the fruit fly Drosophila melanogaster, show remarkable similarities between experimental seizure-like activity and clinical phenotypes [4, 5, 6]. In particular, a group of flies, termed bang-sensitive (bs) mutants have been extensively used to investigate the pathophysiological mechanisms underlying seizure [7, 8, 9, 10, 11, 12]. Seizure phenotype can be measured in larval stages using an electroshock assay, and this behavior in bs mutants is dramatically reduced following ingestion of typical anti-epileptic drugs (AEDs; [13]). In this study we describe a critical period of embryonic development in Drosophila during which manipulation of neural activity is sufficient to significantly influence seizure behavior at postembryonic stages. We show that inhibition of elevated activity, characteristic of bs seizure models, during the critical period is sufficient to suppress seizure. By contrast, increasing neuronal excitation during the same period in wild-type (WT) is sufficient to permanently induce a seizure behavior. Further, we show that induction of seizure in WT correlates with functional alteration of motoneuron inputs that is a characteristic of bs mutants. Induction of seizure is rescued by prior administration of AEDs, opening a new perspective for early drug intervention in the treatment of genetic epilepsy. PMID:26549258

  12. Modulation of fructokinase activity of potato (Solanum tuberosum) results in substantial shifts in tuber metabolism.

    PubMed

    Davies, Howard V; Shepherd, Louise V T; Burrell, Michael M; Carrari, Fernando; Urbanczyk-Wochniak, Ewa; Leisse, Andrea; Hancock, Robert D; Taylor, Mark; Viola, Roberto; Ross, Heather; McRae, Diane; Willmitzer, Lothar; Fernie, Alisdair R

    2005-07-01

    Potato plants (Solanum tuberosum L. cvs Desiree and Record) transformed with sense and antisense constructs of a cDNA encoding the potato fructokinase StFK1 exhibited altered transcription of this gene, altered amount of protein and altered enzyme activities. Measurement of the maximal catalytic activity of fructokinase revealed a 2-fold variation in leaf (from 90 to 180% of wild type activity) and either a 10- or 30-fold variation in tuber (from 10 or 30% to 300% in Record and Desiree, respectively) activity. The comparative effect of the antisense construct in leaf and tuber tissue suggests that this isoform is only a minor contributor to the total fructokinase activity in the leaf but the predominant isoform in the tuber. Antisense inhibition of the fructokinase resulted in a reduced tuber yield; however, its overexpression had no impact on this parameter. The modulation of fructokinase activity had few, consistent effects on carbohydrate levels, with the exception of a general increase in glucose content in the antisense lines, suggesting that this enzyme is not important for the control of starch synthesis. However, when metabolic fluxes were estimated, it became apparent that the transgenic lines display a marked shift in metabolism, with the rate of redistribution of radiolabel to sucrose markedly affected by the activity of fructokinase. These data suggest an important role for fructokinase, acting in concert with sucrose synthase, in maintaining a balance between sucrose synthesis and degradation by a mechanism independent of that controlled by the hexose phosphate-mediated activation of sucrose phosphate synthase. PMID:15890680

  13. Modulation of fructokinase activity of potato (Solanum tuberosum) results in substantial shifts in tuber metabolism.

    PubMed

    Davies, Howard V; Shepherd, Louise V T; Burrell, Michael M; Carrari, Fernando; Urbanczyk-Wochniak, Ewa; Leisse, Andrea; Hancock, Robert D; Taylor, Mark; Viola, Roberto; Ross, Heather; McRae, Diane; Willmitzer, Lothar; Fernie, Alisdair R

    2005-07-01

    Potato plants (Solanum tuberosum L. cvs Desiree and Record) transformed with sense and antisense constructs of a cDNA encoding the potato fructokinase StFK1 exhibited altered transcription of this gene, altered amount of protein and altered enzyme activities. Measurement of the maximal catalytic activity of fructokinase revealed a 2-fold variation in leaf (from 90 to 180% of wild type activity) and either a 10- or 30-fold variation in tuber (from 10 or 30% to 300% in Record and Desiree, respectively) activity. The comparative effect of the antisense construct in leaf and tuber tissue suggests that this isoform is only a minor contributor to the total fructokinase activity in the leaf but the predominant isoform in the tuber. Antisense inhibition of the fructokinase resulted in a reduced tuber yield; however, its overexpression had no impact on this parameter. The modulation of fructokinase activity had few, consistent effects on carbohydrate levels, with the exception of a general increase in glucose content in the antisense lines, suggesting that this enzyme is not important for the control of starch synthesis. However, when metabolic fluxes were estimated, it became apparent that the transgenic lines display a marked shift in metabolism, with the rate of redistribution of radiolabel to sucrose markedly affected by the activity of fructokinase. These data suggest an important role for fructokinase, acting in concert with sucrose synthase, in maintaining a balance between sucrose synthesis and degradation by a mechanism independent of that controlled by the hexose phosphate-mediated activation of sucrose phosphate synthase.

  14. One Decade of Active Avian Influenza Wild Bird Surveillance in Belgium Showed a Higher Viroprevalence in Hunter-Harvested Than in Live-Ringed Birds.

    PubMed

    Steensels, M; Vangeluwe, D; Linden, A; Houdart, Ph; van den Berg, Thierry P; Lambrecht, B

    2016-05-01

    Active monitoring of avian influenza (AI) viruses in wild birds was initiated in Belgium in 2005 in response to the first highly pathogenic avian influenza (HPAI) H5N1 outbreaks occurring in Europe. In Belgium, active wild bird surveillance that targeted live-ringed and hunter-harvested wild birds was developed and maintained from 2005 onward. After one decade, this program assimilated, analyzed, and reported on over 35,000 swabs. The 2009-2014 datasets were used for the current analysis because detailed information was available for this period. The overall prevalence of avian influenza (AI) in samples from live-ringed birds during this period was 0.48% whereas it was 6.12% in hunter-harvested samples. While the ringing sampling targeted a large number of bird species and was realized over the years, the hunting sampling was mainly concentrated on mallard (Anas platyrhynchos) during the hunting season, from mid-August to late January. Even when using just AI prevalence for live-ringed A. platyrhynchos during the hunting season, the value remained significantly lower (2.10%) compared to that detected for hunter-harvested mallards. One explanation for this significant difference in viroprevalence in hunter-harvested mallards was the game restocking practice, which released captive-bred birds in the wild before the hunting period. Indeed, the released game restocking birds, having an AI-naïve immune status, could act as local amplifiers of AI viruses already circulating in the wild, and this could affect AI epidemiology. Also, the release into the wild of noncontrolled restocking birds might lead to the introduction of new strains in the natural environment, leading to increased AI presence in the environment. Consequently, the release of naïve or infected restocking birds may affect AI dynamics. PMID:27309083

  15. One Decade of Active Avian Influenza Wild Bird Surveillance in Belgium Showed a Higher Viroprevalence in Hunter-Harvested Than in Live-Ringed Birds.

    PubMed

    Steensels, M; Vangeluwe, D; Linden, A; Houdart, Ph; van den Berg, Thierry P; Lambrecht, B

    2016-05-01

    Active monitoring of avian influenza (AI) viruses in wild birds was initiated in Belgium in 2005 in response to the first highly pathogenic avian influenza (HPAI) H5N1 outbreaks occurring in Europe. In Belgium, active wild bird surveillance that targeted live-ringed and hunter-harvested wild birds was developed and maintained from 2005 onward. After one decade, this program assimilated, analyzed, and reported on over 35,000 swabs. The 2009-2014 datasets were used for the current analysis because detailed information was available for this period. The overall prevalence of avian influenza (AI) in samples from live-ringed birds during this period was 0.48% whereas it was 6.12% in hunter-harvested samples. While the ringing sampling targeted a large number of bird species and was realized over the years, the hunting sampling was mainly concentrated on mallard (Anas platyrhynchos) during the hunting season, from mid-August to late January. Even when using just AI prevalence for live-ringed A. platyrhynchos during the hunting season, the value remained significantly lower (2.10%) compared to that detected for hunter-harvested mallards. One explanation for this significant difference in viroprevalence in hunter-harvested mallards was the game restocking practice, which released captive-bred birds in the wild before the hunting period. Indeed, the released game restocking birds, having an AI-naïve immune status, could act as local amplifiers of AI viruses already circulating in the wild, and this could affect AI epidemiology. Also, the release into the wild of noncontrolled restocking birds might lead to the introduction of new strains in the natural environment, leading to increased AI presence in the environment. Consequently, the release of naïve or infected restocking birds may affect AI dynamics.

  16. Activation of Hypoxia‐Inducible Factor‐2 in Adipocytes Results in Pathological Cardiac Hypertrophy

    PubMed Central

    Lin, Qun; Huang, Yan; Booth, Carmen J.; Haase, Volker H.; Johnson, Randall S.; Celeste Simon, M.; Giordano, Frank J.; Yun, Zhong

    2013-01-01

    Background Obesity can cause structural and functional abnormalities of the heart via complex but largely undefined mechanisms. Emerging evidence has shown that obesity results in reduced oxygen concentrations, or hypoxia, in adipose tissue. We hypothesized that the adipocyte hypoxia‐signaling pathway plays an essential role in the development of obesity‐associated cardiomyopathy. Methods and Results Using a mouse model in which the hypoxia‐inducible factor (HIF) pathway is activated by deletion of the von Hippel–Lindau gene specifically in adipocytes, we found that mice with adipocyte–von Hippel–Lindau deletion developed lethal cardiac hypertrophy. HIF activation in adipocytes results in overexpression of key cardiomyopathy‐associated genes in adipose tissue, increased serum levels of several proinflammatory cytokines including interleukin‐1β and monocyte chemotactic protein‐1, and activation of nuclear factor–κB and nuclear factor of activated T cells in the heart. Interestingly, genetic deletion of Hif2a, but not Hif1a, was able to rescue cardiac hypertrophy and abrogate adipose inflammation. Conclusion We have discovered a previously uncharacterized mechanism underlying a critical and direct role of the adipocyte HIF‐2 transcription factor in the development of adipose inflammation and pathological cardiac hypertrophy. PMID:24326162

  17. Activity based financing in England: the need for continual refinement of payment by results.

    PubMed

    Street, Andrew; Maynard, Alan

    2007-10-01

    The English National Health Service is introducing activity based tariff systems or Payment by Results (PbR) as the basis for hospital funding. The funding arrangements provide incentives for increasing activity, particularly day surgery, and, uniquely, are based on costing data from all hospitals. But prices should not be based on average costs and the potential of PbR to improve the quality of care is yet to be exploited. Without refinement, PbR threatens to undermine expenditure control, to divert resources away from primary care, and to distort needs based funding. PMID:18634642

  18. Recurrent Selection for Transgene Activity Levels in Maize Results in Proxy Selection for a Native Gene with the Same Promoter.

    PubMed

    Bodnar, Anastasia L; Schroder, Megan N; Scott, M Paul

    2016-01-01

    High activity levels of a transgene can be very useful, making a transgene easier to evaluate for safety and efficacy. High activity levels can also increase the economic benefit of the production of high value proteins in transgenic plants. The goal of this research is to determine if recurrent selection for activity of a transgene will result in higher activity, and if selection for activity of a transgene controlled by a native promoter will also increase protein levels of the native gene with the same promoter. To accomplish this goal we used transgenic maize containing a construct encoding green fluorescent protein controlled by the promoter for the maize endosperm-specific 27 kDa gamma zein seed storage protein. We carried out recurrent selection for fluorescence intensity in two breeding populations. After three generations of selection, both selected populations were significantly more fluorescent and had significantly higher levels of 27 kDa gamma zein than the unselected control populations. These higher levels of the 27 kDa gamma zein occurred independently of the presence of the transgene. The results show that recurrent selection can be used to increase activity of a transgene and that selection for a transgene controlled by a native promoter can increase protein levels of the native gene with the same promoter via proxy selection. Moreover, the increase in native gene protein level is maintained in the absence of the transgene, demonstrating that proxy selection can be used to produce non-transgenic plants with desired changes in gene expression.

  19. Epidermal Platelet-activating Factor Receptor Activation and Ultraviolet B Radiation Result in Synergistic Tumor Necrosis Factor-alpha Production

    PubMed Central

    Wolverton, Jay E.; Al-Hassani, Mohammed; Yao, Yongxue; Zhang, Qiwei; Travers, Jeffrey B.

    2010-01-01

    Ultraviolet B radiation (UVB) is a potent stimulator of epidermal cytokine production which has been implicated in photoaggravated dermatoses. In addition to cytokines such as tumor necrosis factor-α (TNF-α), UVB generates bioactive lipids including platelet-activating factor (PAF). Our previous studies have demonstrated that UVB-mediated production of keratinocyte TNF-α is in part due to PAF. The current studies use a human PAF-receptor (PAF-R) negative epithelial cell line transduced with PAF-Rs and PAF–R-deficient mice to demonstrate that activation of the epidermal PAF-R along with UVB irradiation results in a synergistic production of TNF-α. It should be noted that PAF-R effects are mimicked by the protein kinase C (PKC) agonist phorbol myristic acetate, and are inhibited by pharmacological antagonists of the PKC gamma isoenzyme. These studies suggest that concomitant PAF-R activation and UVB irradiation results in a synergistic production of the cytokine TNF-α which is mediated in part via PKC. These studies provide a novel potential mechanism for photosensitivity responses. PMID:19769579

  20. Anomalous electrical signals associated with microbial activity: Results from Iron and Nitrate-Reducing Columns

    NASA Astrophysics Data System (ADS)

    Aaron, R. B.; Zheng, Q.; Flynn, P.; Singha, K.; Brantley, S.

    2008-12-01

    /m), increased in the iron reducing column (0.2 S/m to 0.8 S/m) and increased markedly in the nitrate reducing column (0.3 S/m to 1.2 S/m). This runs counter to our expectations. We expected to see an increase in σ b as [Fe(II)] increased and a decrease in σ b as nitrate was removed from the columns. All three columns showed little or no IP response at the outset and developed negative chargeabilities over the course of the experiment (as great as -20 mV/V). These values are anomalous and difficult to interpret. SP signals show the most variable response. Initially all three columns had SP values at or very near 0 mV. SP for the nitrate reducing column remained constant around 0mV. The iron reducing column displayed an increasingly negative SP response for the first two months that became constant at about -200mV for the remainder of the experiment. The alternating redox column displayed an oscillating signal recording large positive values (~475 mV) when nitrate concentrations were low and returning to a baseline value (~160mV) when nitrate was introduced to the column. The results of these column experiments indicate that there is a link between microbial activity and geophysical signals and that further research is needed to better quantify these signals.

  1. New alternative splicing BCR/ABL-OOF shows an oncogenic role by lack of inhibition of BCR GTPase activity and an increased of persistence of Rac activation in chronic myeloid leukemia.

    PubMed

    Panuzzo, Cristina; Volpe, Gisella; Cibrario Rocchietti, Elisa; Casnici, Claudia; Crotta, Katia; Crivellaro, Sabrina; Carrà, Giovanna; Lorenzatti, Roberta; Peracino, Barbara; Torti, Davide; Morotti, Alessandro; Camacho-Leal, Maria Pilar; Defilippi, Paola; Marelli, Ornella; Saglio, Giuseppe

    2015-01-01

    In Chronic Myeloid Leukemia 80% of patients present alternative splice variants involving BCR exons 1, 13 or 14 and ABL exon 4, with a consequent impairment in the reading frame of the ABL gene. Therefore BCR/ABL fusion proteins (BCR/ABL-OOF) are characterized by an in-frame BCR portion followed by an amino acids sequence arising from the out of frame (OOF) reading of the ABL gene. The product of this new transcript contains the characteristic BCR domains while lacking the COOH-terminal Rho GTPase GAP domain. The present work aims to characterize the protein functionality in terms of cytoskeleton (re-)modelling, adhesion and activation of canonical oncogenic signalling pathways. Here, we show that BCR/ABL-OOF has a peculiar endosomal localization which affects EGF receptor activation and turnover. Moreover, we demonstrate that BCR/ABL-OOF expression leads to aberrant cellular adhesion due to the activation of Rac GTPase, increase in cellular proliferation, migration and survival. When overexpressed in a BCR/ABL positive cell line, BCR/ABL-OOF induces hyperactivation of Rac signaling axis offering a therapeutic window for Rac-targeted therapy. Our data support a critical role of BCR/ABL-OOF in leukemogenesis and identify a subset of patients that may benefit from Rac-targeted therapies. PMID:26682280

  2. New alternative splicing BCR/ABL-OOF shows an oncogenic role by lack of inhibition of BCR GTPase activity and an increased of persistence of Rac activation in chronic myeloid leukemia

    PubMed Central

    Panuzzo, Cristina; Volpe, Gisella; Rocchietti, Elisa Cibrario; Casnici, Claudia; Crotta, Katia; Crivellaro, Sabrina; Carrà, Giovanna; Lorenzatti, Roberta; Peracino, Barbara; Torti, Davide; Morotti, Alessandro; Camacho-Leal, Maria Pilar; Defilippi, Paola; Marelli, Ornella; Saglio, Giuseppe

    2015-01-01

    In Chronic Myeloid Leukemia 80% of patients present alternative splice variants involving BCR exons 1, 13 or 14 and ABL exon 4, with a consequent impairment in the reading frame of the ABL gene. Therefore BCR/ABL fusion proteins (BCR/ABL-OOF) are characterized by an in-frame BCR portion followed by an amino acids sequence arising from the out of frame (OOF) reading of the ABL gene. The product of this new transcript contains the characteristic BCR domains while lacking the COOH-terminal Rho GTPase GAP domain. The present work aims to characterize the protein functionality in terms of cytoskeleton (re-)modelling, adhesion and activation of canonical oncogenic signalling pathways. Here, we show that BCR/ABL-OOF has a peculiar endosomal localization which affects EGF receptor activation and turnover. Moreover, we demonstrate that BCR/ABL-OOF expression leads to aberrant cellular adhesion due to the activation of Rac GTPase, increase in cellular proliferation, migration and survival. When overexpressed in a BCR/ABL positive cell line, BCR/ABL-OOF induces hyperactivation of Rac signaling axis offering a therapeutic window for Rac-targeted therapy. Our data support a critical role of BCR/ABL-OOF in leukemogenesis and identify a subset of patients that may benefit from Rac-targeted therapies. PMID:26682280

  3. PP2A inhibition results in hepatic insulin resistance despite Akt2 activation.

    PubMed

    Galbo, Thomas; Perry, Rachel J; Nishimura, Erica; Samuel, Varman T; Quistorff, Bjørn; Shulman, Gerald I

    2013-10-01

    In the liver, insulin suppresses hepatic gluconeogenesis by activating Akt, which inactivates the key gluconeogenic transcription factor FoxO1 (Forkhead Box O1). Recent studies have implicated hyperactivity of the Akt phosphatase Protein Phosphatase 2A (PP2A) and impaired Akt signaling as a molecular defect underlying insulin resistance. We therefore hypothesized that PP2A inhibition would enhance insulin-stimulated Akt activity and decrease glucose production. PP2A inhibitors increased hepatic Akt phosphorylation and inhibited FoxO1in vitro and in vivo, and suppressed gluconeogenesis in hepatocytes. Paradoxically, PP2A inhibition exacerbated insulin resistance in vivo. This was explained by phosphorylation of both hepatic glycogen synthase (GS) (inactivation) and phosphorylase (activation) resulting in impairment of glycogen storage. Our findings underline the significance of GS and Phosphorylase as hepatic PP2A substrates and importance of glycogen metabolism in acute plasma glucose regulation. PMID:24150286

  4. Acute ethanol intoxication shows no effect on Ca sup 2+ -uptake of Ca sup 2+ -dependent ATPase activity in myocardial sarcoplasmic reticulum vesicles

    SciTech Connect

    McAllister, K.P.; Horton, J.W.; Kaufman, T.M.; White, D.J. )

    1989-02-09

    We have previously shown that acute ethanolism impairs left ventricular (LV) function. We hypothesized that cardiac dysfunction may be related to altered Ca{sup 2+} pump function by the sarcoplasmic reticulum (SR). In this study, LV function (in isolated perfused hearts) was compared to Ca{sup 2+} transport in SR vesicles isolated from nonperfused hearts in control (C) and acutely intoxicated (ETOH, 2.5 ml/kg IV) guinea pigs. Compared to control hearts, ETOH hearts had significantly lower LV systolic pressure maximal rate of LV pressure rise and fall. Ca{sup 2+}-ATPase activity was not significantly different in either group of animals. Although maximum Ca{sup 2+} uptake tended to be slightly lower in ETOH compared to control hearts coupling ratios (mol Ca{sup 2+} transported/mol ATP hydrolyzed) were not significantly different. We conclude that changes in SR Ca{sup 2+} pump function are not responsible for the depressed LV function seen in acute ethanolism.

  5. {(1R,2R,4R)-4-Methyl-1,2-cyclohexanediamine}oxalatoplatinum(II): A Novel Enantiomerically Pure Oxaliplatin Derivative Showing Improved Anticancer Activity in Vivo

    PubMed Central

    Abramkin, Sergey A.; Jungwirth, Ute; Valiahdi, Seied M.; Dworak, Claudia; Habala, Ladislav; Meelich, Kristof; Berger, Walter; Jakupec, Michael A.; Hartinger, Christian G.; Nazarov, Alexey A.; Galanski, Markus; Keppler, Bernhard K.

    2012-01-01

    Novel derivatives of the clinically established anticancer drug oxaliplatin were synthesized. Cytotoxicity of the compounds was studied in six human cancer cell lines by means of the MTT assay. Additionally, most promising complexes were also investigated in cisplatin- and oxaliplatin-resistant human cancer cell models. The therapeutic efficacy in vivo was studied in the murine L1210 leukemia model. Most remarkably, {(1R,2R,4R)-4-methyl-1,2-cyclohexanediamine}oxalatoplatinum(II), comprising an equatorial methyl substituent at position 4 of the cyclohexane ring, was as potent as oxaliplatin in vitro but distinctly more effective in the L1210 model in vivo at the optimal dose. The advantage observed in the in vivo situation was mainly based on a more favorable therapeutic index. The maximum tolerated dose of the novel analogue was higher than that of oxaliplatin and caused a greater increase in life span (>200% versus 152%), with more animals experiencing long-term survival (5/6 versus 2/6). These data support further (pre)clinical development of the methyl-substituted oxaliplatin analogue with improved anticancer activity. PMID:20886814

  6. A Monoclonal Antibody to O-Acetyl-GD2 Ganglioside and Not to GD2 Shows Potent Anti-Tumor Activity without Peripheral Nervous System Cross-Reactivity

    PubMed Central

    Cochonneau, Denis; Chaumette, Tanguy; Clemenceau, Béatrice; Leprieur, Stéphanie; Bougras, Gwenola; Supiot, Stéphane; Mussini, Jean-Marie; Barbet, Jacques; Saba, Julie; Paris, François; Aubry, Jacques; Birklé, Stéphane

    2011-01-01

    Background Monoclonal antibodies (mAb) against GD2 ganglioside have been shown to be effective for the treatment of neuroblastoma. Beneficial actions are, however, associated with generalized pain due to the binding of anti- GD2 mAbs to peripheral nerve fibers followed by complement activation. Neuroblastoma cells that express GD2 also express its O-acetyl derivative, O-acetyl- GD2 ganglioside (OAcGD2). Hence, we investigated the distribution of OAcGD2 in human tissues using mAb 8B6 to study the cross-reactivity of mAb 8B6 with human tissues. Methodology/Principal Findings The distribution of OAcGD2 was performed in normal and malignant tissues using an immunoperoxydase technique. Anti-tumor properties of mAb 8B6 were studied in vitro and in vivo in a transplanted tumor model in mice. We found that OAcGD2 is not expressed by peripheral nerve fibers. Furthermore, we demonstrated that mAb 8B6 was very effective in the in vitro and in vivo suppression of the growth of tumor cells. Importantly, mAb 8B6 anti-tumor efficacy was comparable to that of mAb 14G2a specific to GD2. Conclusion/Significance Development of therapeutic antibodies specific to OAcGD2 may offer treatment options with reduced adverse side effects, thereby allowing dose escalation of antibodies. PMID:21966461

  7. In vitro studies with renal proximal tubule cells show direct cytotoxicity of Androctonus australis hector scorpion venom triggered by oxidative stress, caspase activation and apoptosis.

    PubMed

    Saidani, Chanez; Hammoudi-Triki, Djelila; Laraba-Djebari, Fatima; Taub, Mary

    2016-09-15

    Scorpion envenomation injures a number of organs, including the kidney. Mechanisms proposed to explain the renal tubule injury include direct effects of venom on tubule epithelial cells, as well as indirect effects of the autonomic nervous system, and inflammation. Here, we report direct effects of Androctonus australis hector (Aah) scorpion venom on the viability of Renal Proximal Tubule (RPT) cells in vitro, unlike distal tubule and collecting duct cells. Extensive NucGreen nuclear staining was observed in immortalized rabbit RPT cells following treatment with Aah venom, consistent with cytotoxicity. The involvement of oxidative stress is supported by the observations that 1) anti-oxidants mitigated the Aah venom-induced decrease in the number of viable RPT cells, and 2) Aah venom-treated RPT cells were intensively stained with the CellROX(®) Deep Red reagent, an indicator of Reactive Oxygen Species (ROS). Relevance to normal RPT cells is supported by the red fluorescence observed in Aah venom treated primary rabbit RPT cell cultures following their incubation with the Flica reagent (indicative of caspase activation and apoptosis), and the green fluorescence of Sytox Green (indicative of dead cells). PMID:27470530

  8. 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).

  9. Versatile members of the DNAJ family show Hsp70 dependent anti-aggregation activity on RING1 mutant parkin C289G

    PubMed Central

    Kakkar, Vaishali; Kuiper, E. F. Elsiena; Pandey, Abhinav; Braakman, Ineke; Kampinga, Harm H.

    2016-01-01

    Parkinson’s disease is one of the most common neurodegenerative disorders and several mutations in different genes have been identified to contribute to the disease. A loss of function parkin RING1 domain mutant (C289G) is associated with autosomal-recessive juvenile-onset Parkinsonism (AR-JP) and displays altered solubility and sequesters into aggregates. Single overexpression of almost each individual member of the Hsp40 (DNAJ) family of chaperones efficiently reduces parkin C289G aggregation and requires interaction with and activity of endogenously expressed Hsp70 s. For DNAJB6 and DNAJB8, potent suppressors of aggregation of polyglutamine proteins for which they rely mainly on an S/T-rich region, it was found that the S/T-rich region was dispensable for suppression of parkin C289G aggregation. Our data implies that different disease-causing proteins pose different challenges to the protein homeostasis system and that DNAJB6 and DNAJB8 are highly versatile members of the DNAJ protein family with multiple partially non-overlapping modes of action with respect to handling disease-causing proteins, making them interesting potential therapeutic targets. PMID:27713507

  10. HIV-1 Tat Protein Increases Microglial Outward K+ Current and Resultant Neurotoxic Activity

    PubMed Central

    Liu, Jianuo; Xu, Peng; Collins, Cory; Liu, Han; Zhang, Jingdong; Keblesh, James P.; Xiong, Huangui

    2013-01-01

    Microglia plays a crucial role in the pathogenesis of HIV-1-associated neurocognitive disorders. Increasing evidence indicates the voltage-gated potassium (Kv) channels are involved in the regulation of microglia function, prompting us to hypothesize Kv channels may also be involved in microglia-mediated neurotoxic activity in HIV-1-infected brain. To test this hypothesis, we investigated the involvement of Kv channels in the response of microglia to HIV-1 Tat protein. Treatment of rat microglia with HIV-1 Tat protein (200 ng/ml) resulted in pro-inflammatory microglial activation, as indicated by increases in TNF-α, IL-1β, reactive oxygen species, and nitric oxide, which were accompanied by enhanced outward K+ current and Kv1.3 channel expression. Suppression of microglial Kv1.3 channel activity, either with Kv1.3 channel blockers Margatoxin, 5-(4-Phenoxybutoxy)psoralen, or broad-spectrum K+ channel blocker 4-Aminopyridine, or by knockdown of Kv1.3 expression via transfection of microglia with Kv1.3 siRNA, was found to abrogate the neurotoxic activity of microglia resulting from HIV-1 Tat exposure. Furthermore, HIV-1 Tat-induced neuronal apoptosis was attenuated with the application of supernatant collected from K+ channel blocker-treated microglia. Lastly, the intracellular signaling pathways associated with Kv1.3 were investigated and enhancement of microglial Kv1.3 was found to correspond with an increase in Erk1/2 mitogen-activated protein kinase activation. These data suggest targeting microglial Kv1.3 channels may be a potential new avenue of therapy for inflammation-mediated neurological disorders. PMID:23738010

  11. Preliminary results of systematic sampling of gas manifestations in geodynamically active areas of Greece

    NASA Astrophysics Data System (ADS)

    Daskalopoulou, Kyriaki; D'Alessandro, Walter; Calabrese, Sergio; Kyriakopoulos, Konstantinos

    2016-04-01

    Greece is located on a convergent plate boundary comprising the subduction of the African Plate beneath the Eurasian, while the Arabian plate approaches the Eurasian in a northwestward motion. It is considered to be one of the most tectonically active regions of Earth with a complex geodynamic setting, deriving from a long and complicated geological history. Due to this specific geological background, conditions for the formation of many thermal springs are favoured. In the past years, almost all the already known sites of degassing (fumaroles, soil gases, mofettes, gas bubbling in cold and thermal waters) located in the Hellenic area were sampled at least one time. Collected samples were analysed for their chemical (He, Ne, Ar, O2, N2, H2, H2S, CO, CH4 and CO2) and isotopic composition (He, C and N). Some of these sites have been selected for systematic sampling. Four of them have records longer than 10 years with tens of samplings also considering some literature data. Two of the sites are located in active volcanic areas (Santorini and Nisyros) while the other two are close to actively spreading graben structures with intense seismic activity (Gulf of Korinth and Sperchios basin). Results allowed to define long term background values and also some interesting variation related to seismic or volcanic activity.

  12. Targeted mutagenesis results in an activation of DNA methyltransferase 1 and confirms an autoinhibitory role of its RFTS domain.

    PubMed

    Bashtrykov, Pavel; Rajavelu, Arumugam; Hackner, Benjamin; Ragozin, Sergey; Carell, Thomas; Jeltsch, Albert

    2014-03-21

    The N-terminal regulatory part of DNA methyltransferase 1 (Dnmt1) contains a replication foci targeting sequence (RFTS) domain, which is involved in the recruitment of Dnmt1 to replication forks. The RFTS domain has been observed in a crystal structure to bind to the catalytic domain of the enzyme and block its catalytic centre. Removal of the RFTS domain led to activation of Dnmt1, thus suggesting an autoinhibitory role of this domain. Here, we destabilised the interaction of the RFTS domain with the catalytic domain by site-directed mutagenesis and purified the corresponding Dnmt1 variants. Our data show that these mutations resulted in an up to fourfold increase in Dnmt1 methylation activity in vitro. Activation of Dnmt1 was not accompanied by a change in its preference for methylation of hemimethylated CpG sites. We also show that the Dnmt1 E572R/D575R variant has a higher DNA methylation activity in human cells after transfection into HCT116 cells, which are hypomorphic for Dnmt1. Our findings strongly support the autoinhibitory role of the RFTS domain, and indicate that it contributes to the regulation of Dnmt1 activity in cells.

  13. Silencing of Doublecortin-Like (DCL) Results in Decreased Mitochondrial Activity and Delayed Neuroblastoma Tumor Growth

    PubMed Central

    Verissimo, Carla S.; Elands, Rachel; Cheng, Sou; Saaltink, Dirk-Jan; ter Horst, Judith P.; Alme, Maria N.; Pont, Chantal; van de Water, Bob; Håvik, Bjarte; Fitzsimons, Carlos P.; Vreugdenhil, Erno

    2013-01-01

    Doublecortin-like (DCL) is a microtubule-binding protein crucial for neuroblastoma (NB) cell proliferation. We have investigated whether the anti-proliferative effect of DCL knockdown is linked to reduced mitochondrial activity. We found a delay in tumor development after DCL knockdown in vivo in doxycycline-inducible NB tumor xenografts. To understand the mechanisms underlying this tumor growth retardation we performed a series of in vitro experiments in NB cell lines. DCL colocalizes with mitochondria, interacts with the mitochondrial outer membrane protein OMP25/ SYNJ2BP and DCL knockdown results in decreased expression of genes involved in oxidative phosphorylation. Moreover, DCL knockdown decreases cytochrome c oxidase activity and ATP synthesis. We identified the C-terminal Serine/Proline-rich domain and the second microtubule-binding area as crucial DCL domains for the regulation of cytochrome c oxidase activity and ATP synthesis. Furthermore, DCL knockdown causes a significant reduction in the proliferation rate of NB cells under an energetic challenge induced by low glucose availability. Together with our previous studies, our results corroborate DCL as a key player in NB tumor growth in which DCL controls not only mitotic spindle formation and the stabilization of the microtubule cytoskeleton, but also regulates mitochondrial activity and energy availability, which makes DCL a promising molecular target for NB therapy. PMID:24086625

  14. F-8 digital fly-by-wire flight test results viewed from an active controls perspective

    NASA Technical Reports Server (NTRS)

    Zalai, K. J.; Deets, D. A.

    1975-01-01

    The results of the NASA F-8 digital fly-by-wire flight test program are presented, along with the implications for active controls applications. The closed loop performance of the digital control system agreed well with the sampled-data system design predictions. The digital fly-by-wire mechanization also met pilot flying qualities requirements. The advantages of mechanizing the control laws in software became apparent during the flight program and were realized without sacrificing overall system reliability. This required strict software management. The F-8 flight test results are shown to be encouraging in light of the requirements that must be met by control systems for flight-critical active controls applications.

  15. [Results of active surveillance in low and intermediate risk prostate cancer].

    PubMed

    Llorente, Carlos; Diaz Goizueta, Francisco Javier; Hernandez, Virginia; de la Morena, Jose Manuel; de la Peña, Enrique

    2014-06-01

    In this article we review the most significant published papers on active surveillance in prostate cancer and present the results of our case series. We used as main response variables the percentage of patients remaining in surveillance and the oncological results presented as global, cancer specific and metastasis free survivals. Globally, in published series 71.2% of patients included in active surveillance programs, 10-year overall survival is 68% in the series with longer follow up, and cancer-specific survival varies from 97% to 100%. In our series of 144 patients with median follow up of 3.2 years, 76.3% of the patients continue on surveillance. 24 patients (15.9%) stopped surveillance due to histological progression. 5 patients (21.3%) out of the 23 undergoing surgery presented unfavorable pathological criteria on prostatectomy specimen. No patient has died or developed metastases.

  16. Stretched View Showing 'Victoria'

    NASA Technical Reports Server (NTRS)

    2006-01-01

    [figure removed for brevity, see original site] Stretched View Showing 'Victoria'

    This pair of images from the panoramic camera on NASA's Mars Exploration Rover Opportunity served as initial confirmation that the two-year-old rover is within sight of 'Victoria Crater,' which it has been approaching for more than a year. Engineers on the rover team were unsure whether Opportunity would make it as far as Victoria, but scientists hoped for the chance to study such a large crater with their roving geologist. Victoria Crater is 800 meters (nearly half a mile) in diameter, about six times wider than 'Endurance Crater,' where Opportunity spent several months in 2004 examining rock layers affected by ancient water.

    When scientists using orbital data calculated that they should be able to detect Victoria's rim in rover images, they scrutinized frames taken in the direction of the crater by the panoramic camera. To positively characterize the subtle horizon profile of the crater and some of the features leading up to it, researchers created a vertically-stretched image (top) from a mosaic of regular frames from the panoramic camera (bottom), taken on Opportunity's 804th Martian day (April 29, 2006).

    The stretched image makes mild nearby dunes look like more threatening peaks, but that is only a result of the exaggerated vertical dimension. This vertical stretch technique was first applied to Viking Lander 2 panoramas by Philip Stooke, of the University of Western Ontario, Canada, to help locate the lander with respect to orbiter images. Vertically stretching the image allows features to be more readily identified by the Mars Exploration Rover science team.

    The bright white dot near the horizon to the right of center (barely visible without labeling or zoom-in) is thought to be a light-toned outcrop on the far wall of the crater, suggesting that the rover can see over the low rim of Victoria. In figure 1, the northeast and southeast rims are labeled

  17. A Holographic Road Show.

    ERIC Educational Resources Information Center

    Kirkpatrick, Larry D.; Rugheimer, Mac

    1979-01-01

    Describes the viewing sessions and the holograms of a holographic road show. The traveling exhibits, believed to stimulate interest in physics, include a wide variety of holograms and demonstrate several physical principles. (GA)

  18. Activity measurements of Sr-90 and Cs-137 in spiked solutions of milk. Results of a national intercomparison in Italy.

    PubMed

    De Felice, P; Laitano, R F; Piermattei, S

    1988-02-01

    A national intercomparison was organized by ENEA for activity measurements of 90Sr and 137Cs in spiked solutions of milk. The participants in the intercomparison were the laboratories belonging to the Italian network for control of radioactivity in the environment. The purpose of these measurements was to check the reliability of measurement procedures and experimental means as routinely used by each participant. This first intercomparison showed appreciable discrepancies among the participants and this was due both to improper procedures and non correct calibrated spectrometers. Soon after a second intercomparison was carried out to check to what extent the previous results were reproducible among the various participants. Methods and results are discussed.

  19. Maps showing estimated sediment yield from coastal landslides and active slope distribution along the Big Sur coast, Monterey and San Luis Obispo Counties, California

    USGS Publications Warehouse

    Hapke, Cheryl J.; Green, Krystal R.; Dallas, Kate

    2004-01-01

    The 1982-83 and 1997-98 El Ni?os brought very high precipitation to California?s central coast; this precipitation resulted in raised groundwater levels, coastal flooding, and destabilized slopes throughout the region. Large landslides in the coastal mountains of Big Sur in Monterey and San Luis Obispo Counties blocked sections of California State Route 1, closing the road for months at a time. Large landslides such as these occur frequently in the winter months along the Big Sur coast due to the steep topography and weak bedrock. A large landslide in 1983 resulted in the closure of Highway 1 for over a year to repair the road and stabilize the slope. Resulting work from the 1983 landslide cost over $7 million and generated 30 million cubic yards of debris from landslide removal and excavations to re-establish the highway along the Big Sur coast. Before establishment of the Monterey Bay National Marine Sanctuary (MBNMS) in 1992, typical road opening measures involved disposal of some landslide material and excess material generated from slope stabilization onto the seaward side of the highway. It is likely that some or most of this disposed material, either directly or indirectly through subsequent erosion, was eventually transported downslope into the ocean. In addition to the landslides that initiate above the road, natural slope failures sometimes occur on the steep slopes below the road and thus deliver material to the base of the coastal mountains where it is eroded and dispersed by waves and nearshore currents. Any coastal-slope landslide, generated through natural or anthropogenic processes, can result in sediment entering the nearshore zone. The waters offshore of the Big Sur coast are part of the MBNMS. Since it was established in 1992, landslide-disposal practices came under question for two reasons. The U.S. Code of Federal Regulations, Title 15, Section 922.132 prohibits discharging or depositing, from beyond the boundary of the Sanctuary, any material

  20. Results From NICLAKES Survey of Active Faulting Beneath Lake Nicaragua, Central American Volcanic Arc

    NASA Astrophysics Data System (ADS)

    Funk, J.; Mann, P.; McIntosh, K.; Wulf, S.; Dull, R.; Perez, P.; Strauch, W.

    2006-12-01

    In May of 2006 we used a chartered ferry boat to collect 520 km of seismic data, 886 km of 3.5 kHz subbottom profiler data, and 35 cores from Lake Nicaragua. The lake covers an area of 7700 km2 within the active Central American volcanic arc, forms the largest lake in Central America, ranks as the twentieth largest freshwater lake in the world, and has never been previously surveyed or cored in a systematic manner. Two large stratovolcanoes occupy the central part of the lake: Concepcion is presently active, Maderas was last active less than 2000 years ago. Four zones of active faulting and doming of the lake floor were mapped with seismic and 3.5 kHz subbottom profiling. Two of the zones consist of 3-5-km-wide, 20-30-km-long asymmetric rift structures that trend towards the inactive cone of Maderas Volcano in a radial manner. The northeastern rift forms a 20-27-m deep depression on the lake bottom that is controlled by a north-dipping normal fault. The southwestern rift forms a 25-35-m deep depression controlled by a northeast-dipping normal fault. Both depressions contain mound-like features inferred to be hydrothermal deposits. Two zones of active faulting are associated with the active Concepcion stratovolcano. A 600-m-wide and 6-km-long fault bounded horst block extends westward beneath the lake from a promontory on the west side of the volcano. Like the two radial rift features of Maderas, the horst points roughly towards the active caldera of Concepcion. A second north-south zone of active faulting, which also forms a high, extends off the north coast of Concepcion and corresponds to a localized zone of folding and faulting mapped by previous workers and inferred by them to have formed by gravitational spreading of the flank of the volcano. The close spatial relation of these faults to the two volcanic cones in the lake suggests that the mechanism for faulting is a result of either crustal movements related to magma intrusion or gravitational sliding and is

  1. OMP gene deletion results in an alteration in odorant-induced mucosal activity patterns.

    PubMed

    Youngentob, S L; Kent, P F; Margolis, F L

    2003-12-01

    Previous behavioral work, using a complex five-odorant identification task, demonstrated that olfactory marker protein (OMP) is critically involved in odor processing to the extent that its loss results in an alteration in odorant quality perception. Exactly how the lack of OMP exerts its influence on the perception of odorant quality is unknown. However, there is considerable neurophysiological evidence that different odorants produce different spatiotemporal patterns of neural activity at the level of the mucosa and that these patterns predict the psychophysically determined perceptual relationship among odorants. In this respect, OMP gene deletion is known to result in a constellation of physiologic defects (i.e., marked reduction in the electroolfactogram (EOG) and altered response and recovery kinetics) that would be expected to alter the odorant-induced spatiotemporal activity patterns that are characteristic of different odorants. This, in turn, would be expected to alter the spatiotemporal patterning of information that results from the mucosal projection onto the bulb, thereby changing odorant quality perception. To test the hypothesis that odorant-induced mucosal activity patterns are altered in mice lacking the gene for OMP, we optically recorded the fluorescent changes in response to odorant stimulation from both the septum and turbinates of both OMP-null and control mice using a voltage-sensitive dye (di-4-ANEPPS Molecular Probes, Eugene, OR) and a Dalsa 120 x 120, 12-bit CCD camera. To maintain continuity with the previous behavioral work, the odorants 2-propanol, citral, carvone, ethylacetoacetate, and propyl acetate were again used. Each odorant was randomly presented to each mucosal surface in a Latin-Square design. The results of this study demonstrated that, for both mouse strains, there do indeed exist different spatiotemporal activity patterns for different odorants. More importantly, however, these patterns significantly differed between OMP

  2. Testing and Oxygen Assessment Results for a Next Generation Extravehicular Activity Portable Life Support System Fan

    NASA Technical Reports Server (NTRS)

    Paul, Heather L.; Jennings, Mallory A.; Rivera, Fatonia L.; Martin, Devin

    2011-01-01

    NASA is designing a next generation Extravehicular Activity (EVA) Portable Life Support System (PLSS) for use in future surface exploration endeavors. To meet the new requirements for ventilation flow at nominal and buddy modes, a fan has been developed and tested. This paper summarizes the results of the performance and life cycle testing efforts conducted at the NASA Johnson Space Center. Additionally, oxygen compatibility assessment results from an evaluation conducted at White Sands Test Facility (WSTF) are provided, and lessons learned and future recommendations are outlined.

  3. Holocene glacier activity on Kerguelen Island: preliminary results from a novel proglacial lake sediment record

    NASA Astrophysics Data System (ADS)

    Støren, Eivind; Bakke, Jostein; Arnaud, Fabien; Poulenard, Jérôme; Fanget, Bernard; Malet, Emmanuel; Sabatier, Pierre

    2016-04-01

    The Polar-regions are changing rapidly as greenhouse warming is continuing with huge impact on e.g. sea ice extent and snow cover. This change triggers teleconnections to low latitude areas challenging societies and human activity. We have, however, very little quantitative information of past climate in the Polar-regions that can be used to evaluate the potential responses and the response patterns to forcing changes and changes in boundary conditions. Whatever anthropogenic changes may occur in the future, they will be superimposed on, and interact with, natural climate variations due to all the forcing we are aware of. This means we need to better document past climate/environmental variability of the Polar-regions. Especially in the Southern Ocean there are few time series recording past climate due to few suitable land areas and the few Sub-Antarctic Islands is remote and has cumbersome logistics. Continuous terrestrial records from this region are therefore urgently needed for constraining future scenarios from earth system models. Glaciers and ice caps are still ubiquitous in the Polar-regions, although they are rapidly shrinking due to the on-going warming. The continuous sedimentary records produced by glaciers, which are stored in downstream lakes, represent supreme archives of past variability wherefrom quantitative information of key climate system components can be extracted. Kerguelen Island is located within the Antarctic Circumpolar Current and the Southern Westerly wind belt and contains several glaciers and smaller ice caps. Terrestrial archives recording past history of the glaciers at Kerguelen thus have a unique potential to record past changes in oceanic and atmospheric circulation patterns from southern mid-latitudes. Here we present preliminary results from the first distal glacier-fed lake that is sampled from Kerguelen Island. A 2.8 m long sediment core was obtained from Lac Guynemer (121masl.) located at the Peninsule Loranchet at the

  4. Overexpression of PAD1 and FDC1 results in significant cinnamic acid decarboxylase activity in Saccharomyces cerevisiae.

    PubMed

    Richard, Peter; Viljanen, Kaarina; Penttilä, Merja

    2015-01-01

    The S. cerevisiae PAD1 gene had been suggested to code for a cinnamic acid decarboxylase, converting trans-cinnamic acid to styrene. This was suggested for the reason that the over-expression of PAD1 resulted in increased tolerance toward cinnamic acid, up to 0.6 mM. We show that by over-expression of the PAD1 together with the FDC1 the cinnamic acid decarboxylase activity can be increased significantly. The strain over-expressing PAD1 and FDC1 tolerated cinnamic acid concentrations up to 10 mM. The cooperation of Pad1p and Fdc1p is surprising since the PAD1 has a mitochondrial targeting sequence and the FDC1 codes for a cytosolic protein. The cinnamic acid decarboxylase activity was also seen in the cell free extract. The activity was 0.019 μmol per minute and mg of extracted protein. The overexpression of PAD1 and FDC1 resulted also in increased activity with the hydroxycinnamic acids ferulic acid, p-coumaric acid and caffeinic acid. This activity was not seen when FDC1 was overexpressed alone. An efficient cinnamic acid decarboxylase is valuable for the genetic engineering of yeast strains producing styrene. Styrene can be produced from endogenously produced L-phenylalanine which is converted by a phenylalanine ammonia lyase to cinnamic acid and then by a decarboxylase to styrene.

  5. Primary patellar tendon repair and early mobilization: results in an active-duty population.

    PubMed

    Enad, J G; Loomis, L L

    2001-01-01

    We retrospectively reviewed 13 patellar tendon repairs done over 32 months at a tertiary care, military medical center. Early mobilization was initiated within 2 weeks postoperatively. Clinical and functional results were statistically examined with relation to age, timing of surgery, length of follow-up, quadriceps atrophy, extensor lag, patella position, and time to full duty. At an average of 24 months' follow-up, six patients (46%) had thigh girth atrophy, and one patient (8%) had an extensor lag >5 degrees. Mean Lysholm score was 84 (range, 57 to 100). Maximum postoperative Tegner activity scores averaged 7.1 (range, 5 to 10). Clinical results classified five cases as excellent, three good, three fair, and two poor. Functional results classified three cases as excellent, four good, two fair, and four poor. Time to return to duty averaged 13 months. Our results suggest that adequate extensor function can be restored after primary repair and immediate motion therapy.

  6. Novel Brentuximab Vedotin Combination Therapies Show Promising Activity in Highly Refractory CD30+ Non-Hodgkin Lymphoma: A Case Series and Review of the Literature

    PubMed Central

    Setlik, Robert; Hassantoufighi, Arash; Daya, Shyam; Selby, Dale; Brown, Alexander

    2016-01-01

    Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of hematologic malignancies which typically respond to standard first-line chemoimmunotherapy regimens. Unfortunately, patients with refractory NHL face a poor prognosis and represent an unmet need for improved therapeutics. We present two cases of refractory CD30+ NHL who responded to novel brentuximab vedotin- (BV-) based regimens. The first is a patient with stage IV anaplastic large cell lymphoma (ALCL) with cranial nerve involvement who failed front-line treatment with cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP) and second line cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with high-dose methotrexate (MTX), and cytarabine (hyperCVAD) with intrathecal- (IT-) MTX and IT-cytarabine, but responded when BV was substituted for vincristine (hyperCBAD). The second patient was a man with stage IV diffuse large B-cell lymphoma (DLBCL) with leptomeningeal involvement whose disease progressed during first-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and progressed despite salvage therapy with rituximab, dexamethasone, cytarabine, and cisplatin (R-DHAP) in whom addition of BV to topotecan resulted in a significant response. This report describes the first successful salvage treatments of highly aggressive, double refractory CD30+ NHL using two unreported BV-based chemoimmunotherapy regimens. Both regimens appear effective and have manageable toxicities. Further clinical trials assessing novel BV combinations are warranted. PMID:27807492

  7. Extracts from Vatica diospyroides type SS fruit show low dose activity against MDA-MB-468 breast cancer cell-line via apoptotic action.

    PubMed

    Srisawat, Theera; Sukpondma, Yaowapa; Chimplee, Siriphon; Kanokwiroon, Kanyanatt; Tedasen, Aman; Graidist, Potchanapond

    2014-01-01

    Very strong antiproliferative action of V. diospyroides type SS fruit extracts (IC50 range of 1.60-17.45 µg/mL) in MDA-MB-468 cell-line was observed in an MTT assay. After dosing of an extract concentration at half IC50 to cell line for 24 to 72 hours, treated cells were subjected to Annexin V-FITC/PI binding assay, followed by FACS and western blot analyses. Significant apoptotic death was observed with all extract treatments and both exposure times. Dosing with acetone extract of pericarp and cotyledon induced the highest apoptotic populations (33 and 32%, resp.), with the lowest populations of viable cells (65 and 67%, resp.). During 24 to 72 hours of dosing with methanolic extract of pericarp, the populations of viable and early apoptotic cells decreased significantly from 72.40 to 71.32% and from 12.00 to 6.36%, respectively, while the late apoptotic and nonviable cell populations continuously increased from 15.30 to 19.18% and from 0.30 to 3.14%, respectively. The expression of Bax increased within 12-48 hours of dosing, confirming apoptosis induced by time-dependent responses. The mutant p53 of MDA-MB-468 cells was expressed. Our results indicate that apoptosis and time-dependent therapeutic actions contribute to the cytotoxic effects of V. diospyroides type SS fruit on MDA-MB-468 cell.

  8. The Fifth International Ice Nucleation Workshop Activities FIN-1 and FIN-2: Overview and Selected Results

    NASA Astrophysics Data System (ADS)

    Moehler, O.; Cziczo, D. J.; DeMott, P. J.; Hiranuma, N.; Petters, M. D.

    2015-12-01

    The role of aerosol particles for ice formation in clouds is one of the largest uncertainties in understanding the Earth's weather and climate systems, which is related to the poor knowledge of ice nucleation microphysics or of the nature and atmospheric abundance of ice nucleating particles (INPs). During the recent years, new mobile instruments were developed for measuring the concentration, size and chemical composition of INPs, which were tested during the three-part Fifth International Ice Nucleation (FIN) workshop. The FIN activities addressed not only instrument issues, but also important science topics like the nature of atmospheric INP and cloud ice residuals, the ice nucleation activity of relevant atmospheric aerosols, or the parameterization of ice formation in atmospheric weather and climate models. The first activity FIN-1 was conducted during November 2014 at the AIDA cloud chamber. It involved co-locating nine single particle mass spectrometers to evaluate how well they resolve the INP and ice residual composition and how spectra from different instruments compare for relevant atmospheric aerosols. We conducted about 90 experiments with mineral, carbonaceous and biological aerosol types, some also coated with organic and inorganic compounds. The second activity FIN-2 was conducted during March 2015 at the AIDA facility. A total of nine mobile INP instruments directly sampled from the AIDA aerosol chambers. Wet suspension and filter samples were also taken for offline INP processing. A refereed blind intercomparison was conducted during two days of the FIN-2 activity. The third activity FIN-3 will take place at the Desert Research Institute's Storm Peak Laboratory (SPL) in order to test the instruments' performance in the field. This contribution will introduce the FIN activities, summarize first results from the formal part of FIN-2, and discuss selected results, mainly from FIN-1 for the effect of coating on the ice nucleation (IN) by mineral

  9. SU-E-T-594: Preliminary Active Scanning Results of KHIMA

    SciTech Connect

    Kim, C; Yang, T; Chang, S; Kim, H; Lee, H; Kim, J; Jang, H; Han, G; Park, D; Hwang, W; Kim, G

    2014-06-01

    Purpose: To verify the design criteria on heavy ion beam irradiation, developing a proto type active scanning system was purposed. The active scanning system consists of scanning magnet, power supplies, beam monitors, energy modulation system, and irradiation control system. Methods: Each components of the active scanning system was designed for carbon beam first. For the fast ramping a laminated yoke was purposed. To measure incoming dose and profile, a plate and strip type of ion chambers were designed. Also, ridge filter and range shifter was manufactured. And, the scanning system was modified to adopt 45 MeV of proton beam because of the absence of carbon ion beam in Korea. The system was installed in a beam line at MC-50, KIRAMS. Also, the irradiation control system and planning software was provided. Results: The scanning experiment was performed by drawing KHIMA logo on GaF film. The logo was scanned by 237 scanning points through time normalized intensity modulation. Also, a grid points scanning was performed to measure the scanning resolution and intensity resolution. Conclusion: A prototype active scanning system was successfully designed and manufactured. Also, an initial experiment to print out a drawing on GaF film through the scanning system was completed. More experiments would be required to specify the system performance.

  10. Activation of thalamus in motor imagery results from gating by hypnosis.

    PubMed

    Müller, Katharina; Bacht, Katrin; Prochnow, Denise; Schramm, Stefanie; Seitz, Rüdiger J

    2013-02-01

    The ability to mentally imagine the performance of automatic movements has been well-established being employed in sports and physiotherapy as a tool for motor learning and rehabilitation. This is probably mediated by engagement of the same brain areas as during real motor performance. Here we investigated the effect of hypnotic trance on the cerebral activation pattern engaged in motor imagery in 16 healthy, right-handed subjects using fMRI. Motor imagery as compared with rest was related to activations in the left medial frontal areas (preSMA/SMA), prefrontal- and frontal areas, putamen and inferior parietal areas. When compared with performance of the same movements motor imagery resulted in activation of the left middle frontal cortex, precuneus, and posterior cingulate. Under hypnotic trance there was one extra-activation in the left thalamus which occurred specifically in the motor imagery condition. The regional beta indices were highly correlated among the areas of the cortical-subcortical motor network. Our data accord with the notion that hypnotic trance enhances the motor control circuit engaged in motor imagery by modulating the gating function of the thalamus.

  11. Massive transfusion protocol activation does not result in preferential use of older red blood cells.

    PubMed

    McDaniel, Lauren M; Triulzi, Darrell J; Cramer, James; Zuckerbraun, Brian S; Sperry, Jason L; Peitzman, Andrew B; Raval, Jay S; Neal, Matthew D

    2014-01-01

    Widespread, anecdotal belief exists that patients receiving massive transfusion, particularly those for whom a massive transfusion protocol (MTP) is activated, are more likely to receive older red blood cells (RBCs). Retrospective review of blood bank records from calendar year 2011 identified 131 patients emergently issued ≥10 RBC units (emergency release (ER)) prior to obtaining a type and screen. This cohort was subclassified based on whether there was MTP activation. For comparison, 176 identified patients transfused with ≥10 RBC units in a routine fashion over 24 hours represented the nonemergency release (nER) cohort. Though the median age of ER RBCs was 5 days older than nER RBCs (ER 20, nER 15 days, P < 0.001), both fell within the third week of storage. Regardless of MTP activation, transfused ER RBCs had the same median age (MTP 20, no-MTP 20 days, P = 0.069). In the ER cohort, transition to type-specific blood components increased the median age of transfused RBC units from 17 to 36 days (P < 0.001). These data refute the anecdotal belief that MTP activation results in transfusion of older RBCs. However, upon transition to type-specific blood components, the age of RBCs enters a range in which it is hypothesized that there may be a significant effect of storage age on clinical outcomes.

  12. Design of a Website on Nutrition and Physical Activity for Adolescents: Results From Formative Research

    PubMed Central

    Cullen, Karen Weber; Boushey, Carol; Konzelmann, Karen

    2012-01-01

    Background Teens do not meet guidelines for healthy eating and physical activity. The Internet may be an effective method for delivering programs that help them adopt healthy behaviors. Objective To collect information to design content and structure for a teen-friendly website promoting healthy eating and physical activity behaviors. Methods Qualitative research, encompassing both focus group and interview techniques, were used to design the website. Participants were 12-17 year olds in Houston, Texas, and West Lafayette, Indiana. Results A total of 133 participants took part in 26 focus groups while 15 participated in one-on-one interviews to provide guidance for the development of teen-friendly content and structure for an online behavior change program promoting healthy eating and physical activity to 12-17 year olds. The youth made suggestions to overcome common barriers to healthy eating and physical activity. Their feedback was used to develop “Teen Choice: Food & Fitness,” a 12-week online behavior change program, populated by 4 cartoon character role models. Conclusions It is critical that members of the target audience be included in formative research to develop behavior change programs that are relevant, appealing, and address their needs and interests. PMID:22538427

  13. Stage a Water Show

    ERIC Educational Resources Information Center

    Frasier, Debra

    2008-01-01

    In the author's book titled "The Incredible Water Show," the characters from "Miss Alaineus: A Vocabulary Disaster" used an ocean of information to stage an inventive performance about the water cycle. In this article, the author relates how she turned the story into hands-on science teaching for real-life fifth-grade students. The author also…

  14. Obesity in show cats.

    PubMed

    Corbee, R J

    2014-12-01

    Obesity is an important disease with a high prevalence in cats. Because obesity is related to several other diseases, it is important to identify the population at risk. Several risk factors for obesity have been described in the literature. A higher incidence of obesity in certain cat breeds has been suggested. The aim of this study was to determine whether obesity occurs more often in certain breeds. The second aim was to relate the increased prevalence of obesity in certain breeds to the official standards of that breed. To this end, 268 cats of 22 different breeds investigated by determining their body condition score (BCS) on a nine-point scale by inspection and palpation, at two different cat shows. Overall, 45.5% of the show cats had a BCS > 5, and 4.5% of the show cats had a BCS > 7. There were significant differences between breeds, which could be related to the breed standards. Most overweight and obese cats were in the neutered group. It warrants firm discussions with breeders and cat show judges to come to different interpretations of the standards in order to prevent overweight conditions in certain breeds from being the standard of beauty. Neutering predisposes for obesity and requires early nutritional intervention to prevent obese conditions. PMID:24612018

  15. Show Me the Way

    ERIC Educational Resources Information Center

    Dicks, Matthew J.

    2005-01-01

    Because today's students have grown up steeped in video games and the Internet, most of them expect feedback, and usually gratification, very soon after they expend effort on a task. Teachers can get quick feedback to students by showing them videotapes of their learning performances. The author, a 3rd grade teacher describes how the seemingly…

  16. The Art Show

    ERIC Educational Resources Information Center

    Scolarici, Alicia

    2004-01-01

    This article describes what once was thought to be impossible--a formal art show extravaganza at an elementary school with 1,000 students, a Department of Defense Dependent School (DODDS) located overseas, on RAF Lakenheath, England. The dream of this this event involved the transformation of the school cafeteria into an elegant art show…

  17. Honored Teacher Shows Commitment.

    ERIC Educational Resources Information Center

    Ratte, Kathy

    1987-01-01

    Part of the acceptance speech of the 1985 National Council for the Social Studies Teacher of the Year, this article describes the censorship experience of this honored social studies teacher. The incident involved the showing of a videotape version of the feature film entitled "The Seduction of Joe Tynan." (JDH)

  18. Whole Blood Activation Results in Altered T Cell and Monocyte Cytokine Production Profiles by Flow Cytometry

    NASA Technical Reports Server (NTRS)

    Crucian, Brian E.; Sams, Clarence F.

    2001-01-01

    An excellent monitor of the immune balance of peripheral circulating cells is to determine their cytokine production patterns in response to stimuli. Using flow cytometry, a positive identification of cytokine producing cells in a mixed culture may be achieved. Recently, the ability to assess cytokine production following a whole-blood activation culture has been described. In this study, whole blood activation was compared to traditional PBMC activation and the individual cytokine secretion patterns for both T cells, T cell subsets and monocytes was determined by flow cytometry. RESULTS: For T cell cytokine assessment (IFNg/IL-10 and IL-21/L-4) following PMA +ionomycin activation: (1) a Significantly greater percentages of T cells producing IFNgamma and IL-2 were observed following whole-blood culture and (2) altered T cell cytokine production kinetics were observed by varying whole blood culture times. Four-color analysiS was used to allow assessment of cytokine production by specific T cell subsets. It was found that IFNgamma production was significantly elevated in the CD3+/CD8+ T cell population as compared to the CD3+/CD8- population following five hours of whole blood activation. Conversely, IL-2 and IL-10 production were Significantly elevated in the CD3+/CD8- T cell population as compared to the CD3+/CD8+ population. Monocyte cytokine production was assessed in both culture systems following LPS activation for 24 hours. A three-color flow cytometric was used to assess two cytokines (IL-1a/IL-12 and TNFa/IL-10) in conjunction with CD14. Nearly all monocytes were stimulated to produce IL-1a, IL-12 and TNFa. equally well in both culture systems, however monocyte production of IL-10 was significantly elevated in whole blood culture as compared to PBMC culture. IL-12 producing monocytes appeared to be a distinct subpopulation of the IL-1a producing set, whereas IL-10 and TNFa producing monocytes were largely mutually exclusive. IL-10 and TNFa producing

  19. Mutation in E1, the ubiquitin activating enzyme, reduces Drosophila lifespan and results in motor impairment.

    PubMed

    Liu, Hsiu-Yu; Pfleger, Cathie M

    2013-01-01

    Neurodegenerative diseases cause tremendous suffering for those afflicted and their families. Many of these diseases involve accumulation of mis-folded or aggregated proteins thought to play a causal role in disease pathology. Ubiquitinated proteins are often found in these protein aggregates, and the aggregates themselves have been shown to inhibit the activity of the proteasome. These and other alterations in the Ubiquitin Pathway observed in neurodegenerative diseases have led to the question of whether impairment of the Ubiquitin Pathway on its own can increase mortality or if ongoing neurodegeneration alters Ubiquitin Pathway function as a side-effect. To address the role of the Ubiquitin Pathway in vivo, we studied loss-of-function mutations in the Drosophila Ubiquitin Activating Enzyme, Uba1 or E1, the most upstream enzyme in the Ubiquitin Pathway. Loss of only one functional copy of E1 caused a significant reduction in adult lifespan. Rare homozygous hypomorphic E1 mutants reached adulthood. These mutants exhibited further reduced lifespan and showed inappropriate Ras activation in the brain. Removing just one functional copy of Ras restored the lifespan of heterozygous E1 mutants to that of wild-type flies and increased the survival of homozygous E1 mutants. E1 homozygous mutants also showed severe motor impairment. Our findings suggest that processes that impair the Ubiquitin Pathway are sufficient to cause early mortality. Reduced lifespan and motor impairment are seen in the human disease X-linked Infantile Spinal Muscular Atrophy, which is associated with mutation in human E1 warranting further analysis of these mutants as a potential animal model for study of this disease.

  20. Changes in the cardiac muscle electric activity as a result of Coronary Artery Bypass Graft operation

    NASA Astrophysics Data System (ADS)

    Grajek, Magdalena; Krzyminiewski, Ryszard; Kalawski, Ryszard; Kulczak, Mariusz

    2008-01-01

    Many bioelectric signals have a complex internal structure that can be a rich source of information on the tissue or cell processes. The structure of such signals can be analysed in detail by applying digital methods of signal processing. Therefore, of substantial use in diagnosis of the coronary arterial disease is the method of digital enhancement of increasing signal resolution ECG (NURSE-ECG), permitting detection of temporary changes in the electric potentials in the cardiac muscle in the process of depolarisation. Thanks to the application of NURSE-ECG it has become possible to detect relatively small changes in the electric activity of particular fragments of the cardiac muscle undetectable by the standard ECG method, caused by ischemia, the effect of a drug or infarct. The aim of this study was to identify and analyse changes in the electric activity of the cardiac muscle as a result of the Coronary Artery Bypass Graft (CABG) operation. In this study the method of NURSE-ECG has been applied in order to identify and analyse changes in the electric activity of the cardiac muscle as a result of the CABG operation. In the study performed in cooperation of the Institute of Physics Adam Mickiewicz University and the Strus Hospital, Cardiac Surgery Ward, 37 patients with advanced coronary arterial disease were asked to participate. The patients were examined prior to the operation, on the day after the operation and two months after the operation and a year after the operation. The ECG recordings were subjected to a numerical procedure of resolution enhancement by a NURSE-ECG program to reveal the tentative changes in the electric potential of the cardiac muscle on its depolarisation. Results of the study have shown that the NURSE ECG method can be applied to monitor changes in the electric activity of the cardiac muscle occurring as a result of CABG operation. One the second day after the operation in the majority of patients (70%) a rapid decrease of the total

  1. TRPA1 activation by lidocaine in nerve terminals results in glutamate release increase

    SciTech Connect

    Piao, L.-H.; Fujita, Tsugumi; Jiang, C.-Y.; Liu Tao; Yue, H.-Y.; Nakatsuka, Terumasa; Kumamoto, Eiichi

    2009-02-20

    We examined the effects of local anesthetics lidocaine and procaine on glutamatergic spontaneous excitatory transmission in substantia gelatinosa (SG) neurons in adult rat spinal cord slices with whole-cell patch-clamp techniques. Bath-applied lidocaine (1-5 mM) dose-dependently and reversibly increased the frequency but not the amplitude of spontaneous excitatory postsynaptic current (sEPSC) in SG neurons. Lidocaine activity was unaffected by the Na{sup +}-channel blocker, tetrodotoxin, and the TRPV1 antagonist, capsazepine, but was inhibited by the TRP antagonist, ruthenium red. In the same neuron, the TRPA1 agonist, allyl isothiocyanate, and lidocaine both increased sEPSC frequency. In contrast, procaine did not produce presynaptic enhancement. These results indicate that lidocaine activates TRPA1 in nerve terminals presynaptic to SG neurons to increase the spontaneous release of L-glutamate.

  2. Social support and physical activity change in Latinas: Results from the Seamos Saludables trial

    PubMed Central

    Marquez, Becky; Dunsiger, Shira I.; Pekmezi, Dori; Larsen, Britta A.; Marcus, Bess H.

    2016-01-01

    Objective Family responsibilities and poor social support are barriers to physical activity among Latinas. This study evaluated the effects of a home- and print-based intervention on social support, moderating effects of familial ties on support and moderate-to-vigorous physical activity (MVPA), and mediating effects of support on MVPA. Methods Participants were randomized to receive through the mail either individually tailored physical activity intervention or general wellness print materials. Familial ties and social support were assessed by marital and child status and the social support for physical activity measure, respectively. MVPA was measured using the 7-day Physical Activity Recall Interview and accelerometer. Assessments were conducted at baseline, 6 months post-treatment, and 12 months follow-up. Results Participants (n=266; 40.6 ± 9.9 years old) were mostly immigrant and Spanish-speaking Latinas. The intervention group achieved greater increases in family and friend support compared to the wellness control group from baseline to post-treatment and follow-up (p<0.05). Intervention changes in support did not depend on marital or child status. The intervention also increased minutes per week of MVPA more than the wellness control (p<0.05) and the effect did not depend on marital or child status. There were significant indirect effects of treatment, indicating the intervention achieved greater increases in MVPA by increasing family (ab=5.21, SE=2.94, 95% CI=0.91–14.11) and friend (ab=6.83, SE=5.15, 95% CI=0.16–20.56) support. Conclusions The intervention improved and sustained support from family and friends and MVPA irrespective of familial ties. Social support mediated increases in MVPA. PMID:26863464

  3. Results From an Intervention to Improve Rural Home Food and Physical Activity Environments

    PubMed Central

    Kegler, Michelle C.; Alcantara, Iris; Veluswamy, J. K.; Haardörfer, Regine; Hotz, James A.; Glanz, Karen

    2013-01-01

    Background Ecological models of healthy eating and physical activity emphasize the influence of behavioral settings such as homes and worksites in shaping behavior. Research on home environments suggests that both social and physical aspects of the home may impact physical activity and healthy eating. Objective Using a community-based participatory research (CBPR) approach, the Emory Prevention Research Center (EPRC), Cancer Coalition of South Georgia, and the EPRC’s Community Advisory Board (CAB) designed and tested a coach-based intervention to make the home environment more supportive of healthy eating and physical activity for rural adults. Methods The 6-week intervention consisted of a tailored home environment profile, goal-setting, and behavioral contracting delivered through two home visits and two telephone calls. The study used a quasi-experimental design with data collected via telephone interviews at baseline, 2 and 4 months post-baseline. Ninety households (n = 90) completed all three telephone interviews. Results Multilevel models indicated that intervention households reported significant improvements in household food inventories, purchasing of fruit and vegetables, healthier meal preparation, meals with the TV off, and family support for healthy eating, relative to comparison households. Intervention households also reported increased exercise equipment and family support for physical activity relative to comparison households. Percent of fat intake decreased significantly, but no changes were observed for fruit and vegetable intake, physical activity, or weight among intervention relative to comparison households, although trends were generally in a positive direction. Conclusion Coaching combined with a focus on the home environment may be a promising strategy for weight gain prevention in adults. PMID:22982840

  4. Long term results of mechanical prostheses for treatment of active infective endocarditis

    PubMed Central

    Guerra, J; Tornos, M; Permanyer-Miralda, G; Almirante, B; Murtra, M; Soler-Soler, J

    2001-01-01

    OBJECTIVE—To analyse the long term results of mechanical prostheses for treating active infective endocarditis.
DESIGN—Prospective cohort study of a consecutive series of patients diagnosed with infective endocarditis and operated on in the active phase of the infection for insertion of a mechanical prosthesis.
SETTING—Tertiary referral centre in a metropolitan area.
RESULTS—Between 1975 and 1997, 637 cases of infective endocarditis were diagnosed in the centre. Of these, 436 were left sided (with overall mortality of 20.3%). Surgical treatment in the active phase of the infection was needed in 141 patients (72% native, 28% prosthetic infective endocarditis). Mechanical prostheses were used in 131 patients. Operative mortality was 30.5% (40 patients). Ninety one survivors were followed up prospectively for (mean (SD)) 5.4 (4.5) years. Thirteen patients developed prosthetic valve dysfunction. Nine patients suffered reinfection: four of these (4%) were early and five were late. The median time from surgery for late reinfection was 1.4 years. During follow up, 12 patients died. Excluding operative mortality, actuarial survival was 86.6% at five years and 83.7% at 10 years; actuarial survival free from death, reoperation, and reinfection was 73.1% at five years and 59.8% at 10 years.
CONCLUSIONS—In patients surviving acute infective endocarditis and receiving mechanical prostheses, the rate of early reinfection compares well with reported results of homografts. In addition, prosthesis dysfunction rate is low and long term survival is good. These data should prove useful for comparison with long term studies, when available, using other types of valve surgery in active infective endocarditis.


Keywords: infective endocarditis; surgery; mechanical prosthesis PMID:11410564

  5. Mouse strain-dependent caspase activation during acetaminophen hepatotoxicity does not result in apoptosis or modulation of inflammation

    SciTech Connect

    Williams, C. David; Koerner, Michael R.; Lampe, Jed N.; Farhood, Anwar; Jaeschke, Hartmut

    2011-12-15

    The mechanisms of acetaminophen (APAP)-mediated hepatic oncotic necrosis have been extensively characterized. However, it was recently demonstrated that fed CD-1 mice have a transient caspase activation which initiates apoptosis. To evaluate these findings in more detail, outbred (Swiss Webster, SW) and inbred (C57BL/6) mice were treated with APAP with or without pan-caspase inhibitor and compared to the apoptosis model of galactosamine (GalN)/endotoxin (ET). Fasted or fed APAP-treated C57BL/6 mice showed no evidence of caspase-3 processing or activity. Interestingly, a minor, temporary increase in caspase-3 processing and activity (150% above baseline) was observed after APAP treatment only in fed SW mice. The degree of caspase-3 activation in SW mice after APAP was minor compared to that observed in GalN/ET-treated mice (1600% above baseline). The pancaspase inhibitor attenuated caspase activation and resulted in increased APAP-induced injury (plasma ALT, necrosis scoring). The caspase inhibitor did not affect apoptosis because regardless of treatment only < 0.5% of hepatocytes showed consistent apoptotic morphology after APAP. In contrast, > 20% apoptotic cells were observed in GalN/ET-treated mice. Presence of the caspase inhibitor altered hepatic glutathione levels in SW mice, which could explain the exacerbation of injury. Additionally, the infiltration of hepatic neutrophils was not altered by the fed state of either mouse strain. Conclusion: Minor caspase-3 activation without apoptotic cell death can be observed only in fed mice of some outbred strains. These findings suggest that although the severity of APAP-induced liver injury varies between fed and fasted animals, the mechanism of cell death does not fundamentally change. -- Highlights: Black-Right-Pointing-Pointer During acetaminophen overdose caspase-3 can be activated in fed mice of certain outbred strains. Black-Right-Pointing-Pointer Hepatic ATP levels are not the determining factor for caspase

  6. Improvement of IVF results and optimisation of quality control by using intermittent activity.

    PubMed

    Frydman, Nelly; Fanchin, Rénato; Le Dû, Anne; Bourrier, Marie Catherine; Tachdjian, Gérard; Frydman, René

    2004-11-01

    For several years the present authors' team had not been satisfied with the pregnancy rate achieved by their unit, especially in comparison with the results achieved by other teams with a similar population. A quality programme was established, and it was decided to switch from non-stop to intermittent activity. It was envisaged that this programme would provide a more realistic view of the team's activity and could also, as a secondary effect, improve its results. The team's experience of an in-series organization was presented for the management of 408 consecutive infertile couples, during 2002. The results obtained during 2002 were compared with those for two previous years. There was a significant increase (P < 0.01) in the clinical pregnancy rate per oocyte retrieval from 28.9% (2000) and 25.2% (2001) to 41% (2002) in IVF and from 23% (2000) and 26% (2001) to 38.5% (2002) in intracytoplasmic sperm injection (ICSI). A significant increase (P < 0.01) was also observed in the implantation rate, from 14.8% and 13.4% to 20% in IVF and from 12.1% and 12.9% to 23.5% in ICSI. The higher pregnancy rate was achieved without an increase in the multiple pregnancy rate. In conclusion, recent data support the hypothesis that the use of a quality management system, can, as in this case, have positive repercussions on pregnancy rates.

  7. Salton Sea Scientific Drilling Project: A summary of drilling and engineering activities and scientific results

    SciTech Connect

    Ross, H.P.; Forsgren, C.K.

    1992-04-01

    The Salton Sea Scientific g Project (SSSDP) completed the first major well in the United States Continental Scientific Drilling Program. The well (State 2-14) was drilled to 10,W ft (3,220 m) in the Salton Sea Geothermal Field in California's Imperial Valley, to permit scientific study of a deep, high-temperature portion of an active geothermal system. The program was designed to investigate, through drilling and testing, the subsurface thermal, chemical, and mineralogical environments of this geothermal area. Extensive samples and data, including cores, cuttings, geothermal fluids and gases, and geophysical logs, were collected for future scientific analysis, interpretation, and publication. Short duration flow tests were conducted on reservoirs at a depth of approximately 6,120 ft (1,865 m) and at 10,136 ft (3,089 m). This report summarizes all major activities of the SSSDP, from project inception in the fall of 1984 through brine-pond cleanup and site restoration, ending in February 1989. This report presents a balanced summary of drilling, coring, logging, and flow-test operations, and a brief summary of technical and scientific results. Frequent reference is made to original records, data, and publication of results. The report also reviews the proposed versus the final well design, and operational summaries, such as the bit record, the casing and cementing program, and the coring program. Summaries are and the results of three flow tests. Several teamed during the project.

  8. Activation of TLR3/interferon signaling pathway by bluetongue virus results in HIV inhibition in macrophages.

    PubMed

    Dai, Ming; Wang, Xu; Li, Jie-Liang; Zhou, Yu; Sang, Ming; Liu, Jin-Biao; Wu, Jian-Guo; Ho, Wen-Zhe

    2015-12-01

    Bluetongue virus (BTV), a nonenveloped double-stranded RNA virus, is a potent inducer of type Ι interferons in multiple cell systems. In this study, we report that BTV16 treatment of primary human macrophages induced both type I and III IFN expression, resulting in the production of multiple antiviral factors, including myxovirus resistance protein A, 2',5'-oligoadenylate synthetase, and the IFN-stimulated gene 56. Additionally, BTV-treated macrophages expressed increased HIV restriction factors (apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3 G/F/H) and CC chemokines (macrophage inflammatory protein 1-α, macrophage inflammatory protein 1-β, regulated on activation of normal T cell expressed and secreted), the ligands for HIV entry coreceptor CC chemokine receptor type 5. BTV16 also induced the expression of tetherin, which restricts HIV release from infected cells. Furthermore, TLR3 signaling of macrophages by BTV16 resulted in the induction of several anti-HIV microRNAs (miRNA-28, -29a, -125b, -150, -223, and -382). More importantly, the induction of antiviral responses by BTV resulted in significant suppression of HIV in macrophages. These findings demonstrate the potential of BTV-mediated TLR3 activation in macrophage innate immunity against HIV.

  9. Long-term Results of a First-Generation Annealed Highly Cross-Linked Polyethylene in Young, Active Patients.

    PubMed

    Ranawat, Chitranjan S; Ranawat, Amar S; Ramteke, Alankar A; Nawabi, Danyal; Meftah, Morteza

    2016-01-01

    The survivorship of total hip arthroplasty in younger patients is dependent on the wear characteristics of the bearing surfaces. Long-term results with conventional polyethylene in young patients show a high failure rate. This study assessed the long-term results of a first-generation annealed highly cross-linked polyethylene (HCLPE) in uncemented total hip arthroplasty in young, active patients. Between 1999 and 2003, 112 total hip arthroplasty procedures performed in 91 patients with an average University of California Los Angeles activity score of 8 and mean age of 53 years (range, 24-65 years) were included from a prospective database. In all patients, a 28-mm metal femoral head on annealed HCLPE (Crossfire; Stryker, Mahwah, New Jersey) was used. At minimum 10-year follow-up (11.5±0.94 years), Kaplan-Meier survivorship was 97% for all failures (1 periprosthetic infection and 1 late dislocation) and 100% for mechanical failure (no revisions for osteolysis or loosening). This study showed low revision rates for wear-related failure and superior survivorship in young, active patients. Oxidation causing failure of the locking mechanism has not been a problem with Crossfire for up to 10 years. PMID:26811959

  10. Proteolysis of decellularized extracellular matrices results in loss of fibronectin and cell binding activity.

    PubMed

    Ramanathan, Anand; Karuri, Nancy

    2015-04-01

    Excessive inflammation in the chronic wound bed is believed to result in increased fibronectin (FN) proteolysis and poor tissue repair. However, FN fragments can prime the immune response and result in higher protease levels. The reciprocity between FN proteolysis and inflammation makes it challenging to determine the specific contribution of FN proteolysis in the extracellular matrix (ECM) on tissue responses. We studied the impact of proteolysis of decellularized extracellular matrices (dECMs) obtained from NIH 3T3 mouse fibroblasts on FN level and activity. The dECMs were treated with α chymotrypsin and proteolysis was stopped at different time points. The protease solution was obtained, the remaining dECM was scrapped and examined by immunoblotting and Bicinchoninic Acid assays. Fibronectin was 9.4 ± 1.8% of the total protein content in the dECM but was more susceptible to proteolysis. After 15 min of protease treatment there was a 67.6% and 11.1% decrease in FN and total protein, respectively, in the dECMs. Fibronectin fragments were present both in the proteolysis solution and in the dECM. Cell adhesion, spreading and actin extensions on dECMs decreased with increasing proteolysis time. Interestingly, the solutions obtained after proteolysis of the dECMs supported cell adhesion and spreading in a time dependent manner, thus demonstrating the presence of FN cell binding activity in the protease solution of dECMs. This study demonstrates the susceptibility of FN in the ECM to proteolysis and the resulting loss of cell adhesion due to the decrease of FN activity and places weight on bioengineering strategies to stabilize FN against proteolysis.

  11. Analysis of the results of the international comparison of activity measurements of a solution of (55)Fe.

    PubMed

    Ratel, G

    2008-01-01

    The results of an international comparison of activity measurements of a solution of (55)Fe organized by the BIPM in 2005 are reported and analysed. This exercise, which follows the procedures of the CIPM mutual recognition arrangement to update older comparisons, is a renewal of the comparison organized by the BIPM that took place in 1978. A EUROMET comparison was organized in 1996 specifically to compare activity measurements of a (55)Fe solution by means of liquid-scintillation techniques. Results of these three comparisons are presented and discussed in this paper. The radionuclide solution was provided by the NPL, which also distributed the samples to the participants. The activity of the ampoules was measured by 16 laboratories using 12 methods producing 25 results. Some general considerations on uncertainty assessments pertaining to the different techniques used are drawn. The outcome of four different estimators is compared from which the presence of at least one outlier can be confirmed. Further measurements should be made to try to reduce the discrepancy between the results. To date the outcome of the present comparison does not show an improvement to that of the 1996 comparison. PMID:18343132

  12. Taking in a Show.

    PubMed

    Boden, Timothy W

    2016-01-01

    Many medical practices have cut back on education and staff development expenses, especially those costs associated with conventions and conferences. But there are hard-to-value returns on your investment in these live events--beyond the obvious benefits of acquired knowledge and skills. Major vendors still exhibit their services and wares at many events, and the exhibit hall is a treasure-house of information and resources for the savvy physician or administrator. Make and stick to a purposeful plan to exploit the trade show. You can compare products, gain new insights and ideas, and even negotiate better deals with representatives anxious to realize returns on their exhibition investments. PMID:27249887

  13. Taking in a Show.

    PubMed

    Boden, Timothy W

    2016-01-01

    Many medical practices have cut back on education and staff development expenses, especially those costs associated with conventions and conferences. But there are hard-to-value returns on your investment in these live events--beyond the obvious benefits of acquired knowledge and skills. Major vendors still exhibit their services and wares at many events, and the exhibit hall is a treasure-house of information and resources for the savvy physician or administrator. Make and stick to a purposeful plan to exploit the trade show. You can compare products, gain new insights and ideas, and even negotiate better deals with representatives anxious to realize returns on their exhibition investments.

  14. Fluctuations and resulting competing pathways in RNA folding: The activation of splicing

    NASA Astrophysics Data System (ADS)

    Fernández, Ariel

    1991-01-01

    We implement a parallel processing Monte Carlo simulation to explore RNA configuration space that takes into account fluctuations in base-pairing patterns. The choice of folding pathways is biased by the refolding events that occur as the chain is being assembled. We prove that fluctuations in the initial stages of folding might lead to either active or inactive emerging structures. As an illustration, competing pathways that are the result of fluctuation propagation are computed for the splicing YC4 intron (a segment of the mitochondrial RNA from fungi), and the emerging structures are proved to be biologically relevant.

  15. Active vibration absorber for the CSI evolutionary model - Design and experimental results. [Controls Structures Interaction

    NASA Technical Reports Server (NTRS)

    Bruner, Anne M.; Belvin, W. Keith; Horta, Lucas G.; Juang, Jer-Nan

    1991-01-01

    The development of control of large flexible structures technology must include practical demonstrations to aid in the understanding and characterization of controlled structures in space. To support this effort, a testbed facility has been developed to study practical implementation of new control technologies under realistic conditions. The paper discusses the design of a second order, acceleration feedback controller which acts as an active vibration absorber. This controller provides guaranteed stability margins for collocated sensor/actuator pairs in the absence of sensor/actuator dynamics and computational time delay. Experimental results in the presence of these factors are presented and discussed. The robustness of this design under model uncertainty is demonstrated.

  16. Charpy impact test results for low activation ferritic alloys irradiated to 30 dpa

    SciTech Connect

    Schubert, L.E.; Hamilton, M.L.; Gelles, D.S.

    1996-04-01

    Miniature specimens of six low activation ferritic alloys have been impact field tested following irradiation at 370{degrees}C to 30 dpa. Comparison of the results with those of control specimens and specimens irradiated to 10 dpa indicates that degradation in the impact behavior appears to have saturated by {approx}10 dpa in at least four of these alloys. The 7.5Cr-2W alloy referred to as GA3X appears most promising for further consideration as a candidate structural material in fusion reactor applications, although the 9Cr-1V alloy may also warrant further investigation.

  17. The Formation of CIRs at Stream-Stream Interfaces and Resultant Geomagnetic Activity

    NASA Technical Reports Server (NTRS)

    Richardson, I. G.

    2005-01-01

    Corotating interaction regions (CIRs) are regions of compressed plasma formed at the leading edges of corotating high-speed solar wind streams originating in coronal holes as they interact with the preceding slow solar wind. Although particularly prominent features of the solar wind during the declining and minimum phases of the 11-year solar cycle, they may also be present at times of higher solar activity. We describe how CIRs are formed, and their geomagnetic effects, which principally result from brief southward interplanetary magnetic field excursions associated with Alfven waves. Seasonal and long-term variations in these effects are briefly discussed.

  18. Video and film analysis with correlation tracking and active result presentation (Abstract Only)

    NASA Astrophysics Data System (ADS)

    Rowa, Per

    1990-08-01

    Experience with a turnkey analysis system featuring high resolution video input and display, a modular video disc system and a 16 mm cine film scanner with 2600-point resolution, is presented. Tracking is performed with a high-speed correlation process, requiring no special markers. Software packages for evaluating two and three-dimensional results are interactively accessible. Combining the original image sequence with real-time graphic overlays and active drawing of graphic diagrams, provides for an excellent understanding and documentation of the motion sequences.

  19. Results from the Nuclear Plant Aging Research Program: Their use in inspection activities

    SciTech Connect

    Gunther, W.; Taylor, J. )

    1990-09-01

    The US NCR's Nuclear Plant Aging Research (NPAR) Program has determined the susceptibility to aging of components and systems, and the potential for aging to impact plant safety and availability. The NPAR Program also identified methods for detecting and mitigating aging in components. This report describes the NPAR results which can enhance NRC inspection activities. Recommendations are provided for communicating pertinent information to NRC inspectors. These recommendations are based on a detailed assessment of the NRC's Inspection Program, and feedback from resident and regional inspectors as described within. Examples of NPAR report summaries and aging inspection guides for components and systems are included. 13 refs., 3 figs., 4 tabs.

  20. Most human CD3+WT31- clones with T cell receptor C gamma 1 rearrangements show strong non-MHC-restricted cytotoxic activity in contrast to those with C gamma 2 rearrangements.

    PubMed

    Christmas, S E

    1989-04-01

    Clones expressing CD3 in the absence of WT31 expression were obtained by growing highly purified WT31- cells in the presence of interleukin 2 and phytohemagglutinin. Most clones showed rearrangements of T cell receptor (TcR) gamma genes on both chromosomes involving all five currently identified J gamma segments. About a third of these clones had a rearranged 12 kb Kpn I band with the J gamma probe, consistent with a V9JPC gamma 1 rearrangement. All clones with both chromosomes rearranged to C gamma 2 had low or intermediate cytotoxic activity while most of those with at least one chromosome rearranged to C gamma 1 had high cytotoxic activity against both natural killer-sensitive and natural killer-resistant targets. This applied both to clones with and without the V9JPC gamma 1 rearrangement. Of three clones with both C gamma 1 and C gamma 2 rearrangements two had high activity and the other was only weakly cytotoxic. In addition, most clones showed rearrangement of TcR beta genes. Some clones were capable of secreting levels of interferon-gamma and tumor necrosis factor-alpha which were as high as those produced by CD3+4+WT31+ T cell clones. The results suggest that most human CD3+WT31- clones expressing a disulfide-linked C gamma 1/delta heterodimer are capable of mediating strong non-major histocompatibility complex-restricted cytotoxicity whereas those expressing non-disulfide-linked C gamma 2/delta heterodimers are not.

  1. Obesity in show dogs.

    PubMed

    Corbee, R J

    2013-10-01

    Obesity is an important disease with a growing incidence. Because obesity is related to several other diseases, and decreases life span, it is important to identify the population at risk. Several risk factors for obesity have