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Sample records for hyalophora cecropia inhibits

  1. Vegetative propagation of Cecropia obtusifolia (Cecropiaceae

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    Louis M. LaPierre

    2001-12-01

    Full Text Available Cecropia is a relatively well-known and well-studied genus in the Neotropics. Methods for the successful propagation of C. obtusifolia Bertoloni. 1840 from cuttings and air layering are described, and the results of an experiment to test the effect of two auxins, naphthalene acetic acid (NAA and indole butyric acid (IBA, on adventitious root production in cuttings are presented. In general. C. obtusifolia cuttings respond well to adventitious root production (58.3 % of cuttings survived to root, but air layering was the better method (93 % of cuttings survived to root. The concentration of auxins used resulted in an overall significantly lower quality of roots produced compared with cuttings without auxin treatment. Future experiments using Cecropia could benefit from the use of isogenic plants produced by vegetative propagationCecropia es un género bien conocido y bien estudiado en los Neotrópicos. Se discuten métodos exitosos para la propagación de C. obtusifolia Bertoloni, 1840 de fragmentos de troncos y acodos aéreos. A continuación se presentan los resultados de un experimento para examinar los efectos de dos tipos de hormonas (NAA e IBA en la producción de raíces adventicias en fragmentos de troncos. En general, los fragmentos de C. abtusifalia responden bien en la producción de raíces adventicias (y sobreviven al azar 58.3% de los cortes, pero el método de acodos aéreos funcionó mejor (sobreviven al azar 93 %. El uso de hormonas resultó en raíces de baja calidad en comparación con cortes sin hormonas. Experimentos en el futuro que usan Cecropia pueden beneficiar al usar plantas isogénicas producidas por propagación vegetativa

  2. Effects of light and temperature on seed germination in Cecropia hololeuca Miq. (Cecropiaceae

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    Godoi Simone

    2004-01-01

    Full Text Available Seeds of Cecropia hololeuca were submitted to regimes of constant and alternating temperatures, associated with photoperiods of white light, "shade light" and continuous darkness under controlled conditions in laboratory. Seeds did not germinate at constant temperatures of 10°C to 20°C and above 35°C. Seeds only germinated in the darkness when the temperature was alternated. "Shade light" inhibited germination. We concluded that the regime of alternating temperatures suppressed the light effects on seed germination of this species.

  3. Distributional patterns of cecropia (Cecropiaceae: a panbiogeographic analysis

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    Franco Rosselli Pilar

    1997-06-01

    Full Text Available A panbiogeographic analysis of the distributional patterns of 60 species of Cecropia was carried out. Based on the distributional ranges of 36 species, we found eight generalized tracks for Cecropia species. whereas distributional patterns of 24 species were uninformative for the analysis. The major concentration of species of Cecropia is in the Neotropical Andean region. where there are three generalized tracks and two nodes. The northern Andes in Colombia and Ecuador are richer than the Central Andes in Perú. they contain two generalized tracks; one to the west and another to the east, formed by individual tracks of eight species each. There are four generalized tracks outside the Andean region: two in the Amazonian region in Guayana-Pará and in Manaus. one in Roraima. one in Serra do Mar in the Atlantic forest of Brazil and one in Central America. Speciation in Cecropia may be related to the Andean first uplift.Con base en la distribución de 60 especies del género Cecropia, se hizo un análisis panbiogeográfico. Se construyeron 8 trazos generalizados con base en el patrón de distribución de 36 especies; la distribución de las demás especies no aportaba información para la definición de los trazos. La región andina tiene la mayor concentración de especies de Cecropia representada por la presencia de tres trazos generalizados y dos nodos; los dos trazos con mayor número de especies se localizan en su parte norte, en Colombia y Ecuador y el otro en los Andes centrales en Perú. Se encontraron además, cuatro trazos extrandinos: dos en la región amazónica, en Pará-Guayana y en Manaus, uno en Roraima, uno en Serra do Mar en la Selva Atlánfíca del Brasil y uno en Centro América. La especiación en Cecropia parece estar relacionada con el primer levantamiento de los Andes.

  4. The status of Cecropia (Urticaceae) introductions in Malesia: addressing the confusion

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    Conn, B.J.; Hadiah, J.T.; Webber, B.L.

    2012-01-01

    As part of the great global movement of plants in the 18th and 19th centuries, many valuable and commercial plants were sent from the Neotropics to Europe as seeds or as live specimens. Cecropia (Urticaceae) was in cultivation in England in 1789, yet species delimitation was not well-understood unti

  5. SOME STRENGTH AND RELATED PROPERTIES OF YAGRUMO HEMBRA (CECROPIA PELTATA) FROM PUERTO RICO.

    Science.gov (United States)

    Evaluations of several mechanical and physical properties were conducted on specimens from five yagrumo hembra (Cecropia peltata) trees from Puerto...Dense yagrumo hembra resembles North American black cottonwood in both specific gravity and mechanical properties. Total shrinkage from green to the

  6. Life history and environment of Cecropia latiloba in Amazonian floodplains

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    Pia Parolin

    2002-06-01

    Full Text Available Cecropia latiloba can be considered to be one of the most efficient colonizers of open areas in the nutrient-rich whitewater floodplains of the Amazon river. Its main strategy to be successful is the high tolerance towards waterlogging and submergence, and the fast vertical growth and reiteration capacity. This, and the tolerance of high irradiation and sediment deposition allow C. latiloba to form large monospecific stands on open sites, and thus the first closed canopy which represents the initial phase of a successional sequence which leads to highly diverse forests. This tree is extremely well adapted to the adverse growth conditions in Amazonian floodplains with prolongued periods of flooding and seedling submergence. The species occurs on the lowest levels in the flooding gradient. Although it belongs to the most often cited species under aspects of taxonomy, species distribution and general descriptions of the ecosystem, little has been published about its ecology. In the present paper the ecological, physiological and phenological characteristics of C. latiloba are described. It is an evergreen species which constantly produces new leaves. With flooding, leaf production is reduced but new leaves are flushed also with prolongued flooding. The peak of flowering and fruiting are in the flooded period. When mature, the fruits are dispersed mainly by water and fish. Seed germination occurs, without dormancy, within 5-13 days after water retreat. In the 7 months before the first flooded period seedlings reach 1 m of height, and height growth increases until a height of 15-20 m is achieved. Photosynthetic assimilation is high, with values of up to 21 mmol CO2m-2s-1 . C. latiloba is a very flood tolerant species, and waterlogged seedlings continuously produce new leaves and adventitiuos rootsCecropia latiloba puede ser considerada una de las especies colonizadoras más eficientes de áreas abiertas en las llanuras inundadas de agua dulce, rica

  7. The Effect of Symbiotic Ant Colonies on Plant Growth: A Test Using an Azteca-Cecropia System: e0120351

    National Research Council Canada - National Science Library

    Oliveira, Karla N; Coley, Phyllis D; Kursar, Thomas A; Kaminski, Lucas A; Moreira, Marcelo Z; Campos, Ricardo I

    2015-01-01

    .... In the field, we measured the growth of Cecropia glaziovii saplings and compared individuals that were naturally colonized by Azteca muelleri ants with uncolonized plants in different seasons (wet and dry...

  8. Seasonal variations in the amount of isoorientin and isovitexin in cecropia glaziovii sneth. leaves over a two-year period

    OpenAIRE

    Costa, Geison; Caroline F. Ortmann; Eloir P. Schenkel; Reginatto,Flávio H.

    2014-01-01

    Cecropia glaziovii Sneth (Urticaceae) is a common tree from Southeast and South of Brazil, being widely used in traditional medicine to treat heart and respiratory conditions. C-glycosylflavonoids have being described as the major compounds for this genus, however, no seasonality studies of individual flavonoids was conducted for any Cecropia specie. In this work, the content of isoorientin and isovitexin in aqueous extract from the leaves of C glaziovii during a two-year period was determine...

  9. An HPLC-DAD method to quantification of main phenolic compounds from leaves of Cecropia Species

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    Geison M. Costa; Caroline F. Ortmann; Eloir P. Schenkel; Reginatto,Flávio H.

    2011-01-01

    An efficient and reproducible HPLC-DAD method was developed and validated for the simultaneous quantification of major compounds (chlorogenic acid, isoorientin, orientin and isovitexin) present in the leaves of two Cecropia species, C. glaziovii and C. pachystachya. From the leaves of C. glaziovii and C. pachystachya were isolated the C-glycosylflavones isoorientin and isovitexin and identified on both species chlorogenic acid (3-O-caffeoylquinic acid) and the O-glycosylflavonol isoquercitrin...

  10. Cecropia pachystachya: A Species with Expressive In Vivo Topical Anti-Inflammatory and In Vitro Antioxidant Effects

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    Natália Ramos Pacheco

    2014-01-01

    Full Text Available Cecropia pachystachya is a species traditionally used in Brazil to treat inflammation. This work aims to evaluate the topical anti-inflammatory and antioxidant activities of the methanolic extract of C. pachystachya (CPM and to perform its chemical fingerprint by HPLC-DAD. The topical anti-inflammatory activity was evaluated using the mouse models of acute ear inflammation induced by croton oil, arachidonic acid, capsaicin, EPP, phenol, and chronic inflammation induced by multiple application of croton oil. The in vitro antioxidant effect of CPM was investigated using DPPH, reducing power, β-carotene bleaching, and TBARS assays. HPLC analysis was performed to quantify the antioxidant phenolics orientin, isoorientin, and chlorogenic acid previously identified in CPM. CPM exhibited significant anti-inflammatory effect in the acute models, in some cases comparable to the reference drugs. Histopathological analysis showed a moderate chronic skin anti-inflammatory effect with decrease in vasodilation, edema, cell infiltration, and epidermal hyperproliferation. It also showed strong in vitro antioxidant activity. The contents of orientin, isoorientin, and chlorogenic acid were 66.5 ± 1.8, 118.8 ± 0.7, and 5.4 ± 0.2 µg/mg extract, respectively. The topical anti-inflammatory activity of CPM could be based on its antioxidant properties, although other effects are probably involved, including COX inhibition and other mechanisms.

  11. Cecropia pachystachya: a species with expressive in vivo topical anti-inflammatory and in vitro antioxidant effects.

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    Pacheco, Natália Ramos; Pinto, Nícolas de Castro Campos; da Silva, Josiane Mello; Mendes, Renata de Freitas; da Costa, Juliana de Carvalho; Aragão, Danielle Maria de Oliveira; Castañon, Maria Christina Marques Nogueira; Scio, Elita

    2014-01-01

    Cecropia pachystachya is a species traditionally used in Brazil to treat inflammation. This work aims to evaluate the topical anti-inflammatory and antioxidant activities of the methanolic extract of C. pachystachya (CPM) and to perform its chemical fingerprint by HPLC-DAD. The topical anti-inflammatory activity was evaluated using the mouse models of acute ear inflammation induced by croton oil, arachidonic acid, capsaicin, EPP, phenol, and chronic inflammation induced by multiple application of croton oil. The in vitro antioxidant effect of CPM was investigated using DPPH, reducing power, β -carotene bleaching, and TBARS assays. HPLC analysis was performed to quantify the antioxidant phenolics orientin, isoorientin, and chlorogenic acid previously identified in CPM. CPM exhibited significant anti-inflammatory effect in the acute models, in some cases comparable to the reference drugs. Histopathological analysis showed a moderate chronic skin anti-inflammatory effect with decrease in vasodilation, edema, cell infiltration, and epidermal hyperproliferation. It also showed strong in vitro antioxidant activity. The contents of orientin, isoorientin, and chlorogenic acid were 66.5 ± 1.8, 118.8 ± 0.7, and 5.4 ± 0.2 µg/mg extract, respectively. The topical anti-inflammatory activity of CPM could be based on its antioxidant properties, although other effects are probably involved, including COX inhibition and other mechanisms.

  12. Remote Sensing observations of Cecropia communities along Amazonian rivers: Mapping and monitoring habitat dynamics with time series datasets

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    Quinteros Casaverde, N. L.; McDonald, K.

    2016-12-01

    Riverine habitats host more than 14% of non-aquatic birds in the Amazon basin, some of them considered vulnerable by the UICN due to habitat destruction. Plant species of the genus Cecropia are known for being a late pioneer species in these riverine habitats creating monospecific stands along the Amazonian rivers. Cecropia biomes are thought to have significant impacts on the avifauna communities and their diversity. Nowadays, these habitats are threatened by the on-going development in the Amazonian countries. There are plans to build hydroelectric facilities, damming important tributaries of the Amazon river. Such large scale land cover change threatens Cecropia communities and the habitats they support and associated biodiversity. Thus, it is imperative to understand the fragility of these ecosystems, their extent and spatial distribution, and seasonal influences to their environments. We employ multiple sources of remote sensing data to assess the ability to use high resolution imagery to map Cecropia communities and multi-temporal observations to assess their seasonal dynamics. This research aims to facilitate the understanding of these communities through time series analyses using remote sensing products such as high resolution images from Synthetic Aperture Radar (SAR) and Landsat to identify the Cecropia stands along the rivers and lower resolution products such as satellite-borne radiometers and scatterometers to assess seasonality. Our goal is to employ combined remote sensing data sources at map and monitor these important habitats.

  13. Myxomycetes occurring on Cecropia adenopus (Cecropiaceae in fragments of Atlantic Rainforest Myxomycetes ocorrentes em Cecropia adenopus (Cecropiaceae em fragmentos de Floresta Atlântica

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    Andrea Carla Caldas Bezerra

    2011-03-01

    Full Text Available Cecropia adenopus (Ambay pumpwood is a frequent native species on the edges of woods and clearings and is considered a pioneer species in re-colonized areas. Despite its distribution from Mexico to Argentina, this substrate has never been examined in detail regarding the presence of Myxomycetes. In the present study, the myxobiota associated with leaf debris of C. adenopus was investigated in two Atlantic Rainforest conservation units located in the Brazilian state of Rio Grande do Norte. Five specimens and one plasmodium were obtained directly from the field and 87 were developed in 43.7% of 200 moist-chamber cultures set up separately with blades and petioles. Fifteen species were identified and illustrated. The two predominant groups were representatives of Trichiales and Physarales. Didymium columella-cavum was recorded for the second time in Brazil and in the world.Cecropia adenopus (embaúba é uma espécie nativa, frequente em bordas de matas e clareiras e tida como espécie pioneira em áreas recolonizadas. Apesar de ocorrer desde o México até a Argentina este substrato nunca tinha sido examinado com detalhe quanto à presença de Myxomycetes. No presente estudo, a mixobiota associada a folhas mortas de C. adenopus foi investigada em duas Unidades de Conservação da Floresta Atlântica, situadas no estado do Rio Grande do Norte. Cinco espécimes e um plasmódio foram obtidos diretamente no campo e 87 desenvolveram-se em 43,7% de 200 câmaras-úmidas, montadas com lâminas foliares e pecíolos separadamente. Quinze espécies de Myxomycetes foram identificadas e ilustradas. Os dois grupos predominantes pertencem às ordens Trichiales e Physarales. Didymium columella-cavum foi encontrado pela segunda vez no Brasil e no mundo.

  14. Continental-scale patterns of Cecropia reproductive phenology: evidence from herbarium specimens.

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    Zalamea, Paul-Camilo; Munoz, François; Stevenson, Pablo R; Paine, C E Timothy; Sarmiento, Carolina; Sabatier, Daniel; Heuret, Patrick

    2011-08-22

    Plant phenology is concerned with the timing of recurring biological events. Though phenology has traditionally been studied using intensive surveys of a local flora, results from such surveys are difficult to generalize to broader spatial scales. In this study, contrastingly, we assembled a continental-scale dataset of herbarium specimens for the emblematic genus of Neotropical pioneer trees, Cecropia, and applied Fourier spectral and cospectral analyses to investigate the reproductive phenology of 35 species. We detected significant annual, sub-annual and continuous patterns, and discuss the variation in patterns within and among climatic regions. Although previous studies have suggested that pioneer species generally produce flowers continually throughout the year, we found that at least one third of Cecropia species are characterized by clear annual flowering behaviour. We further investigated the relationships between phenology and climate seasonality, showing strong associations between phenology and seasonal variations in precipitation and temperature. We also verified our results against field survey data gathered from the literature. Our findings indicate that herbarium material is a reliable resource for use in the investigation of large-scale patterns in plant phenology, offering a promising complement to local intensive field studies.

  15. High-speed countercurrent chromatography as a valuable tool to isolate C-glycosylflavones from Cecropia lyratiloba Miquel.

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    Oliveira, R R; Moraes, M C C; Castilho, R O; Valente, A P; Carauta, J P P; Lopes, D; Kaplan, M A C

    2003-01-01

    A new apigeninglycoside, apigenin 6-C-galactosyl-6"-O-beta-galactopyranoside (1), isoorientin, and a mixture of orientin and isovitexin were isolated from leaves of Cecropia lyratiloba by high-speed countercurrent chromatography using a solvent system containing ethyl acetate, butanol, methanol and water. The structural elucidation of 1 was based on NMR spectroscopy.

  16. The genus Cecropia: a biological clock to estimate the age of recently disturbed areas in the Neotropics.

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    Paul-Camilo Zalamea

    Full Text Available Forest successional processes following disturbance take decades to play out, even in tropical forests. Nonetheless, records of vegetation change in this ecosystem are scarce, increasing the importance of the chronosequence approach to study forest recovery. However, this approach requires accurate dating of secondary forests, which until now was a difficult and/or expensive task. Cecropia is a widespread and abundant pioneer tree genus of the Neotropics. Here we propose and validate a rapid and straightforward method to estimate the age of secondary forest patches based on morphological observations of Cecropia trees. We found that Cecropia-inferred ages were highly correlated with known ages of the forest. We also demonstrate that Cecropia can be used to accurately date disturbances and propose twenty-one species distributed all over the geographical range of the genus as potential secondary forest chronometer species. Our method is limited in applicability by the maximal longevity of Cecropia individuals. Although the oldest chronosequence used in this study was 20 years old, we argue that at least for the first four decades after disturbance, the method described in this study provides very accurate estimations of secondary forest ages. The age of pioneer trees provides not only information needed to calculate the recovery of carbon stocks that would help to improve forest management, but also provides information needed to characterize the initial floristic composition and the rates of species remigration into secondary forest. Our contribution shows how successional studies can be reliably and inexpensively extended without the need to obtain forest ages based on expensive or potentially inaccurate data across the Neotropics.

  17. Estudo comparativo das madeiras de cecropia palmata (imbaúba) e eucalyptus grandis para produção de celulose e papel

    OpenAIRE

    Pupo, Camyla Heckler [UNESP

    2015-01-01

    Much remains to be studied on the Amazonian species, among many varieties can be species with excellent characteristics for the production of pulp and paper that have not yet had their technological potential revealed. The Cecropia palmata is native to the Amazon, which initially presents excellent characteristics for pulp production. Therefore, this study aimed to study the quality of the native wood Cecropia palmata Amazon for the production of pulp and paper, through a comparative study wi...

  18. An HPLC-DAD method to quantification of main phenolic compounds from leaves of Cecropia species

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Geison M.; Ortmann, Caroline F.; Schenkel, Eloir P.; Reginatto, Flavio H., E-mail: freginatto@hotmail.co [Universidade Federal de Santa Catarina (UFSC), Florianopolis (Brazil). Centro de Ciencias da Saude. Dept. de Ciencias Farmaceuticas

    2011-07-01

    An efficient and reproducible HPLC-DAD method was developed and validated for the simultaneous quantification of major compounds (chlorogenic acid, isoorientin, orientin and isovitexin) present in the leaves of two Cecropia species, C. glaziovii and C. pachystachya. From the leaves of C. glaziovii and C. pachystachya were isolated the C-glycosylflavones isoorientin and isovitexin and identified on both species chlorogenic acid (3-O-caffeoylquinic acid) and the O-glycosylflavonol isoquercitrin. The C-glycosylflavone orientin was isolated only from C. pachystachya. Chlorogenic acid was the major compound in both species (11.1 mg g{sup -1} of extract of C. glaziovii and 27.2 mg g{sup -1} of extract of C. pachystachya) and for the flavonoids quantified, isovitexin was the main C-glycosylflavonoid for C. glaziovii (4.6 mg g{sup -1} of extract) and isoorientin the main one for C. pachystachya (17.3 mg g{sup -1} of extract). (author)

  19. In vivo potential hypoglycemic and in vitro vasorelaxant effects of Cecropia glazioviistandardized extracts

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    Daniela Paula Arend

    2015-10-01

    Full Text Available ABSTRACTThe aim of this study is to investigate the effect of Cecropia glaziovii Snethl, Urticaceae, extracts on the oral glucose tolerance curve, on glycemia in alloxan-induced diabetic rats and vasorelaxant effect after the extraction process, and to standardize the extractive solutions. The effects of the process variables and their interactions were calculated in relation to dry residue, pH, total phenolic results and chemical marker content. Furthermore, the effect of the extracts (400 mg/kg, chlorogenic (2 or 15 mg/kg and caffeic acids (2 mg/kg were investigated on the oral glucose tolerance curve and on glycemia in alloxan-induced diabetic rats. Oral administration of ethanol extracts 4d20 and 8d20 significantly improved glucose tolerance in the hyperglycemic rats. Chlorogenic and caffeic acids, as well as the association of the compounds were able to significantly reduce glycemia after oral gavage treatments. On the other hand, the aqueous extracts did not alter the glycemia. The aqueous extracts (8020 and 9030 and only the higher dose of chlorogenic acid presented a significant effect on serum glucose lowering in diabetic rats. Additionally, the IC50 reveals that the ethanol extracts presented more potent vasodilator effects than the aqueous extracts in aortic rings. This study shows that C. glazioviistandardized extracts exhibits antihyperglycemic action, is able to improve glucose tolerance and has a potent vascular relaxing effect. These results are probably linked to concentrations of the main phenolic compounds of the extracts.

  20. Differences on post-fire regeneration of the pioneer trees Cecropia glazioui and Trema micrantha in a lowland Brazilian Atlantic Forest

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    Dalva M Silva-Matos

    2005-06-01

    Full Text Available A study of natural post-fire succession was carried out in a disturbed vegetation around fragments of the Atlantic Rain Forest (National Biological Reserve of Poço das Antas (22 °30 ’-22 °33 ’S,42 °15 ’-42 °19 ’W, Rio de Janeiro State.All the pre-fire individuals of Cecropia and Trema in the area were numbered with plastic labels.In order to check for the presence of new sprouts and mortality,two other censuses were carried out,at 3 and 12 months after the fire.The dominant species were:Pteridium aquilinum,Panicum maximum,Trema micrantha and Cecropia glazioui. Few days after the passage of fire, grasses and ferns spread their area,while the stands of Trema and Cecropia were completely burned. Most of individuals of Cecropia produced some sprouts while most of individuals of Trema died.However,a great number of seedlings of Trema were recruited while only one single seedling of Cecropia were observed during a period of one year.Most of these seedlings died through the year while the sprouts were already reproducing.The uses of Cecropia in places where fire is recurrent could be more appropriate because of its higher chance of survival and faster recovering ability after fire.Rev.Biol.Trop.53(1-2:1-4.Epub 2005 Jun 24Se realizó un estudio sobre la sucesión natural después del fuego en una vegetación alrededor de fragmentos de la selva lluviosa atlántica (Reserva Biológica Nacional de Poço das Antas (22° 30 ’-22° 33 ’ S, 42° 15’- 42° 19’ W, Estado de Río de Janeiro.Todos los individuos de Cecropia y Trema previos del fuego en el área fueron numerados con marcas plásticas. Se realizaron otros dos censos, 3 y 12 meses después del fuego con el objetivo de detectar mortalidad y buscar la presencia de nuevos brotes. Las especies dominantes fueron: Pteridium aquilinum, Panicum maximum, Trema micrantha y Cecropia glazioui. Pocos días después del paso del fuego,los pastos y helechos se dispersaron por el área, mientras

  1. Does exogenic food benefit both partners in an ant-plant mutualism? The case of Cecropia obtusa and its guest Azteca plant-ants.

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    Dejean, Alain; Petitclerc, Frédéric; Roux, Olivier; Orivel, Jérôme; Leroy, Céline

    2012-03-01

    In the mutualisms involving the myrmecophyte Cecropia obtusa and Azteca ovaticeps or A. alfari, both predatory, the ants defend their host trees from enemies and provide them with nutrients (myrmecotrophy). A. ovaticeps provisioned with prey and then (15)N-enriched food produced more individuals than did control colonies (not artificially provisioned). This was not true for A. alfari colonies, possibly due to differences in the degree of maturity of the colonies for the chosen range of host tree sizes (less than 3m in height). Myrmecotrophy was demonstrated for both Azteca species as provisioning the ants with (15)N-enriched food translated into higher δ(15)N values in host plant tissues, indicating that nitrogen passed from the food to the plant. Thus, the predatory activity of their guest ants benefits the Cecropia trees not only because the ants protect them from defoliators since most prey are phytophagous insects but also because the plant absorbs nutrients.

  2. MALDI-TOF MS Analysis of Proanthocyanidins in Two Lowland Tropical Forest Species of Cecropia: A First Look at Their Chemical Structures

    OpenAIRE

    Alex Van Huynh; John M. Bevington

    2014-01-01

    The structural chemistry of proanthocyanidin molecules has been investigated in temperate zone plants, but few studies have been done with plants of the Amazonian lowland tropical wet forests where herbivore pressure is more extensive and diverse. Using MALDI-TOF mass spectrometry, we report unique properties of the proanthocyanidin structural chemistry in two neotropical Cecropia species, C. polystachya, a myrmecophyte with mutualistic ants, and C. sciadophylla, a non-myrmecophyte lacking mu...

  3. Interação planta-inseto: Aspectos biológicos e ecológicos do mutualismo Cecropia-Azteca

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    2015-08-01

    Abstract. A well-known association is the mutualism between plants is between plant species of the genus Cecropia and ants, mostly belonging to the genus Azteca. In this association, the ants nest in domatia present in the hollow trunk of this myrmecophytes and feed on food bodies provided by the plant, known as mullerian bodies. In return, the ants protect the host plant against herbivore attacks and invasion by vines, and nourish it through waste laid in the trunk. However, the effectiveness of this association may vary with several factors, such as the associated ant species and the habitat type of the myrmecophyte. About 10% of Cecropia species lost their attractive characteristics, such as species living in high altitude and inhabit islands. Aspects like associated ant richness and molecular studies show that the colonization of these plants by ants occurred several times and independently by different genera. The selection pressure exerted by some species of ants may have been one of the decisive factors for the development of attractive traits for ants in Cecropia. With the evolution of these features ants might become an effective partner of the plant, facilitating the co-evolution of specific interactions.

  4. MALDI-TOF MS Analysis of Proanthocyanidins in Two Lowland Tropical Forest Species of Cecropia: A First Look at Their Chemical Structures

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    Alex Van Huynh

    2014-09-01

    Full Text Available The structural chemistry of proanthocyanidin molecules has been investigated in temperate zone plants, but few studies have been done with plants of the Amazonian lowland tropical wet forests where herbivore pressure is more extensive and diverse. Using MALDI-TOF mass spectrometry, we report unique properties of the proanthocyanidin structural chemistry in two neotropical Cecropia species, C. polystachya, a myrmecophyte with mutualistic ants, and C. sciadophylla, a non-myrmecophyte lacking mutualistic ants. Our preliminary data suggests the presence of reportedly uncommon propelargonidin subunits in a majority of proanthocyanidin oligomers. The presence of 3-O-gallate proanthocyanidin monomers was also detected in the mass spectra of both species. Unlike other studies that have examined species growing at higher latitudes, oligomers composed of procyanidin, propelargonidin, and their 3-O-gallates were present in both Cecropia species while the presence of oligomers containing prodelphinidin units were absent or at lower levels. These distinctive features may suggest that proanthocyanidins in some tropical plant species may be an untapped source of proanthocyanidin structural complexity that warrants further investigation. Several differences between spectra of the two Cecropia species could also point to the presence of anti-herbivore defense tradeoffs between chemical defense quality and biotic defense between the two species.

  5. Herança e desequilíbrio de ligação em sete locos isoenzimáticos de Cecropia pachystachya. Inheritance and linkage disequilibrium in sevem isozymes loci of Cecropia pachystachya.

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    Luciano Arruda RIBAS

    2004-12-01

    Full Text Available Seis sistemas enzimáticos (ACP,G6PDH, IDH, PGI, PGM e SKDH, codificandosete locos polimórficos (Acp-3, G6pdh-1, Idh-1,Pgi-2, Pgm-1, Pgm-2 e Skdh-1, foram investigadospara a herança e desequilíbrio de ligação emCecropia pachystachya Trec. A herança mendelianafoi confirmada para todos os locos avaliados.Desvios significativos da razão de segregaçãoesperada 1:1 foram detectados apenas em umaprogênies de árvore heterozigótica. O desequilíbriode ligação foi examinado para 21 pares de locosisoenzimáticos, não sendo detectados desequilíbriosentre nenhum deles e, assim, estes podem serutilizados em subseqüentes estudos do sistemade reprodução, diversidade e estrutura genética deC. pachystachya.

  6. Clinical trial of Cecropia obtusifolia and Marrubium vulgare leaf extracts on blood glucose and serum lipids in type 2 diabetics.

    Science.gov (United States)

    Herrera-Arellano, A; Aguilar-Santamaría, L; García-Hernández, B; Nicasio-Torres, P; Tortoriello, J

    2004-11-01

    Cecropia obtusifolia and Marrubium vulgare have been widely used in Mexican traditional medicine for the control of type 2 diabetes. In order to evaluate the clinical effect produced by the aqueous extract from these species on type 2 non-controlled diabetes mellitus, a total of 43 outpatients were included. Based on the European NIDDM (policy group) criteria, only patients with poor response to the conventional treatment were selected. All patients maintained their medical treatment and also received a prepared infusion of the dry leaves of the plant treatment for 21 days. In a double-blind manner, the patients were randomly grouped as follows: 22 patients were treated with C. obtusifolia and 21 with M. vulgare. The fasting blood glucose values were reduced by 15.25% on patients treated with C. obtusifolia, while cholesterol and triglycerides were decreased by 14.62% and 42.0%, respectively (ANOVA pvulgare, the plasma glucose level was reduced by 0.64% and cholesterol and triglycerides by 4.16% and 5.78%, respectively. When the results were compared between groups, significant differences in glucose and cholesterol diminution were found. The obtained results showed that the infusion prepared with the leaves of C. obtusifolia (containing 2.99+/-0.14mg of chlorogenic acid/g of dried plant) produced beneficial effects on carbohydrate and lipid metabolisms when it was administered as an adjunct on patients with type 2 diabetes with poor response to conventional medical treatment.

  7. MORFOLOGÍA DE LOS FRUTIOLOS DE CECROPIA (CECROPIACEAE DEL PACÍFICO COLOMBIANO Y SU VALOR TAXONÓMICO EN EL ESTUDIO DE DIETAS DE MURCIÉLAGOS

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    Linares Edgar

    2010-12-01

    Full Text Available La textura, junto con la forma y el color (no siempre de fácil interpretación por el ojohumano de los frutiolos son caracteres importantes en la delimitación de las especiesde Cecropia del Pacífi co Colombiano estudiadas en esta investigación. La textura dela superfi cie es el carácter más importante, ya que permite separar dos conjuntos deespecies: textura lisa característica de Cecropia bullata, C. membranacea, C. longipes,C. obtusifolia y textura ampollosa o tuberculada de C. angustifolia, C. hispidissima,C. insignis, C. peltata, C. reticulata, C. virgusa. En este grupo se pueden segregartres subgrupos:débilmente ampollosa (C. reticulata, C. virgusa, ampollosa (C.hispidissima, C. insignis, C. peltata y tuberculada (C. angustifolia. La forma y elcolor son caracteres de menor peso que la textura. A partir de la forma se pudieronorganizar los frutiolos en: ovoides (Cecropia insignis, C. reticulata; ovoideo lanceolados(C. angustifolia, C. bullata, C. virgusa; anchamente ovoides (C. longipes, C.obtusifolia; elipsoides (C. peltata, anchamente elipsoides (C. membranacea yglobosos (C. hispidissima. El color de los frutiolos es más bien constante de acuerdocon la similitud encontrada en los frutiolos de especímenes depositados en lascolecciones del Herbario Nacional Colombiano (COL y en los que se encontraronen los contenidos estomacales de los murciélagos. Los tonos pardos (pardo claros,pardo rojizos, pardo oscuros predominaron, y en un solo caso el negro con un tonorojo central (C. obtusifolia. Las especies de Cecropia y sus respectivos consumidoresfueron: Cecropia angustifolia (consumida por Artibeus jamaicensis, Cecropia peltata(encontrada en los contenidos estomacales y heces de Artibeus jamaicensis, Carolliacastanea y Carollia perspicillata, Cecropia membranacea (consumida por Artibeuslituratus, Platyrrhinus helleri, Carollia castanea y Artibeus jamaicensis y Cecropiaobtusifolia (presente en los contenidos estomacales y heces de

  8. The effect of symbiotic ant colonies on plant growth: a test using an Azteca-Cecropia system.

    Science.gov (United States)

    Oliveira, Karla N; Coley, Phyllis D; Kursar, Thomas A; Kaminski, Lucas A; Moreira, Marcelo Z; Campos, Ricardo I

    2015-01-01

    In studies of ant-plant mutualisms, the role that ants play in increasing the growth rates of their plant partners is potentially a key beneficial service. In the field, we measured the growth of Cecropia glaziovii saplings and compared individuals that were naturally colonized by Azteca muelleri ants with uncolonized plants in different seasons (wet and dry). We also measured light availability as well as attributes that could be influenced by the presence of Azteca colonies, such as herbivory, leaf nutrients (total nitrogen and δ(15)N), and investments in defense (total phenolics and leaf mass per area). We found that colonized plants grew faster than uncolonized plants and experienced a lower level of herbivory in both the wet and dry seasons. Colonized plants had higher nitrogen content than uncolonized plants, although the δ(15)N, light environment, total phenolics and leaf mass per area, did not differ between colonized and uncolonized plants. Since colonized and uncolonized plants did not differ in the direct defenses that we evaluated, yet herbivory was lower in colonized plants, we conclude that biotic defenses were the most effective protection against herbivores in our system. This result supports the hypothesis that protection provided by ants is an important factor promoting plant growth. Since C. glaziovii is widely distributed among a variety of forests and ecotones, and since we demonstrated a strong relationship with their ant partners, this system can be useful for comparative studies of ant-plant interactions in different habitats. Also, given this study was carried out near the transition to the subtropics, these results help generalize the geographic distribution of this mutualism and may shed light on the persistence of the interactions in the face of climate change.

  9. The effect of symbiotic ant colonies on plant growth: a test using an Azteca-Cecropia system.

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    Karla N Oliveira

    Full Text Available In studies of ant-plant mutualisms, the role that ants play in increasing the growth rates of their plant partners is potentially a key beneficial service. In the field, we measured the growth of Cecropia glaziovii saplings and compared individuals that were naturally colonized by Azteca muelleri ants with uncolonized plants in different seasons (wet and dry. We also measured light availability as well as attributes that could be influenced by the presence of Azteca colonies, such as herbivory, leaf nutrients (total nitrogen and δ(15N, and investments in defense (total phenolics and leaf mass per area. We found that colonized plants grew faster than uncolonized plants and experienced a lower level of herbivory in both the wet and dry seasons. Colonized plants had higher nitrogen content than uncolonized plants, although the δ(15N, light environment, total phenolics and leaf mass per area, did not differ between colonized and uncolonized plants. Since colonized and uncolonized plants did not differ in the direct defenses that we evaluated, yet herbivory was lower in colonized plants, we conclude that biotic defenses were the most effective protection against herbivores in our system. This result supports the hypothesis that protection provided by ants is an important factor promoting plant growth. Since C. glaziovii is widely distributed among a variety of forests and ecotones, and since we demonstrated a strong relationship with their ant partners, this system can be useful for comparative studies of ant-plant interactions in different habitats. Also, given this study was carried out near the transition to the subtropics, these results help generalize the geographic distribution of this mutualism and may shed light on the persistence of the interactions in the face of climate change.

  10. The Effect of Symbiotic Ant Colonies on Plant Growth: A Test Using an Azteca-Cecropia System

    Science.gov (United States)

    Oliveira, Karla N.; Coley, Phyllis D.; Kursar, Thomas A.; Kaminski, Lucas A.; Moreira, Marcelo Z.; Campos, Ricardo I.

    2015-01-01

    In studies of ant-plant mutualisms, the role that ants play in increasing the growth rates of their plant partners is potentially a key beneficial service. In the field, we measured the growth of Cecropia glaziovii saplings and compared individuals that were naturally colonized by Azteca muelleri ants with uncolonized plants in different seasons (wet and dry). We also measured light availability as well as attributes that could be influenced by the presence of Azteca colonies, such as herbivory, leaf nutrients (total nitrogen and δ15N), and investments in defense (total phenolics and leaf mass per area). We found that colonized plants grew faster than uncolonized plants and experienced a lower level of herbivory in both the wet and dry seasons. Colonized plants had higher nitrogen content than uncolonized plants, although the δ15N, light environment, total phenolics and leaf mass per area, did not differ between colonized and uncolonized plants. Since colonized and uncolonized plants did not differ in the direct defenses that we evaluated, yet herbivory was lower in colonized plants, we conclude that biotic defenses were the most effective protection against herbivores in our system. This result supports the hypothesis that protection provided by ants is an important factor promoting plant growth. Since C. glaziovii is widely distributed among a variety of forests and ecotones, and since we demonstrated a strong relationship with their ant partners, this system can be useful for comparative studies of ant-plant interactions in different habitats. Also, given this study was carried out near the transition to the subtropics, these results help generalize the geographic distribution of this mutualism and may shed light on the persistence of the interactions in the face of climate change. PMID:25811369

  11. Evaluation of potentical use of the wood of Schizolobium amazonicum “Paricá” and Cecropia hololeuca “Embaúba” for wood cement board manufacture

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    Vinicius Yurk da Rocha

    2012-06-01

    Full Text Available This research was developed to evaluate the potential use of Schizolobium amazonicum “Paricá” and Cecropia hololeuca “Embaúba” wood for wood cement board manufacture. Panels with the density of 1.200 kg/m³ were made, using cement CP V ARI as mineral bonding and wood particles without treatment and treated with immersion in cold water, hot water and sodium hydroxide. The panels were pressed at the pressure of 40 kgf/cm², room temperature and press / clipping time of 24 hours and maturation time of 28 days. The evaluation of the properties of water absorption, thickness swelling, internal bond, modulus of elasticity and modulus of rupture, showed that Schizolobium amazonicum “Paricá” and Cecropia hololeuca “Embaúba” wood are technically feasible for wood-cement board manufacture. It was also found that the panels of embaúba exhibit some properties superior to those of the paricá, and the particles do not necessarily need treatment.

  12. PHOSPHATE AND INOCULATION WITH ARBUSCULAR MYCORRHIZAL FUNGI ON THE GROWTH OF Cecropia pachystachya (Trec SEEDLINGS FÓSFORO E INOCULAÇÃO COM FUNGOS MICORRÍZICOS ARBUSCULARES NO ESTABELECIMENTO DE MUDAS DE EMBAÚBA (Cecropia pachystachya Trec

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    Marco Aurélio Carbone Carneiro

    2007-09-01

    Full Text Available

    The objective of this study was to evaluate the effect of the inoculation with arbuscular mycorrhizal fungi (FMA in different levels of P2O5 on the growth of Cecropia pachystachya seedlings in the field. The study consisted of a 5x2 factorial with five levels of P2O5 (zero, 85, 170, 255 and 340 mg.kg-1, with and ithout inoculation with a mixture of FMA. It was used four replications, each one with twelve seedlings. The seeds were sowed in plastic tubes with capacity of 50 cm3 of substratum and stored for 120 days. After this period the seedlings were transplanted to the field, where they remained for another 150 days. Seedling diameter and height were measured at 60 and 120 days, aerial part and root dry matter, and arbuscular mycorrhizal colonization. Diameter, height, leaf area, aerial part dry matter and the number of surviving seedlings were determined after 150 days. None of the factors tested had any effect on seedling growth with one exception; inoculated plants with FMA had more root dry matter. Plants inoculated with smaller doses of P2O5 showed a larger percentage of surviving individuals and more vigorous seedlings. Results suggest that in low fertility soils of and subject to the hydric stress the C. pachystachya seedlings should be inoculated with FMA.

    KEY-WORDS: Native vegetation; mycorrhiza fungi; native species; seedling production; inoculation.

    O objetivo deste estudo foi avaliar o efeito da inoculação com fungos micorrízicos arbusculares (FMA em diferentes doses de P2O5 na formação de mudas de embaúba (Cecropia pachystachya e no seu estabelecimento em campo. O estudo constou de um experimento fatorial 5x2, sendo cinco doses de P2O5

  13. Tissue culture of Cecropia glaziovii Sneth (urticaceae: vegetative micropropagation and plant regeneration from callus Cultura de tecidos de Cecropia glaziovii Sneth (Urticaceae: micropropagação vegetativa e regeneração de plantas via calos

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    Marcos Nopper Alves

    2010-10-01

    Full Text Available Cecropia glaziovii is a tree with used in Brazilian popular medicine. Methods allowing the clonal propagation of this species are of great interest for superior genotype multiplication and perpetuation. For this reason, we examined the effect of different culture media and different types of explants on adventitious shoot regeneration from callus and buds of C. glaziovii. Leaves, petioles and stipules obtained from aseptically grown seedlings or from pre-sterilized plants were used to initiate cultures. Adventitious shoot regeneration was achieved when apical and axillary buds were inoculated on gelled Murashige & Skoog (MS medium supplemented with 6-benzylaminopurine alone (BAP (1.0, 5.0 or 10.0 mg L-1 or combined with -naphthalene acetic acid (NAA (1.0 or 2.0 mg L-1, after 40 days of culture. Best callus production was obtained after 30 days of petioles' culture on gelled MS medium with 2,4 dichlorophenoxyacetic acid (2,4-D (5.0 mg L-1 combined with BAP (1.0 mg L-1. Successful shoot regeneration from callus was achieved when MS medium supplemented with zeatin (ZEA (0.1 mg L-1 alone or combined with 2,4-D (1.0 or 5.0 mg L-1 was inoculated with friable callus obtained from petioles. All shoots were rooted by inoculation on MS medium supplemented with indole-3-acetic acid (IAA (1.0 mg L-1. Rooted plants transferred to potting soil were successfully established. All in vitro regenerated plantlets showed to be normal, without morphological variations, being also identical to the source plant. Our study has shown that C. glaziovii can be propagated by tissue culture methods, allowing large scale multiplication of superior plants for pharmacological purposes.Cecropia glaziovii é uma planta lenhosa, popularmente usada no Brasil como medicinal. Métodos que visem a sua propagação clonal podem ser de grande utilidade na preservação de seus genótipos de elite. Foram examinados efeitos de diferentes reguladores de crescimento e explantes na forma

  14. Frugivoria de morcegos (Mammalia, Chiroptera em Cecropia pachystachya (Urticaceae e seus efeitos na germinação das sementes

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    Therys Midori Sato

    2008-01-01

    Full Text Available Os morcegos frugívoros são componentes fundamentais na manutenção e regeneração de florestas tropicais, pois ao se alimentarem, promovem a mobilidade das sementes dos frutos em que se alimentaram. Muito se discute sobre os efeitos da passagem das sementes no trato digestivo dos morcegos sobre a taxa e velocidade de germinação. O objetivo deste trabalho foi examinar a dieta das espécies de morcegos frugívoros na Estação Experimental de Itirapina para descobrir quais utilizam significativamente os frutos de Cecropia pachystachya. Foi testada a importância dos quirópteros na dispersão e germinação desta espécie de planta. Para isso, os morcegos foram capturados no período de agosto de 2005 a julho de 2006, suas fezes foram recolhidas e as sementes de C. pachystachya separadas. Os testes de germinação foram feitos para duas espécies de morcegos, Artibeus liuratus e Platyrrhinus lineatus, e suas taxas de germinação comparadas com amostras de sementes coletadas da planta (controle. Foram feitos cinco repetições com 30 sementes em cada gerbox para cada teste. Os testes foram realizados em câmaras germinadoras " Mangelsdorf" , com temperatura de 25°C, luminosidade e umidade constante por 40 dias. Houve uma alta porcentagem de germinação das sementes encontradas em A. lituratus (79,3% e não diferiu estatisticamente das sementes controle (76%. Esses resultados foram superiores a P. lineatus (52%. Em relação ao Índice de Velocidade de Germinação (IVG, esse resultado foi semelhante, sendo 2,73 para A. lituratus, 2,66 para o controle e 1,80 para P. lineatus. Com esse resultado, tem-se que a passagem das sementes de C. pachystachya pelos morcegos não aumentou a porcentagem, nem a velocidade de germinação delas, quando comparado com o controle, sendo até menor para P. lineatus. Com os resultados obtidos, conclui-se que, o efeito da passagem do trato digestivo dos morcegos na germinação pode sofrer influências que

  15. Avaliação do potencial de utilização da madeira de Schizolobium amazonicum "Paricá" e Cecropia hololeuca "Embaúba" para produção de painéis aglomerados Evaluation of potential use of the wood of Schizolobium amazonicum "Paricá" and Cecropia hololeuca "Embaúba" to particleboard manufacture

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    Setsuo Iwakiri

    2010-01-01

    Full Text Available Esta pesquisa teve por objetivo avaliar o potencial de utilização de madeira de Schizolobium amazonicum (Paricá e Cecropia hololeuca (Embaúba para produção de painéis aglomerados. Foram produzidos painéis experimentais com densidade nominal de 0,70 g/cm³, utilizando a resina uréia-formaldeído e partículas de madeira de Paricá e Embaúba, e mistura destas, em proporções de 75, 50 e 25%. A madeira de Pinus taeda foi utilizada como testemunha. Os painéis foram prensados com pressão específica de 40 kgf/cm², temperatura de 160ºC e tempo de prensagem de 8 minutos. Os resultados das avaliações de propriedades de absorção de água, inchamento em espessura, ligação interna, módulo de elasticidade e módulo de ruptura, indicaram que as madeiras de Schizolobium amazonicum (Paricá e Cecropia hololeuca (Embaúba são tecnicamente viáveis para produção de painéis aglomerados.This research was developed to evaluate the potential use of the woods Schizolobium amazonicum (Paricá and Cecropia hololeuca (Embaúba for manufacturing particleboard. Were made panels with the densities of 0.70 g/cm³, using mixtures of urea-formaldehyde resin and wood particles of Paricá and Embaúba, in proportions of 75, 50 and 25%. The Pinus taeda wood was used as the reference. The panels were pressed at the temperature of 160ºC, pressure of 40 kgf/cm², for 8 minutes. The evaluations of the properties of water absorption, thickness swelling, internal bond, modulus of elasticity and modulus of ruptures, showed that the woods of Schizolobium amazonicum (Paricá e Cecropia hololeuca (Embaúba are technically feasible for particleboard manufacture.

  16. Nest structure and occurrence of three species of Azteca (Hymenoptera, Formicidae in Cecropia pachystachya (Urticaceae in non-floodable and floodable pantanal areas Arquitetura de ninho e ocorrência de três espécies de Azteca (Hymenoptera, Formicidae em Cecropia pachystachya (Urticaceae em ambiente alagável e não alagável no Pantanal

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    Alexsandro S. Vieira

    2010-01-01

    Full Text Available Thirty Cecropia pachystachya trees were examined in non-floodable and floodable areas to investigate the association between C. pachystachya and Azteca ants in the Pantanal of Mato Grosso do Sul, Brazil. The species Azteca ovaticeps, Azteca isthmica, and Azteca alfari were found nesting inside domatia of C. pachystachya. A. ovaticeps was the most frequent species in the trees in the floodable area, while A. isthmica and A. alfari, in the non-floodable area. A. ovaticeps and A. isthmica maintained more entrance/exit holes in comparison to A. alfari. All Azteca species maintained entrance/exit holes in the closest domatia to the apical area of the branch, due to proximity to Müllerian and pearl bodies, suggesting that these species of Azteca were influenced by their environment during evolution and became specialized. All internodal septa of each examined branch were perforated by ants, indicating the branches were inhabited by a single colony.Foram analisadas 30 plantas de Cecropia pachystachya em cada ambiente alagável e não alagável no Pantanal sul-mato-grossense, Brasil, com o objetivo de investigar a associação entre formigas Azteca e C. pachystachya. Foram encontradas as espécies Azteca ovaticeps, Azteca isthmica e Azteca alfari nidificando nas domáceas da planta. A. ovaticeps foi mais frequente em plantas de área alagável, enquanto A. isthmica e A. alfari em plantas em área não alagável. A. ovaticeps e A. isthmica apresentaram maior quantidade de orifícios de entrada/saída em relação à A. alfari e todas as espécies mantêm próximo da região apical do ramo, orifícios de entrada/saída nas domáceas, devido à proximidade com os corpúsculos müellerianos e pérola. Isto é, essas espécies de Azteca especializaram-se ao longo da evolução influenciadas pelo ambientes. Todos os septos internodais de cada ramo analisados apresentaram-se perfurados pelas formigas, sugerindo que os mesmos são habitados por uma única colônia.

  17. Taxa e velocidade de germinação de sementes de Cecropia pachystachya Trécul (Cecropiaceae ingeridas por Artibeus lituratus (Olfers, 1818 (Chiroptera: Phyllostomidae = Germination rate and velocity of seeds of Cecropia pachystachya Trécul (Cecropiaceae eaten by Artibeus lituratus (Olfers, 1818 (Chiroptera: Phyllostomidae

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    Ricardo Anghinoni Bocchese

    2007-10-01

    Full Text Available O objetivo deste trabalho foi verificar se o morcego frugívoro Artibeus lituratus pode ser considerado indutor na germinação de sementes de Cecropia pachystachya, sendo avaliadas a taxa e a velocidade de germinação das sementes em diferentes condições. Osmorcegos e os frutos foram coletados na região central de Campo Grande, Estado do Mato Grosso do Sul; o experimento foi dividido em cinco tratamentos. O primeiro contou com sementes retiradas dos frutos; o segundo, com sementes retiradas das fezes, e o terceirodividido em três tratamentos ácidos, com concentrações de pH 1, 2 e 3. As sementes que passaram pelo sistema digestório dos animais germinaram com maior velocidade (p 0,05 quandocomparada às sementes sem tratamento. O tratamento com pH igual a 3 foi estatisticamente igual ao grupo sem tratamento e ao grupo experimental, com sementes retiradas das fezes, indicando o valor aproximado da concentração dos ácidos estomacais desta espéciefrugívora. Conclui-se que Artibeus lituratus pode ser considerado indutor do aumento da velocidade de germinação nas sementes desta espécie vegetal, refletindo na importância desta espécie frugívora na manutenção ecológica dos ecossistemas tropicais, principalmenteem áreas de Cerrado.The objective with this study was to verify whether frugivorous bat Artibeus lituratus can be considered an efficient germination inducer for Cecropia pachystachya seeds. Bats and fruits were collected in Campo Grande (Mato Grosso do Sul State, Brazil, with the experimentbeing divided in five treatments: one composed by seeds taken from natural fresh fruits, another with seeds taken from the bats’ excrements, and the last one sub-divided in three sub-groups with different acid treatments that corresponded to pH 1, 2 and 3. The seeds that passed through the digestive tract of the animals presented a higher germination velocity index (p 0.05 when compared with the seeds without any treatment. The

  18. Chlorinated tyrosine derivatives in insect cuticle

    DEFF Research Database (Denmark)

    Andersen, Svend Olav

    2004-01-01

    during sample hydrolysis. Mono- and dichlorotyrosine are also present in cuticular samples from other insect species, such as the beetle, Tenebrio molitor, the moth Hyalophora cecropia, the cockroach Blaberus craniifer, and the bug Rhodnius prolixus, but not in the sclerotized puparial cuticle...... of the blowfly, Calliphora vicina, or in sclerotized ootheca from the cockroach, Periplaneta americana. Cuticular sclerotization and formation of chlorotyrosines occur simultaneously in locust legs; sclerotized cuticles tend to have a higher content of chlorotyrosines than unsclerotized cuticles...

  19. Alfa-glucosidase-inhibiting activity of some Mexican plants used in the treatment of type 2 diabetes.

    Science.gov (United States)

    Andrade-Cetto, Adolfo; Becerra-Jiménez, Jaime; Cárdenas-Vázquez, René

    2008-02-28

    Type 2 diabetes is an endocrine disease, which accounts for 9% of deaths worldwide. The aim of oral therapy is to reach normoglycemia to prevent later complications. Among glucose-lowering medications, alpha-glucosidase inhibitors delay the absorption of ingested carbohydrates, reducing the postprandial glucose and insulin peaks. In the present study, we tested the butanolic extracts of four Mexican plants with respect to their alpha-glucosidase inhibition activity, without excluding other possible mechanisms of action. The plants Cecropia obtusifolia Bertol., Equisetum myriochaetum Schlecht & Cham, Acosmium panamense (Benth.) Yacolev and Malmea depressa (Baill) R.E. Fries are used in traditional medicine to treat type 2 diabetes. In previous studies, we have demonstrated these plants' hypoglycemic activity and determined the phytochemical composition of their extracts. Our results in n-STZ diabetic rats loaded with maltose showed that Malmea and Acosmium extracts decreased plasma glucose significantly from 30 min on resembling the effect of acarbose. Cecropia extract produced the highest reduction of plasma glucose, and at 90 min, the glucose level was lower than the fasting level, which suggests another mechanism of action. Equisetum did not exert any effect. In vitro assays of alpha-glucosidase activity showed an IC(50) of 14 microg/ml for Cecropia, 21 microg/ml for Malmea, and 109 microg/ml for Acosmium, which were lower than that of acarbose (128 microg/ml). Equisetum did not show any significant effect on this assay, either. These results contribute to understand the mechanism of action of these plants on glucose metabolism.

  20. Taxa e velocidade de germinação de sementes de Cecropia pachystachya Trécul (Cecropiaceae ingeridas por Artibeus lituratus (Olfers, 1818 (Chiroptera: Phyllostomidae - DOI: 10.4025/actascibiolsci.v29i4.879 Germination rate and velocity of seeds of Cecropia pachystachya Trécul (Cecropiaceae eaten by Artibeus lituratus (Olfers, 1818 (Chiroptera: Phyllostomidae - DOI: 10.4025/actascibiolsci.v29i4.879

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    Eliane Cristine Vicente

    2008-02-01

    Full Text Available O objetivo deste trabalho foi verificar se o morcego frugívoro Artibeus lituratus pode ser considerado indutor na germinação de sementes de Cecropia pachystachya, sendo avaliadas a taxa e a velocidade de germinação das sementes em diferentes condições. Os morcegos e os frutos foram coletados na região central de Campo Grande, Estado do Mato Grosso do Sul; o experimento foi dividido em cinco tratamentos. O primeiro contou com sementes retiradas dos frutos; o segundo, com sementes retiradas das fezes, e o terceiro dividido em três tratamentos ácidos, com concentrações de pH 1, 2 e 3. As sementes que passaram pelo sistema digestório dos animais germinaram com maior velocidade (p 0,05 quando comparada às sementes sem tratamento. O tratamento com pH igual a 3 foi estatisticamente igual ao grupo sem tratamento e ao grupo experimental, com sementes retiradas das fezes, indicando o valor aproximado da concentração dos ácidos estomacais desta espécie frugívora. Conclui-se que Artibeus lituratus pode ser considerado indutor do aumento da velocidade de germinação nas sementes desta espécie vegetal, refletindo na importância desta espécie frugívora na manutenção ecológica dos ecossistemas tropicais, principalmente em áreas de Cerrado.The objective with this study was to verify whether frugivorous bat Artibeus lituratus can be considered an efficient germination inducer for Cecropia pachystachya seeds. Bats and fruits were collected in Campo Grande (Mato Grosso do Sul State, Brazil, with the experiment being divided in five treatments: one composed by seeds taken from natural fresh fruits, another with seeds taken from the bats’ excrements, and the last one sub-divided in three sub-groups with different acid treatments that corresponded to pH 1, 2 and 3. The seeds that passed through the digestive tract of the animals presented a higher germination velocity index (p 0.05 when compared with the seeds without any treatment. The

  1. Avaliação do efeito mutagênico do extrato hidroalcoólico bruto, por meio de bioensaios in vivo e prospecção fitoquímica de Cecropia glaziovii Sneth (embaúba, Cecropiaceae Evaluation of mutagenic effect of crude hydroalchoolic extract, using in vivo alive bioassays and phytochemical screening of Cecropia glaziovii Sneth (embaúba, Cecropiaceae

    Directory of Open Access Journals (Sweden)

    Victor S. Stange

    2009-06-01

    Full Text Available O gênero Cecropia é conhecido popularmente por "embaúba" e apresenta várias espécies medicinais, sendo que estudos com a espécie C. glaziovii Sneth indicam que o extrato aquoso apresenta efeitos broncodilatador, anti-hipertensivo e antidepressivo, provavelmente, atribuídos às catequinas, procianidinas e flavonóides. O presente estudo objetivou avaliar os potenciais efeitos tóxico, citotóxicos, clastogênicos e aneugênicos do extrato bruto hidroalcoólico de folhas de C. glaziovii, por meio da dose letal média (DL50, da análise de micronúcleo em células de medula óssea de roedores e do teste com Allium cepa e realizar a prospecção fitoquímica. Os resultados demonstraram que as concentrações testadas não causaram toxicidade aguda, nem apresentaram atividade clastogênica e aneugênica, sugerindo que o extrato de C. glaziovii não interferem na divisão celular. A prospecção fitoquímica indicou a presença de taninos, flavonóides, fenóis, antraquinonas, cumarinas, catequinas, proteínas, açúcares redutores, depsídeos/depsidonas e triterpenos. Mesmo assim, esses resultados não prescrevem o consumo terapêutico da espécie, sem continuidade da sua avaliação e do cumprimento de todas as etapas pré-clínicas e clínicas.The genus Cecropia is as known popularly "embaúba" and presents several medical species. Studies with the species C. glaziovii Sneth indicates that the hydroalchoolic extracts presents bronchodilator, anti-hypertensive and antidepressive effects, probably due its contests catechins, procyanidins and flavonoids. The aim of this study was to assess the potential toxic, cytotoxic, clastogenic and aneugenic effects of the crude hydroalchoolic extract of leaves of C. glaziovii, by means of the determination of the median lethal dose (LD50, the analysis of micronucleus in cells from bone marrow of rodents and through the Allium cepa assay, and also to performe the phytochemical screening. The results showed

  2. Storage hexamer utilization in two lepidopterans: differences correlated with the timing of egg formation

    Directory of Open Access Journals (Sweden)

    M.L. Pan

    2001-04-01

    Full Text Available Most insects produce two or more storage hexamers whose constituents and developmental profiles are sufficiently different to suggest specialization in the ways that they support metamorphosis and reproduction. Hexamerin specializations are compared here in the Cecropia moth (Hyalophora cecropia, which produces eggs during the pupal-adult molt, and the Monarch butterfly (Danaus plexippus, which produces eggs under long-day conditions after adult eclosion. In both sexes of both species, reserves of arylphorin (ArH were exhausted by the end of metamorphosis. In Cecropia, the same was true for the high-methionine hexamerins, V-MtH and M-MtH. But in short day Monarch females 20-30% of the pupal reserves of V-MtH and M-MtH survived metamorphosis, persisting until long-day conditions were imposed to stimulate egg formation. Differences in storage sites have been documented in other lepidopterans, with MtH reserves being found primarily in fat body protein granules and the ArH reserve being found primarily in the hemolymph. Similar differences could explain how a fraction of the MtH's, but not of ArH, escapes utilization during metamorphosis in a species with post-eclosion egg formation. No differences in utilization schedules were detected between V- and M-MtH, despite divergent compositions and antigenic reactivity.

  3. Triagem fitoquímica e avaliação das atividades trombolítica e citotóxica de Cecropia hololeuca Miq. (Urticaceae, Lippia alba (Mill. N.E.Br. ex P. Wilson (Verbenaceae e Zanthoxylum rhoifolium Lam (Rutaceae

    Directory of Open Access Journals (Sweden)

    João Victor Dutra GOMES1 ; Rafael Destefani FAITANIN

    2016-03-01

    Full Text Available Cecropia hololeuca, Lippia alba, e Zanthoxylum rhoifolium são espécies vegetais de ocorrência natural no Brasil, características de regiões de Mata Atlântica e, dentro de suas finalidades medicinais, estão incluídas ação anti-hipertensiva, digestiva e no tratamento de malária. Neste estudo, foram avaliados o perfil fitoquímico e as atividades citotóxica e trombolítica do extrato etanólico das folhas destas espécies vegetais. O perfil químico dos extratos foi obtido por meio de ensaios fitoquímicos clássicos, a fim de identificar as classes químicas presentes. A toxicidade preliminar foi avaliada frente Artemia salina e a atividade trombolítica foi determinada in vitro a partir da lise de coágulo de sangue humano. Os testes fitoquímicos indicaram a presença de alcaloides e flavonoides nos três extratos investigados. Saponinas, triterpenos e naftoquinonas foram detectados apenas em C. hololeuca. Essa não demonstrou toxicidade frente Artemia salina (DL50 >1000 ppm, enquanto Z. rhoifolium apresentou DL50 igual a 719,44 ppm e L. alba <250 ppm, o que indica atenção quanto à segurança no uso desta planta medicinal. A atividade trombolítica de L. alba e C. hololeuca foi de 6,43 ±2,08 e 9,64 ±1,83 %, respectivamente, mostrando baixa atividade. Por sua vez, Z. rhoifolium alcançou lise de 24,71 ±10,52 %, indicando promissora atividade (p <0,001. A atividade trombolítica de Z. rhoifolium justifica novos estudos, a fim de investigar os componentes responsáveis pela atividade. Perante a literatura, este é o primeiro relato da avaliação da atividade trombolítica destas espécies vegetais. Os resultados encontrados neste trabalho contribuem para o conhecimento químico-biológico das respectivas espécies.

  4. Production of transgenic medaka with increased resistance to bacterial pathogens.

    Science.gov (United States)

    Sarmasik, Aliye; Warr, Gregory; Chen, Thomas T

    2002-06-01

    Cecropins, first identified in silk moth (Hyalophora cecropia), are a group of antimicrobial peptides with bactericidal activity against a broad spectrum of bacteria. In this study we investigated whether (1) this group of antimicrobial peptides could exhibit bactericidal activity toward known fish bacterial pathogens and (2) expression of cecropin transgenes in transgenic medaka (Oryzias latipas) could result in increasing resistance of the transgenic fish to infection by fish bacterial pathogens. Cecropin gene construct containing silk moth preprocecropin B, procecropin B and cecropin B, and porcine cecropin P1 driven by a cytomegalovirus (CMV) promoter were transfected into chinook salmon embryonic cells (CHSE-214) by lipofection, and the resulting permanent transformants were collected. In an "inhibition zone" assay medium isolated from each transformant exhibited strong bactericidal activity toward known fish bacterial pathogens such as Pseudomonas fluorescens, Aeromonas hydrophila, and Vibrio anguillarum. The same cecropin transgene constructs were introduced into newly fertilized medaka eggs by electroporation to produce transgenic fish. About 40% to 60% of the embryos survived from electroporation, and about 5% to 11% of the surviving fish were shown to contain cecropin transgenes by polymerase chain reaction analysis of genomic DNA samples isolated from presumptive transgenic fish. These P1 transgenic fish were used as founder stocks, and following generations of successive breeding, a total of 20 F2 families of transgenic fish were established. Expression of cecropin transgenes was detected in the F2 transgenics by reverse transcriptase polymerase chain reaction analysis. Southern blot analysis of genomic DNA isolated from different F2 fish showed that cecropin transgenes were integrated into the genomes of F2 transgenic fish. To determine whether transgenic fish carrying cecropin transgenes could exhibit resistance to infection by known fish bacterial

  5. Reciprocal inhibition in man.

    Science.gov (United States)

    Crone, C

    1993-11-01

    Reciprocal inhibition is the automatic antagonist alpha motor neurone inhibition which is evoked by contraction of the agonist muscle. This so-called natural reciprocal inhibition is a ubiquitous and pronounced phenomenon in man and must be suspected of playing a major role in the control of voluntary movements. The spinal pathways underlying this inhibitory phenomenon were studied. The disynaptic reciprocal Ia inhibitory pathway between the tibial anterior muscle and the soleus alpha motor neurones was identified and described in man. It was shown that the inhibition can be evoked in most healthy subjects at rest, but the degree of inhibition varies considerably from one subject to another. It was concluded that it corresponds to the disynaptic reciprocal Ia inhibitory pathway which has been extensively described in animal experiments. The disynaptic reciprocal inhibition was shown to increase during the dynamic phase of a dorsiflexion movement of the foot, but not during the tonic phase. However, when the peripheral afferent feedback from the contracting muscle was blocked by ischaemia, an increase of the inhibition was revealed also during the tonic phase of the dorsiflexion. The concealment of this increase during unrestrained peripheral feedback from the muscle was thought to be due to the post-activation depression mechanism; a mechanism which was described further and which probably involves reduced transmitter release at Ia afferent terminals as a result of previous activation of these afferent fibers. Hence the hypothesis was supported that alpha motor neurones and the corresponding inhibitory interneurones, which project reciprocal inhibition to the antagonist motor neurones, are activated in parallel during voluntary contraction of agonist muscles. An additional reciprocal inhibitory mechanism, the long latency reciprocal inhibition, was described between the tibial anterior muscle and the soleus alpha motor neurones. It was shown to be evoked by group I

  6. Potentiation of latent inhibition.

    Science.gov (United States)

    Rodriguez, Gabriel; Hall, Geoffrey

    2008-07-01

    Rats were given exposure either to an odor (almond) or a compound of odor plus taste (almond plus saline), prior to training in which the odor served as the conditioned stimulus. It was found, for both appetitive and aversive procedures, that conditioning was retarded by preexposure (a latent inhibition effect), and the extent of the retardation was greater in rats preexposed to the compound (i.e., latent inhibition to the odor was potentiated by the presence of the taste). In contrast, the presence of the taste during conditioning itself overshadowed learning about the odor. We argue that the presence of the salient taste in compound with the odor enhances the rate of associative learning, producing a rapid loss in the associability of the odor. This loss of associability will generate both overshadowing and the potentiation of latent inhibition that is observed after preexposure to the compound.

  7. Quorum sensing inhibition

    DEFF Research Database (Denmark)

    Persson, T.; Givskov, Michael Christian; Nielsen, J.

    2005-01-01

    /receptor transcriptional regulator in some clinically relevant Gram-negative bacteria. The present review contains all reported compound types that are currently known to inhibit the QS transcriptional regulator in Gram-negative bacteria. These compounds are sub-divided into two main groups, one comprising structural...

  8. Enzyme inhibition by iminosugars

    DEFF Research Database (Denmark)

    López, Óscar; Qing, Feng-Ling; Pedersen, Christian Marcus

    2013-01-01

    Imino- and azasugar glycosidase inhibitors display pH dependant inhibition reflecting that both the inhibitor and the enzyme active site have groups that change protonation state with pH. With the enzyme having two acidic groups and the inhibitor one basic group, enzyme-inhibitor complexes...

  9. Plastics for corrosion inhibition

    CERN Document Server

    Goldade, Victor A; Makarevich, Anna V; Kestelman, Vladimir N

    2005-01-01

    The development of polymer composites containing inhibitors of metal corrosion is an important endeavour in modern materials science and technology. Corrosion inhibitors can be located in a polymer matrix in the solid, liquid or gaseous phase. This book details the thermodynamic principles for selecting these components, their compatibility and their effectiveness. The various mechanisms of metal protection – barrier, inhibiting and electromechanical – are considered, as are the conflicting requirements placed on the structure of the combined material. Two main classes of inhibited materials (structural and films/coatings) are described in detail. Examples are given of structural plastics used in friction units subjected to mechano-chemical wear and of polymer films/coatings for protecting metal objects against corrosion.

  10. Inhibition and Brain Work

    OpenAIRE

    Buzsáki, György; Kaila, Kai; Raichle, Marcus

    2007-01-01

    The major part of the brain’s energy budget (~60%–80%) is devoted to its communication activities. While inhibition is critical to brain function, relatively little attention has been paid to its metabolic costs. Understanding how inhibitory interneurons contribute to brain energy consumption (brain work) is not only of interest in understanding a fundamental aspect of brain function but also in understanding functional brain imaging techniques which rely on measurements related to blood flow...

  11. Latent inhibition in schizophrenia.

    Science.gov (United States)

    Swerdlow, N R; Braff, D L; Hartston, H; Perry, W; Geyer, M A

    1996-05-01

    Latent inhibition (LI) refers to the retarded acquisition of a conditioned response that occurs if the subject being tested is first preexposed to the to-be-conditioned stimulus (CS) without the paired unconditioned stimulus (UCS). Because the 'irrelevance' of the to-be-conditioned stimulus is established during non-contingent preexposure, the slowed acquisition of the CS-UCS association is thought to reflect the process of overcoming this learned irrelevance. Latent inhibition has been reported to be diminished in acutely hospitalized schizophrenia patients. If acutely hospitalized schizophrenia patients are preexposed to the CS, they learn the association as fast as, and perhaps faster than, patients who are not preexposed to the CS. This finding has been interpreted as reflecting the inability of acute schizophrenia patients to ignore irrelevant stimuli. In this study, the LI paradigm was identical to the one used in previous reports of LI deficits in schizophrenia patients (Baruch et al., 1988). Latent inhibition was observed in normal control subjects (n = 73), including individuals identified as 'psychosis-prone' based on established screening criteria, and in anxiety (n = 19) and mood disorder (n = 13) patients. Learning scores (trials to criterion) in "acutely' hospitalized as well as "chronic' hospitalized schizophrenia patients (n = 45) were significantly elevated in both preexposed and non-preexposed subjects, compared to controls. Acute schizophrenia patients exhibited intact LI. Separate cohorts of acute and chronic schizophrenia patients (n = 23) and normal controls (n = 34) exhibited intact LI when tested in a new, easier-to-acquire computerized LI paradigm. These results fail to identify specific LI deficits in schizophrenia patients, and raise the possibility that previously observed LI deficits in schizophrenia patients may reflect, at least in part, performance deficits related to learning acquisition.

  12. Beneficial bacteria inhibit cachexia.

    Science.gov (United States)

    Varian, Bernard J; Goureshetti, Sravya; Poutahidis, Theofilos; Lakritz, Jessica R; Levkovich, Tatiana; Kwok, Caitlin; Teliousis, Konstantinos; Ibrahim, Yassin M; Mirabal, Sheyla; Erdman, Susan E

    2016-03-15

    Muscle wasting, known as cachexia, is a debilitating condition associated with chronic inflammation such as during cancer. Beneficial microbes have been shown to optimize systemic inflammatory tone during good health; however, interactions between microbes and host immunity in the context of cachexia are incompletely understood. Here we use mouse models to test roles for bacteria in muscle wasting syndromes. We find that feeding of a human commensal microbe, Lactobacillus reuteri, to mice is sufficient to lower systemic indices of inflammation and inhibit cachexia. Further, the microbial muscle-building phenomenon extends to normal aging as wild type animals exhibited increased growth hormone levels and up-regulation of transcription factor Forkhead Box N1 [FoxN1] associated with thymus gland retention and longevity. Interestingly, mice with a defective FoxN1 gene (athymic nude) fail to inhibit sarcopenia after L. reuteri therapy, indicating a FoxN1-mediated mechanism. In conclusion, symbiotic bacteria may serve to stimulate FoxN1 and thymic functions that regulate inflammation, offering possible alternatives for cachexia prevention and novel insights into roles for microbiota in mammalian ontogeny and phylogeny.

  13. Remediación de suelos contaminados con mercurio utilizando guarumo (Cecropia peltata

    Directory of Open Access Journals (Sweden)

    Jhon Víctor Vidal Durango

    2010-01-01

    Full Text Available La contaminación de suelos por el mercurio resultante de la explotación aurífera puede ser remediada mediante la utilización de plantas que lo acumulan en sus tejidos, disminuyendo su impacto sobre los ecosistemas y la salud humana. En este trabajo se determinó la influencia del grado de contaminación, la aplicación de ácido cítrico y tiempo de crecimiento del guarumo, sobre la tasa de remoción de mercurio en suelo. Después de 4 meses de crecimiento, los porcentajes de remoción estuvieron entre 15.7% y 33.7% debido a la capacidad del guarumo para acumular grandes cantidades del metal sin presentar efectos tóxicos considerables, así como al alto contenido de mercurio biodisponible en los suelos contaminados, lo que conllevó también a que el ácido cítrico no tuviera una influencia significativa sobre la recuperación de Hg; por lo cual se concluyó, que el guarumo es una especie con capacidad fitorremediadora.

  14. In vitro phytochemical characteristics and antioxidant capacity of Aloe vera, Plukenetia volubilis, Caiophora carduifolia, Cecropia membranacea

    OpenAIRE

    Franco Quino, César; Unidad de Posgrado, Facultad de Farmacia y Bioquímica, Universidad Nacional Mayor de San Marcos, Lima, Perú; Laboratorio de Fisiología y Farmacología, Facultad de Odontología, UNMSM, Lima, Perú; Muñoz Espinoza, Danny; Unidad de Posgrado, Facultad de Farmacia y Bioquímica, Universidad Nacional Mayor de San Marcos, Lima, Perú; Facultad de Ciencias Químicas, Universidad de Guayaquil, Ecuador; Gómez Herreros, César; Unidad de Posgrado, Facultad de Farmacia y Bioquímica, Universidad Nacional Mayor de San Marcos, Lima, Perú; Chau Miranda, Gina; Unidad de Posgrado, Facultad de Farmacia y Bioquímica, Universidad Nacional Mayor de San Marcos, Lima, Perú; Cueva Piña, Liliana; Unidad de Posgrado, Facultad de Farmacia y Bioquímica, Universidad Nacional Mayor de San Marcos, Lima, Perú; Guardia Ortiz, Eliza; Unidad de Posgrado, Facultad de Farmacia y Bioquímica, Universidad Nacional Mayor de San Marcos, Lima, Perú; Saavedra Yucra, Santos; Unidad de Posgrado, Facultad de Farmacia y Bioquímica, Universidad Nacional Mayor de San Marcos, Lima, Perú; Arroyo Acevedo, Jorge; Laboratorio de Farmacología Experimental, Facultad de Medicina Humana, UNMSM, Lima, Perú; Instituto de Investigaciones Clínicas, UNMSM, Lima, Perú; Herrera Calderón, Oscar; Facultad de Fisiología y Fisiopatología, Facultad de Farmacia y Bioquímica, Universidad Nacional San Luis Gonzaga, Ica, Perú

    2016-01-01

    Introduction. Antioxidants have shown chemopreventive potential in degenerative, inflammatory, autoimmune, oncology and respiratory distress associated pathologies. Objective. To assess the phytochemical and antioxidant properties in vitro by DPPH and ABTS method. Design. Observational analytical. Location. Laboratory of Experimental Pharmacology, Faculty of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru. Biological/Chemical Material. Aloe vera leaves, Plukenetia volubilis see...

  15. Can Arousal Modulate Response Inhibition?

    Science.gov (United States)

    Weinbach, Noam; Kalanthroff, Eyal; Avnit, Amir; Henik, Avishai

    2015-01-01

    The goal of the present study was to examine if and how arousal can modulate response inhibition. Two competing hypotheses can be drawn from previous literature. One holds that alerting cues that elevate arousal should result in an impulsive response and therefore impair response inhibition. The other suggests that alerting enhances processing of…

  16. Lateral inhibition during nociceptive processing

    DEFF Research Database (Denmark)

    Quevedo, Alexandre S.; Mørch, Carsten Dahl; Andersen, Ole Kæseler

    2017-01-01

    of skin. Thus, the stimulation of the skin region between the endpoints of the lines appears to produce inhibition. These findings indicate that lateral inhibition limits spatial summation of pain and is an intrinsic component of nociceptive information processing. Disruption of such lateral inhibition......Spatial summation of pain is the increase of perceived intensity that occurs as the stimulated area increases. Spatial summation of pain is sub-additive in that increasing the stimulus area produces a disproportionately small increase in the perceived intensity of pain. A possible explanation...... for sub-additive summation may be that convergent excitatory information is modulated by lateral inhibition. To test the hypothesis that lateral inhibition may limit spatial summation of pain, we delivered different patterns of noxious thermal stimuli to the abdomens of 15 subjects using a computer...

  17. Lateral inhibition during nociceptive processing.

    Science.gov (United States)

    Quevedo, Alexandre S; Mørch, Carsten Dahl; Andersen, Ole K; Coghill, Robert C

    2017-06-01

    Spatial summation of pain (SSP) is the increase of perceived intensity that occurs as the stimulated area increases. Spatial summation of pain is subadditive in that increasing the stimulus area produces a disproportionately small increase in the perceived intensity of pain. A possible explanation for subadditive summation may be that convergent excitatory information is modulated by lateral inhibition. To test the hypothesis that lateral inhibition may limit SSP, we delivered different patterns of noxious thermal stimuli to the abdomens of 15 subjects using a computer-controlled CO2 laser. Lines (5 mm wide) of variable lengths (4, 8 cm) were compared with 2-point stimuli delivered at the same position/separation as the length of lines. When compared with one-point control stimuli, 2-point stimulus patterns produced statistically significant SSP, while no such summation was detected during line stimulus patterns. Direct comparison of pain intensity evoked by 2-point pattern stimuli with line pattern stimuli revealed that 2-point patterns were perceived as significantly more painful, despite the fact that the 2-point pattern stimulated far smaller areas of skin. Thus, the stimulation of the skin region between the endpoints of the lines appears to produce inhibition. These findings indicate that lateral inhibition limits SSP and is an intrinsic component of nociceptive information processing. Disruption of such lateral inhibition may contribute substantially to the radiation of some types of chronic pain.

  18. Activated sludge inhibition capacity index

    Directory of Open Access Journals (Sweden)

    V. Surerus

    2014-06-01

    Full Text Available Toxic compounds in sewage or industrial wastewater may inhibit the biological activity of activated sludge impairing the treatment process. This paper evaluates the Inhibition Capacity Index (ICI for the assessment of activated sludge in the presence of toxicants. In this study, activated sludge was obtained from industrial treatment plants and was also synthetically produced. Continuous respirometric measurements were carried out in a reactor, and the oxygen uptake rate profile obtained was used to evaluate the impact of inhibiting toxicants, such as dissolved copper, phenol, sodium alkylbenzene sulfonate and amoxicillin, on activated sludge. The results indicate that ICI is an efficient tool to quantify the intoxication capacity. The activated sludge from the pharmaceutical industry showed higher resistance than the sludge from other sources, since toxicants are widely discharged in the biological treatment system. The ICI range was from 58 to 81% when compared to the synthetic effluent with no toxic substances.

  19. Homo economicus belief inhibits trust.

    Directory of Open Access Journals (Sweden)

    Ziqiang Xin

    Full Text Available As a foundational concept in economics, the homo economicus assumption regards humans as rational and self-interested actors. In contrast, trust requires individuals to believe partners' benevolence and unselfishness. Thus, the homo economicus belief may inhibit trust. The present three experiments demonstrated that the direct exposure to homo economicus belief can weaken trust. And economic situations like profit calculation can also activate individuals' homo economicus belief and inhibit their trust. It seems that people's increasing homo economicus belief may serve as one cause of the worldwide decline of trust.

  20. Homo economicus belief inhibits trust.

    Science.gov (United States)

    Xin, Ziqiang; Liu, Guofang

    2013-01-01

    As a foundational concept in economics, the homo economicus assumption regards humans as rational and self-interested actors. In contrast, trust requires individuals to believe partners' benevolence and unselfishness. Thus, the homo economicus belief may inhibit trust. The present three experiments demonstrated that the direct exposure to homo economicus belief can weaken trust. And economic situations like profit calculation can also activate individuals' homo economicus belief and inhibit their trust. It seems that people's increasing homo economicus belief may serve as one cause of the worldwide decline of trust.

  1. Strigolactone inhibition of shoot branching

    NARCIS (Netherlands)

    Gomez-Roldan, M.V.; Fermas, S.; Brewer, P.B.; Puech-Pages, V.; Dun, E.A.; Pillot, J.P.; Letisse, F.; Matusova, R.; Danoun, S.; Portais, J.C.; Bouwmeester, H.J.; Becard, G.; Beveridge, C.A.; Rameau, C.; Rochange, S.F.

    2008-01-01

    A carotenoid-derived hormonal signal that inhibits shoot branching in plants has long escaped identification. Strigolactones are compounds thought to be derived from carotenoids and are known to trigger the germination of parasitic plant seeds and stimulate symbiotic fungi. Here we present evidence

  2. Strigolactone inhibition of shoot branching

    NARCIS (Netherlands)

    Gomez-Roldan, M.V.; Fermas, S.; Brewer, P.B.; Puech-Pages, V.; Dun, E.A.; Pillot, J.P.; Letisse, F.; Matusova, R.; Danoun, S.; Portais, J.C.; Bouwmeester, H.J.; Becard, G.; Beveridge, C.A.; Rameau, C.; Rochange, S.F.

    2008-01-01

    A carotenoid-derived hormonal signal that inhibits shoot branching in plants has long escaped identification. Strigolactones are compounds thought to be derived from carotenoids and are known to trigger the germination of parasitic plant seeds and stimulate symbiotic fungi. Here we present evidence

  3. Methanogenic inhibition by arsenic compounds.

    Science.gov (United States)

    Sierra-Alvarez, Reyes; Cortinas, Irail; Yenal, Umur; Field, Jim A

    2004-09-01

    The acute acetoclastic methanogenic inhibition of several inorganic and organic arsenicals was assayed. Trivalent species, i.e., methylarsonous acid and arsenite, were highly inhibitory, with 50% inhibitory concentrations of 9.1 and 15.0 microM, respectively, whereas pentavalent species were generally nontoxic. The nitrophenylarsonate derivate, roxarsone, displayed moderate toxicity.

  4. Inhibition of carcinogenesis by tea.

    Science.gov (United States)

    Yang, Chung S; Maliakal, Pius; Meng, Xiaofeng

    2002-01-01

    Tea has received a great deal of attention because tea polyphenols are strong antioxidants, and tea preparations have inhibitory activity against tumorigenesis. The bioavailability and biotransformation of tea polyphenols, however, are key factors limiting these activities in vivo. The inhibition of tumorigenesis by green or black tea preparations has been demonstrated in animal models on different organ sites such as skin, lung, oral cavity, esophagus, forestomach, stomach, small intestine, colon, pancreas, and mammary gland. Epidemiological studies, however, have not yielded clear conclusions concerning the protective effects of tea consumption against cancer formation in humans. The discrepancy between the results from humans and animal models could be due to 1) the much higher doses of tea used in animals in comparison to human consumption, 2) the differences in causative factors between the cancers in humans and animals, and 3) confounding factors limiting the power of epidemiological studies to detect an effect. It is possible that tea may be only effective against specific types of cancer caused by certain etiological factors. Many mechanisms have been proposed for the inhibition of carcinogenesis by tea, including the modulation of signal transduction pathways that leads to the inhibition of cell proliferation and transformation, induction of apoptosis of preneoplastic and neoplastic cells, as well as inhibition of tumor invasion and angiogenesis. These mechanisms need to be evaluated and verified in animal models or humans in order to gain more understanding on the effect of tea consumption on human cancer.

  5. Testing of Biologically Inhibiting Surface

    DEFF Research Database (Denmark)

    Bill Madsen, Thomas; Larsen, Erup

    2003-01-01

    The main purpose of this course is to examine a newly developed biologically inhibiting material with regards to galvanic corrosion and electrochemical properties. More in detail, the concern was how the material would react when exposed to cleaning agents, here under CIP cleaning (Cleaning...

  6. Islam Does Not Inhibit Science.

    Science.gov (United States)

    Shanavas, T. O.

    1999-01-01

    Compares the science/religion relationship in both Christian and Islamic countries. Presents Muslim scholars' ideas about the presence of humans on earth. Presents ideas on active nature, Noah's curse, and the age of the universe. Refutes the notion that Islam inhibited science and advocates the belief that Islam promoted science. (YDS)

  7. Epigallocatechin gallate inhibits endothelial exocytosis.

    Science.gov (United States)

    Yamakuchi, Munekazu; Bao, Clare; Ferlito, Marcella; Lowenstein, Charles J

    2008-07-01

    Consumption of green tea is associated with a decrease in cardiovascular mortality. The beneficial health effects of green tea are attributed in part to polyphenols, organic compounds found in tea that lower blood pressure, reduce body fat, decrease LDL cholesterol, and inhibit inflammation. We hypothesized that epigallocatechin gallate (EGCG), the most abundant polyphenol in tea, inhibits endothelial exocytosis, the initial step in leukocyte trafficking and vascular inflammation. To test this hypothesis, we treated human umbilical-vein endothelial cells with EGCG and other polyphenols, and then measured endothelial exocytosis. We found that EGCG decreases endothelial exocytosis in a concentration-dependent manner, with the effects most prominent after 4 h of treatment. Other catechin polyphenols had no effect on endothelial cells. By inhibiting endothelial exocytosis, EGCG decreases leukocyte adherence to endothelial cells. In searching for the mechanism by which EGCG affects endothelial cells, we found that EGCG increases Akt phosphorylation, eNOS phosphorylation, and nitric oxide (NO) production. NOS inhibition revealed that NO mediates the anti-inflammatory effects of EGCG. Our data suggest that polyphenols can decrease vascular inflammation by increasing the synthesis of NO, which blocks endothelial exocytosis.

  8. Infant Predictors of Behavioural Inhibition

    Science.gov (United States)

    Moehler, Eva; Kagan, Jerome; Oelkers-Ax, Rieke; Brunner, Romuald; Poustka, Luise; Haffner, Johann; Resch, Franz

    2008-01-01

    Behavioural inhibition in the second year of life is a hypothesized predictor for shyness, social anxiety and depression in later childhood, adolescence and even adulthood. To search for the earliest indicators of this fundamental temperamental trait, this study examined whether behavioural characteristics in early infancy can predict behavioural…

  9. Corrosion Chemistry in Inhibited HDA.

    Science.gov (United States)

    1980-11-30

    Titanium and chromium have sufficiently low Flade potentials to pass- ivate in non-oxidising acids, but Iron will only exhibit self-passivity if the...inhibition e.g. involving organic and pickling inhibitors* the rest potential can actually 4.5,4.6become more negative " This is due to cathodic rather...media. 321 stainless steel, titanium stabilised, was the particular steel studied, being very similar in composition to the 347also stainless steel

  10. Notch Signaling Inhibits Axon Regeneration

    OpenAIRE

    Bejjani, Rachid El; Hammarlund, Marc

    2012-01-01

    Many neurons have limited capacity to regenerate their axons after injury. Neurons in the mammalian CNS do not regenerate, and even neurons in the PNS often fail to regenerate to their former targets. This failure is likely due in part to pathways that actively restrict regeneration; however, only a few factors that limit regeneration are known. Here, using single-neuron analysis of regeneration in vivo, we show that Notch/lin-12 signaling inhibits the regeneration of mature C. elegans neuron...

  11. Th2 cytokines inhibit lymphangiogenesis.

    Directory of Open Access Journals (Sweden)

    Ira L Savetsky

    Full Text Available Lymphangiogenesis is the process by which new lymphatic vessels grow in response to pathologic stimuli such as wound healing, inflammation, and tumor metastasis. It is well-recognized that growth factors and cytokines regulate lymphangiogenesis by promoting or inhibiting lymphatic endothelial cell (LEC proliferation, migration and differentiation. Our group has shown that the expression of T-helper 2 (Th2 cytokines is markedly increased in lymphedema, and that these cytokines inhibit lymphatic function by increasing fibrosis and promoting changes in the extracellular matrix. However, while the evidence supporting a role for T cells and Th2 cytokines as negative regulators of lymphatic function is clear, the direct effects of Th2 cytokines on isolated LECs remains poorly understood. Using in vitro and in vivo studies, we show that physiologic doses of interleukin-4 (IL-4 and interleukin-13 (IL-13 have profound anti-lymphangiogenic effects and potently impair LEC survival, proliferation, migration, and tubule formation. Inhibition of these cytokines with targeted monoclonal antibodies in the cornea suture model specifically increases inflammatory lymphangiogenesis without concomitant changes in angiogenesis. These findings suggest that manipulation of anti-lymphangiogenic pathways may represent a novel and potent means of improving lymphangiogenesis.

  12. Conditioned inhibition and reinforcement rate.

    Science.gov (United States)

    Harris, Justin A; Kwok, Dorothy W S; Andrew, Benjamin J

    2014-07-01

    We investigated conditioned inhibition in a magazine approach paradigm. Rats were trained on a feature negative discrimination between an auditory conditioned stimulus (CS) reinforced at one rate versus a compound of that CS and a visual stimulus (L) reinforced at a lower rate. This training established L as a conditioned inhibitor. We then tested the inhibitory strength of L by presenting it in compound with other auditory CSs. L reduced responding when tested with a CS that had been reinforced at a high rate, but had less or even no inhibitory effect when tested with a CS that had been reinforced at a low rate. The inhibitory strength of L was greater if it signaled a decrease in reinforcement from an already low rate than if it signaled an equivalent decrease in reinforcement from a high rate. We conclude that the strength of inhibition is not a linear function of the change in reinforcement that it signals. We discuss the implications of this finding for models of learning (e.g., Rescorla & Wagner, 1972) that identify inhibition with a difference (subtraction) rule.

  13. Self-regulation, ego depletion, and inhibition.

    Science.gov (United States)

    Baumeister, Roy F

    2014-12-01

    Inhibition is a major form of self-regulation. As such, it depends on self-awareness and comparing oneself to standards and is also susceptible to fluctuations in willpower resources. Ego depletion is the state of reduced willpower caused by prior exertion of self-control. Ego depletion undermines inhibition both because restraints are weaker and because urges are felt more intensely than usual. Conscious inhibition of desires is a pervasive feature of everyday life and may be a requirement of life in civilized, cultural society, and in that sense it goes to the evolved core of human nature. Intentional inhibition not only restrains antisocial impulses but can also facilitate optimal performance, such as during test taking. Self-regulation and ego depletion- may also affect less intentional forms of inhibition, even chronic tendencies to inhibit. Broadly stated, inhibition is necessary for human social life and nearly all societies encourage and enforce it.

  14. Reflex excitability regulates prepulse inhibition.

    Science.gov (United States)

    Schicatano, E J; Peshori, K R; Gopalaswamy, R; Sahay, E; Evinger, C

    2000-06-01

    Presentation of a weak stimulus, a prepulse, before a reflex-evoking stimulus decreases the amplitude of the reflex response relative to reflex amplitude evoked without a preceding prepulse. For example, presenting a brief tone before a trigeminal blink-eliciting stimulus significantly reduces reflex blink amplitude. A common explanation of such data are that sensory processing of the prepulse modifies reflex circuit behavior. The current study investigates the converse hypothesis that the intrinsic characteristics of the reflex circuit rather than prepulse processing determine prepulse modification of trigeminal and acoustic reflex blinks. Unilateral lesions of substantia nigra pars compacta neurons created rats with hyperexcitable trigeminal reflex blinks but normally excitable acoustic reflex blinks. In control rats, presentation of a prepulse reduced the amplitude of both trigeminal and acoustic reflex blinks. In 6-OHDA-lesioned rats, however, the same acoustic prepulse facilitated trigeminal reflex blinks but inhibited acoustic reflex blinks. The magnitude of prepulse modification correlated with reflex excitability. Humans exhibited the same pattern of prepulse modification. An acoustic prepulse facilitated the trigeminal reflex blinks of subjects with hyperexcitable trigeminal reflex blinks caused by Parkinson's disease. The same prepulse inhibited trigeminal reflex blinks of age-matched control subjects. Prepulse modification also correlated with trigeminal reflex blink excitability. These data show that reflex modification by a prepulse reflects the intrinsic characteristics of the reflex circuit rather than an external adjustment of the reflex circuit by the prepulse.

  15. Graphene: corrosion-inhibiting coating.

    Science.gov (United States)

    Prasai, Dhiraj; Tuberquia, Juan Carlos; Harl, Robert R; Jennings, G Kane; Rogers, Bridget R; Bolotin, Kirill I

    2012-02-28

    We report the use of atomically thin layers of graphene as a protective coating that inhibits corrosion of underlying metals. Here, we employ electrochemical methods to study the corrosion inhibition of copper and nickel by either growing graphene on these metals, or by mechanically transferring multilayer graphene onto them. Cyclic voltammetry measurements reveal that the graphene coating effectively suppresses metal oxidation and oxygen reduction. Electrochemical impedance spectroscopy measurements suggest that while graphene itself is not damaged, the metal under it is corroded at cracks in the graphene film. Finally, we use Tafel analysis to quantify the corrosion rates of samples with and without graphene coatings. These results indicate that copper films coated with graphene grown via chemical vapor deposition are corroded 7 times slower in an aerated Na(2)SO(4) solution as compared to the corrosion rate of bare copper. Tafel analysis reveals that nickel with a multilayer graphene film grown on it corrodes 20 times slower while nickel surfaces coated with four layers of mechanically transferred graphene corrode 4 times slower than bare nickel. These findings establish graphene as the thinnest known corrosion-protecting coating.

  16. Greener Approach towards Corrosion Inhibition

    Directory of Open Access Journals (Sweden)

    Neha Patni

    2013-01-01

    Full Text Available Corrosion control of metals is technically, economically, environmentally, and aesthetically important. The best option is to use inhibitors for protecting metals and alloys against corrosion. As organic corrosion inhibitors are toxic in nature, so green inhibitors which are biodegradable, without any heavy metals and other toxic compounds, are promoted. Also plant products are inexpensive, renewable, and readily available. Tannins, organic amino acids, alkaloids, and organic dyes of plant origin have good corrosion-inhibiting abilities. Plant extracts contain many organic compounds, having polar atoms such as O, P, S, and N. These are adsorbed on the metal surface by these polar atoms, and protective films are formed, and various adsorption isotherms are obeyed. Various types of green inhibitors and their effect on different metals are mentioned in the paper.

  17. Inhibiting scale in oil wells

    Energy Technology Data Exchange (ETDEWEB)

    D' Errico, M.J.; Adler, S.F.

    1972-09-27

    An oil well treatment is described to inhibit the formation of hard scale by precipitation from the oil well brine of scale-forming water insoluble sulfate, carbonate, and other salts. The process consists of incorporating into the oil well during a fracturing treatment, a fluid containing a solid polymeric material characterized by molecular weight in the range of 1,000 to 15,000 and a substantially linear structure, derived by the linear polymerization of at least one monoolefinically unsaturated compound through the olefinically unsaturated group. The linear structure has pendent groups, 50% of which are carboxy groups, the carboxy groups being neutralized with a sufficient proportion of at least one compound having a cation of a metal selected from alkaline earth metals, chromium, aluminum, iron, cobalt, zinc, nickel or copper to render the polymer soluble in water at 25$C to a concentration of not more than 50 ppm. (8 claims)

  18. Latent inhibition in human adults without masking.

    Science.gov (United States)

    Escobar, Martha; Arcediano, Francisco; Miller, Ralph R

    2003-09-01

    Latent inhibition refers to attenuated responding to Cue X observed when the X-outcome pairings are preceded by X-alone presentations. It has proven difficult to obtain in human adults unless the preexposure (X-alone) presentations are embedded within a masking (i.e., distracting) task. The authors hypothesized that the difficulty in obtaining latent inhibition with unmasked tasks is related to the usual training procedures, in which the preexposure and conditioning experiences are separated by a set of instructions. Experiment 1 reports latent inhibition without masking in a task in which preexposure and conditioning occur without interruption. Experiments 2 and 3 demonstrate that this attenuation in responding to target Cue X does not pass a summation test for conditioned inhibition and is context specific, thereby confirming that it is latent inhibition. Experiments 3 and 4 confirm that introducing instructions between preexposure and conditioning disrupts latent inhibition.

  19. Enhanced latent inhibition in high schizotypy individuals

    OpenAIRE

    Granger, Kiri T.; Moran, Paula M.; Buckley, Matthew G.; Haselgrove, Mark

    2016-01-01

    Latent inhibition refers to a retardation in learning about a stimulus that has been rendered familiar by non-reinforced preexposure, relative to a non-preexposed stimulus. Latent inhibition has been shown to be inversely correlated with schizotypy, and abnormal in people with schizophrenia, but these findings are inconsistent. One potential contributing factor to this inconsistency is that many tasks that purport to measure latent inhibition are confounded by alternative effects that also re...

  20. Collaborative inhibition in spatial memory retrieval

    National Research Council Canada - National Science Library

    Sjolund, Lori A; Erdman, Matthew; Kelly, Jonathan W

    2014-01-01

    .... Two experiments were designed to explore whether collaborative inhibition, which has heretofore been studied using traditional memory stimuli such as word lists, also characterizes spatial memory retrieval...

  1. Inhibition of the dorsal premotor cortex does not repair surround inhibition in writer's cramp patients.

    Science.gov (United States)

    Veugen, Lidwien C; Hoffland, Britt S; Stegeman, Dick F; van de Warrenburg, Bart P

    2013-03-01

    Writer's cramp is a task-specific form of focal dystonia, characterized by abnormal movements and postures of the hand and arm during writing. Two consistent abnormalities in its pathophysiology are a loss of surround inhibition and overactivity of the dorsal premotor cortex (PMd). This study aimed to assess a possible link between these two phenomena by investigating whether PMd inhibition leads to an improvement of surround inhibition, in parallel with previously demonstrated writing improvement. Fifteen writer's cramp patients and ten controls performed a simple motor hand task during which surround inhibition was measured using transcranial magnetic stimulation. Motor cortical excitability was measured of the active and surround muscles at three phases of the task. Surround inhibition and writing performance were assessed before and after PMd inhibitory continuous theta burst stimulation. In contrast to healthy controls, patients did not show inhibition of the abductor digiti minimi muscle during movement initiation of the first dorsal interosseus muscle, confirming the loss of surround inhibition. PMd inhibition led to an improvement of writing speed in writer's cramp patients. However, in both groups, no changes in surround inhibition were observed. The results confirm a role for the PMd in the pathophysiology of writer's cramp. We show that PMd inhibition does not lead to restoration of the surround inhibition defect in writer's cramp, despite the improvement in writing. This questions the involvement of the PMd in the loss of surround inhibition, and perhaps also the direct link between surround inhibition and dystonia.

  2. Molecular characterization and expression of prothoracicotropic hormone during development and pupal diapause in the cotton bollworm, Helicoverpa armigera.

    Science.gov (United States)

    Wei, Zhao-Jun; Zhang, Qi-Rui; Kang, Le; Xu, Wei-Hua; Denlinger, David L

    2005-06-01

    Using a strategy of rapid amplification of cDNA ends, the cDNA encoding prothoracicotropic hormone (PTTH) was cloned from the brain of Helicoverpa armigera (Hearm). The Hearm-PTTH cDNA contains an open reading frame encoding a 226-amino acid preprohormone, which shows high identity with the closely related noctuid moths, Helicoverpa zea (98%) and Heliothis virescens (94%), and low identity with five species of Bombycoidea: Bombyx mori (57%), Manduca sexta (55%), Hyalophora cecropia (52%), Samia cynthia ricini (49%) and Antheraea peryni (48%). Hearm-PTTH cDNA shares important structural characterization known from other PTTHs, such as seven cysteine residues, proteolytic cleavage site, glycosylation site, and hydrophobic regions within the mature peptides. Northern blot analysis indicated a 0.9kb transcript present only in the brain. Using the more sensitive technique of RT-PCR, PTTH mRNA was also detected in the subesophageal ganglion, thoracic ganglion, abdominal ganglion, midgut and fat body. During the pupal stage, PTTH mRNA in the brain remained at a constant high level in nondiapausing individuals, was low in diapausing pupae, but increased again at diapause termination. The PTTH protein was detected only in the brain by Western blot analysis. Immunocytochemical results revealed that Hearm-PTTH is localized in two pairs of dorsolateral neurosecretory cells within the brain. Recombinant Hearm-PTTH was successfully expressed in E. coli, and purified recombinant-PTTH was effective in breaking pupal diapause. The results are consistent with a role for PTTH in the regulation of diapause in this species.

  3. Reduced surround inhibition in musicians.

    Science.gov (United States)

    Shin, Hae-Won; Kang, Suk Y; Hallett, Mark; Sohn, Young H

    2012-06-01

    To investigate whether surround inhibition (SI) in the motor system is altered in professional musicians, we performed a transcranial magnetic stimulation (TMS) study in 10 professional musicians and 15 age-matched healthy non-musicians. TMS was set to be triggered by self-initiated flexion of the index finger at different intervals ranging from 3 to 1,000 ms. Average motor evoked potential (MEP) amplitudes obtained from self-triggered TMS were normalized to average MEPs of the control TMS at rest and expressed as a percentage. Normalized MEP amplitudes of the abductor digiti minimi (ADM) muscles were compared between the musicians and non-musicians with the primary analysis being the intervals between 3 and 80 ms (during the movement). A mixed-design ANOVA revealed a significant difference in normalized ADM MEPs during the index finger flexion between groups, with less SI in the musicians. This study demonstrated that the functional operation of SI is less strong in musicians than non-musicians, perhaps due to practice of movement synergies involving both muscles. Reduced SI, however, could lead susceptible musicians to be prone to develop task-specific dystonia.

  4. Cellulase Inhibition by High Concentrations of Monosaccharides

    DEFF Research Database (Denmark)

    Hsieh, Chia-Wen; Cannella, David; Jørgensen, Henning

    2014-01-01

    that low free water availability contributes to cellulase inhibition. Of the hydrolytic enzymes involved, those acting on the cellulose substrate, that is, exo- and endoglucanases, were the most inhibited. The β -glucosidases were shown to be less sensitive to high monosaccharide concentrations except...

  5. A Qualitative Approach to Enzyme Inhibition

    Science.gov (United States)

    Waldrop, Grover L.

    2009-01-01

    Most general biochemistry textbooks present enzyme inhibition by showing how the basic Michaelis-Menten parameters K[subscript m] and V[subscript max] are affected mathematically by a particular type of inhibitor. This approach, while mathematically rigorous, does not lend itself to understanding how inhibition patterns are used to determine the…

  6. Inhibited and Uninhibited Types of Children.

    Science.gov (United States)

    Kagan, Jerome; And Others

    1989-01-01

    Investigates the preservation of inhibited and uninhibited behaviors in 100 children of 14, 20, 32, and 48 months. Children who had been extremely inhibited or uninhibited at 14 and 20 months differed significantly at 4 years of age in behavior and cardiac acceleration. (RJC)

  7. Inhibition: Mental Control Process or Mental Resource?

    Science.gov (United States)

    Im-Bolter, Nancie; Johnson, Janice; Ling, Daphne; Pascual-Leone, Juan

    2015-01-01

    The current study tested 2 models of inhibition in 45 children with language impairment and 45 children with normally developing language; children were aged 7 to 12 years. Of interest was whether a model of inhibition as a mental-control process (i.e., executive function) or as a mental resource would more accurately reflect the relations among…

  8. Quorum Sensing Inhibition, Relevance to Periodontics

    OpenAIRE

    Yada, Sudheer; Kamalesh, B; Sonwane, Siddharth; Guptha, Indra; Swetha, R K

    2015-01-01

    Quorum sensing helps bacteria to communicate with each other and in coordinating their behavior. Many diseases of human beings, plants, and animals are mediated by quorum sensing. Various approaches are being tried to inhibit this communication to control the diseases caused by bacteria. Periodontal pathogens also communicate through quorum sensing and new approaches to treat periodontal disease using quorum sensing inhibition need to explored.

  9. A Qualitative Approach to Enzyme Inhibition

    Science.gov (United States)

    Waldrop, Grover L.

    2009-01-01

    Most general biochemistry textbooks present enzyme inhibition by showing how the basic Michaelis-Menten parameters K[subscript m] and V[subscript max] are affected mathematically by a particular type of inhibitor. This approach, while mathematically rigorous, does not lend itself to understanding how inhibition patterns are used to determine the…

  10. Quorum sensing inhibition, relevance to periodontics.

    Science.gov (United States)

    Yada, Sudheer; Kamalesh, B; Sonwane, Siddharth; Guptha, Indra; Swetha, R K

    2015-01-01

    Quorum sensing helps bacteria to communicate with each other and in coordinating their behavior. Many diseases of human beings, plants, and animals are mediated by quorum sensing. Various approaches are being tried to inhibit this communication to control the diseases caused by bacteria. Periodontal pathogens also communicate through quorum sensing and new approaches to treat periodontal disease using quorum sensing inhibition need to explored.

  11. Inhibition in Autism: Children with Autism Have Difficulty Inhibiting Irrelevant Distractors but Not Prepotent Responses

    Science.gov (United States)

    Adams, Nena C.; Jarrold, Christopher

    2012-01-01

    Resistance to distractor inhibition tasks have previously revealed impairments in children with autism. However, on the classic Stroop task and other prepotent response tasks, children with autism show intact inhibition. These data may reflect a distinction between prepotent response and resistance to distractor inhibition. The current study…

  12. Inhibition of ethylene production by rhizobitoxine

    Energy Technology Data Exchange (ETDEWEB)

    Owens, L.D.; Lieberman, M.; Kunishi, A.

    1970-01-01

    Rhizobitoxine, an inhibitor of methionine biosynthesis in Salmonella typhimurium, inhibited ethylene production about 75% in light-grown sorghum seedlings and in senescent apple tissue. Ethylene production stimulated by indoleacetic acid and kinetin in sorghum was similarly inhibited. With both apple and sorghum, the inhibition could only be partially relieved by additions of methionine. A methionine analogue, ..cap alpha..-keto-..gamma..-methylthiobutyric acid, which has been suggested as an intermediate between methionine and ethylene, had no effect on the inhibition. Incorporation of /sup 14/C from added methionine-/sup 14/C into ethylene was curtailed by rhizobitoxine to about the same extent as was ethylene production. These results suggest that rhizobitoxine interferes with ethylene biosynthesis by blocking the conversion of methionine to ethylene and not indirectly by inhibiting the biosynthesis of methionine. Ethylene production by Penicillium digitatum, a fungus which produces ethylene via pathways not utilizing methionine as a precursor, was not affected by rhizobitoxine. 16 references, 2 figures, 4 tables.

  13. Habituation, latent inhibition, and extinction.

    Science.gov (United States)

    Jordan, Wesley P; Todd, Travis P; Bucci, David J; Leaton, Robert N

    2015-06-01

    In two conditioned suppression experiments with a latent inhibition (LI) design, we measured the habituation of rats in preexposure, their LI during conditioning, and then extinction over days. In the first experiment, lick suppression, the preexposed group (PE) showed a significant initial unconditioned response (UR) to the target stimulus and significant long-term habituation (LTH) of that response over days. The significant difference between the PE and nonpreexposed (NPE) groups on the first conditioning trial was due solely to the difference in their URs to the conditioned stimulus (CS)-a habituated response (PE) and an unhabituated response (NPE). In the second experiment, bar-press suppression, little UR to the target stimulus was apparent during preexposure, and no detectable LTH. Thus, there was no difference between the PE and NPE groups on the first conditioning trial. Whether the UR to the CS confounds the interpretation of LI (Exp. 1) or not (Exp. 2) can only be known if the UR is measured. In both experiments, LI was observed in acquisition. Also in both experiments, rats that were preexposed and then conditioned to asymptote were significantly more resistant to extinction than were the rats not preexposed. This result contrasts with the consistently reported finding that preexposure either produces less resistance to extinction or has no effect on extinction. The effect of stimulus preexposure survived conditioning to asymptote and was reflected directly in extinction. These two experiments provide a cautionary procedural note for LI experiments and have shown an unexpected extinction effect that may provide new insights into the interpretation of LI.

  14. Fear inhibition in high trait anxiety.

    Science.gov (United States)

    Kindt, Merel; Soeter, Marieke

    2014-01-01

    Trait anxiety is recognized as an individual risk factor for the development of anxiety disorders but the neurobiological mechanisms remain unknown. Here we test whether trait anxiety is associated with impaired fear inhibition utilizing the AX+/BX- conditional discrimination procedure that allows for the independent evaluation of startle fear potentiation and inhibition of fear. Sixty undergraduate students participated in the study--High Trait Anxious: n = 28 and Low Trait Anxious: n = 32. We replicated earlier findings that a transfer of conditioned inhibition for startle responses requires contingency awareness. However, contrary to the fear inhibition hypothesis, our data suggest that high trait anxious individuals show a normal fear inhibition of conditioned startle responding. Only at the cognitive level the high trait anxious individuals showed evidence for impaired inhibitory learning of the threat cue. Together with other findings where impaired fear inhibition was only observed in those PTSD patients who were either high on hyperarousal symptoms or with current anxiety symptoms, we question whether impaired fear inhibition is a biomarker for the development of anxiety disorders.

  15. BST2/Tetherin Inhibition of Alphavirus Exit

    Directory of Open Access Journals (Sweden)

    Yaw Shin Ooi

    2015-04-01

    Full Text Available Alphaviruses such as chikungunya virus (CHIKV and Semliki Forest virus (SFV are small enveloped RNA viruses that bud from the plasma membrane. Tetherin/BST2 is an interferon-induced host membrane protein that inhibits the release of many enveloped viruses via direct tethering of budded particles to the cell surface. Alphaviruses have highly organized structures and exclude host membrane proteins from the site of budding, suggesting that their release might be insensitive to tetherin inhibition. Here, we demonstrated that exogenously-expressed tetherin efficiently inhibited the release of SFV and CHIKV particles from host cells without affecting virus entry and infection. Alphavirus release was also inhibited by the endogenous levels of tetherin in HeLa cells. While rubella virus (RuV and dengue virus (DENV have structural similarities to alphaviruses, tetherin inhibited the release of RuV but not DENV. We found that two recently identified tetherin isoforms differing in length at the N-terminus exhibited distinct capabilities in restricting alphavirus release. SFV exit was efficiently inhibited by the long isoform but not the short isoform of tetherin, while both isoforms inhibited vesicular stomatitis virus exit. Thus, in spite of the organized structure of the virus particle, tetherin specifically blocks alphavirus release and shows an interesting isoform requirement.

  16. The IFITMs Inhibit Zika Virus Replication

    Directory of Open Access Journals (Sweden)

    George Savidis

    2016-06-01

    Full Text Available Zika virus has emerged as a severe health threat with a rapidly expanding range. The IFITM family of restriction factors inhibits the replication of a broad range of viruses, including the closely related flaviruses West Nile virus and dengue virus. Here, we show that IFITM1 and IFITM3 inhibit Zika virus infection early in the viral life cycle. Moreover, IFITM3 can prevent Zika-virus-induced cell death. These results suggest that strategies to boost the actions and/or levels of the IFITMs might be useful for inhibiting a broad range of emerging viruses.

  17. Reversible Inhibition of Cellular Metabolism by Ribavirin

    Science.gov (United States)

    Larsson, Alf; Stenberg, Kjell; Öberg, Bo

    1978-01-01

    The broad spectrum antiviral drug ribavirin (Virazole, 1-β-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) inhibits cellular macromolecular synthesis as well as cell division in eucaryotic cells. The concentration and time dependence have been studied. One-hour treatment with 25 μM ribavirin or 18 h with 2 μM inhibited the deoxyribonucleic acid synthesis to 50%. Higher concentrations of ribavirin were required to obtain a similar inhibition of ribonucleic acid and protein synthesis. This effect on cell metabolism and cell division can be reversed by removing the drug from the cells. PMID:646339

  18. Lobelane inhibits methamphetamine-evoked dopamine release via inhibition of the vesicular monoamine transporter-2.

    Science.gov (United States)

    Nickell, Justin R; Krishnamurthy, Sairam; Norrholm, Seth; Deaciuc, Gabriela; Siripurapu, Kiran B; Zheng, Guangrong; Crooks, Peter A; Dwoskin, Linda P

    2010-02-01

    Lobeline is currently being evaluated in clinical trials as a methamphetamine abuse treatment. Lobeline interacts with nicotinic receptor subtypes, dopamine transporters (DATs), and vesicular monoamine transporters (VMAT2s). Methamphetamine inhibits VMAT2 and promotes dopamine (DA) release from synaptic vesicles, resulting ultimately in increased extracellular DA. The present study generated structure-activity relationships by defunctionalizing the lobeline molecule and determining effects on [(3)H]dihydrotetrabenazine binding, inhibition of [(3)H]DA uptake into striatal synaptic vesicles and synaptosomes, the mechanism of VMAT2 inhibition, and inhibition of methamphetamine-evoked DA release. Compared with lobeline, the analogs exhibited greater potency inhibiting DA transporter (DAT) function. Saturated analogs, lobelane and nor-lobelane, exhibited high potency (K(i) = 45 nM) inhibiting vesicular [(3)H]DA uptake, and lobelane competitively inhibited VMAT2 function. Lobeline and lobelane exhibited 67- and 35-fold greater potency, respectively, in inhibiting VMAT2 function compared to DAT function. Lobelane potently decreased (IC(50) = 0.65 microM; I(max) = 73%) methamphetamine-evoked DA overflow, and with a greater maximal effect compared with lobeline (IC(50) = 0.42 microM, I(max) = 56.1%). These results provide support for VMAT2 as a target for inhibition of methamphetamine effects. Both trans-isomers and demethylated analogs of lobelane had reduced or unaltered potency inhibiting VMAT2 function and lower maximal inhibition of methamphetamine-evoked DA release compared with lobelane. Thus, defunctionalization, cis-stereochemistry of the side chains, and presence of the piperidino N-methyl are structural features that afford greatest inhibition of methamphetamine-evoked DA release and enhancement of selectivity for VMAT2. The current results reveal that lobelane, a selective VMAT2 inhibitor, inhibits methamphetamine-evoked DA release and is a promising lead for

  19. Lobelane Inhibits Methamphetamine-Evoked Dopamine Release via Inhibition of the Vesicular Monoamine Transporter-2S⃞

    Science.gov (United States)

    Nickell, Justin R.; Krishnamurthy, Sairam; Norrholm, Seth; Deaciuc, Gabriela; Siripurapu, Kiran B.; Zheng, Guangrong; Crooks, Peter A.

    2010-01-01

    Lobeline is currently being evaluated in clinical trials as a methamphetamine abuse treatment. Lobeline interacts with nicotinic receptor subtypes, dopamine transporters (DATs), and vesicular monoamine transporters (VMAT2s). Methamphetamine inhibits VMAT2 and promotes dopamine (DA) release from synaptic vesicles, resulting ultimately in increased extracellular DA. The present study generated structure-activity relationships by defunctionalizing the lobeline molecule and determining effects on [3H]dihydrotetrabenazine binding, inhibition of [3H]DA uptake into striatal synaptic vesicles and synaptosomes, the mechanism of VMAT2 inhibition, and inhibition of methamphetamine-evoked DA release. Compared with lobeline, the analogs exhibited greater potency inhibiting DA transporter (DAT) function. Saturated analogs, lobelane and nor-lobelane, exhibited high potency (Ki = 45 nM) inhibiting vesicular [3H]DA uptake, and lobelane competitively inhibited VMAT2 function. Lobeline and lobelane exhibited 67- and 35-fold greater potency, respectively, in inhibiting VMAT2 function compared to DAT function. Lobelane potently decreased (IC50 = 0.65 μM; Imax = 73%) methamphetamine-evoked DA overflow, and with a greater maximal effect compared with lobeline (IC50 = 0.42 μM, Imax = 56.1%). These results provide support for VMAT2 as a target for inhibition of methamphetamine effects. Both trans-isomers and demethylated analogs of lobelane had reduced or unaltered potency inhibiting VMAT2 function and lower maximal inhibition of methamphetamine-evoked DA release compared with lobelane. Thus, defunctionalization, cis-stereochemistry of the side chains, and presence of the piperidino N-methyl are structural features that afford greatest inhibition of methamphetamine-evoked DA release and enhancement of selectivity for VMAT2. The current results reveal that lobelane, a selective VMAT2 inhibitor, inhibits methamphetamine-evoked DA release and is a promising lead for the development of a

  20. Inhibition of urinary calculi -- a spectroscopic study

    Science.gov (United States)

    Manciu, Felicia; Govani, Jayesh; Durrer, William; Reza, Layra; Pinales, Luis

    2008-10-01

    Although a considerable number of investigations have already been undertaken and many causes such as life habits, metabolic disorders, and genetic factors have been noted as sources that accelerate calculi depositions and aggregations, there are still plenty of unanswered questions regarding efficient inhibition and treatment mechanisms. Thus, in an attempt to acquire more insights, we propose here a detailed scientific study of kidney stone formation and growth inhibition based on a traditional medicine approach with Rotula Aquatica Lour (RAL) herbal extracts. A simplified single diffusion gel growth technique was used for synthesizing the samples for the present study. The unexpected Zn presence in the sample with RAL inhibitor, as revealed by XPS measurements, explains the inhibition process and the dramatic reflectance of the incident light observed in the infrared transmission studies. Raman data demonstrate potential binding of the inhibitor with the oxygen of the kidney stone. Photoluminescence results corroborate to provide additional evidence of Zn-related inhibition.

  1. Toxicants inhibiting anaerobic digestion: a review.

    Science.gov (United States)

    Chen, Jian Lin; Ortiz, Raphael; Steele, Terry W J; Stuckey, David C

    2014-12-01

    Anaerobic digestion is increasingly being used to treat wastes from many sources because of its manifold advantages over aerobic treatment, e.g. low sludge production and low energy requirements. However, anaerobic digestion is sensitive to toxicants, and a wide range of compounds can inhibit the process and cause upset or failure. Substantial research has been carried out over the years to identify specific inhibitors/toxicants, and their mechanism of toxicity in anaerobic digestion. In this review we present a detailed and critical summary of research on the inhibition of anaerobic processes by specific organic toxicants (e.g., chlorophenols, halogenated aliphatics and long chain fatty acids), inorganic toxicants (e.g., ammonia, sulfide and heavy metals) and in particular, nanomaterials, focusing on the mechanism of their inhibition/toxicity. A better understanding of the fundamental mechanisms behind inhibition/toxicity will enhance the wider application of anaerobic digestion.

  2. Glycerol inhibition of ruminal lipolysis in vitro

    Science.gov (United States)

    Supplemental glycerol inhibits rumen lipolysis, a prerequisite for rumen biohydrogenation, which is responsible for the saturation of dietary fatty acids consumed by ruminant animals. Feeding excess glycerol, however, adversely affects dry matter digestibility. To more clearly define the effect of...

  3. Neomycin inhibits angiogenin-induced angiogenesis

    OpenAIRE

    1998-01-01

    A class of angiogenesis inhibitor has emerged from our mechanistic study of the action of angiogenin, a potent angiogenic factor. Neomycin, an aminoglycoside antibiotic, inhibits nuclear translocation of human angiogenin in human endothelial cells, an essential step for angiogenin-induced angiogenesis. The phospholipase C-inhibiting activity of neomycin appears to be involved, because U-73122, another phospholipase C inhibitor, has a similar effect. In contrast, genistein, oxophenylarsine, an...

  4. Neomycin inhibits angiogenin-induced angiogenesis

    OpenAIRE

    Hu, Guo-fu

    1998-01-01

    A class of angiogenesis inhibitor has emerged from our mechanistic study of the action of angiogenin, a potent angiogenic factor. Neomycin, an aminoglycoside antibiotic, inhibits nuclear translocation of human angiogenin in human endothelial cells, an essential step for angiogenin-induced angiogenesis. The phospholipase C-inhibiting activity of neomycin appears to be involved, because U-73122, another phospholipase C inhibitor, has a similar effect. In contrast, genistein, oxophenylarsine, an...

  5. Inhibited solid propellant composition containing beryllium hydride

    Science.gov (United States)

    Thompson, W. W. (Inventor)

    1978-01-01

    An object of this invention is to provide a composition of beryllium hydride and carboxy-terminated polybutadiene which is stable. Another object of this invention is to provide a method for inhibiting the reactivity of beryllium hydride toward carboxy-terminated polybutadiene. It was found that a small amount of lecithin inhibits the reaction of beryllium hydride with the acid groups in carboxy terminated polybutadiene.

  6. The inhibition of monoamine oxidase by esomeprazole

    OpenAIRE

    2013-01-01

    Virtual screening of a library of drugs has suggested that esomeprazole, the S-enantiomer of omeprazole, may possess binding affinities for the active sites of the monoamine oxidase (MAO) A and B enzymes. Based on this finding, the current study examines the MAO inhibitory properties of esomeprazole. Using recombinant human MAO-A and MAO-B, IC50 values for the inhibition of these enzymes by esomeprazole were experimentally determined. To examine the reversibility of MAO inhibition by esomepra...

  7. Piperine, a dietary phytochemical, inhibits angiogenesis

    OpenAIRE

    2012-01-01

    Angiogenesis plays an important role in tumor progression. Piperine, a major alkaloid constituent of black pepper, has diverse physiological actions including killing of cancer cells; however, the effect of piperine on angiogenesis is not known. Here we show that piperine inhibited the proliferation and G1/S transition of human umbilical vein endothelial cells (HUVECs) without causing cell death. Piperine also inhibited HUVEC migration and tubule formation in vitro, as well as collagen-induce...

  8. Inhibition in the Human Auditory Cortex.

    Directory of Open Access Journals (Sweden)

    Koji Inui

    Full Text Available Despite their indispensable roles in sensory processing, little is known about inhibitory interneurons in humans. Inhibitory postsynaptic potentials cannot be recorded non-invasively, at least in a pure form, in humans. We herein sought to clarify whether prepulse inhibition (PPI in the auditory cortex reflected inhibition via interneurons using magnetoencephalography. An abrupt increase in sound pressure by 10 dB in a continuous sound was used to evoke the test response, and PPI was observed by inserting a weak (5 dB increase for 1 ms prepulse. The time course of the inhibition evaluated by prepulses presented at 10-800 ms before the test stimulus showed at least two temporally distinct inhibitions peaking at approximately 20-60 and 600 ms that presumably reflected IPSPs by fast spiking, parvalbumin-positive cells and somatostatin-positive, Martinotti cells, respectively. In another experiment, we confirmed that the degree of the inhibition depended on the strength of the prepulse, but not on the amplitude of the prepulse-evoked cortical response, indicating that the prepulse-evoked excitatory response and prepulse-evoked inhibition reflected activation in two different pathways. Although many diseases such as schizophrenia may involve deficits in the inhibitory system, we do not have appropriate methods to evaluate them; therefore, the easy and non-invasive method described herein may be clinically useful.

  9. Inhibition of Heme Peroxidases by Melamine

    Directory of Open Access Journals (Sweden)

    Pattaraporn Vanachayangkul

    2012-01-01

    Full Text Available In 2008 melamine-contaminated infant formula and dairy products in China led to over 50,000 hospitalizations of children due to renal injuries. In North America during 2007 and in Asia during 2004, melamine-contaminated pet food products resulted in numerous pet deaths due to renal failure. Animal studies have confirmed the potent renal toxicity of melamine combined with cyanuric acid. We showed previously that the solubility of melamine cyanurate is low at physiologic pH and ionic strength, provoking us to speculate how toxic levels of these compounds could be transported through the circulation without crystallizing until passing into the renal filtrate. We hypothesized that melamine might be sequestered by heme proteins, which could interfere with heme enzyme activity. Four heme peroxidase enzymes were selected for study: horseradish peroxidase (HRP, lactoperoxidase (LPO, and cyclooxygenase-1 and -2 (COX-1 and -2. Melamine exhibited noncompetitive inhibition of HRP (9.5±0.7mM, and LPO showed a mixed model of inhibition (14.5±4.7mM. The inhibition of HRP and LPO was confirmed using a chemiluminescent peroxidase assay. Melamine also exhibited COX-1 inhibition, but inhibition of COX-2 was not detected. Thus, our results demonstrate that melamine inhibits the activity of three heme peroxidases.

  10. Scale Inhibition of Green Inhibitor Polyepoxysuccinic Sodium

    Institute of Scientific and Technical Information of China (English)

    Feng Hui-xia; Wang Yi; Yu Shu-rong; Liang Bao-feng

    2004-01-01

    Polyepoxysuccinic acid (PESA) is the green water treatment agents recognized all over the world[1-3]. It is found that when PESA is used alone, it had good scale inhibition. PESA should be included in the category of green scale inhibitor.PESA is synthesized with maleicanhydride in the presence of catalysts. The effect on scale-in-hibiting property of the product from amount and feed times of catalyst, the reaction temperature, the reaction time were investigated. The optimum reaction conditions are as follows:n(maleic anhydride):n(Ca(OH)2):n(NaOH)=1:0.05-0.2:0.5, reaction temperature 95C, reaction time 4h.In all the references about PESA, PESA is researched as a kind of highly effective scale inhibitor or chelate. In this paper, the performance of scale inhibition of PESA is evaluated by scale static inhibitor.The results are shown in Figture1.It is evident from our experimental data (Figture1) that when inhibition for CaCO3.With the increase of PESA dosage, scale inhibition increases. When dosage is more than 6mg/L, inhibition efficiency is over 50%. The formulas give scale inhibition efficiency more than 95% at 12mg/L of total dosage.

  11. Spatially reciprocal inhibition of inhibition within a stimulus selection network in the avian midbrain.

    Science.gov (United States)

    Goddard, C Alex; Mysore, Shreesh P; Bryant, Astra S; Huguenard, John R; Knudsen, Eric I

    2014-01-01

    Reciprocal inhibition between inhibitory projection neurons has been proposed as the most efficient circuit motif to achieve the flexible selection of one stimulus among competing alternatives. However, whether such a motif exists in networks that mediate selection is unclear. Here, we study the connectivity within the nucleus isthmi pars magnocellularis (Imc), a GABAergic nucleus that mediates competitive selection in the midbrain stimulus selection network. Using laser photostimulation of caged glutamate, we find that feedback inhibitory connectivity is global within the Imc. Unlike typical lateral inhibition in other circuits, intra-Imc inhibition remains functionally powerful over long distances. Anatomically, we observed long-range axonal projections and retrograde somatic labeling from focal injections of bi-directional tracers in the Imc, consistent with spatial reciprocity of intra-Imc inhibition. Together, the data indicate that spatially reciprocal inhibition of inhibition occurs throughout the Imc. Thus, the midbrain selection circuit possesses the most efficient circuit motif possible for fast, reliable, and flexible selection.

  12. Neomycin inhibits angiogenin-induced angiogenesis.

    Science.gov (United States)

    Hu, G F

    1998-08-18

    A class of angiogenesis inhibitor has emerged from our mechanistic study of the action of angiogenin, a potent angiogenic factor. Neomycin, an aminoglycoside antibiotic, inhibits nuclear translocation of human angiogenin in human endothelial cells, an essential step for angiogenin-induced angiogenesis. The phospholipase C-inhibiting activity of neomycin appears to be involved, because U-73122, another phospholipase C inhibitor, has a similar effect. In contrast, genistein, oxophenylarsine, and staurosporine, inhibitors of tyrosine kinase, phosphotyrosine phosphatase, and protein kinase C, respectively, do not inhibit nuclear translocation of angiogenin. Neomycin inhibits angiogenin-induced proliferation of human endothelial cells in a dose-dependent manner. At 50 microM, neomycin abolishes angiogenin-induced proliferation but does not affect the basal level of proliferation and cell viability. Other aminoglycoside antibiotics, including gentamicin, streptomycin, kanamycin, amikacin, and paromomycin, have no effect on angiogenin-induced cell proliferation. Most importantly, neomycin completely inhibits angiogenin-induced angiogenesis in the chicken chorioallantoic membrane at a dose as low as 20 ng per egg. These results suggest that neomycin and its analogs are a class of agents that may be developed for anti-angiogenin therapy.

  13. Aspartate inhibits Staphylococcus aureus biofilm formation.

    Science.gov (United States)

    Yang, Hang; Wang, Mengyue; Yu, Junping; Wei, Hongping

    2015-04-01

    Biofilm formation renders Staphylococcus aureus highly resistant to conventional antibiotics and host defenses. Four D-amino acids (D-Leu, D-Met, D-Trp and D-Tyr) have been reported to be able to inhibit biofilm formation and disassemble established S. aureus biofilms. We report here for the first time that both D- and L-isoforms of aspartate (Asp) inhibited S. aureus biofilm formation on tissue culture plates. Similar biofilm inhibition effects were also observed against other staphylococcal strains, including S. saprophyticus, S. equorum, S. chromogenes and S. haemolyticus. It was found that Asp at high concentrations (>10 mM) inhibited the growth of planktonic N315 cells, but at subinhibitory concentrations decreased the cellular metabolic activity without influencing cell growth. The decreased cellular metabolic activity might be the reason for the production of less protein and DNA in the matrix of the biofilms formed in the presence of Asp. However, varied inhibition efficacies of Asp were observed for biofilms formed by clinical staphylococcal isolates. There might be mechanisms other than decreasing the metabolic activity, e.g. the biofilm phenotypes, affecting biofilm formation in the presence of Asp.

  14. Matrix metalloproteinase inhibition in atherosclerosis and stroke.

    Science.gov (United States)

    Roycik, M D; Myers, J S; Newcomer, R G; Sang, Q-X A

    2013-09-01

    Matrix metalloproteinases (MMPs) are a family of tightly regulated, zinc-dependent proteases that degrade extracellular matrix (ECM), cell surface, and intracellular proteins. Vascular remodeling, whether as a function of normal physiology or as a consequence of a myriad of pathological processes, requires degradation of the ECM. Thus, the expression and activity of many MMPs are up-regulated in numerous conditions affecting the vasculature and often exacerbate vascular dysfunction. A growing body of evidence supports the rationale of using MMP inhibitors for the treatment of cardiovascular diseases, stroke, and chronic vascular dementia. This manuscript will examine promising targets for MMP inhibition in atherosclerosis and stroke, reviewing findings in preclinical animal models and human patient studies. Strategies for MMP inhibition have progressed beyond chelating the catalytic zinc to functional blocking antibodies and peptides that target either the active site or exosites of the enzyme. While the inhibition of MMP activity presents a rational therapeutic avenue, the multiplicity of roles for MMPs and the non-selective nature of MMP inhibitors that cause unintended side-effects hinder full realization of MMP inhibition as therapy for vascular disease. For optimal therapeutic effects to be realized, specific targets for MMP inhibition in these pathologies must first be identified and then attacked by potent and selective agents during the most appropriate timepoint.

  15. Genistein inhibits differentiation of primary human adipocytes.

    Science.gov (United States)

    Park, Hea Jin; Della-Fera, Mary Anne; Hausman, Dorothy B; Rayalam, Srujana; Ambati, Suresh; Baile, Clifton A

    2009-02-01

    Genistein, a major soy isoflavone, has been reported to exhibit antiadipogenic and proapoptotic potential in vivo and in vitro. It is also a phytoestrogen which has high affinity to estrogen receptor beta. In this study, we determined the effect of genistein on adipogenesis and estrogen receptor (ER) alpha and beta expression during differentiation in primary human preadipocytes. Genistein inhibited lipid accumulation in a dose-dependent manner at concentrations of 6.25 microM and higher, with 50 microM genistein inhibiting lipid accumulation almost completely. Low concentrations of genistein (3.25 microM) increased cell viability and higher concentrations (25 and 50 microM) decreased it by 16.48+/-1.35% (P<.0001) and 50.68+/-1.34% (P<.0001). Oil Red O staining was used to confirm the effects on lipid accumulation. The inhibition of lipid accumulation was associated with inhibition of glycerol-3-phosphate dehydrogenase activity and down-regulation of expression of adipocyte-specific genes, including peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein alpha, glycerol-3-phosphate dehydrogenase, adipocyte fatty acid binding protein, fatty acid synthase, sterol regulatory element-binding protein 1, perilipin, leptin, lipoprotein lipase and hormone-sensitive lipase. These effects of genistein during the differentiation period were associated with down-regulation of ERalpha and ERbeta expression. This study adds to the elucidation of the molecular pathways involved in the inhibition of adipogenesis by phytoestrogens.

  16. Inhibition of ethylene production by putrescine alleviates aluminium-induced root inhibition in wheat plants.

    Science.gov (United States)

    Yu, Yan; Jin, Chongwei; Sun, Chengliang; Wang, Jinghong; Ye, Yiquan; Zhou, Weiwei; Lu, Lingli; Lin, Xianyong

    2016-01-08

    Inhibition of root elongation is one of the most distinct symptoms of aluminium (Al) toxicity. Although putrescine (Put) has been identified as an important signaling molecule involved in Al tolerance, it is yet unknown how Put mitigates Al-induced root inhibition. Here, the possible mechanism was investigated by using two wheat genotypes differing in Al resistance: Al-tolerant Xi Aimai-1 and Al-sensitive Yangmai-5. Aluminium caused more root inhibition in Yangmai-5 and increased ethylene production at the root apices compared to Xi Aimai-1, whereas the effects were significantly reversed by ethylene biosynthesis inhibitors. The simultaneous exposure of wheat seedlings to Al and ethylene donor, ethephon, or ethylene biosynthesis precursor, 1-aminocyclopropane-1-carboxylic acid (ACC), increased ethylene production and aggravated root inhibition, which was more pronounced in Xi Aimai-1. In contrast, Put treatment decreased ethylene production and alleviated Al-induced root inhibition in both genotypes, and the effects were more conspicuous in Yangmai-5. Furthermore, our results indicated that Al-induced ethylene production was mediated by ACC synthase (ACS) and ACC oxidase, and that Put decreased ethylene production by inhibiting ACS. Altogether, these findings indicate that ethylene is involved in Al-induced root inhibition and this process could be alleviated by Put through inhibiting ACS activity.

  17. The role of (dis)inhibition in creativity: decreased inhibition improves idea generation.

    Science.gov (United States)

    Radel, Rémi; Davranche, Karen; Fournier, Marion; Dietrich, Arne

    2015-01-01

    There is now a large body of evidence showing that many different conditions related to impaired fronto-executive functioning are associated with the enhancement of some types of creativity. In this paper, we pursue the possibility that the central mechanism associated with this effect might be a reduced capacity to exert inhibition. We tested this hypothesis by exhausting the inhibition efficiency through prolonged and intensive practice of either the Simon or the Eriksen Flanker task. Performance on another inhibition task indicated that only the cognitive resources for inhibition of participants facing high inhibition demands were impaired. Subsequent creativity tests revealed that exposure to high inhibition demands led to enhanced fluency in a divergent thinking task (Alternate Uses Task), but no such changes occurred in a convergent task (Remote Associate Task; studies 1a and 1b). The same manipulation also led to a hyper-priming effect for weakly related primes in a Lexical Decision Task (Study 2). Together, these findings suggest that inhibition selectively affects some types of creative processes and that, when resources for inhibition are lacking, the frequency and the originality of ideas was facilitated.

  18. Structural basis for transcription inhibition by tagetitoxin.

    Science.gov (United States)

    Vassylyev, Dmitry G; Svetlov, Vladimir; Vassylyeva, Marina N; Perederina, Anna; Igarashi, Noriyuki; Matsugaki, Naohiro; Wakatsuki, Soichi; Artsimovitch, Irina

    2005-12-01

    Tagetitoxin (Tgt) inhibits transcription by an unknown mechanism. A structure at a resolution of 2.4 A of the Thermus thermophilus RNA polymerase (RNAP)-Tgt complex revealed that the Tgt-binding site within the RNAP secondary channel overlaps that of the stringent control effector ppGpp, which partially protects RNAP from Tgt inhibition. Tgt binding is mediated exclusively through polar interactions with the beta and beta' residues whose substitutions confer resistance to Tgt in vitro. Importantly, a Tgt phosphate, together with two active site acidic residues, coordinates the third Mg(2+) ion, which is distinct from the two catalytic metal ions. We show that Tgt inhibits all RNAP catalytic reactions and propose a mechanism in which the Tgt-bound Mg(2+) ion has a key role in stabilization of an inactive transcription intermediate. Remodeling of the active site by metal ions could be a common theme in the regulation of catalysis by nucleic acid enzymes.

  19. Mapuche herbal medicine inhibits blood platelet aggregation.

    Science.gov (United States)

    Falkenberg, Susan Skanderup; Tarnow, Inge; Guzman, Alfonso; Mølgaard, Per; Simonsen, Henrik Toft

    2012-01-01

    12 plant species traditionally used by the Mapuche people in Chile to treat wounds and inflammations have been evaluated for their direct blood platelet inhibition. Seven of the 12 tested plant species showed platelet inhibitory effect in sheep blood, and four of these were also able to inhibit the ADP- (5.0 μM) and collagen- (2.0 μg/mL) induced aggregations in human blood. These four species in respective extracts (in brackets) were Blechnum chilense (MeOH), Luma apiculata (H(2)O), Amomyrtus luma (DCM : MeOH 1 : 1) and Cestrum parqui (DCM : MeOH 1 : 1). The platelet aggregating inhibitory effects of A. luma (DCM : MeOH 1 : 1), and L. apiculata (H(2)O) were substantial and confirmed by inhibition of platelet surface activation markers.

  20. Anticancer Alkaloid Lamellarins Inhibit Protein Kinases

    Directory of Open Access Journals (Sweden)

    Laurent Meijer

    2008-10-01

    Full Text Available Lamellarins, a family of hexacyclic pyrrole alkaloids originally isolated from marine invertebrates, display promising anti-tumor activity. They induce apoptotic cell death through multi-target mechanisms, including inhibition of topoisomerase I, interaction with DNA and direct effects on mitochondria. We here report that lamellarins inhibit several protein kinases relevant to cancer such as cyclin-dependent kinases, dualspecificity tyrosine phosphorylation activated kinase 1A, casein kinase 1, glycogen synthase kinase-3 and PIM-1. A good correlation is observed between the effects of lamellarins on protein kinases and their action on cell death, suggesting that inhibition of specific kinases may contribute to the cytotoxicity of lamellarins. Structure/activity relationship suggests several paths for the optimization of lamellarins as kinase inhibitors.

  1. Mapuche Herbal Medicine Inhibits Blood Platelet Aggregation

    Directory of Open Access Journals (Sweden)

    Susan Skanderup Falkenberg

    2012-01-01

    Full Text Available 12 plant species traditionally used by the Mapuche people in Chile to treat wounds and inflammations have been evaluated for their direct blood platelet inhibition. Seven of the 12 tested plant species showed platelet inhibitory effect in sheep blood, and four of these were also able to inhibit the ADP- (5.0 μM and collagen- (2.0 μg/mL induced aggregations in human blood. These four species in respective extracts (in brackets were Blechnum chilense (MeOH, Luma apiculata (H2O, Amomyrtus luma (DCM : MeOH 1 : 1 and Cestrum parqui (DCM : MeOH 1 : 1. The platelet aggregating inhibitory effects of A. luma (DCM : MeOH 1 : 1, and L. apiculata (H2O were substantial and confirmed by inhibition of platelet surface activation markers.

  2. Complete corrosion inhibition through graphene defect passivation.

    Science.gov (United States)

    Hsieh, Ya-Ping; Hofmann, Mario; Chang, Kai-Wen; Jhu, Jian Gang; Li, Yuan-Yao; Chen, Kuang Yao; Yang, Chang Chung; Chang, Wen-Sheng; Chen, Li-Chyong

    2014-01-28

    Graphene is expected to enable superior corrosion protection due to its impermeability and chemical inertness. Previous reports, however, demonstrate limited corrosion inhibition and even corrosion enhancement of graphene on metal surfaces. To enable the reliable and complete passivation, the origin of the low inhibition efficiency of graphene was investigated. Combining electrochemical and morphological characterization techniques, nanometer-sized structural defects in chemical vapor deposition grown graphene were found to be the cause for the limited passivation effect. Extremely fast mass transport on the order of meters per second both across and parallel to graphene layers results in an inhibition efficiency of only ∼50% for Cu covered with up to three graphene layers. Through selective passivation of the defects by atomic layer deposition (ALD) an enhanced corrosion protection of more than 99% was achieved, which compares favorably with commercial corrosion protection methods.

  3. Mesoporous silica nanoparticles inhibit cellular respiration.

    Science.gov (United States)

    Tao, Zhimin; Morrow, Matthew P; Asefa, Tewodros; Sharma, Krishna K; Duncan, Cole; Anan, Abhishek; Penefsky, Harvey S; Goodisman, Jerry; Souid, Abdul-Kader

    2008-05-01

    We studied the effect of two types of mesoporous silica nanoparticles, MCM-41 and SBA-15, on mitochondrial O 2 consumption (respiration) in HL-60 (myeloid) cells, Jurkat (lymphoid) cells, and isolated mitochondria. SBA-15 inhibited cellular respiration at 25-500 microg/mL; the inhibition was concentration-dependent and time-dependent. The cellular ATP profile paralleled that of respiration. MCM-41 had no noticeable effect on respiration rate. In cells depleted of metabolic fuels, 50 microg/mL SBA-15 delayed the onset of glucose-supported respiration by 12 min and 200 microg/mL SBA-15 by 34 min; MCM-41 also delayed the onset of glucose-supported respiration. Neither SBA-15 nor MCM-41 affected cellular glutathione. Both nanoparticles inhibited respiration of isolated mitochondria and submitochondrial particles.

  4. Quantifying hydrate formation and kinetic inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Sloan, E.D.; Subramanian, S.; Matthews, P.N.; Lederhos, J.P.; Khokhar, A.A. [Colorado School of Mines, Golden, CO (United States). Center for Hydrate Research

    1998-08-01

    In the Prausnitz tradition, molecular and macroscopic evidence of hydrate formation and kinetic inhibition is presented. On the microscopic level, the first Raman spectra are presented for the formation of both uninhibited and inhibited methane hydrates with time. This method has the potential to provide a microscopic-based kinetics model. Three macroscopic aspects of natural gas hydrate kinetic inhibition are also reported: (1) The effect of hydrate dissociation residual structures was measured, which has application in decreasing the time required for subsequent formation. (2) The performance of a kinetic inhibitor (poly(N-vinylcaprolactam) or PVCap) was measured and correlated as a function of PVCap molecular weight and concentrations of PVCap, methanol, and salt in the aqueous phase. (3) Long-duration test results indicated that the use of PVCap can prevent pipeline blockage for a time exceeding the aqueous phase residence time in some gas pipelines.

  5. Inhibition of aluminum corrosion using Opuntia extract

    Energy Technology Data Exchange (ETDEWEB)

    El-Etre, A.Y

    2003-11-01

    The inhibitive action of the mucilage extracted from the modified stems of prickly pears, toward acid corrosion of aluminum, is tested using weight loss, thermometry, hydrogen evolution and polarization techniques. It was found that the extract acts as a good corrosion inhibitor for aluminum corrosion in 2.0 M HCl solution. The inhibition action of the extract was discussed in view of Langmuir adsorption isotherm. It was found that the adsorption of the extract on aluminum surface is a spontaneous process. The inhibition efficiency (IE) increases as the extract concentration is increased. The effect of temperature on the IE was studied. It was found that the presence of extract increases the activation energy of the corrosion reaction. Moreover, the thermodynamic parameters of the adsorption process were calculated. It was found also that the Opuntia extract provides a good protection to aluminum against pitting corrosion in chloride ion containing solutions.

  6. Silver-Palladium Surfaces Inhibit Biofilm Formation

    DEFF Research Database (Denmark)

    Chiang, Wen-Chi; Schroll, Casper; Hilbert, Lisbeth Rischel

    2009-01-01

    Undesired biofilm formation is a major concern in many areas. In the present study, we investigated biofilm-inhibiting properties of a silver-palladium surface that kills bacteria by generating microelectric fields and electrochemical redox processes. For evaluation of the biofilm inhibition...... efficacy and study of the biofilm inhibition mechanism, the silver-sensitive Escherichia coli J53 and the silver-resistant E. coli J53[pMG101] strains were used as model organisms, and batch and flow chamber setups were used as model systems. In the case of the silver-sensitive strain, the silver......-palladium surfaces killed the bacteria and prevented biofilm formation under conditions of low or high bacterial load. In the case of the silver-resistant strain, the silver-palladium surfaces killed surface-associated bacteria and prevented biofilm formation under conditions of low bacterial load, whereas under...

  7. Neural inhibition enables selection during language processing.

    Science.gov (United States)

    Snyder, Hannah R; Hutchison, Natalie; Nyhus, Erika; Curran, Tim; Banich, Marie T; O'Reilly, Randall C; Munakata, Yuko

    2010-09-21

    Whether grocery shopping or choosing words to express a thought, selecting between options can be challenging, especially for people with anxiety. We investigate the neural mechanisms supporting selection during language processing and its breakdown in anxiety. Our neural network simulations demonstrate a critical role for competitive, inhibitory dynamics supported by GABAergic interneurons. As predicted by our model, we find that anxiety (associated with reduced neural inhibition) impairs selection among options and associated prefrontal cortical activity, even in a simple, nonaffective verb-generation task, and the GABA agonist midazolam (which increases neural inhibition) improves selection, whereas retrieval from semantic memory is unaffected when selection demands are low. Neural inhibition is key to choosing our words.

  8. Pyrilamine inhibits nicotine-induced catecholamine secretion.

    Science.gov (United States)

    Kim, Dong-Chan; Yun, So Jeong; Park, Yong-Soo; Jun, Dong-Jae; Kim, Dongjin; Jiten Singh, N; Kim, Sanguk; Kim, Kyong-Tai

    2014-07-01

    Function of nicotine, which induces activation of all parts of the body including our brain, has been receiving much attention for a long period of time and also been actively studied by researchers for its pharmacological actions in the central nervous system. The modulation of nicotine concentration and the inhibition of nicotine binding on target receptors in the brain are the key factors for smoking addiction therapy. In previous studies showed that influx of nicotine at the blood-brain barrier was through the pyrilamine-sensitive organic cation transporters. But the direct interacting mechanism of pyrilamine on the nicotine binding target receptors has not yet been clarified. The aim of the present study is to investigate the direct binding mechanisms of a pyrilamine on the nicotinic acetylcholine receptors (nAChRs). We found that pyrilamine shares the same ligand binding pocket of nicotine (NCT) on nAChRs but interacts with more amino acid residues than NCT does. The extended part of pyrilamine interacts with additional residues in the ligand binding pocket of nAChRs which are located nearby the entrance of the binding pocket. The catecholamine (CA) secretion induced by nAChR agonist (NCT') was significantly inhibited by the pyrilamine pretreatment. Real time carbon-fiber amperometry confirmed the inhibition of the NCT'-induced exocytosis by pyrilamine in a single cell level. We also found that pyrilamine inhibited the NCT'-induced [Ca(2+)]i. In contrast, pyrilamine did not affect the increase in calcium induced by high K(+). Overall, these data suggest that pyrilamine directly docks into the ligand binding site of nAChRs and specifically inhibits the nAChR-mediated effects thereby causing inhibition of CA secretion. Therefore, pyrilamine may play an important role to explore new treatments to aid smoking cessation.

  9. Peptide inhibition of human cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Morris Cindy A

    2011-02-01

    Full Text Available Abstract Background Human cytomegalovirus (HCMV is the most prevalent congenital viral infection in the United States and Europe causing significant morbidity and mortality to both mother and child. HCMV is also an opportunistic pathogen in immunocompromised individuals, including human immunodeficiency virus (HIV- infected patients with AIDS, and solid organ and allogeneic stem cell transplantation recipients. Current treatments for HCMV-associated diseases are insufficient due to the emergence of drug-induced resistance and cytotoxicity, necessitating novel approaches to limit HCMV infection. The aim of this study was to develop therapeutic peptides targeting glycoprotein B (gB, a major glycoprotein of HCMV that is highly conserved across the Herpesviridae family, that specifically inhibit fusion of the viral envelope with the host cell membrane preventing HCMV entry and infection. Results Using the Wimley-White Interfacial Hydrophobicity Scale (WWIHS, several regions within gB were identified that display a high potential to interact with lipid bilayers of cell membranes and hydrophobic surfaces within proteins. The ability of synthetic peptides analogous to WWIHS-positive sequences of HCMV gB to inhibit viral infectivity was evaluated. Human foreskin fibroblasts (HFF were infected with the Towne-GFP strain of HCMV (0.5 MOI, preincubated with peptides at a range of concentrations (78 nm to 100 μM, and GFP-positive cells were visualized 48 hours post-infection by fluorescence microscopy and analyzed quantitatively by flow cytometry. Peptides that inhibited HCMV infection demonstrated different inhibitory concentration curves indicating that each peptide possesses distinct biophysical properties. Peptide 174-200 showed 80% inhibition of viral infection at a concentration of 100 μM, and 51% and 62% inhibition at concentrations of 5 μM and 2.5 μM, respectively. Peptide 233-263 inhibited infection by 97% and 92% at concentrations of 100

  10. Many Putative Endocrine Disruptors Inhibit Prostaglandin Synthesis

    DEFF Research Database (Denmark)

    Kristensen, David M.; Skalkam, Maria L.; Audouze, Karine Marie Laure

    2011-01-01

    Background: Prostaglandins (PGs) play key roles in development and maintenance of homeostasis of the adult body. Despite these important roles, it remains unclear whether the PG pathway is a target for endocrine disruption. However, several known endocrine disrupting compounds (EDCs) share a high...... of endocrine disruption. Results: We found that many known EDCs inhibit the PG pathway in a mouse Sertoli cell line and in human primary mast cells. The EDCs also reduced PG synthesis in ex vivo rat testis and it was correlated with a reduced testosterone production. The inhibition of PG synthesis occurs...

  11. Inhibition of spinach bolting by growth regulators

    Directory of Open Access Journals (Sweden)

    Jan Borkowski

    2015-06-01

    Full Text Available Spinach (Spinacia oleracea L. plants must be harvested during a short period of time because they bolt just after producing some edible leaves. Maleic hydrazide (MH and its commercial preparation "Antyrost" were found to inhibit bolting very strongly. The preparation Off-shoot-O showed very weak activity in suppressing bolting but diminished markedly the resistance of spinach plants to fungus diseases. Triiodobenzoic acid stimulated bolting, and the retardant succinic acid-2-2-dimethylhydrazide (SADH did not affect bolting. Application of MH to inhibit spinach bolting cannot be recommended in practice before investigating the residues of this compound in leaves.

  12. Phytic Acid Inhibits Lipid Peroxidation In Vitro

    OpenAIRE

    Alicja Zajdel; Adam Wilczok; Ludmiła Węglarz; Zofia Dzierżewicz

    2013-01-01

    Phytic acid (PA) has been recognized as a potent antioxidant and inhibitor of iron-catalyzed hydroxyl radical formation under in vitro and in vivo conditions. Therefore, the aim of the present study was to investigate, with the use of HPLC/MS/MS, whether PA is capable of inhibiting linoleic acid autoxidation and Fe(II)/ascorbate-induced peroxidation, as well as Fe(II)/ascorbate-induced lipid peroxidation in human colonic epithelial cells. PA at 100 μM and 500 μM effectively inhibited the deca...

  13. Cerebellar cortical inhibition and classical eyeblink conditioning.

    Science.gov (United States)

    Bao, Shaowen; Chen, Lu; Kim, Jeansok J; Thompson, Richard F

    2002-02-01

    The cerebellum is considered a brain structure in which memories for learned motor responses (e.g., conditioned eyeblink responses) are stored. Within the cerebellum, however, the relative importance of the cortex and the deep nuclei in motor learning/memory is not entirely clear. In this study, we show that the cerebellar cortex exerts both basal and stimulus-activated inhibition to the deep nuclei. Sequential application of a gamma-aminobutyric acid type A receptor (GABA(A)R) agonist and a noncompetitive GABA(A)R antagonist allows selective blockade of stimulus-activated inhibition. By using the same sequential agonist and antagonist methods in behaving animals, we demonstrate that the conditioned response (CR) expression and timing are completely dissociable and involve different inhibitory inputs; although the basal inhibition modulates CR expression, the conditioned stimulus-activated inhibition is required for the proper timing of the CR. In addition, complete blockade of cerebellar deep nuclear GABA(A)Rs prevents CR acquisition. Together, these results suggest that different aspects of the memories for eyeblink CRs are encoded in the cerebellar cortex and the cerebellar deep nuclei.

  14. Hawthorn extract inhibits human isolated neutrophil functions.

    Science.gov (United States)

    Dalli, Ernesto; Milara, Javier; Cortijo, Julio; Morcillo, Esteban J; Cosín-Sales, Juan; Sotillo, José Francisco

    2008-06-01

    Hawthorn extract is a popular herbal medicine given as adjunctive treatment for chronic heart failure. In contrast to the cardiac properties of hawthorn extract, its anti-inflammatory effect has been scarcely investigated. This study examines the effects of a dry extract of leaves and flowers of Crataegus laevigata on various functional outputs of human neutrophils in vitro. Incubation of human neutrophils obtained from peripheral blood of healthy donors with C. laevigata extract (0.75-250 microg/ml) inhibited N-formyl-Met-Leu-Phe (FMLP)-induced superoxide anion generation, elastase release and chemotactic migration with potency values of 43.6, 21.9, and 31.6 microg/ml, respectively. By contrast, serum-opsonized zymosan-induced phagocytosis was unaltered by plant extract. C. laevigata extract (125 microg/ml) reduced FMLP-induced leukotriene B(4) production and lipopolysaccharide-induced generation of tumour necrosis factor-alpha and interleukin-8. Extract inhibited FMLP-induced intracellular calcium signal with potency of 17.4 microg/ml. Extract also markedly inhibited the extracellular calcium entry into calcium-depleted neutrophils, and the thapsigargin-induced intracellular calcium response. In conclusion, C. laevigata extract inhibited various functional outputs of activated human neutrophils which may be relevant to the pathophysiology of cardiac failure.

  15. Stress kinase inhibition modulates acute experimental pancreatitis

    Institute of Scientific and Technical Information of China (English)

    F. Fleischer; R. Dabew; B. Goke; ACC Wagner

    2001-01-01

    AIM To examine the role of p38 during acute experimental cerulein pancreatitis.METHODS Rats were treated with cerulein with or without a specific JNK inhibitor (CEP1347)andy or a specific p38 inhbitor (SB203380) and pancreatic stress kinase activity wasdetermined. Parameters to assess pancreatitis included trypsin, amylase, lipase, pancreatic weight and histology.RESULTS JNK inhibition with CEP1347ameliorated pancreatitis, reducing pancreatic edema. In contrast, p38 inhibition with SB203580aggravated pancreatitis with higher trypsinlevels and, with induction of acinar necrosis not normally found after cerulein hyperstimulation.Simultaneous treatment with both CEP1347 and SB203580 mutually abolished the effects of either compound on cerulein pancreatitis.CONCLUSION Stress kinases modulatepancreatitis differentially. JNK seems to promote pancreatitis development, possibly by supporting inflammatory reactions such as edema formation while its inhibition ameliorates pancreatitis. In contrast, p38 may help reduce organ destruction while inhibition of p38 during induction of cerulein pancreatitis leads to the occurrence of acinar necrosis.

  16. Inhibition of denitrification by ultraviolet radiation

    Science.gov (United States)

    Mancinelli, R. L.; White, M. R.

    It has been shown that UV-A (λ = 320- 400 nm) and UV-B (λ = 280 - 320 nm) inhibit photosynthesis, nitrogen fixation and nitrification. The purpose of this study was to determine the effects, if any, on denitrification in a microbial community inhabiting the intertidal. The community studied is the microbial mat consisting primarily of Lyngbya that inhabits the Pacific marine intertidal, Baja California, Mexico. Rates of denitrification were determined using the acetylene blockage technique. Pseudomonas fluorescens (ATCC # 17400) was used as a control organism, and treated similarly to the mat samples. Samples were incubated either beneath a PAR transparent, UV opaque screen (OP3), or a mylar screen to block UV-B, or a UV transparent screen (UVT) for 2 to 3 hours. Sets of samples were also treated with nitrapyrin to inhibit nitrification, or DCMU to inhibit photosynthesis and treated similarly. Denitrification rates were greater in the UV protected samples than in the UV exposed samples the mat samples as well as for the Ps. fluorescens cultures. Killed controls exhibited no activity. In the DCMU and nitrapyrin treated samples denitrification rates were the same as in the untreated samples. These data indicate that denitrification is directly inhibited by UV radiation.

  17. Acidosis inhibits mineralization in human osteoblasts.

    Science.gov (United States)

    Takeuchi, Shoko; Hirukawa, Koji; Togari, Akifumi

    2013-09-01

    Osteoblasts and osteoclasts maintain bone volume. Acidosis affects the function of these cells including mineral metabolism. We examined the effect of acidosis on the expression of transcription factors and mineralization in human osteoblasts in vitro. Human osteoblasts (SaM-1 cells) derived from the ulnar periosteum were cultured with α-MEM containing 50 μg/ml ascorbic acid and 5 mM β-glycerophosphate (calcifying medium). Acidosis was induced by incubating the SaM-1 cells in 10 % CO₂ (pH approximately 7.0). Mineralization, which was augmented by the calcifying medium, was completely inhibited by acidosis. Acidosis depressed c-Jun mRNA and increased osteoprotegerin (OPG) production in a time-dependent manner. Depressing c-Jun mRNA expression using siRNA increased OPG production and inhibited mineralization. In addition, depressing OPG mRNA expression with siRNA enhanced mineralization in a dose-dependent manner. Acidosis or the OPG protein strongly inhibited mineralization in osteoblasts from neonatal mice. The present study was the first to demonstrate that acidosis inhibited mineralization, depressed c-Jun mRNA expression, and induced OPG production in human osteoblasts. These results suggest that OPG is involved in mineralization via c-Jun in human osteoblasts.

  18. Temporal Preparation, Response Inhibition and Impulsivity

    Science.gov (United States)

    Correa, Angel; Trivino, Monica; Perez-Duenas, Carolina; Acosta, Alberto; Lupianez, Juan

    2010-01-01

    Temporal preparation and impulsivity involve overlapping neural structures (prefrontal cortex) and cognitive functions (response inhibition and time perception), however, their interrelations had not been investigated. We studied such interrelations by comparing the performance of groups with low vs. high non-clinical trait impulsivity during a…

  19. Targeted inhibition of cancer-inflammation

    NARCIS (Netherlands)

    Gomes Coimbra, M.J.

    2012-01-01

    The new paradigm in cancer treatment that aims to inhibit the smoldering inflammatory response in tumors is explored to develop new anticancer treatments. It appears that targeted drug delivery is essential in this concept as high local levels of anti-inflammatory agents are needed to observe the

  20. Fear inhibition in high trait anxiety

    NARCIS (Netherlands)

    Kindt, M.; Soeter, M.

    2014-01-01

    Trait anxiety is recognized as an individual risk factor for the development of anxiety disorders but the neurobiological mechanisms remain unknown. Here we test whether trait anxiety is associated with impaired fear inhibition utilizing the AX+/BX- conditional discrimination procedure that allows f

  1. Serum amyloid P inhibits dermal wound healing

    Science.gov (United States)

    The repair of open wounds depends on granulation tissue formation and contraction, which is primarily mediated by myofibroblasts. A subset of myofibroblasts originates from bone-marrow-derived monocytes which differentiate into fibroblast-like cells called fibrocytes. Serum amyloid P (SAP) inhibits ...

  2. Targeted inhibition of tumor growth and angiogenesis

    NARCIS (Netherlands)

    van der Meel, R.

    2013-01-01

    Two main strategies have been pursued for the development of an effective and targeted anti-cancer treatment. The first strategy comprised the generation of a targeted nanomedicine for the inhibition of tumor cell proliferation by blocking growth factor receptor pathways. The epidermal growth factor

  3. Targeted inhibition of cancer-inflammation

    NARCIS (Netherlands)

    Gomes Coimbra, M.J.

    2012-01-01

    The new paradigm in cancer treatment that aims to inhibit the smoldering inflammatory response in tumors is explored to develop new anticancer treatments. It appears that targeted drug delivery is essential in this concept as high local levels of anti-inflammatory agents are needed to observe the be

  4. Inhibiting Intuitive Thinking in Mathematics Education

    Science.gov (United States)

    Thomas, Michael O. J.

    2015-01-01

    The papers in this issue describe recent collaborative research into the role of inhibition of intuitive thinking in mathematics education. This commentary reflects on this research from a mathematics education perspective and draws attention to some of the challenges that arise in collaboration between research fields with different cultures,…

  5. Nickel inhibits mitochondrial fatty acid oxidation.

    Science.gov (United States)

    Uppala, Radha; McKinney, Richard W; Brant, Kelly A; Fabisiak, James P; Goetzman, Eric S

    2015-08-07

    Nickel exposure is associated with changes in cellular energy metabolism which may contribute to its carcinogenic properties. Here, we demonstrate that nickel strongly represses mitochondrial fatty acid oxidation-the pathway by which fatty acids are catabolized for energy-in both primary human lung fibroblasts and mouse embryonic fibroblasts. At the concentrations used, nickel suppresses fatty acid oxidation without globally suppressing mitochondrial function as evidenced by increased glucose oxidation to CO2. Pre-treatment with l-carnitine, previously shown to prevent nickel-induced mitochondrial dysfunction in neuroblastoma cells, did not prevent the inhibition of fatty acid oxidation. The effect of nickel on fatty acid oxidation occurred only with prolonged exposure (>5 h), suggesting that direct inhibition of the active sites of metabolic enzymes is not the mechanism of action. Nickel is a known hypoxia-mimetic that activates hypoxia inducible factor-1α (HIF1α). Nickel-induced inhibition of fatty acid oxidation was blunted in HIF1α knockout fibroblasts, implicating HIF1α as one contributor to the mechanism. Additionally, nickel down-regulated the protein levels of the key fatty acid oxidation enzyme very long-chain acyl-CoA dehydrogenase (VLCAD) in a dose-dependent fashion. In conclusion, inhibition of fatty acid oxidation by nickel, concurrent with increased glucose metabolism, represents a form of metabolic reprogramming that may contribute to nickel-induced carcinogenesis.

  6. Search Asymmetry, Sustained Attention, and Response Inhibition

    Science.gov (United States)

    Stevenson, Hugh; Russell, Paul N.; Helton, William S.

    2011-01-01

    In the present experiment, we used search asymmetry to test whether the sustained attention to response task is a better measure of response inhibition or sustained attention. Participants performed feature present and feature absent target detection tasks using either a sustained attention to response task (SART; high Go low No-Go) or a…

  7. Target Predictability, Sustained Attention, and Response Inhibition

    Science.gov (United States)

    Carter, Leonie; Russell, Paul N.; Helton, William S.

    2013-01-01

    We examined whether the sustained attention to response task is a better measure of response inhibition or sustained attention. Participants performed a number detection task for 37.3 min using either a Sustained Attention to Response Task (SART; high Go low No-Go) or a more traditionally formatted vigilance task (TFT; high No-Go low Go) response…

  8. Salinomycin, a polyether ionophoric antibiotic, inhibits adipogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Szkudlarek-Mikho, Maria; Saunders, Rudel A. [Department of Medicine, Biochemistry and Cancer Biology, Center for Diabetes and Endocrine Research, College of Medicine, University of Toledo, Toledo, OH 43614 (United States); Yap, Sook Fan [Faculty of Medicine and Health Sciences, Department of Pre-Clinical Sciences, University of Tunku Abdul Rahman (Malaysia); Ngeow, Yun Fong [Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603 (Malaysia); Chin, Khew-Voon, E-mail: khew-voon.chin@utoledo.edu [Department of Medicine, Biochemistry and Cancer Biology, Center for Diabetes and Endocrine Research, College of Medicine, University of Toledo, Toledo, OH 43614 (United States)

    2012-11-30

    Highlights: Black-Right-Pointing-Pointer Salinomycin inhibits preadipocyte differentiation into adipocytes. Black-Right-Pointing-Pointer Salinomycin inhibits transcriptional regulation of adipogenesis. Black-Right-Pointing-Pointer Pharmacological effects of salinomycin suggest toxicity in cancer therapy. -- Abstract: The polyether ionophoric antibiotics including monensin, salinomycin, and narasin, are widely used in veterinary medicine and as food additives and growth promoters in animal husbandry including poultry farming. Their effects on human health, however, are not fully understood. Recent studies showed that salinomycin is a cancer stem cell inhibitor. Since poultry consumption has risen sharply in the last three decades, we asked whether the consumption of meat tainted with growth promoting antibiotics might have effects on adipose cells. We showed in this report that the ionophoric antibiotics inhibit the differentiation of preadipocytes into adipocytes. The block of differentiation is not due to the induction of apoptosis nor the inhibition of cell proliferation. In addition, salinomycin also suppresses the transcriptional activity of the CCAAT/enhancer binding proteins and the peroxisome proliferator-activated receptor {gamma}. These results suggest that the ionophoric antibiotics can be exploited as novel anti-obesity therapeutics and as pharmacological probes for the study of adipose biology. Further, the pharmacological effects of salinomycin could be a harbinger of its toxicity on the adipose tissue and other susceptible target cells in cancer therapy.

  9. Illustrating Enzyme Inhibition Using Gibbs Energy Profiles

    Science.gov (United States)

    Bearne, Stephen L.

    2012-01-01

    Gibbs energy profiles have great utility as teaching and learning tools because they present students with a visual representation of the energy changes that occur during enzyme catalysis. Unfortunately, most textbooks divorce discussions of traditional kinetic topics, such as enzyme inhibition, from discussions of these same topics in terms of…

  10. LOX1 inhibition with small molecules

    DEFF Research Database (Denmark)

    Gousiadou, Chryssoula; Kouskoumvekaki, Irene

    2016-01-01

    the attention as targets and great effort has been made for the discovery and design of suitable inhibitors, to which end both pharmacological and computational methods have been employed. In the present work, using pharmacophore modeling and docking, we attempt to elucidate the inhibition of LOX1 with a new...

  11. Bioluminescence inhibition of bacterial luciferase by aliphatic alcohol, amine and carboxylic acid: inhibition potency and mechanism.

    Science.gov (United States)

    Yamasaki, Shinya; Yamada, Shuto; Takehara, Kô

    2013-01-01

    The inhibitory effects of hydrophobic molecules on the bacterial luciferase, BL, luminescence reaction were analyzed using an electrochemically-controlled BL luminescence system. The inhibition potency of alkyl amines, C(n)NH(2), and fatty acids, C(m)COOH (m = n - 1), on the BL reaction increased with an increase in the alkyl chain-length of these aliphatic compounds. C(m)COOH showed lower inhibition potency than C(n)NH(2) and alkyl alcohols, C(n)OH, data for which have been previously reported. To make clear the inhibition mechanisms of the aliphatic compounds on the BL reaction, the initial rate of the BL reaction was measured and analyzed using the Dixon plot and Cornish-Bowden plot. The C(12)OH inhibited the BL reaction in competition with the substrate C(11)CHO, while C(12)NH(2) and C(11)COOH inhibited in an uncompetitive manner with the C(11)CHO. These results suggest that the alkyl chain-length and the terminal unit of the aliphatic compound determine the inhibition potency and the inhibition mechanism, respectively.

  12. Gold Nanoparticles Inhibit Matrix Metalloproteases without Cytotoxicity.

    Science.gov (United States)

    Hashimoto, M; Sasaki, J I; Yamaguchi, S; Kawai, K; Kawakami, H; Iwasaki, Y; Imazato, S

    2015-08-01

    Nanoparticles (NPs) are currently the focus of considerable attention for dental applications; however, their biological effects have not been fully elucidated. The long-term, slow release of matrix metalloproteases (MMPs) digests collagen fibrils within resin-dentin bonds. Therefore, MMP inhibitors can prolong the durability of resin-dentin bonds. However, there have been few reports evaluating the combined effect of MMP inhibition and the cytotoxic effects of NPs for dentin bonding. The aim of this study was to evaluate MMP inhibition and cytotoxic responses to gold (AuNPs) and platinum nanoparticles (PtNPs) stabilized by polyvinylpyrrolidone (PVP) in cultured murine macrophages (RAW264) by using MMP inhibition assays, measuring cell viability and inflammatory responses (quantitative reverse transcription polymerase chain reaction [RT-qPCR]), and conducting a micromorphological analysis by fluorescence and transmission electron microscopy. Cultured RAW264 cells were exposed to metal NPs at various concentrations (1, 10, 100, and 400 µg/mL). AuNPs and PtNPs markedly inhibited MMP-8 and MMP-9 activity. Although PtNPs were cytotoxic at high concentrations (100 and 400 µg/mL), no cytotoxic effects were observed for AuNPs at any concentration. Transmission electron microscopy images showed a significant nonrandom intercellular distribution for AuNPs and PtNPs, which were mostly observed to be localized in lysosomes but not in the nucleus. RT-qPCR analysis demonstrated inflammatory responses were not induced in RAW264 cells by AuNPs or PtNPs. The cytotoxicity of nanoparticles might depend on the core metal composition and arise from a "Trojan horse" effect; thus, MMP inhibition could be attributed to the surface charge of PVP, which forms the outer coating of NPs. The negative charge of the surface coating of PVP binds to Zn(2+) from the active center of MMPs by chelate binding and results in MMP inhibition. In summary, AuNPs are attractive NPs that effectively

  13. WEE1 inhibition sensitizes osteosarcoma to radiotherapy

    Directory of Open Access Journals (Sweden)

    Helder Marco N

    2011-04-01

    Full Text Available Abstract Background The use of radiotherapy in osteosarcoma (OS is controversial due to its radioresistance. OS patients currently treated with radiotherapy generally are inoperable, have painful skeletal metastases, refuse surgery or have undergone an intralesional resection of the primary tumor. After irradiation-induced DNA damage, OS cells sustain a prolonged G2 cell cycle checkpoint arrest allowing DNA repair and evasion of cell death. Inhibition of WEE1 kinase leads to abrogation of the G2 arrest and could sensitize OS cells to irradiation induced cell death. Methods WEE1 expression in OS was investigated by gene-expression data analysis and immunohistochemistry of tumor samples. WEE1 expression in OS cell lines and human osteoblasts was investigated by Western blot. The effect of WEE1 inhibition on the radiosensitivity of OS cells was assessed by cell viability and caspase activation analyses after combination treatment. The presence of DNA damage was visualized using immunofluorescence microscopy. Cell cycle effects were investigated by flow cytometry and WEE1 kinase regulation was analyzed by Western blot. Results WEE1 expression is found in the majority of tested OS tissue samples. Small molecule drug PD0166285 inhibits WEE1 kinase activity. In the presence of WEE1-inhibitor, irradiated cells fail to repair their damaged DNA, and show higher levels of caspase activation. The inhibition of WEE1 effectively abrogates the irradiation-induced G2 arrest in OS cells, forcing the cells into premature, catastrophic mitosis, thus enhancing cell death after irradiation treatment. Conclusion We show that PD0166285, a small molecule WEE1 kinase inhibitor, can abrogate the G2 checkpoint in OS cells, pushing them into mitotic catastrophe and thus sensitizing OS cells to irradiation-induced cell death. This suggests that WEE1 inhibition may be a promising strategy to enhance the radiotherapy effect in patients with OS.

  14. Inhibition of lung tumorigenesis by tea.

    Science.gov (United States)

    Yang, Chung S; Liao, Jie; Yang, Guang-yu; Lu, Gary

    2005-01-01

    Tea and tea constituents have been shown by different investigators to inhibit lung tumorigenesis in different animal model systems. This includes lung tumorigenesis in A/J mice induced by 4-(methylnitrosamino)-1-(3pyridyl)-1-butanone (NNK), N-nitrosodiethylamine, benzo[a]pyrene, N-nitrosomethylurea, or cisplatin. Inhibition of lung tumorigenesis has also been demonstrated in C3H mice treated with N-nitrosodiethylamine. In most of these experiments, reduction in tumor number and tumor size has been observed in the tea-treated group, and in some experiments, decreased tumor incidence has also been observed. The green tea constituent, epigallocatechin-3-gallate (EGCG), and the black tea constituent, theaflavins, have also been shown to be effective. Black tea preparations have been shown to reduce the incidence and number of spontaneously generated lung adenocarcinomas and rhabdomyosarcoma in A/J mice, as well as inhibit the progression of lung adenoma to adenocarcinoma. The mechanisms for the inhibitory action have not been well elucidated. It may be related to the antiproliferative, proapoptotic, and antiangiogenic activities of tea constituents that have been demonstrated in some experiments. These activities may be a result of the inhibition of key protein kinases involved in signal transduction and cell cycle regulation. Tea catechins, such as EGCG, have been suggested to be the effective components. However, a study suggests that caffeine is the key effective constituent for the inhibitory activity of lung tumorigenesis in Fisher 344 rats by black tea. In many of the experiments, tea consumption resulted in the reduction of body fat and body weight; these factors may also contribute to the inhibition of tumorigenesis.

  15. Amiloride inhibits the initiation of Coxsackievirus and poliovirus RNA replication by inhibiting VPg uridylylation.

    Science.gov (United States)

    Ogram, Sushma A; Boone, Christopher D; McKenna, Robert; Flanegan, James B

    2014-09-01

    The mechanism of amiloride inhibition of Coxsackievirus B3 (CVB3) and poliovirus type 1 (PV1) RNA replication was investigated using membrane-associated RNA replication complexes. Amiloride was shown to inhibit viral RNA replication and VPgpUpU synthesis. However, the drug had no effect on polymerase elongation activity during either (-) strand or (+) strand synthesis. These findings indicated that amiloride inhibited the initiation of RNA synthesis by inhibiting VPg uridylylation. In addition, in silico binding studies showed that amiloride docks in the VPg binding site on the back of the viral RNA polymerase, 3D(pol). Since VPg binding at this site on PV1 3D(pol) was previously shown to be required for VPg uridylylation, our results suggest that amiloride inhibits VPg binding to 3D(pol). In summary, our findings are consistent with a model in which amiloride inhibits VPgpUpU synthesis and viral RNA replication by competing with VPg for binding to 3D(pol).

  16. Emotional inhibition: a discourse analysis of disclosure.

    Science.gov (United States)

    Ellis, Darren; Cromby, John

    2012-01-01

    Evidence generated within the emotional disclosure paradigm (EDP) suggests that talking or writing about emotional experiences produces health benefits, but recent meta-analyses have questioned its efficacy. Studies within the EDP typically rely upon a unidimensional and relatively unsophisticated notion of emotional inhibition, and tend to use quantitative forms of content analysis to identify associations between percentages of word types and positive or negative health outcomes. In this article, we use a case study to show how a qualitative discourse analysis has the potential to identify more of the complexity linking the disclosure practices and styles that may be associated with emotional inhibition. This may illuminate the apparent lack of evidence for efficacy of the EDP by enabling more comprehensive theorisations of the variations within it.

  17. Inhibition Controls Asynchronous States of Neuronal Networks

    Science.gov (United States)

    Treviño, Mario

    2016-01-01

    Computations in cortical circuits require action potentials from excitatory and inhibitory neurons. In this mini-review, I first provide a quick overview of findings that indicate that GABAergic neurons play a fundamental role in coordinating spikes and generating synchronized network activity. Next, I argue that these observations helped popularize the notion that network oscillations require a high degree of spike correlations among interneurons which, in turn, produce synchronous inhibition of the local microcircuit. The aim of this text is to discuss some recent experimental and computational findings that support a complementary view: one in which interneurons participate actively in producing asynchronous states in cortical networks. This requires a proper mixture of shared excitation and inhibition leading to asynchronous activity between neighboring cells. Such contribution from interneurons would be extremely important because it would tend to reduce the spike correlation between neighboring pyramidal cells, a drop in redundancy that could enhance the information-processing capacity of neural networks. PMID:27274721

  18. Product inhibition of five Hypocrea jecorina cellulases

    DEFF Research Database (Denmark)

    Murphy, Leigh; Westh, Peter; Bohlin, Christina

    2013-01-01

    on individual cellulases hydrolyzing insoluble cellulose remains insufficient. Such knowledge is necessary to pinpoint and quantify inhibitory weak-links in cellulose hydrolysis, but has proven challenging to come by. Here we show that product inhibition of mono-component cellulases hydrolyzing unmodified...... cellulose may be monitored by calorimetry. The key advantage of this approach is that it directly measures the rate of hydrolysis while being essentially blind to the background of added product. We investigated the five major cellulases from Hypocrea jecorina (anamorph: Tricoderma reesei), Cel7A (formerly......Product inhibition of cellulolytic enzymes has been deemed a critical factor in the industrial saccharification of cellulosic biomass. Several investigations have addressed this problem using crude enzyme preparations or commercial (mixed) cellulase products, but quantitative information...

  19. Direct renin inhibition in chronic kidney disease

    DEFF Research Database (Denmark)

    Persson, Frederik; Rossing, Peter; Parving, Hans-Henrik

    2013-01-01

    that renin inhibition could hold potential for improved treatment in patients with chronic kidney disease, with diabetic nephropathy as an obvious group of patients to investigate, as the activity of the renin-angiotensin-aldosterone system is enhanced in these patients and as there is an unmet need...... early as a beneficial effect was unlikely and there was an increased frequency of side effects. Also in non-diabetic kidney disease a few intervention studies have been carried out, but there is no ongoing hard outcome study. In this review we provide the current evidence for renin inhibition in chronic...... kidney disease by reporting of the studies published so far as well as perspective on the future possibilites....

  20. How x rays inhibit amphibian limb regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Maden, M.; Wallace, H.

    1976-07-01

    The effects of an inhibiting dose of 2,000 rad of x-rays on the regenerating limbs of axolotl larvae have been examined in a histological and cytological study. Particular attention was paid to the mitotic indices of normal and irradiated epidermal and blastemal cells. Both the characteristic pattern of epidermal mitotic stimulation which normally follows amputation and the later increase in blastemal mitoses are suppressed by irradiation. In most cells the effects are permanent, but in a small proportion a mitotic delay is induced and upon subsequent division chromosome damage in the form of micronuclei is revealed. Thus irradiated cells which do divide almost certainly die. These results are discussed in relation to other theories of x-ray inhibition of regeneration with particular reference to the view that irradiated cells can be reactivated.

  1. Sulfate inhibition effect on sulfate reducing bacteria

    Directory of Open Access Journals (Sweden)

    Sulaiman Al Zuhair

    2008-12-01

    Full Text Available There is an increasing interest in the potential of bacterial sulfate reduction as an alternative method for sulfate removal from wastewater. Under anaerobic conditions, sulfate-reducing bacteria (SRB utilize sulfate to oxidize organic compounds and generate sulfide (S2-. SRB were successfully isolated from sludge samples obtained from a local petroleum refinery, and used for sulfate removal. The effects of initial sulfate concentration, temperature and pH on the rate of bacterial growth and anaerobic sulfate removal were investigated and the optimum conditions were identified. The experimental data were used to determine the parameters of two proposed kinetic model, which take into consideration substrate inhibition effect. Keywords: Sulfate Reducing Bacteria, Sulfate, Kinetic Model, Biotreatement, Inhibition Received: 31 August 2008 / Received in revised form: 18 September 2008, Accepted: 18 September 2008 Published online: 28 September 2008

  2. Theobromine inhibits sensory nerve activation and cough.

    Science.gov (United States)

    Usmani, Omar S; Belvisi, Maria G; Patel, Hema J; Crispino, Natascia; Birrell, Mark A; Korbonits, Márta; Korbonits, Dezso; Barnes, Peter J

    2005-02-01

    Cough is a common and protective reflex, but persistent coughing is debilitating and impairs quality of life. Antitussive treatment using opioids is limited by unacceptable side effects, and there is a great need for more effective remedies. The present study demonstrates that theobromine, a methylxanthine derivative present in cocoa, effectively inhibits citric acid-induced cough in guinea-pigs in vivo. Furthermore, in a randomized, double-blind, placebo-controlled study in man, theobromine suppresses capsaicin-induced cough with no adverse effects. We also demonstrate that theobromine directly inhibits capsaicin-induced sensory nerve depolarization of guinea-pig and human vagus nerve suggestive of an inhibitory effect on afferent nerve activation. These data indicate the actions of theobromine appear to be peripherally mediated. We conclude theobromine is a novel and promising treatment, which may form the basis for a new class of antitussive drugs.

  3. Cross-domain inhibition of TACE ectodomain

    DEFF Research Database (Denmark)

    Tape, Christopher J; Willems, Sofie H; Dombernowsky, Sarah L;

    2011-01-01

    Proteolytic release from the cell surface is an essential activation event for many growth factors and cytokines. TNF-a converting enzyme (TACE) is a membrane-bound metalloprotease responsible for solubilizing many pathologically significant membrane substrates and is an attractive therapeutic...... target for the treatment of cancer and arthritis. Prior attempts to antagonize cell-surface TACE activity have focused on small-molecule inhibition of the metalloprotease active site. Given the highly conserved nature of metalloprotease active sites, this paradigm has failed to produce a truly specific...... individual antibody variable domains to desired epitopes. The resulting "cross-domain" human antibody is a previously undescribed selective TACE antagonist and provides a unique alternative to small-molecule metalloprotease inhibition....

  4. Antibiotic inhibition of group I ribozyme function.

    Science.gov (United States)

    von Ahsen, U; Davies, J; Schroeder, R

    1991-09-26

    The discovery of catalytically active RNA has provided the basis for the evolutionary concept of an RNA world. It has been proposed that during evolution the functions of ancient catalytic RNA were modulated by low molecular weight effectors, related to antibiotics, present in the primordial soup. Antibiotics and RNA may have coevolved in the formation of the modern ribosome. Here we report that a set of aminoglycoside antibiotics, which are known to interact with the decoding region of the 16S ribosomal RNA of Escherichia coli, inhibit the second step of splicing of the T4 phage-derived td intron. Thus catalytic RNA seems to interact not only with a mononucleotide and an amino acid, but also with another class of biomolecules, the sugars. Splicing of other group I introns but not group II introns was inhibited. The similarity in affinity and specificity of these antibiotics for group I introns and rRNAs may result from recognition of evolutionarily conserved structures.

  5. AMPA receptor inhibition by synaptically released zinc.

    Science.gov (United States)

    Kalappa, Bopanna I; Anderson, Charles T; Goldberg, Jacob M; Lippard, Stephen J; Tzounopoulos, Thanos

    2015-12-22

    The vast amount of fast excitatory neurotransmission in the mammalian central nervous system is mediated by AMPA-subtype glutamate receptors (AMPARs). As a result, AMPAR-mediated synaptic transmission is implicated in nearly all aspects of brain development, function, and plasticity. Despite the central role of AMPARs in neurobiology, the fine-tuning of synaptic AMPA responses by endogenous modulators remains poorly understood. Here we provide evidence that endogenous zinc, released by single presynaptic action potentials, inhibits synaptic AMPA currents in the dorsal cochlear nucleus (DCN) and hippocampus. Exposure to loud sound reduces presynaptic zinc levels in the DCN and abolishes zinc inhibition, implicating zinc in experience-dependent AMPAR synaptic plasticity. Our results establish zinc as an activity-dependent, endogenous modulator of AMPARs that tunes fast excitatory neurotransmission and plasticity in glutamatergic synapses.

  6. Blocking of potentiation of latent inhibition.

    Science.gov (United States)

    Hall, Geoffrey; Rodriguez, Gabriel

    2011-01-01

    We present a theory of latent inhibition based on the Pearce-Hall (Pearce & Hall, 1980) model for classical conditioning. Its central features are (1) that the associability of a stimulus declines as it comes to predict its consequences and (2) that nonreinforced exposure to a stimulus engages an associative learning process that makes the stimulus an accurate predictor of its consequences (in this case, the occurrence of no event). A formalization of this theory is shown to accommodate the finding that preexposure in compound with another cue can potentiate latent inhibition to the target cue. It further predicts that preexposure to the added cue will eliminate the potentiation effect. An experiment using rats and the flavor-aversion procedure confirmed this prediction.

  7. The Kinetics of Carrier Transport Inhibition

    DEFF Research Database (Denmark)

    Rosenberg, T.; Wilbrandt, Robert Walter

    1962-01-01

    The kinetical treatment of enzymatic carrier transports as given in previous communications has been extended to conditions of inhibition. Various possible types of inhibitors have been considered differing in the site of attack (enzyme or carrier), in the mode of action (competing...... with the substrate for the enzyme or the carrier or for both, competing with the carrier for the enzyme, or non-competitive) and in the ability of penetrating the membrane. Experiments are reported on the inhibition of glucose and fructose transport across the human red cell membrane by phlorizine, phloretine...... the first order asymmetry severalfold (“second order asymmetry”). It was shown that a substrate competitive mode of action involving competition both for the enzyme and for the enzyme-bound carrier will result in a behaviour resembling the observed “second order asymmetry”. It is felt, therefore...

  8. Non-Classical Inhibition of Carbonic Anhydrase

    Science.gov (United States)

    Lomelino, Carrie L.; Supuran, Claudiu T.; McKenna, Robert

    2016-01-01

    Specific isoforms from the carbonic anhydrase (CA) family of zinc metalloenzymes have been associated with a variety of diseases. Isoform-specific carbonic anhydrase inhibitors (CAIs) are therefore a major focus of attention for specific disease treatments. Classical CAIs, primarily sulfonamide-based compounds and their bioisosteres, are examined as antiglaucoma, antiepileptic, antiobesity, antineuropathic pain and anticancer compounds. However, many sulfonamide compounds inhibit all CA isoforms nonspecifically, diluting drug effectiveness and causing undesired side effects due to off-target inhibition. In addition, a small but significant percentage of the general population cannot be treated with sulfonamide-based compounds due to a sulfa allergy. Therefore, CAIs must be developed that are not only isoform specific, but also non-classical, i.e. not based on sulfonamides, sulfamates, or sulfamides. This review covers the classes of non-classical CAIs and the recent advances in the development of isoform-specific inhibitors based on phenols, polyamines, coumarins and their derivatives. PMID:27438828

  9. Inhibition Controls Asynchronous States of Neuronal Networks.

    Science.gov (United States)

    Treviño, Mario

    2016-01-01

    Computations in cortical circuits require action potentials from excitatory and inhibitory neurons. In this mini-review, I first provide a quick overview of findings that indicate that GABAergic neurons play a fundamental role in coordinating spikes and generating synchronized network activity. Next, I argue that these observations helped popularize the notion that network oscillations require a high degree of spike correlations among interneurons which, in turn, produce synchronous inhibition of the local microcircuit. The aim of this text is to discuss some recent experimental and computational findings that support a complementary view: one in which interneurons participate actively in producing asynchronous states in cortical networks. This requires a proper mixture of shared excitation and inhibition leading to asynchronous activity between neighboring cells. Such contribution from interneurons would be extremely important because it would tend to reduce the spike correlation between neighboring pyramidal cells, a drop in redundancy that could enhance the information-processing capacity of neural networks.

  10. Hydroxyapatite growth inhibition by osteopontin hexapeptide sequences.

    Science.gov (United States)

    Silverman, L D; Saadia, M; Ishal, J S; Tishbi, N; Leiderman, E; Kuyunov, I; Recca, B; Reitblat, C; Viswanathan, R

    2010-06-15

    The effects of three acidic hexapeptides on in vitro hydroxyapatite growth were characterized by pH-stat kinetic studies, adsorption isotherms, and molecular modeling. The three peptides, pSDEpSDE, SDESDE, and DDDDDD, are equal-length model compounds for the acidic sequences in osteopontin, a protein that inhibits mineral formation in both calcified and noncalcified tissues. Growth rates from 1.67 mM calcium and 1.00 mM phosphate solution were measured at pH 7.4 and 37 degrees C in 150 mM NaCl. pSDEpSDE was a strong growth inhibitor when preadsorbed onto hydroxyapatite (HA) seeds from > or = 0.67 mM solutions, concentrations where adsorption isotherms showed relatively complete surface coverage. The nonphosphorylated SDESDE control showed no growth inhibition. Although it adsorbed to almost the same extent as pSDEpSDE, it rapidly desorbed under the pH-stat growth conditions while pSDEpSDE did not. DDDDDD exhibited weak inhibition as its concentration was increased and similar adsorption/desorption behavior to pSDEpSDE. Molecular modeling yielded binding energy trends based on simple adsorption of peptides on the [100] surface that were consistent with observed inhibition, but not for the [001] surface. The relatively unfavorable binding energies for peptides on the [001] surface suggest that their absorption will be primarily on the [100] face. The kinetic and adsorption data are consistent with phosphorylation of osteopontin acting to control mineral formation.

  11. An Activation Threshold Model for Response Inhibition

    Science.gov (United States)

    MacDonald, Hayley J.; McMorland, Angus J. C.; Stinear, Cathy M.; Coxon, James P.; Byblow, Winston D.

    2017-01-01

    Reactive response inhibition (RI) is the cancellation of a prepared response when it is no longer appropriate. Selectivity of RI can be examined by cueing the cancellation of one component of a prepared multi-component response. This substantially delays execution of other components. There is debate regarding whether this response delay is due to a selective neural mechanism. Here we propose a computational activation threshold model (ATM) and test it against a classical “horse-race” model using behavioural and neurophysiological data from partial RI experiments. The models comprise both facilitatory and inhibitory processes that compete upstream of motor output regions. Summary statistics (means and standard deviations) of predicted muscular and neurophysiological data were fit in both models to equivalent experimental measures by minimizing a Pearson Chi-square statistic. The ATM best captured behavioural and neurophysiological dynamics of partial RI. The ATM demonstrated that the observed modulation of corticomotor excitability during partial RI can be explained by nonselective inhibition of the prepared response. The inhibition raised the activation threshold to a level that could not be reached by the original response. This was necessarily followed by an additional phase of facilitation representing a secondary activation process in order to reach the new inhibition threshold and initiate the executed component of the response. The ATM offers a mechanistic description of the neural events underlying RI, in which partial movement cancellation results from a nonselective inhibitory event followed by subsequent initiation of a new response. The ATM provides a framework for considering and exploring the neuroanatomical constraints that underlie RI. PMID:28085907

  12. Evidence of dopaminergic processing of executive inhibition.

    Directory of Open Access Journals (Sweden)

    Rajendra D Badgaiyan

    Full Text Available Inhibition of unwanted response is an important function of the executive system. Since the inhibitory system is impaired in patients with dysregulated dopamine system, we examined dopamine neurotransmission in the human brain during processing of a task of executive inhibition. The experiment used a recently developed dynamic molecular imaging technique to detect and map dopamine released during performance of a modified Eriksen's flanker task. In this study, young healthy volunteers received an intravenous injection of a dopamine receptor ligand ((11C-raclopride after they were positioned in the PET camera. After the injection, volunteers performed the flanker task under Congruent and Incongruent conditions in a single scan session. They were required to inhibit competing options to select an appropriate response in the Incongruent but not in the Congruent condition. The PET data were dynamically acquired during the experiment and analyzed using two variants of the simplified reference region model. The analysis included estimation of a number of receptor kinetic parameters before and after initiation of the Incongruent condition. We found increase in the rate of ligand displacement (from receptor sites and decrease in the ligand binding potential in the Incongruent condition, suggesting dopamine release during task performance. These changes were observed in small areas of the putamen and caudate bilaterally but were most significant on the dorsal aspect of the body of left caudate. The results provide evidence of dopaminergic processing of executive inhibition and demonstrate that neurochemical changes associated with cognitive processing can be detected and mapped in a single scan session using dynamic molecular imaging.

  13. Matrix Extracellular Phosphoglycoprotein Inhibits Phosphate Transport

    OpenAIRE

    Marks, J; Churchill, L J; Debnam, E. S.; Unwin, R J

    2008-01-01

    The role of putative humoral factors, known as phosphatonins, in phosphate homeostasis and the relationship between phosphate handling by the kidney and gastrointestinal tract are incompletely understood. Matrix extracellular phosphoglycoprotein (MEPE), one of several candidate phosphatonins, promotes phosphaturia, but whether it also affects intestinal phosphate absorption is unknown. Here, using the in situ intestinal loop technique, we demonstrated that short-term infusion of MEPE inhibits...

  14. Caffeine Inhibits Acetylcholinesterase, But Not Butyrylcholinesterase

    Directory of Open Access Journals (Sweden)

    Petr Dobes

    2013-05-01

    Full Text Available Caffeine is an alkaloid with a stimulant effect in the body. It can interfere in transmissions based on acetylcholine, epinephrine, norepinephrine, serotonin, dopamine and glutamate. Clinical studies indicate that it can be involved in the slowing of Alzheimer disease pathology and some other effects. The effects are not well understood. In the present work, we focused on the question whether caffeine can inhibit acetylcholinesterase (AChE and/or, butyrylcholinesterase (BChE, the two enzymes participating in cholinergic neurotransmission. A standard Ellman test with human AChE and BChE was done for altering concentrations of caffeine. The test was supported by an in silico examination as well. Donepezil and tacrine were used as standards. In compliance with Dixon’s plot, caffeine was proved to be a non-competitive inhibitor of AChE and BChE. However, inhibition of BChE was quite weak, as the inhibition constant, Ki, was 13.9 ± 7.4 mol/L. Inhibition of AChE was more relevant, as Ki was found to be 175 ± 9 µmol/L. The predicted free energy of binding was −6.7 kcal/mol. The proposed binding orientation of caffeine can interact with Trp86, and it can be stabilize by Tyr337 in comparison to the smaller Ala328 in the case of human BChE; thus, it can explain the lower binding affinity of caffeine for BChE with reference to AChE. The biological relevance of the findings is discussed.

  15. Fermentation of lignocellulosic hydrolysates: Inhibition and detoxification

    Energy Technology Data Exchange (ETDEWEB)

    Palmqvist, E.

    1998-02-01

    The ethanol yield and productivity obtained during fermentation of lignocellulosic hydrolysates is decreased due to the presence of inhibiting compounds, such as weak acids, furans and phenolic compounds produced during hydrolysis. Evaluation of the effect of various biological, physical and chemical detoxification treatments by fermentation assays using Saccharomyces cerevisiae was used to characterise inhibitors. Inhibition of fermentation was decreased after removal of the non-volatile compounds, pre-fermentation by the filamentous fungus Trichoderma reesei, treatment with the lignolytic enzyme laccase, extraction with ether, and treatment with alkali. Yeast growth in lignocellulosic hydrolysates was inhibited below a certain fermentation pH, most likely due to high concentrations of undissociated weak acids. The effect of individual compounds were studied in model fermentations. Furfural is reduced to furfuryl alcohol by yeast dehydrogenases, thereby affecting the intracellular redox balance. As a result, acetaldehyde accumulated during furfural reduction, which most likely contributed to inhibition of growth. Acetic acid (10 g 1{sup -1}) and furfural (3 g 1{sup -1}) interacted antagonistically causing decreased specific growth rate, whereas no significant individual or interaction effects were detected by the lignin-derived compound 4-hydroxybenzoic acid (2 g 1{sup -1}). By maintaining a high cell mass density in the fermentor, the process was less sensitive to inhibitors affecting growth and to fluctuations in fermentation pH, and in addition the depletion rate of bioconvertible inhibitors was increased. A theoretical ethanol yield and high productivity was obtained in continuous fermentation of spruce hydrolysate when the cell mass concentration was maintained at a high level by applying cell recirculation 164 refs, 16 figs, 5 tabs

  16. Inhibition of SIRT2 suppresses hepatic fibrosis.

    Science.gov (United States)

    Arteaga, Maribel; Shang, Na; Ding, Xianzhong; Yong, Sherri; Cotler, Scott J; Denning, Mitchell F; Shimamura, Takashi; Breslin, Peter; Lüscher, Bernhard; Qiu, Wei

    2016-06-01

    Liver fibrosis can progress to cirrhosis and result in serious complications of liver disease. The pathogenesis of liver fibrosis involves the activation of hepatic stellate cells (HSCs), the underlying mechanisms of which are not fully known. Emerging evidence suggests that the classic histone deacetylases play a role in liver fibrosis, but the role of another subfamily of histone deacetylases, the sirtuins, in the development of hepatic fibrosis remains unknown. In this study, we found that blocking the activity of sirtuin 2 (SIRT2) by using inhibitors or shRNAs significantly suppressed fibrogenic gene expression in HSCs. We further demonstrated that inhibition of SIRT2 results in the degradation of c-MYC, which is important for HSC activation. In addition, we discovered that inhibition of SIRT2 suppresses the phosphorylation of ERK, which is critical for the stabilization of c-MYC. Moreover, we found that Sirt2 deficiency attenuates the hepatic fibrosis induced by carbon tetrachloride (CCl4) and thioacetamide (TAA). Furthermore, we showed that SIRT2, p-ERK, and c-MYC proteins are all overexpressed in human hepatic fibrotic tissues. These data suggest a critical role for the SIRT2/ERK/c-MYC axis in promoting hepatic fibrogenesis. Inhibition of the SIRT2/ERK/c-MYC axis represents a novel strategy to prevent and to potentially treat liver fibrosis and cirrhosis.

  17. ROCK inhibition prevents early mouse embryo development.

    Science.gov (United States)

    Duan, Xing; Chen, Kun-Lin; Zhang, Yu; Cui, Xiang-Shun; Kim, Nam-Hyung; Sun, Shao-Chen

    2014-08-01

    ROCK is a Rho-GTPase effector that is important for actin assembly and is involved in various cellular functions, including cell contraction, migration, motility, and tumor cell invasion. In this study, we investigated ROCK expression and function during early mouse embryo development. Inhibiting ROCK by Y-27632 treatment at the zygote stage resulted in first cleavage failure, and most embryos failed to develop to the 8-cell stage. When adding Y-27632 at the 8-cell stage, embryos failed to undergo compaction and could not develop into blastocysts. In addition, fluorescence staining intensity analysis indicated that actin expression at blastomere membranes was significantly reduced. After ROCK inhibition, two or more nuclei were observed in a cell, which indicated possible cytokinesis failure. Moreover, after ROCK inhibition with Y-27632, the phosphorylation levels of LIMK1/2, a downstream molecule of ROCK, were decreased at blastomere membranes. Thus, our results showed conserved roles for ROCK in this mammalian embryo model and indicated that a ROCK-LIMK1/2-actin pathway might regulate cleavage and blastocyst formation during early mouse embryo development.

  18. Alpha-amylase inhibition kinetics by caulerpenyne

    Directory of Open Access Journals (Sweden)

    S. CENGIZ

    2010-03-01

    Full Text Available Many algae have important secretions which are generally used for defensive purposes. These secretions take attentions of a lot of researchers who are wondering if these metabolites can be used for medical researches or not. Among these metabolites, caulerpenyne (CYN which is the main metabolite of Caulerpa species, have had an important place in Caulerpa researches since the results related to its determined properties such as cytotoxic, antiviral, antiproliferative and apoptotic effects have been proven by many scientific reports. In the present study, the inhibitory effect of CYN isolated from C. prolifera on alpha-amylase was investigated. The inhibition experiments were done with CYN by spectrophotometric determination method. In order to evaluate the type of inhibition Lineweaver–Burk plot was produced. The results obtained from enzyme kinetic studies exhibited an un-competitive type of inhibition, which is characterized by the difference of Vmax and KM from those of the free enzyme, of alpha-amylase in the presence of CYN. The present study showed that Caulerpa species can be a potential target for producing diabetic drugs in the light of the results obtained for CYN.

  19. Gas hydrate inhibition of drilling fluid additives

    Energy Technology Data Exchange (ETDEWEB)

    Xiaolan, L.; Baojiang, S.; Shaoran, R. [China Univ. of Petroleum, Dongying (China). Inst. of Petroleum Engineering

    2008-07-01

    Gas hydrates that form during offshore well drilling can have adverse impacts on well operational safety. The hydrates typically form in the risers and the annulus between the casing and the drillstring, and can stop the circulation of drilling fluids. In this study, experiments were conducted to measure the effect of drilling fluid additives on hydrate inhibition. Polyalcohols, well-stability control agents, lubricating agents, and polymeric materials were investigated in a stirred tank reactor at temperatures ranging from -10 degree C to 60 degrees C. Pressure, temperature, and torque were used to detect onset points of hydrate formation and dissociation. The inhibitive effect of the additives on hydrate formation was quantified. Phase boundary shifts were measured in terms of temperature difference or sub-cooling gained when chemicals were added to pure water. Results showed that the multiple hydroxyl groups in polyalcohol chemicals significantly inhibited hydrate formation. Polymeric and polyacrylamide materials had only a small impact on hydrate formation, while sulfonated methyl tannins were found to increase hydrate formation. 6 refs., 1 tab., 4 figs.

  20. Inhibition of enveloped viruses infectivity by curcumin.

    Directory of Open Access Journals (Sweden)

    Tzu-Yen Chen

    Full Text Available Curcumin, a natural compound and ingredient in curry, has antiinflammatory, antioxidant, and anticarcinogenic properties. Previously, we reported that curcumin abrogated influenza virus infectivity by inhibiting hemagglutination (HA activity. This study demonstrates a novel mechanism by which curcumin inhibits the infectivity of enveloped viruses. In all analyzed enveloped viruses, including the influenza virus, curcumin inhibited plaque formation. In contrast, the nonenveloped enterovirus 71 remained unaffected by curcumin treatment. We evaluated the effects of curcumin on the membrane structure using fluorescent dye (sulforhodamine B; SRB-containing liposomes that mimic the viral envelope. Curcumin treatment induced the leakage of SRB from these liposomes and the addition of the influenza virus reduced the leakage, indicating that curcumin disrupts the integrity of the membranes of viral envelopes and of liposomes. When testing liposomes of various diameters, we detected higher levels of SRB leakage from the smaller-sized liposomes than from the larger liposomes. Interestingly, the curcumin concentration required to reduce plaque formation was lower for the influenza virus (approximately 100 nm in diameter than for the pseudorabies virus (approximately 180 nm and the vaccinia virus (roughly 335 × 200 × 200 nm. These data provide insights on the molecular antiviral mechanisms of curcumin and its potential use as an antiviral agent for enveloped viruses.

  1. Inhibition of acetylcholinesterase by Tea Tree oil.

    Science.gov (United States)

    Mills, Clive; Cleary, Brian J; Gilmer, John F; Walsh, John J

    2004-03-01

    Pediculosis is a widespread condition reported in schoolchildren. Treatment most commonly involves the physical removal of nits using fine-toothcombs and the chemical treatment of adult lice and eggs with topical preparations. The active constituents of these preparations frequently exert their effects through inhibition of acetylcholinesterase (AChE, EC 3.1.1.7). Increasing resistance to many preparations has led to the search for more effective treatments. Tea Tree oil, otherwise known as Melaleuca oil, has been added to several preparations as an alternative treatment of head lice infestations. In this study two major constituents of Tea Tree oil, 1,8-cineole and terpinen-4-ol, were shown to inhibit acetylcholinesterase at IC50 values (inhibitor concentrations required to give 50% inhibition) of 0.04 and 10.30 mM, respectively. Four samples of Tea Tree oil tested (Tisserand, Body Treats, Main Camp and Irish Health Culture Association Pure Undiluted) showed anticholinesterase activity at IC50 values of 0.05, 0.10, 0.08 and 0.11 microL mL(-1), respectively. The results supported the hypothesis that the insecticidal activity of Tea Tree oil was attributable, in part, to the anticholinesterase activity of Tea Tree oil.

  2. Wnt signaling inhibits CTL memory programming.

    Science.gov (United States)

    Xiao, Zhengguo; Sun, Zhifeng; Smyth, Kendra; Li, Lei

    2013-12-01

    Induction of functional CTLs is one of the major goals for vaccine development and cancer therapy. Inflammatory cytokines are critical for memory CTL generation. Wnt signaling is important for CTL priming and memory formation, but its role in cytokine-driven memory CTL programming is unclear. We found that wnt signaling inhibited IL-12-driven CTL activation and memory programming. This impaired memory CTL programming was attributed to up-regulation of eomes and down-regulation of T-bet. Wnt signaling suppressed the mTOR pathway during CTL activation, which was different to its effects on other cell types. Interestingly, the impaired memory CTL programming by wnt was partially rescued by mTOR inhibitor rapamycin. In conclusion, we found that crosstalk between wnt and the IL-12 signaling inhibits T-bet and mTOR pathways and impairs memory programming which can be recovered in part by rapamycin. In addition, direct inhibition of wnt signaling during CTL activation does not affect CTL memory programming. Therefore, wnt signaling may serve as a new tool for CTL manipulation in autoimmune diseases and immune therapy for certain cancers.

  3. Deubiquitinase inhibition as a cancer therapeutic strategy.

    Science.gov (United States)

    D'Arcy, Padraig; Wang, Xin; Linder, Stig

    2015-03-01

    The ubiquitin proteasome system (UPS) is the main system for controlled protein degradation and a key regulator of fundamental cellular processes. The dependency of cancer cells on a functioning UPS has made this an attractive target for development of drugs that show selectivity for tumor cells. Deubiquitinases (DUBs, ubiquitin isopeptidases) are components of the UPS that catalyze the removal of ubiquitin moieties from target proteins or polyubiquitin chains, resulting in altered signaling or changes in protein stability. A number of DUBs regulate processes associated with cell proliferation and apoptosis, and as such represent candidate targets for cancer therapeutics. The majority of DUBs are cysteine proteases and are likely to be more "druggable" than E3 ligases. Cysteine residues in the active sites of DUBs are expected to be reactive to various electrophiles. Various compounds containing α,β-unsaturated ketones have indeed been demonstrated to inhibit cellular DUB activity. Inhibition of proteasomal cysteine DUB enzymes (i.e. USP14 and UCHL5) can be predicted to be particularly cytotoxic to cancer cells as it leads to blocking of proteasome function and accumulation of proteasomal substrates. We here provide an overall review of DUBs relevant to cancer and of various small molecules which have been demonstrated to inhibit DUB activity.

  4. Phytic Acid Inhibits Lipid Peroxidation In Vitro

    Directory of Open Access Journals (Sweden)

    Alicja Zajdel

    2013-01-01

    Full Text Available Phytic acid (PA has been recognized as a potent antioxidant and inhibitor of iron-catalyzed hydroxyl radical formation under in vitro and in vivo conditions. Therefore, the aim of the present study was to investigate, with the use of HPLC/MS/MS, whether PA is capable of inhibiting linoleic acid autoxidation and Fe(II/ascorbate-induced peroxidation, as well as Fe(II/ascorbate-induced lipid peroxidation in human colonic epithelial cells. PA at 100 μM and 500 μM effectively inhibited the decay of linoleic acid, both in the absence and presence of Fe(II/ascorbate. The observed inhibitory effect of PA on Fe(II/ascorbate-induced lipid peroxidation was lower (10–20% compared to that of autoxidation. PA did not change linoleic acid hydroperoxides concentration levels after 24 hours of Fe(II/ascorbate-induced peroxidation. In the absence of Fe(II/ascorbate, PA at 100 μM and 500 μM significantly suppressed decomposition of linoleic acid hydroperoxides. Moreover, PA at the tested nontoxic concentrations (100 μM and 500 μM significantly decreased 4-hydroxyalkenal levels in Caco-2 cells which structurally and functionally resemble the small intestinal epithelium. It is concluded that PA inhibits linoleic acid oxidation and reduces the formation of 4-hydroxyalkenals. Acting as an antioxidant it may help to prevent intestinal diseases induced by oxygen radicals and lipid peroxidation products.

  5. Phytic acid inhibits lipid peroxidation in vitro.

    Science.gov (United States)

    Zajdel, Alicja; Wilczok, Adam; Węglarz, Ludmiła; Dzierżewicz, Zofia

    2013-01-01

    Phytic acid (PA) has been recognized as a potent antioxidant and inhibitor of iron-catalyzed hydroxyl radical formation under in vitro and in vivo conditions. Therefore, the aim of the present study was to investigate, with the use of HPLC/MS/MS, whether PA is capable of inhibiting linoleic acid autoxidation and Fe(II)/ascorbate-induced peroxidation, as well as Fe(II)/ascorbate-induced lipid peroxidation in human colonic epithelial cells. PA at 100 μM and 500 μM effectively inhibited the decay of linoleic acid, both in the absence and presence of Fe(II)/ascorbate. The observed inhibitory effect of PA on Fe(II)/ascorbate-induced lipid peroxidation was lower (10-20%) compared to that of autoxidation. PA did not change linoleic acid hydroperoxides concentration levels after 24 hours of Fe(II)/ascorbate-induced peroxidation. In the absence of Fe(II)/ascorbate, PA at 100 μM and 500 μM significantly suppressed decomposition of linoleic acid hydroperoxides. Moreover, PA at the tested nontoxic concentrations (100 μM and 500 μM) significantly decreased 4-hydroxyalkenal levels in Caco-2 cells which structurally and functionally resemble the small intestinal epithelium. It is concluded that PA inhibits linoleic acid oxidation and reduces the formation of 4-hydroxyalkenals. Acting as an antioxidant it may help to prevent intestinal diseases induced by oxygen radicals and lipid peroxidation products.

  6. Trace element inhibition of phytase activity.

    Science.gov (United States)

    Santos, T; Connolly, C; Murphy, R

    2015-02-01

    Nowadays, 70 % of global monogastric feeds contains an exogenous phytase. Phytase supplementation has enabled a more efficient utilisation of phytate phosphorous (P) and reduction of P pollution. Trace minerals, such as iron (Fe), zinc (Zn), copper (Cu) and manganese (Mn) are essential for maintaining health and immunity as well as being involved in animal growth, production and reproduction. Exogenous sources of phytase and trace elements are regularly supplemented to monogastric diets and usually combined in a premix. However, the possibility for negative interaction between individual components within the premix is high and is often overlooked. Therefore, this initial study focused on assessing the potential in vitro interaction between inorganic and organic chelated sources of Fe, Zn, Cu and Mn with three commercially available phytase preparations. Additionally, this study has investigated if the degree of enzyme inhibition was dependent of the type of chelated sources. A highly significant relationship between phytase inhibition, trace mineral type as well as mineral source and concentration, p phytases for Fe and Zn, as well as for Cu with E. coli and Aspergillus niger phytases. Different chelate trace mineral sources demonstrated diversifying abilities to inhibit exogenous phytase activity.

  7. Gabapentin inhibits central sensitization during migraine

    Institute of Scientific and Technical Information of China (English)

    Yanbo Zhang; Guo Shao; Wei Zhang; Sijie Li; Jingzhong Niu; Dongmei Hu; Mingfeng Yang; Xunming Ji

    2013-01-01

    Peripheral and central sensitizations are phenomena that occur during migraine. The role of pentin, a migraine preventive drug, on central sensitization remains unclear. In this study, a rat model of migraine was established by electrical stimulation of the trigeminal ganglion, and the an-imals were given intragastric gabapentin. Changes in amino acid content in the cerebrospinal fluid and protein kinase C membrane translocation in the spinal trigeminal nucleus were examined to clarify the mechanisms underlying the efficacy of gabapentin in the treatment of central sensitization during migraine. Electrophysiology, liquid chromatography-mass spectrometry and western blot analysis results revealed that gabapentin reduces neuronal excitability in the spinal nucleus in the trigeminal nerve, decreases excitatory amino acid content and inhibits the activation of protein ki-nase C. This provides evidence that excitatory amino acids and protein kinase C are involved in the formation and maintenance of central sensitization during migraine. Gabapentin inhibits migraine by reducing excitatory amino acid content in the cerebrospinal fluid and inhibiting protein kinase C ac-tivation.

  8. Response inhibition in motor conversion disorder.

    Science.gov (United States)

    Voon, Valerie; Ekanayake, Vindhya; Wiggs, Edythe; Kranick, Sarah; Ameli, Rezvan; Harrison, Neil A; Hallett, Mark

    2013-05-01

    Conversion disorders (CDs) are unexplained neurological symptoms presumed to be related to a psychological issue. Studies focusing on conversion paralysis have suggested potential impairments in motor initiation or execution. Here we studied CD patients with aberrant or excessive motor movements and focused on motor response inhibition. We also assessed cognitive measures in multiple domains. We compared 30 CD patients and 30 age-, sex-, and education-matched healthy volunteers on a motor response inhibition task (go/no go), along with verbal motor response inhibition (color-word interference) and measures of attention, sustained attention, processing speed, language, memory, visuospatial processing, and executive function including planning and verbal fluency. CD patients had greater impairments in commission errors on the go/no go task (P conversion. Patients with nonepileptic seizures, a different form of conversion disorder, are commonly reported to have lower IQ and multiple cognitive deficits. Our results point toward potential differences between conversion disorder subgroups. © 2013 Movement Disorder Society. Copyright © 2013 Movement Disorder Society.

  9. A resorcinarene for inhibition of Aβ fibrillation.

    Science.gov (United States)

    Han, Xu; Park, Jiyong; Wu, Wei; Malagon, Andres; Wang, Lingyu; Vargas, Edgar; Wikramanayake, Athula; Houk, K N; Leblanc, Roger M

    2017-03-01

    Amyloid-β peptides (Aβ) fibrillation is the hallmark of Alzheimer's disease (AD). However, it has been challenging to discover potent agents in order to inhibit Aβ fibrillation. Herein, we demonstrated the effect of resorcinarene on inhibiting Aβ fibrillation in vitro via experimental and computational methods. Aβ were incubated with different concentrations of resorcinarene so as to monitor the kinetics by using thioflavin T binding assay. The results, which were further confirmed by far-UV CD spectroscopy and atomic force microscopy, strongly indicated that the higher concentration of resorcinarene, the more effective the inhibition of Aβ fibrillation. A cytotoxicity study showed that when sea urchin embryos were exposed to the resorcinarene, the majority survived due to the resorcinarene low toxicity. In addition, when the resorcinarene was added, the formation of toxic Aβ 42 species was delayed. Computational studies of Aβ fibrillation, including docking simulations and MD simulations, illustrated that the interaction between inhibitor resorcinarene and Aβ is driven by the non-polar interactions. These studies display a novel strategy for the exploration of promising antiamyloiddogenic agents for AD treatments.

  10. Bioassays for the determination of nitrification inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Grunditz, Camilla

    1999-07-01

    Requirements for nitrogen reduction in wastewater treatment plants were introduced in Sweden in the early 1990's. This was a governmental move to reduce the nitrogen discharges to the Baltic and Kattegat in order to prevent eutrophication. The nitrification process in wastewater treatment plants is performed by nitrifying bacteria. These are susceptible to inhibition and it is of great importance that the influent water does not contain toxic compounds. Therefore, there is a need for assays for the determination of nitrification inhibition. This thesis describes the development and applications of such bioassays. Pure cultures of Nitrosomonas sp. and Nitrobacter sp. were isolated from activated sludge of a wastewater treatment plant. These cultures were used as test organisms in the development of bioassays for nitrification inhibition measurements. The assays are based on two different principles; cell suspensions of the bacteria, performed in test tubes, and mediated amperometric biosensors with the bacteria immobilised. Ammonia oxidation and nitrite oxidation are studied separately without interference from other organisms, which makes it easier to interpret the results. The cell suspension assays were applied to samples of industrial and municipal wastewater. The Nitrosomonas and Nitrobacter assays showed to have different inhibition patterns. A large percentage of the Swedish municipal wastewater treatment plants were found to receive inhibitory influent water, but the inhibition level was generally low. Compared to an assay based on activated sludge, the screening method, the pure culture assays found more samples of influent water strongly inhibitory or stimulating. The highest correlation was found between the screening method and the Nitrosomonas assay. The Nitrobacter assay was found to be the most sensitive method. Assessment of toxicity of a number of chemical substances was studied using the biosensors, together with the cell suspension assays

  11. Antiarrhythmic Mechanisms of SK Channel Inhibition in the Rat Atrium

    DEFF Research Database (Denmark)

    Skibsbye, Lasse; Wang, Xiaodong; Axelsen, Lene Nygaard

    2015-01-01

    remains unclear. OBJECTIVES: We speculated that together with a direct inhibition of repolarizing SK current, the previously observed depolarization of the atrial resting membrane potential (RMP) after SK channel inhibition reduces sodium channel availability thereby prolonging the effective refractory...

  12. Allosteric Partial Inhibition of Monomeric Proteases. Sulfated Coumarins Induce Regulation, not just Inhibition, of Thrombin

    Science.gov (United States)

    Verespy III, Stephen; Mehta, Akul Y.; Afosah, Daniel; Al-Horani, Rami A.; Desai, Umesh R.

    2016-01-01

    Allosteric partial inhibition of soluble, monomeric proteases can offer major regulatory advantages, but remains a concept on paper to date; although it has been routinely documented for receptors and oligomeric proteins. Thrombin, a key protease of the coagulation cascade, displays significant conformational plasticity, which presents an attractive opportunity to discover small molecule probes that induce sub-maximal allosteric inhibition. We synthesized a focused library of some 36 sulfated coumarins to discover two agents that display sub-maximal efficacy (~50%), high potency (150-fold). Michaelis-Menten, competitive inhibition, and site-directed mutagenesis studies identified exosite 2 as the site of binding for the most potent sulfated coumarin. Stern-Volmer quenching of active site-labeled fluorophore suggested that the allosteric regulators induce intermediate structural changes in the active site as compared to those that display ~80–100% efficacy. Antithrombin inactivation of thrombin was impaired in the presence of the sulfated coumarins suggesting that allosteric partial inhibition arises from catalytic dysfunction of the active site. Overall, sulfated coumarins represent first-in-class, sub-maximal inhibitors of thrombin. The probes establish the concept of allosteric partial inhibition of soluble, monomeric proteins. This concept may lead to a new class of anticoagulants that are completely devoid of bleeding. PMID:27053426

  13. Foxp3+ T cells inhibit antitumor immune memory modulated by mTOR inhibition.

    Science.gov (United States)

    Wang, Yanping; Sparwasser, Tim; Figlin, Robert; Kim, Hyung L

    2014-04-15

    Inhibition of mTOR signaling enhances antitumor memory lymphocytes. However, pharmacologic mTOR inhibition also enhances regulatory T-cell (Treg) activity. To counter this effect, Treg control was added to mTOR inhibition in preclinical models. Tregs were controlled with CD4-depleting antibodies because CD4 depletion has high translational potential and already has a well-established safety profile in patients. The antitumor activity of the combination therapy was CD8 dependent and controlled growth of syngeneic tumors even when an adoptive immunotherapy was not used. Lymphocytes resulting from the combination therapy could be transferred into naïve mice to inhibit aggressive growth of lung metastases. The combination therapy enhanced CD8 memory formation as determined by memory markers and functional studies of immune recall. Removal of FoxP3-expressing T lymphocytes was the mechanism underlying immunologic memory formation following CD4 depletion. This was confirmed using transgenic DEREG (depletion of regulatory T cells) mice to specifically remove Foxp3(+) T cells. It was further confirmed with reciprocal studies where stimulation of immunologic memory because of CD4 depletion was completely neutralized by adoptively transferring tumor-specific Foxp3(+) T cells. Also contributing to tumor control, Tregs that eventually recovered following CD4 depletion were less immunosuppressive. These results provide a rationale for further study of mTOR inhibition and CD4 depletion in patients. ©2014 AACR.

  14. A fusion-inhibiting peptide against Rift Valley fever virus inhibits multiple, diverse viruses.

    Directory of Open Access Journals (Sweden)

    Jeffrey W Koehler

    Full Text Available For enveloped viruses, fusion of the viral envelope with a cellular membrane is critical for a productive infection to occur. This fusion process is mediated by at least three classes of fusion proteins (Class I, II, and III based on the protein sequence and structure. For Rift Valley fever virus (RVFV, the glycoprotein Gc (Class II fusion protein mediates this fusion event following entry into the endocytic pathway, allowing the viral genome access to the cell cytoplasm. Here, we show that peptides analogous to the RVFV Gc stem region inhibited RVFV infectivity in cell culture by inhibiting the fusion process. Further, we show that infectivity can be inhibited for diverse, unrelated RNA viruses that have Class I (Ebola virus, Class II (Andes virus, or Class III (vesicular stomatitis virus fusion proteins using this single peptide. Our findings are consistent with an inhibition mechanism similar to that proposed for stem peptide fusion inhibitors of dengue virus in which the RVFV inhibitory peptide first binds to both the virion and cell membranes, allowing it to traffic with the virus into the endocytic pathway. Upon acidification and rearrangement of Gc, the peptide is then able to specifically bind to Gc and prevent fusion of the viral and endocytic membranes, thus inhibiting viral infection. These results could provide novel insights into conserved features among the three classes of viral fusion proteins and offer direction for the future development of broadly active fusion inhibitors.

  15. Zinc ions bind to and inhibit activated protein C

    DEFF Research Database (Denmark)

    Zhu, Tianqing; Ubhayasekera, Wimal; Nickolaus, Noëlle

    2010-01-01

    Zn2+ ions were found to efficiently inhibit activated protein C (APC), suggesting a potential regulatory function for such inhibition. APC activity assays employing a chromogenic peptide substrate demonstrated that the inhibition was reversible and the apparent K I was 13 +/- 2 microM. k cat was ...

  16. SIRT1 controls cell proliferation by regulating contact inhibition.

    Science.gov (United States)

    Cho, Elizabeth H; Dai, Yan

    2016-09-16

    Contact inhibition keeps cell proliferation in check and serves as a built-in protection against cancer development by arresting cell division upon cell-cell contact. Yet the complete mechanism behind this anti-cancer process remains largely unclear. Here we present SIRT1 as a novel regulator of contact inhibition. SIRT1 performs a wide variety of functions in biological processes, but its involvement in contact inhibition has not been explored to date. We used NIH3T3 cells, which are sensitive to contact inhibition, and H460 and DU145 cancer cells, which lack contact inhibition, to investigate the relationship between SIRT1 and contact inhibition. We show that SIRT1 overexpression in NIH3T3 cells overcomes contact inhibition while SIRT1 knockdown in cancer cells restores their lost contact inhibition. Moreover, we demonstrate that p27 protein expression is controlled by SIRT1 in contact inhibition. Overall, our findings underline the critical role of SIRT1 in contact inhibition and suggest SIRT1 inhibition as a potential strategy to suppress cancer cell growth by restoring contact inhibition. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Inhibition of acetylcholinesterase activity by essential oil from Citrus paradisi.

    Science.gov (United States)

    Miyazawa, M; Tougo, H; Ishihara, M

    2001-01-01

    Inhibition of acetylcholinesterase (AChE) activity by essential oils of Citrus paradisi (grapefruit pink in USA) was studied. Inhibition of AChE was measured by the colorimetric method. Nootkatone and auraptene were isolated from C. paradisi oil and showed 17-24% inhibition of AChE activity at the concentration of 1.62 microg/mL.

  18. Inhibition by somatostatin interneurons in olfactory cortex

    Directory of Open Access Journals (Sweden)

    Adam M Large

    2016-08-01

    Full Text Available Inhibitory circuitry plays an integral cortical network activity. The development of transgenic mouse lines targeting unique interneuron classes has significantly advanced our understanding of the functional roles of specific inhibitory circuits in neocortical sensory processing. In contrast, considerably less is known about the circuitry and function of interneuron classes in piriform cortex, a paleocortex responsible for olfactory processing. In this study, we sought to utilize transgenic technology to investigate inhibition mediated by somatostatin (SST interneurons onto pyramidal cells, parvalbumin (PV interneurons and other interneuron classes. As a first step, we characterized the anatomical distributions and intrinsic properties of SST and PV interneurons in four transgenic lines (SST-cre, GIN, PV-cre and G42 that are commonly interbred to investigate inhibitory connectivity. Surprisingly, the distributions SST and PV cell subtypes targeted in the GIN and G42 lines were sparse in piriform cortex compared to neocortex. Moreover, two-thirds of interneurons recorded in the SST-cre line had electrophysiological properties similar to fast spiking (FS interneurons rather than regular (RS or low threshold spiking (LTS phenotypes. Nonetheless, like neocortex, we find that SST-cells broadly inhibit a number of unidentified interneuron classes including putatively identified PV cells and surprisingly, other SST cells. We also confirm that SST-cells inhibit pyramidal cell dendrites and thus, influence dendritic integration of afferent and recurrent inputs to the piriform cortex. Altogether, our findings suggest that somatostatin interneurons play an important role in regulating both excitation and the global inhibitory network during olfactory processing.

  19. Interferon-γ Inhibits Ebola Virus Infection.

    Science.gov (United States)

    Rhein, Bethany A; Powers, Linda S; Rogers, Kai; Anantpadma, Manu; Singh, Brajesh K; Sakurai, Yasuteru; Bair, Thomas; Miller-Hunt, Catherine; Sinn, Patrick; Davey, Robert A; Monick, Martha M; Maury, Wendy

    2015-01-01

    Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks.

  20. Brain hyaluronan binding protein inhibits tumor growth

    Institute of Scientific and Technical Information of China (English)

    高锋; 曹曼林; 王蕾

    2004-01-01

    Background Great efforts have been made to search for the angiogenic inhibitors in avascular tissues. Several proteins isolated from cartilage have been proved to have anti-angiogenic or anti-tumour effects. Because cartilage contains a great amount of hyaluronic acid (HA) oligosaccharides and abundant HA binding proteins (HABP), therefore, we speculated that HABP might be one of the factors regulating vascularization in cartilage or anti-angiogenesis in tumours. The purpose of this research was to evaluale the effects of hyaluronan binding protein on inhibiting tumour growth both in vivo and vitro. Methods A unique protein termed human brain hyaluronan (HA) binding protein (b-HABP) was cloned from human brain cDNA library. MDA-435 human breast cancer cell line was chosen as a transfectant. The in vitro underlying mechanisms were investigated by determining the possibilities of MDA-435/b-HABP colony formation on soft agar, the effects of the transfectant on the proliferation of endothelial cells and the expression levels of caspase 3 and FasL from MDA-435/b-HABP. The in vivo study included tumour growth on the chorioallantoic membrane (CAM) of chicken embryos and nude mice. Results Colony formation assay revealed that the colonies formed by MDA-435/b-HABP were greatly reduced compared to mock transfectants. The conditioned media from MDA-435/b-HABP inhibited the growth of endothelial cells in culture. Caspase 3 and FasL expressions were induced by MDA-435/b-HABP. The size of tumours of MDA-435/b-HABP in both CAM and nude mice was much smaller than that of MDA-435 alone. Conclusions Human brain hyaluronan binding protein (b-HABP) may represent a new kind of naturally existing anti-tumour substance. This brain-derived glycoprotein may block tumour growth by inducing apoptosis of cancer cells or by decreasing angiogenesis in tumour tissue via inhibiting proliferation of endothelial cells.

  1. Reliability of Transcallosal Inhibition in Healthy Adults

    Science.gov (United States)

    Fleming, Melanie K.; Newham, Di J.

    2017-01-01

    Transcallosal inhibition (TCI), assessed using transcranial magnetic stimulation, can provide insight into the neurophysiology of aging and of neurological disorders such as stroke. However, the reliability of TCI using the ipsilateral silent period (iSP) has not been formally assessed, despite its use in longitudinal studies. This study aimed to determine the reliability of iSP onset latency, duration and depth in healthy young and older adults. A sample of 18 younger (mean age 27.7 years, range: 19–42) and 13 older healthy adults (mean age 68.1 years, range: 58–79) attended four sessions whereby the iSP was measured from the first dorsal interosseous (FDI) muscle of each hand. 20 single pulse stimuli were delivered to each primary motor cortex at 80% maximum stimulator output while the participant maintained an isometric contraction of the ipsilateral FDI. The average onset latency, duration of the iSP, and depth of inhibition relative to baseline electromyography activity was calculated for each hand in each session. Intraclass correlation coefficients (ICCs) were calculated for all four sessions, or the first two sessions only. For iSP onset latency the reliability ranged from poor to good. For iSP duration there was moderate to good reliability (ICC > 0.6). Depth of inhibition demonstrated variation in reproducibility depending on which hand was assessed and whether two or four sessions were compared. Bland and Altman analyses showed wide limits of agreement between the first two sessions, particularly for iSP depth. However, there was no systematic pattern to the variability. These results indicate that although iSP duration is reliable in healthy adults, changes in longitudinal studies should be interpreted with caution, particularly for iSP depth. Future studies are needed to determine reliability in clinical populations. PMID:28119588

  2. Interferon-γ Inhibits Ebola Virus Infection.

    Directory of Open Access Journals (Sweden)

    Bethany A Rhein

    Full Text Available Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks.

  3. A novel approach to inhibit bone resorption

    DEFF Research Database (Denmark)

    Panwar, Preety; Søe, Kent; Guido, Rafael VC;

    2016-01-01

    -dihydrotanshinone (DHT1), and the active site inhibitor, odanacatib (ODN), on bone resorption and TGF-ß1 degradation. Cell cultures, Western blot, light and scanning electron microscopy as well as energy dispersive X-ray spectroscopy, molecular modelling and enzymatic assays were used to evaluate the inhibitors. KEY...... RESULTS: DHT1 selectively inhibited the collagenase activity of CatK, without affecting the viability of osteoclasts. Both inhibitors abolished the formation of resorption trenches, with DHT1 having a slightly higher IC50 value than ODN. Maximal reductions of other resorption parameters by DHT1 and ODN...

  4. Linking algal growth inhibition to chemical activity

    DEFF Research Database (Denmark)

    Schmidt, Stine N.; Mayer, Philipp

    to chemical activity, as opposed to e.g. the total concentration. Baseline toxicity (narcosis) for neutral hydrophobic organic compounds has been shown to initiate in the narrow chemical activity range of 0.01 to 0.1. This presentation focuses on linking algal growth inhibition to chemical activity....... High-quality toxicity data are carefully selected from peer-reviewed scientific literature and QSAR databases. This presentation shows how the chemical activity concept can be used to compare and combine toxicity data across compounds and species in order to characterize toxicity – and further how...

  5. Inhibition of intestinal disaccharidase activity by pentoses

    DEFF Research Database (Denmark)

    Halschou-Jensen, Kia

    digestive enzymes. In paper 3, D-xylose and L-arabinose was investigated in vitro and in vivo. This study found that D-xylose and Larabinose inhibit both sucrase and maltase when tested in a Caco-2 cell model. In addition, 13 healthy subjects completed a randomized double-blinded cross-over study......The current health problems regarding the obesity epidemic, development of type 2 diabetes mellitus (T2D) and cardiovascular disease are a major challenge for healthcare systems worldwide.No simple or unique cure has been documented to prevent or treat this major health problem regarding T2D...

  6. Homochiral growth through enantiomeric cross-inhibition

    CERN Document Server

    Brandenburg, A; Höfner, S; Nilsson, M

    2004-01-01

    The stability and conservation properties of a recently proposed polymerization model are studied. The achiral (racemic) solution is linearly unstable once the relevant control parameter (here the fidelity of the catalyst) exceeds a critical value. The growth rate is calculated for different fidelity parameters and cross-inhibition rates. A chirality parameter is defined and shown to be conserved by the nonlinear terms of the model. Finally, a truncated version of the model is used to derive a set of two ordinary differential equations and it is argued that these equations are more realistic than those used in earlier models of that form.

  7. Novel agents inhibit human leukemic cells

    Institute of Scientific and Technical Information of China (English)

    Wei-ping YU; Juan LI

    2012-01-01

    Ouabain (OUA) and pyrithione zinc (PZ) have been proved as the potential drugs for treating acute myeloid leukemia (AML).Selected from a screening among 1040 Food and Drug Administration-approved pharmacological agents,both drugs showability to induce apoptosis of the culturing AML cells,exhibiting the poisoning effect on the cells.Studies also reveal the efficiency of the drugs in inhibiting the growth of human AML cells injected into the mice lacking of immunity and killing primary AML cells from the peripheral blood of AML patients[1].

  8. Basis of pyruvate inhibition in Thiobacillus thiooxidans.

    Science.gov (United States)

    Rao, G S; Berger, L R

    1970-05-01

    Addition of 10(-3)m pyruvic acid to cultures of Thiobacillus thiooxidans, at pH 2.3, results in its rapid intracellular accumulation and in the cessation of sulfur oxidation, CO(2) fixation, and oxygen consumption; at pH 7.0, pyruvate neither inhibits oxygen uptake nor accumulates appreciably intracellularly. Pyruvate does not affect CO(2) fixation in cell-free extracts. The data suggest that the cells of T. thiooxidans are passively permeable to pyruvic acid at low pH. Thus entry of pyruvic acid causes accumulation of pyruvate with a concomitant decrease in intracellular pH.

  9. Research on inhibition of corneal neovascularization

    Directory of Open Access Journals (Sweden)

    Zhang-Hui Yang

    2015-12-01

    Full Text Available Corneal transparency is the basis of the normal physiological functions.However, corneal neovascularization(CNVmay occur in the infection, mechanical and chemical injury or under other pathological conditions,which make the cornea lose original transparency and severe visual impairment. In recent years, along with the development of immunology, molecular biology, biochemistry and other disciplines, there is more in-depth understanding on the CNV, and clinical treatment of CNV has made new breakthroughs. This article provides an overview of the inhibition of CNV.

  10. Quassinoid inhibition of AP-1 function does not correlate with cytotoxicity or protein synthesis inhibition.

    Science.gov (United States)

    Beutler, John A; Kang, Moon-Il; Robert, Francis; Clement, Jason A; Pelletier, Jerry; Colburn, Nancy H; McKee, Tawnya C; Goncharova, Ekaterina; McMahon, James B; Henrich, Curtis J

    2009-03-27

    Several quassinoids were identified in a high-throughput screening assay as inhibitors of the transcription factor AP-1. Further biological characterization revealed that while their effect was not specific to AP-1, protein synthesis inhibition and cell growth assays were inconsistent with a mechanism of simple protein synthesis inhibition. Numerous plant extracts from the plant family Simaroubaceae were also identified in the same screen; bioassay-guided fractionation of one extract (Ailanthus triphylla) yielded two known quassinoids, ailanthinone (3) and glaucarubinone (4), which were also identified in the pure compound screening procedure.

  11. Thymoquinone Inhibits Escherichia coli ATP Synthase and Cell Growth

    OpenAIRE

    2015-01-01

    We examined the thymoquinone induced inhibition of purified F1 or membrane bound F1FO E. coli ATP synthase. Both purified F1 and membrane bound F1FO were completely inhibited by thymoquinone with no residual ATPase activity. The process of inhibition was fully reversible and identical in both membrane bound F1Fo and purified F1 preparations. Moreover, thymoquinone induced inhibition of ATP synthase expressing wild-type E. coli cell growth and non-inhibition of ATPase gene deleted null control...

  12. Copper, aluminum, iron and calcium inhibit human acetylcholinesterase in vitro.

    Science.gov (United States)

    Pohanka, Miroslav

    2014-01-01

    Acetylcholinesterase (AChE) is an important part of cholinergic nerves where it participates in termination of neurotransmission. AChE can be inhibited by e.g. some Alzheimer disease drugs, nerve agents, and secondary metabolites. In this work, metal salts aluminum chloride, calcium chloride, cupric chloride, ferric chloride, potassium chloride, magnesium chloride and sodium chloride were tested for their ability to inhibit AChE. Standard Ellman assay based on human recombinant AChE was done and inhibition was measured using Dixon plot. No inhibition was proved for sodium, potassium and magnesium ions. However, aluminum, cupric, ferric and calcium ions were able to inhibit AChE via noncompetitive mechanism of inhibition. Though the inhibition is much weaker when compared to e.g. drugs with noncompetitive mechanism of action, biological relevance of the findings can be anticipated.

  13. A comparator view of Pavlovian and differential inhibition.

    Science.gov (United States)

    Urcelay, Gonzalo P; Miller, Ralph R

    2006-07-01

    In 3 experiments using rats as subjects, the authors varied trial spacing to investigate the conditions under which Pavlovian and differential inhibition are observed. Experiment 1 compared Pavlovian and differential inhibition with spaced training trials. Spaced trials resulted in only the Pavlovian inhibitor passing both summation and retardation tests. Conversely, Experiment 2 compared these 2 types of inhibition with massed training trials. This training resulted in only the differential inhibitor passing both tests for conditioned inhibition. Finally, in Experiment 3 all subjects experienced Pavlovian inhibition training with massed trials. Although this training by itself did not result in behavior indicative of inhibition, subjects that also experienced posttraining extinction of the training context did pass both tests for inhibition. Overall, these results are anticipated by the extended comparator hypothesis (Denniston, Savastano, & Miller, 2001) but are problematic for most contemporary associative learning theories.

  14. Optogenetic and chemogenetic strategies for sustained inhibition of pain

    Science.gov (United States)

    Iyer, Shrivats M.; Vesuna, Sam; Ramakrishnan, Charu; Huynh, Karen; Young, Stephanie; Berndt, Andre; Lee, Soo Yeun; Gorini, Christopher J.; Deisseroth, Karl; Delp, Scott L.

    2016-01-01

    Spatially targeted, genetically-specific strategies for sustained inhibition of nociceptors may help transform pain science and clinical management. Previous optogenetic strategies to inhibit pain have required constant illumination, and chemogenetic approaches in the periphery have not been shown to inhibit pain. Here, we show that the step-function inhibitory channelrhodopsin, SwiChR, can be used to persistently inhibit pain for long periods of time through infrequent transdermally delivered light pulses, reducing required light exposure by >98% and resolving a long-standing limitation in optogenetic inhibition. We demonstrate that the viral expression of the hM4D receptor in small-diameter primary afferent nociceptor enables chemogenetic inhibition of mechanical and thermal nociception thresholds. Finally, we develop optoPAIN, an optogenetic platform to non-invasively assess changes in pain sensitivity, and use this technique to examine pharmacological and chemogenetic inhibition of pain. PMID:27484850

  15. Ehrlich tumor inhibition using doxorubicin containing liposomes.

    Science.gov (United States)

    Elbialy, Nihal Saad; Mady, Mohsen Mahmoud

    2015-04-01

    Ehrlich tumors were grown in female balb mice by subcutaneous injection of Ehrlich ascites carcinoma cells. Mice bearing Ehrlich tumor were injected with saline, DOX in solution or DOX encapsulated within liposomes prepared from DMPC/CHOL/DPPG/PEG-PE (100:100:60:4) in molar ratio. Cytotoxicity assay showed that the IC50 of liposomes containing DOX was greater than that DOX only. Tumor growth inhibition curves in terms of mean tumor size (cm(3)) were presented. All the DOX formulations were effective in preventing tumor growth compared to saline. Treatment with DOX loaded liposomes displayed a pronounced inhibition in tumor growth than treatment with DOX only. Histopathological examination of the entire tumor sections for the various groups revealed marked differences in cellular features accompanied by varying degrees in necrosis percentage ranging from 12% for saline treated mice to 70% for DOX loaded liposome treated mice. The proposed liposomal formulation can efficiently deliver the drug into the tumor cells by endocytosis (or passive diffusion) and lead to a high concentration of DOX in the tumor cells. The study showed that the formulation of liposomal doxorubicin improved the therapeutic index of DOX and had increased anti-tumor activity against Ehrlich tumor models.

  16. In search of lost presynaptic inhibition.

    Science.gov (United States)

    Rudomin, Pablo

    2009-06-01

    This chapter presents an historical review on the development of some of the main findings on presynaptic inhibition. Particular attention is given to recent studies pertaining the differential GABAa control of the synaptic effectiveness of muscle, cutaneous and articular afferents, to some of the problems arising with the identification of the interneurons mediating the GABAergic depolarization of primary afferents (PAD) of muscle afferents, on the influence of the spontaneous activity of discrete sets of dorsal horn neurons on the pathways mediating PAD of muscle and cutaneous afferents, and to the unmasking of the cutaneous-evoked responses in the lumbosacral spinal cord and associated changes in tonic PAD that follow acute and chronic section of cutaneous nerves. The concluding remarks are addressed to several issues that need to be considered to have a better understanding of the functional role of presynaptic inhibition and PAD on motor performance and sensory processing and on their possible contribution to the shaping of a higher coherence between the cortically programmed and the executed movements.

  17. Safrole oxide inhibits angiogenesis by inducing apoptosis.

    Science.gov (United States)

    Zhao, Jing; Miao, Junying; Zhao, Baoxiang; Zhang, Shangli; Yin, Deling

    2005-06-01

    Our previous studies indicate that 3, 4-(methylenedioxy)-1-(2', 3'-epoxypropyl)-benzene (safrole oxide), a newly synthesized compound, induces apoptosis in vascular endothelial cells (VECs) and A549 lung cancer cells. To our knowledge, the inhibition of angiogenesis by safrole oxide has not been reported yet. We report here that cultured rat aorta treated with safrole oxide exhibited a significant microvessel reduction as determined by counting the number of microvessels in a phase contrast microscope. There were more microvessels formed in the presence of A549 lung cancer cells in rat aorta model, while a dramatic inhibition of angiogenesis was obtained by adding 220-450 micromol l(-1) of safrole oxide to the growth medium (Psafrole oxide produced only some abortive endothelial cells but not microvessels. Furthermore, safrole oxide induced antiangiogenic effect in the chorioallantoic membranes (CAM) as a dose dependent manner. Eggs treated with 2-11 micromol 100 microl(-1) per egg of the safrole oxide for 48 h exhibited a significant reduction in blood vessel area of the CAM, a process likely mediated by apoptosis as demonstrated by DNA fragmentation. Our results suggest that safrole oxide has antiangiogenic activity and this effect might occur by induction of cellular apoptosis.

  18. Phenols displaying tyrosinase inhibition from Humulus lupulus.

    Science.gov (United States)

    Kim, Dae Wook; Woo, Hyun Sim; Kim, Jeong Yoon; Ryuk, Jin Ah; Park, Ki Hun; Ko, Byoung Seob

    2016-10-01

    Tyrosinase is the rate-limiting enzyme for the production of melanin and other pigments via the oxidation of l-tyrosine. The methanol extract from Humulus lupulus showed potent inhibition against mushroom tyrosinase. The bioactivity-guided fractionation of this methanol extract resulted in the isolation of seven flavonoids (1-7), identified as xanthohumol (1), 4'-O-methylxanthohumol (2), xanthohumol C (3), flavokawain C (4), xanthoumol B (5), 6-prenylnaringenin (6) and isoxanthohumol (7). All isolated flavonoids (1-7) effectively inhibited the monophenolase (IC50s = 15.4-58.4 µM) and diphenolase (IC50s = 27.1-117.4 µM) activities of tyrosinase. Kinetic studies using Lineweaver-Burk and Dixon-plots revealed that chalcones (1-5) were competitive inhibitors, whereas flavanones (6 and 7) exhibited both mixed and non-competitive inhibitory characteristics. In conclusion, this study is the first to demonstrate that the phenolic phytochemicals of H. lupulus display potent inhibitory activities against tyrosinase.

  19. Therapeutic proteasome inhibition in experimental acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Tamás Letoha; Tamás Takács; Liliána Z Fehér; László Pecze; Csaba Somlai; Ilona Varga; József Kaszaki; Gábor Tóth; Csaba Vizier; László Tiszlavicz

    2007-01-01

    AIM: To establish the therapeutic potential of proteasome inhibition, we examined the therapeutic effects of MG132 (Z-Leu-Leu-Leu-aldehyde) in an experimental model of acute pancreatitis.METHODS: Pancreatitis was induced in rats by two hourly intraperitoneal (ip) injections of cholecystokinin octapeptide (CCK; 2 × 100 μg/kg) and the proteasome inhibitor MG132 (10 mg/kg ip) was administered 30 min after the second CCK injection. Animals were sacrificed 4 h after the first injection of CCK.RESULTS: Administering the proteasome inhibitor MG132 (at a dose of 10 mg/kg, ip) 90 min after the onset of pancreatic inflammation induced the expression of cell-protective 72 kDa heat shock protein (HSP72) and decreased DNA-binding of nuclear factor-κB (NF-κB).Furthermore MG132 treatment resulted in milder inflammatory response and cellular damage, as revealed by improved laboratory and histological parameters of pancreatitis and associated oxidative stress.CONCLUSION: Our findings suggest that proteasome inhibition might be beneficial not only for the prevention,but also for the therapy of acute pancreatitis.

  20. Platelets Inhibit Migration of Canine Osteosarcoma Cells.

    Science.gov (United States)

    Bulla, S C; Badial, P R; Silva, R C; Lunsford, K; Bulla, C

    2017-01-01

    The interaction between platelets and tumour cells is important for tumour growth and metastasis. Thrombocytopenia or antiplatelet treatment negatively impact on cancer metastasis, demonstrating potentially important roles for platelets in tumour progression. To our knowledge, there is no information regarding the role of platelets in cancer progression in dogs. This study was designed to test whether canine platelets affected the migratory behaviour of three canine osteosarcoma cell lines and to give insights of molecular mechanisms. Intact platelets, platelet lysate and platelet releasate inhibited the migration of canine osteosarcoma cell lines. Addition of blood leucocytes to the platelet samples did not alter the inhibitory effect on migration. Platelet treatment also significantly downregulated the transcriptional levels of SNAI2 and TWIST1 genes. The interaction between canine platelets or molecules released during platelet activation and these tumour cell lines inhibits their migration, which suggests that canine platelets might antagonize metastasis of canine osteosarcoma. This effect is probably due to, at least in part, downregulation of genes related to epithelial-mesenchymal transition. Copyright © 2016. Published by Elsevier Ltd.

  1. Understanding biocatalyst inhibition by carboxylic acids.

    Science.gov (United States)

    Jarboe, Laura R; Royce, Liam A; Liu, Ping

    2013-09-03

    Carboxylic acids are an attractive biorenewable chemical in terms of their flexibility and usage as precursors for a variety of industrial chemicals. It has been demonstrated that such carboxylic acids can be fermentatively produced using engineered microbes, such as Escherichia coli and Saccharomyces cerevisiae. However, like many other attractive biorenewable fuels and chemicals, carboxylic acids become inhibitory to these microbes at concentrations below the desired yield and titer. In fact, their potency as microbial inhibitors is highlighted by the fact that many of these carboxylic acids are routinely used as food preservatives. This review highlights the current knowledge regarding the impact that saturated, straight-chain carboxylic acids, such as hexanoic, octanoic, decanoic, and lauric acids can have on E. coli and S. cerevisiae, with the goal of identifying metabolic engineering strategies to increase robustness. Key effects of these carboxylic acids include damage to the cell membrane and a decrease of the microbial internal pH. Certain changes in cell membrane properties, such as composition, fluidity, integrity, and hydrophobicity, and intracellular pH are often associated with increased tolerance. The availability of appropriate exporters, such as Pdr12, can also increase tolerance. The effect on metabolic processes, such as maintaining appropriate respiratory function, regulation of Lrp activity and inhibition of production of key metabolites such as methionine, are also considered. Understanding the mechanisms of biocatalyst inhibition by these desirable products can aid in the engineering of robust strains with improved industrial performance.

  2. Understanding biocatalyst inhibition by carboxylic acids

    Directory of Open Access Journals (Sweden)

    Laura R Jarboe

    2013-09-01

    Full Text Available Carboxylic acids are an attractive biorenewable chemical in terms of their flexibility and usage as precursors for a variety of industrial chemicals. It has been demonstrated that such carboxylic acids can be fermentatively produced using engineered microbes, such as Escherichia coli and Saccharomyces cerevisiae. However, like many other attractive biorenewable fuels and chemicals, carboxylic acids become inhibitory to these microbes at concentrations below the desired yield and titer. In fact, their potency as microbial inhibitors is highlighted by the fact that many of these carboxylic acids are routinely used as food preservatives. This review highlights the current knowledge regarding the impact that saturated, straight-chain carboxylic acids, such as hexanoic, octanoic, decanoic and lauric acids can have on E. coli and S. cerevisiae, with the goal of identifying metabolic engineering strategies to increase robustness. Key effects of these carboxylic acids include damage to the cell membrane and a decrease of the microbial internal pH. Certain changes in cell membrane properties, such as composition, fluidity, integrity and hydrophobicity, and intracellular pH are often associated with increased tolerance. The availability of appropriate exporters, such as Pdr12, can also increase tolerance. The effect on metabolic processes, such as maintaining appropriate respiratory function, regulation of Lrp activity and inhibition of production of key metabolites such as methionine, are also considered. Understanding the mechanisms of biocatalyst inhibition by these desirable products can aid in the engineering of robust strains with improved industrial performance.

  3. Calcineurin/NFAT signalling inhibits myeloid haematopoiesis.

    Science.gov (United States)

    Fric, Jan; Lim, Clarice X F; Koh, Esther G L; Hofmann, Benjamin; Chen, Jinmiao; Tay, Hock Soon; Mohammad Isa, Siti Aminah Bte; Mortellaro, Alessandra; Ruedl, Christiane; Ricciardi-Castagnoli, Paola

    2012-04-01

    Nuclear factor of activated T cells (NFAT) comprises a family of transcription factors that regulate T cell development, activation and differentiation. NFAT signalling can also mediate granulocyte and dendritic cell (DC) activation, but it is unknown whether NFAT influences their development from progenitors. Here, we report a novel role for calcineurin/NFAT signalling as a negative regulator of myeloid haematopoiesis. Reconstituting lethally irradiated mice with haematopoietic stem cells expressing an NFAT-inhibitory peptide resulted in enhanced development of the myeloid compartment. Culturing bone marrow cells in media supplemented with Flt3-L in the presence of the calcineurin/NFAT inhibitor Cyclosporin A increased numbers of differentiated DC. Global gene expression analysis of untreated DC and NFAT-inhibited DC revealed differential expression of transcripts that regulate cell cycle and apoptosis. In conclusion, these results provide evidence that calcineurin/NFAT signalling negatively regulates myeloid lineage development. The finding that inhibition of NFAT enhances myeloid development provides a novel insight into understanding how the treatment with drugs targeting calcineurin/NFAT signalling influence the homeostasis of the innate immune system.

  4. Tigecycline inhibits proliferation of Acanthamoeba castellanii.

    Science.gov (United States)

    Jha, Bijay Kumar; Seo, Incheol; Kong, Hyun-Hee; Suh, Seong-Il; Suh, Min-Ho; Baek, Won-Ki

    2015-03-01

    Acanthamoeba is an opportunistic protozoan parasite responsible for different diseases in humans, such as granulomatous amoebic encephalitis and amoebic keratitis. Tigecycline, a third-generation tetracycline antibiotic, has potential activity to treat most of the antibiotic resistant bacterial infections. The effects of tigecycline in eukaryotic cells as well as parasites are less well studied. In the present study, we tested the effects of tigecycline on trophozoites of Acanthamoeba castellanii. The inhibitory effect of tigecycline on Acanthamoeba was determined by resazurin reduction and trypan blue exclusion assays. We found that tigecycline significantly inhibited the growth of Acanthamoeba (46.4 % inhibition at the concentration of 100 μM) without affecting cell viability and induction of encystation, whereas other tetracycline groups of antibiotics such as tetracycline and doxycycline showed no inhibitory effects. Furthermore, tigecycline decreased cellular adenosine triphosphate (ATP) level by 26 % than the control and increased mitochondrial mass, suggesting mitochondrial dysfunction in tigecycline-treated cells. These findings suggest that mitochondrial dysfunction with decreased ATP production might play an important mechanism of tigecycline in suppression of Acanthamoeba proliferation.

  5. Effects of renin inhibition in systemic hypertension.

    Science.gov (United States)

    Anderson, P W; Do, Y S; Schambelan, M; Horton, R; Boger, R S; Luther, R R; Hsueh, W A

    1990-12-01

    The effect of the direct renin inhibitor enalkiren (Abbott Laboratories) was examined in 8 healthy patients with essential hypertension. With an unrestricted sodium diet, plasma renin concentration was inhibited within 10 minutes by intravenous enalkiren and remained essentially undetectable for greater than or equal to 6 hours (11.9 +/- 4 to 1.0 +/- 0.6 ng angiotensin I/ml/hour, p less than 0.05). Mean arterial blood pressure declined gradually (108 +/- 5 to 84 +/- 4 mm Hg, p = 0.02), as did plasma aldosterone concentration (14.4 +/- 3.8 to 4.4 +/- 0.8 ng/dl, p = 0.03), whereas plasma immunoreactive active renin concentration increased progressively (35 +/- 14 to 160 +/- 60 pg/ml, p greater than 0.05). Urinary excretion of the stable metabolite of prostacyclin (6-keto-prostaglandin F1 alpha) decreased slightly, but not significantly (42 +/- 10 to 33 +/- 11 ng/g creatinine, p = 0.13). The addition of a diuretic decreased baseline blood pressure and increased baseline plasma renin and aldosterone values. Blood pressure responses to enalkiren were slightly (though not significantly) greater than those observed before diuretic administration. We conclude that enalkiren is effective in decreasing blood pressure and in inhibiting the renin system, without significantly altering urinary prostacyclin excretion, in patients with essential hypertension. These results suggest that the renin system contributes to the maintenance of elevated blood pressure in some patients with essential hypertension.

  6. Kaempferol inhibits thrombosis and platelet activation.

    Science.gov (United States)

    Choi, Jun-Hui; Park, Se-Eun; Kim, Sung-Jun; Kim, Seung

    2015-08-01

    The objectives of the present study were to investigate whether kaempferol affects pro-coagulant proteinase activity, fibrin clot formation, blood clot and thrombin (or collagen/epinephrine)-stimulated platelet activation, thrombosis, and coagulation in ICR (Imprinting Control Region) mice and SD (Sprague-Dawley) rats. Kaempferol significantly inhibited the enzymatic activities of thrombin and FXa by 68 ± 1.6% and 52 ± 2.4%, respectively. Kaempferol also inhibited fibrin polymer formation in turbidity. Microscopic analysis was performed using a fluorescent conjugate. Kaempferol completely attenuated phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, p38, c-Jun N-terminal kinase (JNK) 1/2, and phosphoinositide 3-kinase (PI3K)/PKB (AKT) in thrombin-stimulated platelets and delayed aggregation time (clotting) by 34.6% in an assay of collagen/epinephrine-stimulated platelet activation. Moreover, kaempferol protected against thrombosis development in 3 animal models, including collagen/epinephrine- and thrombin-induced acute thromboembolism models and an FeCl3-induced carotid arterial thrombus model. The ex vivo anticoagulant effect of kaempferol was further confirmed in ICR mice. This study demonstrated that kaempferol may be clinically useful due to its ability to reduce or prevent thrombotic challenge.

  7. Inhibition of saccades elicits attentional suppression.

    Science.gov (United States)

    Dhawan, Saurabh; Deubel, Heiner; Jonikaitis, Donatas

    2013-05-17

    Visuospatial attention has been shown to have a central role in planning and generation of saccades but what role, if any, it plays in inhibition of saccades remains unclear. In this study, we used an oculomotor delayed match- or nonmatch-to-sample task in which a cued location has to be encoded and memorized for one of two very different goals-to plan a saccade to it or to avoid making a saccade to it. We measured the spatial allocation of attention during the delay and found that while marking a location as a future saccade target resulted in an attentional benefit at that location, marking it as forbidden to saccades led to an attentional cost. Additionally, saccade trajectories were found to deviate away more from the "don't look" location than from a saccade-irrelevant distractor confirming greater inhibition of an actively forbidden location in oculomotor programming. Our finding that attention is suppressed at locations forbidden to saccades confirms and complements the claim of a selective and obligatory coupling between saccades and attention-saccades at the memorized location could neither be planned nor suppressed independent of a corresponding effect on attentional performance.

  8. Targeting Sphingosine Kinase-1 To Inhibit Melanoma

    Science.gov (United States)

    Madhunapantula, SubbaRao V.; Hengst, Jeremy; Gowda, Raghavendra; Fox, Todd E.; Yun, Jong K; Robertson, Gavin P.

    2012-01-01

    SUMMARY Resistance to therapies develops rapidly for melanoma leading to more aggressive disease. Therefore, agents are needed that specifically inhibit proteins or pathways controlling the development of this disease, which can be combined, dependent on genes deregulated in a particular patient’s tumors. This study shows that elevated sphingosine-1-phosphate (S-1-P) levels resulting from increased activity of sphingosine kinase-1 (SPHK1) occur in advanced melanomas. Targeting SPHK1 using siRNA decreased anchorage dependent and independent growth as well as sensitized melanoma cells to apoptosis inducing agents. Pharmacological SPHK1 inhibitors SKI-I but not SKI-II decreased S-1-P content, elevated ceramide levels, caused a G2-M block and induced apoptotic cell death in melanomas. Targeting SPHK1 using siRNA or the pharmacological agent called SKI-I, decreased the levels of pAKT. Furthermore, SKI-I inhibited the expression of CYCLIN D1 protein and increased the activity of caspase-3/7, which in turn led to the degradation of PARP. In animals, SKI-I but not SKI-II retarded melanoma growth by 25-40%. Thus, targeting SPHK1 using siRNAs or SKI-I has therapeutic potential for melanoma treatment either alone or in combination with other targeted agents. PMID:22236408

  9. Diacylglycerol Kinase Inhibition and Vascular Function.

    Science.gov (United States)

    Choi, Hyehun; Allahdadi, Kyan J; Tostes, Rita C A; Webb, R Clinton

    2009-01-01

    Diacylglycerol kinases (DGKs), a family of lipid kinases, convert diacylglycerol (DG) to phosphatidic acid (PA). Acting as a second messenger, DG activates protein kinase C (PKC). PA, a signaling lipid, regulates diverse functions involved in physiological responses. Since DGK modulates two lipid second messengers, DG and PA, regulation of DGK could induce related cellular responses. Currently, there are 10 mammalian isoforms of DGK that are categorized into five groups based on their structural features. These diverse isoforms of DGK are considered to activate distinct cellular functions according to extracellular stimuli. Each DGK isoform is thought to play various roles inside the cell, depending on its subcellular localization (nuclear, ER, Golgi complex or cytoplasm). In vascular smooth muscle, vasoconstrictors such as angiotensin II, endothelin-1 and norepinephrine stimulate contraction by increasing inositol trisphosphate (IP(3)), calcium, DG and PKC activity. Inhibition of DGK could increase DG availability and decrease PA levels, as well as alter intracellular responses, including calcium-mediated and PKC-mediated vascular contraction. The purpose of this review is to demonstrate a role of DGK in vascular function. Selective inhibition of DGK isoforms may represent a novel therapeutic approach in vascular dysfunction.

  10. Chromosome tips damaged in anaphase inhibit cytokinesis.

    Directory of Open Access Journals (Sweden)

    Norman M Baker

    Full Text Available Genome maintenance is ensured by a variety of biochemical sensors and pathways that repair accumulated damage. During mitosis, the mechanisms that sense and resolve DNA damage remain elusive. Studies have demonstrated that damage accumulated on lagging chromosomes can activate the spindle assembly checkpoint. However, there is little known regarding damage to DNA after anaphase onset. In this study, we demonstrate that laser-induced damage to chromosome tips (presumptive telomeres in anaphase of Potorous tridactylis cells (PtK2 inhibits cytokinesis. In contrast, equivalent irradiation of non-telomeric chromosome regions or control irradiations in either the adjacent cytoplasm or adjacent to chromosome tips near the spindle midzone during anaphase caused no change in the eventual completion of cytokinesis. Damage to only one chromosome tip caused either complete absence of furrow formation, a prolonged delay in furrow formation, or furrow regression. When multiple chromosome tips were irradiated in the same cell, the cytokinesis defects increased, suggesting a potential dose-dependent mechanism. These results suggest a mechanism in which dysfunctional telomeres inhibit mitotic exit.

  11. Ribosome Inactivating Proteins from Plants Inhibiting Viruses

    Institute of Scientific and Technical Information of China (English)

    Inderdeep Kaur; R C Gupta; Munish Puri

    2011-01-01

    Many plants contain ribosome inactivating proteins (RIPs) with N-glycosidase activity,which depurinate large ribosomal RNA and arrest protein synthesis.RIPs so far tested inhibit replication of mRNA as well as DNA viruses and these proteins,isolated from plants,are found to be effective against a broad range of viruses such as human immunodeficiency virus (HIV),hepatitis B virus (HBV) and herpes simplex virus (HSV).Most of the research work related to RIPs has been focused on antiviral activity against HIV; however,the exact mechanism of antiviral activity is still not clear.The mechanism of antiviral activity was thought to follow inactivation of the host cell ribosome,leading to inhibition of viral protein translation and host cell death.Enzymatic activity of RIPs is not hmited to depurination of the large rRNA,in addition they can depurinate viral DNA as well as RNA.Recently,Phase Ⅰ/Ⅱ clinical trials have demonstrated the potential use of RIPs for treating patients with HIV disease.The aim of this review is to focus on various RIPs from plants associated with anti-HIV activity.

  12. Inhibition by acrolein of light-induced stomatal opening through inhibition of inward-rectifying potassium channels in Arabidopsis thaliana.

    Science.gov (United States)

    Islam, Md Moshiul; Ye, Wenxiu; Matsushima, Daiki; Khokon, Md Atiqur Rahman; Munemasa, Shintaro; Nakamura, Yoshimasa; Murata, Yoshiyuki

    2015-01-01

    Acrolein is a reactive α,β-unsaturated aldehyde derived from lipid peroxides, which are produced in plants under a variety of stress. We investigated effects of acrolein on light-induced stomatal opening using Arabidopsis thaliana. Acrolein inhibited light-induced stomatal opening in a dose-dependent manner. Acrolein at 100 μM inhibited plasma membrane inward-rectifying potassium (Kin) channels in guard cells. Acrolein at 100 μM inhibited Kin channel KAT1 expressed in a heterologous system using Xenopus leaves oocytes. These results suggest that acrolein inhibits light-induced stomatal opening through inhibition of Kin channels in guard cells.

  13. Distinct Neural Correlates for Two Types of Inhibition in Bilinguals: Response Inhibition versus Interference Suppression

    Science.gov (United States)

    Luk, Gigi; Anderson, John A. E.; Craik, Fergus I. M.; Grady, Cheryl; Bialystok, Ellen

    2010-01-01

    To examine the effects of bilingualism on cognitive control, we studied monolingual and bilingual young adults performing a flanker task with functional MRI. The trial types of primary interest for this report were incongruent and no-go trials, representing interference suppression and response inhibition, respectively. Response times were similar…

  14. Ketoconazole inhibits the cellular uptake of anandamide via inhibition of FAAH at pharmacologically relevant concentrations.

    Directory of Open Access Journals (Sweden)

    Emmelie Björklund

    Full Text Available BACKGROUND: The antifungal compound ketoconazole has, in addition to its ability to interfere with fungal ergosterol synthesis, effects upon other enzymes including human CYP3A4, CYP17, lipoxygenase and thromboxane synthetase. In the present study, we have investigated whether ketoconazole affects the cellular uptake and hydrolysis of the endogenous cannabinoid receptor ligand anandamide (AEA. METHODOLOGY/PRINCIPAL FINDINGS: The effects of ketoconazole upon endocannabinoid uptake were investigated using HepG2, CaCo2, PC-3 and C6 cell lines. Fatty acid amide hydrolase (FAAH activity was measured in HepG2 cell lysates and in intact C6 cells. Ketoconazole inhibited the uptake of AEA by HepG2 cells and CaCo2 cells with IC50 values of 17 and 18 µM, respectively. In contrast, it had modest effects upon AEA uptake in PC-3 cells, which have a low expression of FAAH. In cell-free HepG2 lysates, ketoconazole inhibited FAAH activity with an IC50 value (for the inhibitable component of 34 µM. CONCLUSIONS/SIGNIFICANCE: The present study indicates that ketoconazole can inhibit the cellular uptake of AEA at pharmacologically relevant concentrations, primarily due to its effects upon FAAH. Ketoconazole may be useful as a template for the design of dual-action FAAH/CYP17 inhibitors as a novel strategy for the treatment of prostate cancer.

  15. 3-Bromopyruvate inhibits human gastric cancer tumor growth in nude mice via the inhibition of glycolysis.

    Science.gov (United States)

    Xian, Shu-Lin; Cao, Wei; Zhang, Xiao-Dong; Lu, Yun-Fei

    2015-02-01

    Tumor cells primarily depend upon glycolysis in order to gain energy. Therefore, the inhibition of glycolysis may inhibit tumor growth. Our previous study demonstrated that 3-bromopyruvate (3-BrPA) inhibited gastric cancer cell proliferation in vitro. However, the ability of 3-BrPA to suppress tumor growth in vivo, and its underlying mechanism, have yet to be elucidated. The aim of the present study was to investigate the inhibitory effect of 3-BrPA in an animal model of gastric cancer. It was identified that 3-BrPA exhibited strong inhibitory effects upon xenograft tumor growth in nude mice. In addition, the antitumor function of 3-BrPA exhibited a dose-effect association, which was similar to that of the chemotherapeutic agent, 5-fluorouracil. Furthermore, 3-BrPA exhibited low toxicity in the blood, liver and kidneys of the nude mice. The present study hypothesized that the inhibitory effect of 3-BrPA is achieved through the inhibition of hexokinase activity, which leads to the downregulation of B-cell lymphoma 2 (Bcl-2) expression, the upregulation of Bcl-2-associated X protein expression and the subsequent activation of caspase-3. These data suggest that 3-BrPA may be a novel therapy for the treatment of gastric cancer.

  16. Effects of lorazepam on short latency afferent inhibition and short latency intracortical inhibition in humans.

    Science.gov (United States)

    Di Lazzaro, V; Oliviero, A; Saturno, E; Dileone, M; Pilato, F; Nardone, R; Ranieri, F; Musumeci, G; Fiorilla, T; Tonali, P

    2005-04-15

    Experimental studies have demonstrated that the GABAergic system modulates acetylcholine release and, through GABA(A) receptors, tonically inhibits cholinergic activity. Little is known about the effects of GABA on the cholinergic activity in the human central nervous system. In vivo evaluation of some cholinergic circuits of the human brain has recently been introduced using a transcranial magnetic stimulation (TMS) protocol based on coupling peripheral nerve stimulation with TMS of the motor cortex. Peripheral nerve inputs have an inhibitory effect on motor cortex excitability at short intervals (short latency afferent inhibition, SAI). We investigated whether GABA(A) activity enhancement by lorazepam modifies SAI. We also evaluated the effects produced by lorazepam on a different TMS protocol of cortical inhibition, the short interval intracortical inhibition (SICI), which is believed to be directly related to GABA(A) activity. In 10 healthy volunteers, the effects of lorazepam were compared with those produced by quetiapine, a psychotropic drug with sedative effects with no appreciable affinity at cholinergic muscarinic and benzodiazepine receptors, and with those of a placebo using a randomized double-blind study design. Administration of lorazepam produced a significant increase in SICI (F(3,9) = 3.19, P = 0.039). In contrast to SICI, SAI was significantly reduced by lorazepam (F(3,9) = 9.39, P = 0.0002). Our findings demonstrate that GABA(A) activity enhancement determines a suppression of SAI and an increase of SICI.

  17. Inhibition of the V-ATPase by Archazolid A - a new strategy to inhibit EMT.

    Science.gov (United States)

    Merk, Henriette; Messer, Philipp; Ardelt, Maximilian A; Lamb, Don C; Zahler, Stefan; Müller, Rolf; Vollmar, Angelika M; Pachmayr, Johanna

    2017-08-03

    Epithelial-mesenchymal transition (EMT) induces tumor-initiating cells (TICs) which account for tumor recurrence, metastasis and therapeutic resistance. Strategies to interfere with EMT are rare but urgently needed to improve cancer therapy. By using the myxobacterial natural compound Archazolid A as a tool, we elucidate the V-ATPase, a multimeric proton pump that regulates lysosomal acidification, as a crucial player in EMT and identify the inhibition of V-ATPase by Archazolid A as promising strategy to block EMT. Genetic knockdown and pharmacologic inhibition of the V-ATPase by Archazolid A interfere with the EMT process and inhibit TIC generation, as shown by a reduced formation of mammospheres and decreased cell motility. As underlying mechanism, V-ATPase-inhibition by Archazolid A disturbs the turnover of E-cadherin: Archazolid abrogates E-cadherin loss during EMT by interfering with its internalization and recycling. Our study elucidates V-ATPase as essential player in EMT by regulating E-cadherin turnover.  Archazolid A is suggested as a promising therapeutic agent to block EMT and the generation of TICs. Copyright ©2017, American Association for Cancer Research.

  18. Doxycycline inhibits leukemic cell migration via inhibition of matrix metalloproteinases and phosphorylation of focal adhesion kinase.

    Science.gov (United States)

    Wang, Chunhuai; Xiang, Ru; Zhang, Xiangzhong; Chen, Yunxian

    2015-09-01

    Doxycycline, a tetracycline-based antibiotic, has been reported to attenuate melanoma cell migration through inhibiting the focal adhesion kinase (FAK) signaling pathway. However, it remains to be elucidated whether doxycycline exerts this effect on leukemia cell migration. The present study aimed to examine the role of doxycycline in leukemia cell migration. The invasion capacities of the human leukemia cell lines KG1a (acute myelogenous leukemia) and K562 (chronic myelogenous leukemia) were evaluated using Matrigel® matrix‑coated Transwell® chamber assays; leukemic cell lines treated with doxycycline (1 µg/ml) or anti‑β1‑integrin antibodies were added to the upper chamber, while untreated cells were included as controls. Reverse transcription quantitative polymerase chain reaction was performed in order to further understand the influence of doxycycline treatment on the expression of FAK and gelatinases in the KG1a and K562 leukemic cell lines. In addition, FAK protein expression and phosphorylation were determined using western blot analysis in order to investigate the mechanism by which doxycycline inhibited leukemic cell migration. The results revealed that doxycycline treatment significantly attenuated the migration of KG1a and K562 cells, which was demonstrated to be associated with inhibition of the expression and phosphorylation of FAK. In addition, doxycycline treatment inhibited matrix metalloproteinase (MMP)‑2 and MMP‑9 expression. Furthermore, incubation with blocking anti‑β1‑integrin antibodies had an analogous inhibitory effect on leukemic cell migration to that of doxycycline. In conclusion, the results of the present study suggested that doxycycline attenuated leukemic cell migration through inhibiting the FAK signaling pathway. Therefore, doxycycline may have potential for use as a novel strategy for the treatment of leukemia.

  19. Equol inhibits growth, induces atresia, and inhibits steroidogenesis of mouse antral follicles in vitro.

    Science.gov (United States)

    Mahalingam, Sharada; Gao, Liying; Gonnering, Marni; Helferich, William; Flaws, Jodi A

    2016-03-15

    Equol is a non-steroidal estrogen metabolite produced by microbial conversion of daidzein, a major soy isoflavone, in the gut of some humans and many animal species. Isoflavones and their metabolites can affect endogenous estradiol production, action, and metabolism, potentially influencing ovarian follicle function. However, no studies have examined the effects of equol on intact ovarian antral follicles, which are responsible for sex steroid synthesis and further development into ovulatory follicles. Thus, the present study tested the hypothesis that equol inhibits antral follicle growth, increases follicle atresia, and inhibits steroidogenesis in the adult mouse ovary. To test this hypothesis, antral follicles isolated from adult CD-1 mice were cultured with vehicle control (dimethyl sulfoxide; DMSO) or equol (600 nM, 6 μM, 36 μM, and 100 μM) for 48 and 96 h. Every 24h, follicle diameters were measured to monitor growth. At 48 and 96 h, the culture medium was subjected to measurement of hormone levels, and the cultured follicles were subjected to gene expression analysis. Additionally, follicles were histologically evaluated for signs of atresia after 96 h of culture. The results indicate that equol (100 μM) inhibited follicle growth, altered the mRNA levels of bcl2-associated X protein and B cell leukemia/lymphoma 2, and induced follicle atresia. Further, equol decreased the levels of estradiol, testosterone, androstenedione, and progesterone, and it decreased mRNA levels of cholesterol side-chain cleavage, steroid 17-α-hydroxalase, and aromatase. Collectively, these data indicate that equol inhibits growth, increases atresia, and inhibits steroidogenesis of cultured mouse antral follicles.

  20. Neural and behavioral mechanisms of proactive and reactive inhibition.

    Science.gov (United States)

    Meyer, Heidi C; Bucci, David J

    2016-10-01

    Response inhibition is an important component of adaptive behavior. Substantial prior research has focused on reactive inhibition, which refers to the cessation of a motor response that is already in progress. More recently, a growing number of studies have begun to examine mechanisms underlying proactive inhibition, whereby preparatory processes result in a response being withheld before it is initiated. It has become apparent that proactive inhibition is an essential component of the overall ability to regulate behavior and has implications for the success of reactive inhibition. Moreover, successful inhibition relies on learning the meaning of specific environmental cues that signal when a behavioral response should be withheld. Proactive inhibitory control is mediated by stopping goals, which reflect the desired outcome of inhibition and include information about how and when inhibition should be implemented. However, little is known about the circuits and cellular processes that encode and represent features in the environment that indicate the necessity for proactive inhibition or how these representations are implemented in response inhibition. In this article, we will review the brain circuits and systems involved in implementing inhibitory control through both reactive and proactive mechanisms. We also comment on possible cellular mechanisms that may contribute to inhibitory control processes, noting that substantial further research is necessary in this regard. Furthermore, we will outline a number of ways in which the temporal dynamics underlying the generation of the proactive inhibitory signal may be particularly important for parsing out the neurobiological correlates that contribute to the learning processes underlying various aspects of inhibitory control.

  1. Ubiquitylation of terminal deoxynucleotidyltransferase inhibits its activity.

    Directory of Open Access Journals (Sweden)

    So Maezawa

    Full Text Available Terminal deoxynucleotidyltransferase (TdT, which template-independently synthesizes DNA during V(DJ recombination in lymphoid cells, is ubiquitylated by a BPOZ-2/Cul3 complex, as the ubiquitin ligase, and then degraded by the 26 S proteasome. We show here that TdT is ubiquitylated by the Cul3-based ubiquitylation system in vitro. Because TdT could also be ubiquitylated in the absence of Cul/BPOZ-2, we determined that it could also be directly ubiquitylated by the E2 proteins UbcH5a/b/c and UbcH6, E3-independently. Furthermore, the ubiquitylated TdT inhibited its nucleotidyltransferase activity.

  2. Inhibiting bacterial toxins by channel blockage.

    Science.gov (United States)

    Bezrukov, Sergey M; Nestorovich, Ekaterina M

    2016-03-01

    Emergent rational drug design techniques explore individual properties of target biomolecules, small and macromolecule drug candidates, and the physical forces governing their interactions. In this minireview, we focus on the single-molecule biophysical studies of channel-forming bacterial toxins that suggest new approaches for their inhibition. We discuss several examples of blockage of bacterial pore-forming and AB-type toxins by the tailor-made compounds. In the concluding remarks, the most effective rationally designed pore-blocking antitoxins are compared with the small-molecule inhibitors of ion-selective channels of neurophysiology. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Transcranial magnetic stimulation (TMS) inhibits cortical dendrites.

    Science.gov (United States)

    Murphy, Sean C; Palmer, Lucy M; Nyffeler, Thomas; Müri, René M; Larkum, Matthew E

    2016-03-18

    One of the leading approaches to non-invasively treat a variety of brain disorders is transcranial magnetic stimulation (TMS). However, despite its clinical prevalence, very little is known about the action of TMS at the cellular level let alone what effect it might have at the subcellular level (e.g. dendrites). Here, we examine the effect of single-pulse TMS on dendritic activity in layer 5 pyramidal neurons of the somatosensory cortex using an optical fiber imaging approach. We find that TMS causes GABAB-mediated inhibition of sensory-evoked dendritic Ca(2+) activity. We conclude that TMS directly activates fibers within the upper cortical layers that leads to the activation of dendrite-targeting inhibitory neurons which in turn suppress dendritic Ca(2+) activity. This result implies a specificity of TMS at the dendritic level that could in principle be exploited for investigating these structures non-invasively.

  4. IL-1β Inhibits Human Osteoblast Migration

    Science.gov (United States)

    Hengartner, Nina-Emily; Fiedler, Jörg; Ignatius, Anita; Brenner, Rolf E

    2013-01-01

    Bone has a high capacity for self-renewal and repair. Prolonged local secretion of interleukin 1β (IL-1β), however, is known to be associated with severe bone loss and delayed fracture healing. Since induction of bone resorption by IL-1β may not sufficiently explain these pathologic processes, we investigated, in vitro, if and how IL-1β affects migration of multipotent mesenchymal stromal cells (MSC) or osteoblasts. We found that homogenous exposure to IL-1β significantly diminished both nondirectional migration and site-directed migration toward the chemotactic factors platelet-derived growth factor (PDGF)-BB and insulinlike growth factor 1 (IGF-1) in osteoblasts. Exposure to a concentration gradient of IL-1β induced an even stronger inhibition of migration and completely abolished the migratory response of osteoblasts toward PDGF-BB, IGF-1, vascular endothelial growth factor A (VEGF-A) and the complement factor C5a. IL-1β induced extracellular signal-regulated kinases 1 and 2 (ERK1/2) and c-Jun N-terminal kinases (JNK) activation and inhibition of these signaling pathways suggested an involvement in the IL-1β effects on osteoblast migration. In contrast, basal migration of MSC and their migratory activity toward PDGF-BB was found to be unaffected by IL-1β. These results indicate that the presence of IL-1β leads to impaired recruitment of osteoblasts which might influence early stages of fracture healing and could have pathological relevance for bone remodeling in inflammatory bone disease. PMID:23508571

  5. Inhibition of Quorum Sensing in Staphylococcus spp.

    Science.gov (United States)

    Brackman, Gilles; Coenye, Tom

    2015-01-01

    The Gram-positive, facultative anaerobic coccus-shaped bacteria of the genus Staphylococcus are among the most important causative agents of acute and chronic bacterial infections in humans as well as in animals. Treatment of Staphylococcus infections has become increasingly challenging due to the growing problem of antibiotic resistance. For this reason innovative antimicrobials with novel targets and modes of action are needed. Since the discovery that QS is used by Staphylococcus spp. to coordinate the expression of several genes involved in virulence, biofilm formation and pathogenicity, QS inhibition has gained increasing attention as an alternative anti-pathogenic strategy. A major advantage compared with antibiotic therapy is that QSIs are used in concentrations that do not affect bacterial growth. For this reason, it is expected that these compounds would exert less pressure towards the development of resistance. However, some important points still need to be addressed. Although several inhibitors have proven to be active antipathogenic agents in vitro and in several in vivo models, it is still unknown whether these compounds will also be useful in humans. Furthermore, several fundamental mechanisms by which the different QS systems in Staphylococcus spp. exert their regulatory functions and how they are inhibited by QSIs are still poorly understood. In order to achieve real-life applications with QSIs, these challenges should be addressed and more research will be needed. In this article, we will discuss the different QS systems present in Staphylococcus spp., how they are used to control virulence and biofilm formation and how they can be blocked.

  6. Inhibition of morphine metabolism by ketamine.

    Science.gov (United States)

    Qi, Xiaoxin; Evans, Allan M; Wang, Jiping; Miners, John O; Upton, Richard N; Milne, Robert W

    2010-05-01

    Clinical observation of a synergistic effect of ketamine on morphine analgesia remains controversial. Although a pharmacodynamic basis for an interaction has been explored in animal and clinical studies, the possibility of a pharmacokinetic mechanism has not been investigated. Whereas both morphine and morphine-6-glucuronide are effective analgesics, morphine-3-glucuronide (M3G) lacks activity. Thus, changes in the metabolism and disposition of morphine may result in an altered response. First, we investigated the interaction between morphine and ketamine in the isolated perfused rat liver preparation. The clearance of morphine was decreased from 16.8 +/- 4.6 ml/min in the control period to 7.7 +/- 2.8 ml/min in the ketamine-treatment period, with the formation clearance of M3G decreasing from 8.0 +/- 4.1 ml/min to 2.1 +/- 1.1 ml/min. Fractional conversion of morphine to M3G was significantly decreased from 0.46 +/- 0.17 in the control period to 0.28 +/- 0.14 upon the addition of ketamine. The possible mechanism of the interaction was further investigated in vitro with rat liver microsomes as the enzyme source. The formation of M3G followed single-enzyme Michaelis-Menten kinetics, with a mean apparent K(m) of 2.18 +/- 0.45 mM and V(max) of 8.67 +/- 0.59 nmol/min/mg. Ketamine inhibited morphine 3-glucuronidation noncompetitively, with a mean K(i) value of 33.3 +/- 7.9 microM. The results demonstrate that ketamine inhibits the glucuronidation of morphine in a rat model.

  7. Enoxacin Directly Inhibits Osteoclastogenesis without Inducing Apoptosis*

    Science.gov (United States)

    Toro, Edgardo J.; Zuo, Jian; Ostrov, David A.; Catalfamo, Dana; Bradaschia-Correa, Vivian; Arana-Chavez, Victor; Caridad, Aliana R.; Neubert, John K.; Wronski, Thomas J.; Wallet, Shannon M.; Holliday, L. Shannon

    2012-01-01

    Enoxacin has been identified as a small molecule inhibitor of binding between the B2-subunit of vacuolar H+-ATPase (V-ATPase) and microfilaments. It inhibits bone resorption by calcitriol-stimulated mouse marrow cultures. We hypothesized that enoxacin acts directly and specifically on osteoclasts by disrupting the interaction between plasma membrane-directed V-ATPases, which contain the osteoclast-selective a3-subunit of V-ATPase, and microfilaments. Consistent with this hypothesis, enoxacin dose-dependently reduced the number of multinuclear cells expressing tartrate-resistant acid phosphatase (TRAP) activity produced by RANK-L-stimulated osteoclast precursors. Enoxacin (50 μm) did not induce apoptosis as measured by TUNEL and caspase-3 assays. V-ATPases containing the a3-subunit, but not the “housekeeping” a1-subunit, were isolated bound to actin. Treatment with enoxacin reduced the association of V-ATPase subunits with the detergent-insoluble cytoskeleton. Quantitative PCR revealed that enoxacin triggered significant reductions in several osteoclast-selective mRNAs, but levels of various osteoclast proteins were not reduced, as determined by quantitative immunoblots, even when their mRNA levels were reduced. Immunoblots demonstrated that proteolytic processing of TRAP5b and the cytoskeletal protein l-plastin was altered in cells treated with 50 μm enoxacin. Flow cytometry revealed that enoxacin treatment favored the expression of high levels of DC-STAMP on the surface of osteoclasts. Our data show that enoxacin directly inhibits osteoclast formation without affecting cell viability by a novel mechanism that involves changes in posttranslational processing and trafficking of several proteins with known roles in osteoclast function. We propose that these effects are downstream to blocking the binding interaction between a3-containing V-ATPases and microfilaments. PMID:22474295

  8. Enoxacin directly inhibits osteoclastogenesis without inducing apoptosis.

    Science.gov (United States)

    Toro, Edgardo J; Zuo, Jian; Ostrov, David A; Catalfamo, Dana; Bradaschia-Correa, Vivian; Arana-Chavez, Victor; Caridad, Aliana R; Neubert, John K; Wronski, Thomas J; Wallet, Shannon M; Holliday, L Shannon

    2012-05-18

    Enoxacin has been identified as a small molecule inhibitor of binding between the B2-subunit of vacuolar H+-ATPase (V-ATPase) and microfilaments. It inhibits bone resorption by calcitriol-stimulated mouse marrow cultures. We hypothesized that enoxacin acts directly and specifically on osteoclasts by disrupting the interaction between plasma membrane-directed V-ATPases, which contain the osteoclast-selective a3-subunit of V-ATPase, and microfilaments. Consistent with this hypothesis, enoxacin dose-dependently reduced the number of multinuclear cells expressing tartrate-resistant acid phosphatase (TRAP) activity produced by RANK-L-stimulated osteoclast precursors. Enoxacin (50 μM) did not induce apoptosis as measured by TUNEL and caspase-3 assays. V-ATPases containing the a3-subunit, but not the "housekeeping" a1-subunit, were isolated bound to actin. Treatment with enoxacin reduced the association of V-ATPase subunits with the detergent-insoluble cytoskeleton. Quantitative PCR revealed that enoxacin triggered significant reductions in several osteoclast-selective mRNAs, but levels of various osteoclast proteins were not reduced, as determined by quantitative immunoblots, even when their mRNA levels were reduced. Immunoblots demonstrated that proteolytic processing of TRAP5b and the cytoskeletal protein L-plastin was altered in cells treated with 50 μM enoxacin. Flow cytometry revealed that enoxacin treatment favored the expression of high levels of DC-STAMP on the surface of osteoclasts. Our data show that enoxacin directly inhibits osteoclast formation without affecting cell viability by a novel mechanism that involves changes in posttranslational processing and trafficking of several proteins with known roles in osteoclast function. We propose that these effects are downstream to blocking the binding interaction between a3-containing V-ATPases and microfilaments.

  9. Cartilage proteoglycans inhibit fibronectin-mediated adhesion

    Science.gov (United States)

    Rich, A. M.; Pearlstein, E.; Weissmann, G.; Hoffstein, S. T.

    1981-09-01

    Normal tissues and organs show, on histological examination, a pattern of cellular and acellular zones that is characteristic and unique for each organ or tissue. This pattern is maintained in health but is sometimes destroyed by disease. For example, in mobile joints, the articular surfaces consist of relatively acellular hyaline cartilage, and the joint space is enclosed by a capsule of loose connective tissue with a lining of fibroblasts and macrophages. In the normal joint these cells are confined to the synovial lining and the articular surface remains acellular. In in vitro culture, macrophages and their precursor monocytes are very adhesive, and fibroblasts can migrate and overgrow surfaces such as collagen or plastic used for tissue culture. The fibroblasts adhere to collagen by means of fibronectin, which they synthesize and secrete1. Because the collagen of cartilage is capable of binding serum fibronectin2 and fibronectin is present in cartilage during its development3, these cells should, in theory, slowly migrate from the synovial lining to the articular surface. It is their absence from the articular cartilage in normal circumstances, and then presence in such pathological states as rheumatoid arthritis, that is striking. We therefore set out to determine whether a component of cartilage could prevent fibroblast adherence in a defined adhesion assay. As normal cartilage is composed of 50% proteoglycans and 50% collagen by dry weight4, we tested the possibility that the proteoglycans in cartilage inhibit fibroblast adhesion to collagen. We present here evidence that fibroblast spreading and adhesion to collagenous substrates is inhibited by cartilage proteoglycans.

  10. Reconciling the role of serotonin in behavioral inhibition and aversion: acute tryptophan depletion abolishes punishment-induced inhibition in humans.

    Science.gov (United States)

    Crockett, Molly J; Clark, Luke; Robbins, Trevor W

    2009-09-23

    The neuromodulator serotonin has been implicated in a large number of affective and executive functions, but its precise contribution to motivation remains unclear. One influential hypothesis has implicated serotonin in aversive processing; another has proposed a more general role for serotonin in behavioral inhibition. Because behavioral inhibition is a prepotent reaction to aversive outcomes, it has been a challenge to reconcile these two accounts. Here, we show that serotonin is critical for punishment-induced inhibition but not overall motor response inhibition or reporting aversive outcomes. We used acute tryptophan depletion to temporarily lower brain serotonin in healthy human volunteers as they completed a novel task designed to obtain separate measures of motor response inhibition, punishment-induced inhibition, and sensitivity to aversive outcomes. After a placebo treatment, participants were slower to respond under punishment conditions compared with reward conditions. Tryptophan depletion abolished this punishment-induced inhibition without affecting overall motor response inhibition or the ability to adjust response bias in line with punishment contingencies. The magnitude of reduction in punishment-induced inhibition depended on the degree to which tryptophan depletion reduced plasma tryptophan levels. These findings extend and clarify previous research on the role of serotonin in aversive processing and behavioral inhibition and fit with current theorizing on the involvement of serotonin in predicting aversive outcomes.

  11. Firing regulation of fast-spiking interneurons by autaptic inhibition

    Science.gov (United States)

    Guo, Daqing; Chen, Mingming; Perc, Matjaž; Wu, Shengdun; Xia, Chuan; Zhang, Yangsong; Xu, Peng; Xia, Yang; Yao, Dezhong

    2016-05-01

    Fast-spiking (FS) interneurons in the brain are self-innervated by powerful inhibitory GABAergic autaptic connections. By computational modelling, we investigate how autaptic inhibition regulates the firing response of such interneurons. Our results indicate that autaptic inhibition both boosts the current threshold for action potential generation and modulates the input-output gain of FS interneurons. The autaptic transmission delay is identified as a key parameter that controls the firing patterns and determines multistability regions of FS interneurons. Furthermore, we observe that neuronal noise influences the firing regulation of FS interneurons by autaptic inhibition and extends their dynamic range for encoding inputs. Importantly, autaptic inhibition modulates noise-induced irregular firing of FS interneurons, such that coherent firing appears at an optimal autaptic inhibition level. Our results reveal the functional roles of autaptic inhibition in taming the firing dynamics of FS interneurons.

  12. Btk inhibition treats TLR7/IFN driven murine lupus.

    Science.gov (United States)

    Bender, Andrew T; Pereira, Albertina; Fu, Kai; Samy, Eileen; Wu, Yin; Liu-Bujalski, Lesley; Caldwell, Richard; Chen, Yi-Ying; Tian, Hui; Morandi, Federica; Head, Jared; Koehler, Ursula; Genest, Melinda; Okitsu, Shinji L; Xu, Daigen; Grenningloh, Roland

    2016-03-01

    Bruton's tyrosine kinase (Btk) is expressed in a variety of immune cells and previous work has demonstrated that blocking Btk is a promising strategy for treating autoimmune diseases. Herein, we utilized a tool Btk inhibitor, M7583, to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon. In BXSB-Yaa lupus mice, Btk inhibition reduced autoantibodies, nephritis, and mortality. In the pristane-induced DBA/1 lupus model, Btk inhibition suppressed arthritis, but autoantibodies and the IFN gene signature were not significantly affected; suggesting efficacy was mediated through inhibition of Fc receptors. In vitro studies using primary human macrophages revealed that Btk inhibition can block activation by immune complexes and TLR7 which contributes to tissue damage in SLE. Overall, our results provide translational insight into how Btk inhibition may provide benefit to a variety of SLE patients by affecting both BCR and FcR signaling.

  13. Latent inhibition and autonomic responses: a psychophysiological approach.

    Science.gov (United States)

    Vaitl, D; Lipp, O V

    1997-10-01

    Latent inhibition, retarded learning after preexposure to the to-be-conditioned stimulus, has been implied as a tool for the investigation of attentional deficits in schizophrenia and related disorders. The present paper reviews research that used Pavlovian conditioning as indexed by autonomic responses (electrodermal, vasomotor, cardiac) to investigate latent inhibition in adult humans. Latent inhibition has been demonstrated repeatedly in healthy subjects in absence of a masking task that is required in other latent inhibition paradigms. Moreover, latent inhibition of Pavlovian conditioning is stimulus-specific and increases with an increased number of preexposure trials which mirrors results from research in animals. A reduction of latent inhibition has been shown in healthy subjects who score high on questionnaire measures of psychosis proneness and in unmedicated schizophrenic patients. The latter result was obtained in a within-subject paradigm that holds promise for research with patient samples.

  14. Molecular mechanisms of DNA repair inhibition by caffeine

    Energy Technology Data Exchange (ETDEWEB)

    Selby, C.P.; Sancar, A. (Univ. of North Carolina School of Medicine, Chapel Hill (USA))

    1990-05-01

    Caffeine potentiates the mutagenic and lethal effects of genotoxic agents. It is thought that this is due, at least in some organisms, to inhibition of DNA repair. However, direct evidence for inhibition of repair enzymes has been lacking. Using purified Escherichia coli DNA photolyase and (A)BC excinuclease, we show that the drug inhibits photoreactivation and nucleotide excision repair by two different mechanisms. Caffeine inhibits photoreactivation by interfering with the specific binding of photolyase to damaged DNA, and it inhibits nucleotide excision repair by promoting nonspecific binding of the damage-recognition subunit, UvrA, of (A)BC excinuclease. A number of other intercalators, including acriflavin and ethidium bromide, appear to inhibit the excinuclease by a similar mechanism--that is, by trapping the UvrA subunit in nonproductive complexes on undamaged DNA.

  15. [Inhibition of aromatics on ammonia-oxidizing activity of sediment].

    Science.gov (United States)

    Dong, Chun-hong; Hu, Hong-ying; Wei, Dong-bin; Huang, Xia; Qian, Yi

    2004-03-01

    The inhibition of 24 aromatics on ammonia-oxidizing activity of nitrifying bacteria in sediment was measured. The effects of the kind, number and position of substituted groups on ammonia-oxidizing activity of nitrifying bacteria were discussed. The inhibition of mono-substituted benzenes on ammonia-oxidizing activity of nitrifying bacteria were in order of -OH > -NO2 > -NH2 > -Cl > -CH3 > -H. The position of substituted groups of di-substituted benzenes also affected the inhibition, and the inhibitions of dimethylbenzenes(xylene) were in order of meta-> ortho-> para-. The increase in number of substituted group on benzene-ring enhanced the inhibition of aromatics studied in this study on nitrifying bacteria. There was a linear relationship between inhibition (IC50, mumol.L-1) of aromatics on ammonia-oxidizing activity and total electronegativity (sigma E) of aromatics: lgIC50 = 14.72 - 0.91 sigma E.

  16. Study on the Inhibition of Fermented Soybean to Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    LU Yan; WANG Wei; SHAN Yi; E Zhiqiang; WANG Liqun

    2009-01-01

    In the experiment, the inhibition of isoflavones extracted from soybean and tempe to SP2/0 and Hela cells was studied,and the inhibition rate of each unit for cancer cells was also studied. The results showed that the inhibition rate of tempe isoflavones to SP2/0 was 96.9% and to Hela cells was 69.5% when the concentration was 20 μg·mL-1. In the same condition, the inhibition rate of soybean isoflavones was 83.16% and 60.5%. With the decline of concentration, the inhibition rate decreased. The inhibition of isoflavones to SP2/0 did not exist when the concentration was 5-1.25 μg·mL-1.

  17. Inhibition of Action, Thought, and Emotion: A Selective Neurobiological Review

    OpenAIRE

    Dillon, Daniel; Pizzagalli, Diego

    2007-01-01

    The neural bases of inhibitory function are reviewed, covering data from paradigms assessing inhibition of motor responses (antisaccade, go/nogo, stop-signal), cognitive sets (e.g., Wisconsin Card Sort Test), and emotion (fear extinction). The frontal cortex supports performance on these paradigms, but the specific neural circuitry varies: response inhibition depends upon fronto-basal ganglia networks, inhibition of cognitive sets is supported by orbitofrontal cortex, and retention of fear ex...

  18. Inhibition of poliovirus RNA synthesis by brefeldin A.

    OpenAIRE

    Maynell, L A; Kirkegaard, K; Klymkowsky, M W

    1992-01-01

    Brefeldin A (BFA), a fungal metabolite that blocks transport of newly synthesized proteins from the endoplasmic reticulum, was found to inhibit poliovirus replication 10(5)- to 10(6)-fold. BFA does not inhibit entry of poliovirus into the cell or translation of viral RNA. Poliovirus RNA synthesis, however, is completely inhibited by BFA. A specific class of membranous vesicles, with which the poliovirus replication complex is physically associated, is known to proliferate in poliovirus-infect...

  19. Acute inhibition of corticosteroidogenesis by inhibitors of calmodulin action.

    Science.gov (United States)

    Carsia, R V; Moyle, W R; Wolff, D J; Malamed, S

    1982-11-01

    To identify the possible role of calmodulin in ACTH function, we tested the ability of chlorpromazine (CP) and other calmodulin antagonists to inhibit steroidogenesis of isolated adrenocortical cells of the rat. CP reversibly inhibited maximal ACTH-induced corticosterone (B) production. The presence of the drug did not alter the ED50 of ACTH stimulation (3.2 X 10(3) pg/ml), suggesting that it inhibited ACTH-induced steroidogenesis in a noncompetitive manner. The CP concentration required for half-maximal inhibition was 8.2 microM, a value close to the dissociation constant of the CP-calmodulin complex (5.3 microM). Concentrations greater than 40 microM resulted in complete inhibition. Similar concentrations of CP inhibited ACTH-induced cAMP accumulation in a dose-dependent manner, indicating an effect of the drug on early events in ACTH action. In addition, CP also apparently acted at a site distal to the point of cAMP formation, as shown by the finding that it inhibited cAMP-induced B production. CP inhibition of ACTH-induced B production was independent of the Ca2+ concentration, suggesting that the drug did not compete with Ca2+ directly. Concentrations of CP greater than 20 microM inhibited protein synthesis as measured by leucine incorporation into cellular proteins. Thus, although the inhibitory effect of high concentrations of CP on steroidogenesis might be explained by an effect on protein synthesis, the inhibition seen at 10 microM appeared to be independent of protein synthesis. Other antagonists of calmodulin action inhibited maximal ACTH-induced B production with the following relative potencies: trifluoperazine greater than CP greater than haloperidol greater than chlordiazepoxide. This order is similar to that reported for inhibition of calmodulin-activated phosphodiesterase and for binding to calmodulin. These findings suggest that calmodulin may modulate the effect of ACTH on steroidogenesis at multiple sites.

  20. High molecular weight polysaccharide that binds and inhibits virus

    Science.gov (United States)

    Konowalchuk, Thomas W

    2014-01-14

    This invention provides a high molecular weight polysaccharide capable of binding to and inhibiting virus and related pharmaceutical formulations and methods on inhibiting viral infectivity and/or pathogenicity, as well as immunogenic compositions. The invention further methods of inhibiting the growth of cancer cells and of ameliorating a symptom of aging. Additionally, the invention provides methods of detecting and/or quantifying and/or isolating viruses.

  1. Inhibition of human aromatase complex (CYP19) by antiepileptic drugs

    DEFF Research Database (Denmark)

    Jacobsen, Naja Wessel; Halling-Sørensen, Bent; Birkved, Franziska Maria A Kramer

    2008-01-01

    transfected insect cells using dibenzylfluorescein as substrate. The drugs inhibiting CYP19 were: lamotrigine, oxcarbazepine, tiagabine, phenobarbital, phenytoin, ethosuximide, and valproate. The inhibitory effects (50% reduction in activity compared to enzymes without inhibitor present) were in the range...... with valproate and phenobarbital. When adding carbamazepine to a range of valproate concentrations no additional inhibition was seen. The data for some of the AEDs show that side effects on steroid synthesis in humans due to inhibition of aromatase should be considered....

  2. Are individual differences in arithmetic fact retrieval related to inhibition?

    OpenAIRE

    Bellon, Elien

    2016-01-01

    Although it has been proposed that inhibition is related to individual differences in mathematical achievement, it is not clear how it is related to specific aspects of mathematical skills, such as arithmetic fact retrieval. The present study therefore investigated the association between inhibition and arithmetic fact retrieval and further examined the unique role of inhibition in individual differences in arithmetic fact retrieval, in addition to numerical magnitude processin...

  3. High molecular weight polysaccharide that binds and inhibits virus

    Energy Technology Data Exchange (ETDEWEB)

    Konowalchuk, Thomas W.; Konowalchuk, Jack

    2017-07-18

    This invention provides a high molecular weight polysaccharide capable of binding to and inhibiting virus and related pharmaceutical formulations and methods of inhibiting viral infectivity and/or pathogenicity, as well as immunogenic compositions. The invention further includes methods of inhibiting the growth of cancer cells and of ameliorating a symptom of aging. Additionally, the invention provides methods of detecting and/or quantifying and/or isolating viruses.

  4. Functional networks underlying latent inhibition learning in the mouse brain

    OpenAIRE

    Puga, Frank; Barrett, Douglas W.; Bastida, Christel C.; Gonzalez-Lima, F.

    2007-01-01

    The present study reports the first comprehensive map of brain networks underlying latent inhibition learning and the first application of structural equation modeling to cytochrome oxidase data. In latent inhibition, repeated exposure to a stimulus results in a latent form of learning that inhibits subsequent associations with that stimulus. As neuronal energy demand to form learned associations changes, so does the induction of the respiratory enzyme cytochrome oxidase. Therefore, cytochrom...

  5. Protection from Latent Inhibition Provided by a Conditioned Inhibitor

    OpenAIRE

    McConnell, Bridget L.; Wheeler, Daniel S.; Urcelay, Gonzalo P; Miller, Ralph R.

    2009-01-01

    Two conditioned suppression experiments with rats investigated the influence on latent inhibition of compounding a Pavlovian conditioned inhibitor with the target cue during preexposure treatment. Results were compared to subjects that received conventional latent inhibition training, no preexposure, or preexposure to the target cue in compound with a neutral stimulus. In Experiment 1, greater attenuation of the latent inhibition effect was observed in subjects that received target preexposur...

  6. A small yeast RNA inhibits HCV IRES mediated translation and inhibits replication of poliovirus in vivo

    Institute of Scientific and Technical Information of China (English)

    Xue-Song Liang; Jian-Qi Lian; Yong-Xing Zhou; Qing-He Nie; Chun-Qiu Hao

    2003-01-01

    AIM: To investigate the anti-virus infection activity of internal ribosome entry site (IRES) specific inhibitor RNA (IRNA).METHODS: IRNA eukaryotic vector pcRz-IRNA or mIRNA eukaryotic vector pcRz-mIRNA was tansfected into human hepatocarcinoma cells (HHCC), then selected with neomycin G418 for 4 to 8 weeks, and then infected with polio virus vaccinas line. The cytopethogenesis effect was investigated and the cell extract was collected. At last the polio virus titer of different cells was determined by plaque assay.RESULTS: Constitutive expression of IRNA was not detrimental to cell growth. HCV IRES-mediated capindependent translation was markedly inhibited in cells constitutively expressing IRNA compared to control hepatoma cells. However, cap-dependent translation was not significantly affected in these cell line. Additionally, HHCC cells constitutively expressing IRNA became refractory to infection of polio virus.CONCLUSION: IRES specific IRNA can inhibit HCV IRES mediated translation and poliovirus replication.

  7. Schedule of Punishment and Inhibition of Aggression in Children

    Science.gov (United States)

    Parke, Ross D.; Deur, Jan L.

    1972-01-01

    Data showed that consistent punishment resulted in faster inhibition than inconsistent punishment; subjects who were punished showed less persistence than subjects placed on an extinction schedule. (Authors)

  8. Selective and nonselective inhibition of competitors in picture naming.

    Science.gov (United States)

    Shao, Zeshu; Meyer, Antje S; Roelofs, Ardi

    2013-11-01

    The present study examined the relation between nonselective inhibition and selective inhibition in picture naming performance. Nonselective inhibition refers to the ability to suppress any unwanted response, whereas selective inhibition refers to the ability to suppress specific competing responses. The degree of competition in picture naming was manipulated by presenting targets along with distractor words that could be semantically related (e.g., a picture of a dog combined with the word cat) or unrelated (tree) to the picture name. The mean naming response time (RT) was longer in the related than in the unrelated condition, reflecting semantic interference. Delta plot analyses showed that participants with small mean semantic interference effects employed selective inhibition more effectively than did participants with larger semantic interference effects. The participants were also tested on the stop-signal task, which taps nonselective inhibition. Their performance on this task was correlated with their mean naming RT but, importantly, not with the selective inhibition indexed by the delta plot analyses and the magnitude of the semantic interference effect. These results indicate that nonselective inhibition ability and selective inhibition of competitors in picture naming are separable to some extent.

  9. Inhibition behavior for copper corrosion by photoelectrochemical methods

    Institute of Scientific and Technical Information of China (English)

    徐群杰; 周国定

    2003-01-01

    The application of photoelectrochemical methods in the inhibition effects for copper corrosion was described. The methods include cyclic voltammetry photocurrent measurements, intensity modulated photocurrent spectrum(IMPS) and laser-scanning photoelectrochemical microscopic method(PEM) which have been applied to the evaluation of inhibitors and inhibition behavior. The inhibition effect of BTA for copper corrosion is better than that of 4CBTA, 5CBTA, CBT-1, PTD, BT-250, CBTME and CBTBE at the same concentration. The inhibition mechanism of the derivatives of BTA with-COOH group(4CBTA, 5CBTA, CBT-1) is different from those with estergroup(CBTME, CBTBE).

  10. Osmotic stress inhibits thymidine incorporation into soybean protoplast DNA.

    Science.gov (United States)

    Cress, D E

    1982-10-01

    DNA synthesis in protoplasts isolated from soybean cell suspension cultures has been investigated by [(3)H] thymidine uptake and incorporation kinetics. Initial rates of incorporation in exponential and 5-fluorodeoxyuridine synchronized protoplasts are inhibited by increased osmolarities of the medium. The inhibition was not readily reversible during 3 h culture in low osmotic medium. Velocity sedimentation analyses of replicating DNA from such protoplasts shows a complex pattern of inhibition. The inhibition probably effects replicon initiation as well as strand elongation and ligation of replication intermediates.

  11. Glyphosate and AMPA inhibit cancer cell growth through inhibiting intracellular glycine synthesis

    Directory of Open Access Journals (Sweden)

    Li Q

    2013-07-01

    Full Text Available Qingli Li,1,2 Mark J Lambrechts,1 Qiuyang Zhang,1 Sen Liu,1 Dongxia Ge,1 Rutie Yin,2 Mingrong Xi,2 Zongbing You1 1Departments of Structural and Cellular Biology and Orthopaedic Surgery, Tulane Cancer Center and Louisiana Cancer Research Consortium, Tulane Center for Stem Cell Research and Regenerative Medicine, and Tulane Center for Aging, Tulane University Health Sciences Center, New Orleans, LA, USA; 2Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China Abstract: Glycine is a nonessential amino acid that is reversibly converted from serine intracellularly by serine hydroxymethyltransferase. Glyphosate and its degradation product, aminomethylphosphonic acid (AMPA, are analogs to glycine, thus they may inhibit serine hydroxymethyltransferase to decrease intracellular glycine synthesis. In this study, we found that glyphosate and AMPA inhibited cell growth in eight human cancer cell lines but not in two immortalized human normal prostatic epithelial cell lines. AMPA arrested C4-2B and PC-3 cancer cells in the G1/G0 phase and inhibited entry into the S phase of the cell cycle. AMPA also promoted apoptosis in C4-2B and PC-3 cancer cell lines. AMPA upregulated p53 and p21 protein levels as well as procaspase 9 protein levels in C4-2B cells, whereas it downregulated cyclin D3 protein levels. AMPA also activated caspase 3 and induced cleavage of poly (adenosine diphosphate [ADP]-ribose polymerase. This study provides the first evidence that glyphosate and AMPA can inhibit proliferation and promote apoptosis of cancer cells but not normal cells, suggesting that they have potentials to be developed into a new anticancer therapy. Keywords: serine hydroxymethyltransferase, prostate cancer, apoptosis

  12. Nifuroxazide inhibits survival of multiple myeloma cells by directly inhibiting STAT3

    OpenAIRE

    2008-01-01

    Constitutive activation of the transcription factor STAT3 contributes to the pathogenesis of many cancers, including multiple myeloma (MM). Since STAT3 is dispensable in most normal tissue, targeted inhibition of STAT3 is an attractive therapy for patients with these cancers. To identify STAT3 inhibitors, we developed a transcriptionally based assay and screened a library of compounds known to be safe in humans. We found the drug nifuroxazide to be an effective inhibitor of STAT3 function. Ni...

  13. Pirfenidone inhibits post-traumatic proliferative vitreoretinopathy.

    Science.gov (United States)

    Khanum, B N M K; Guha, R; Sur, V P; Nandi, S; Basak, S K; Konar, A; Hazra, S

    2017-03-17

    PurposeThe purpose of the study was to evaluate the efficacy and safety of intravitreal pirfenidone for inhibition of proliferative vitreoretinopathy (PVR) in a model of penetrating ocular injury.Patients and methodsPenetrating trauma was induced on the retina of rabbit and treated either with 0.1 ml of phosphate-buffered saline (PBS) or 0.1 ml of 0.5% pirfenidone, and development of PVR was evaluated clinically and graded after 1 month. Histopathology and immunohistochemistry with transforming growth factor beta (TGFβ), alpha smooth muscle actin (αSMA), and collagen-1 were performed to assess the fibrotic changes. Expression of cytokines in the vitro-retinal tissues at different time points following pirfenidone and PBS injection was examined by RT-PCR. Availability of pirfenidone in the vitreous of rabbit at various time points was determined by high-performance liquid chromatography following injection of 0.1 ml of 0.5% pirfenidone. In normal rabbit eye, 0.1 ml of 0.5% pirfenidone was injected to evaluate any toxic effect.ResultsClinical assessment and grading revealed prevention of PVR formation in pirfenidone-treated animals, gross histology, and histopathology confirmed the observation. Immunohistochemistry showed prevention in the expression of collagen-I, αSMA, and TGFβ in the pirfenidone-treated eyes compared to the PBS-treated eyes. Pirfenidone inhibited increased gene expression of cytokines observed in control eyes. Pirfenidone could be detected up to 48 h in the vitreous of rabbit eye following single intravitreal injection. Pirfenidone did not show any adverse effect following intravitreal injection; eyes were devoid of any abnormal clinical sign, intraocular pressure, and electroretinography did not show any significant change and histology of retina remained unchanged.ConclusionThis animal study shows that pirfenidone might be a potential therapy for PVR. Further clinical study will be useful to evaluate the clinical application of

  14. Inhibition of autophagy induced by proteasome inhibition increases cell death in human SHG-44 glioma cells

    Institute of Scientific and Technical Information of China (English)

    Peng-fei GE; Ji-zhou ZHANG; Xiao-fei WANG; Fan-kai MENG; Wen-chen LI; Yong-xin LUAN; Feng LING; Yi-nan LUO

    2009-01-01

    Aim:The ubiquitin-proteasome system (UPS) and lysosome-dependent macroautophagy (autophagy) are two major intracellular pathways for protein degradation.Recent studies suggest that proteasome inhibitors may reduce tumor growth and activate autophagy.Due to the dual roles of autophagy in tumor cell survival and death,the effect of autophagy on the destiny of glioma cells remains unclear.In this study,we sought to investigate whether inhibition of the proteasome can induce autophagy and the effects of autophagy on the fate of human SHG-44 glioma cells.Methods:The proteasome inhibitor MG-132 was used to induce autophagy in SHG-44 glioma cells,and the effect of autophagy on the survival of SHG-44 glioma cells was investigated using an autophagy inhibitor 3-MA.Cell viability was measured by MTT assay.Apoptosis and cell cycle were detected by flow cytometry.The expression of autophagy related proteins was determined by Western blot.Results:MG-132 inhibited cell proliferation,induced cell death and cell cycle arrest at G~JM phase,and activated autophagy in SHG-44 glioma cells.The expression of autophagy-related Beclin-1 and LC3-1 was significantly up-regulated and part of LC3-1 was converted into LC3-11.However,when SHG-44 glioma cells were co-treated with MG-132 and 3-MA,the cells became less viable,but cell death and cell numbers at G2/M phase increased.Moreover,the accumulation of acidic vesicular organelles was decreased,the expression of Beclin-1 and LC3 was significantly down-regulated and the conversion of LC3-11 from LC3-1 was also inhibited.Conclusion:Inhibition of the proteasome can induce autophagy in human SHG-44 glioma cells,and inhibition of autophagy increases cell death.This discovery may shed new light on the effect of autophagy on modulating the fate of SHG-44 glioma cells.

  15. Pharmacologic inhibition of lactate production prevents myofibroblast differentiation.

    Science.gov (United States)

    Kottmann, Robert Matthew; Trawick, Emma; Judge, Jennifer L; Wahl, Lindsay A; Epa, Amali P; Owens, Kristina M; Thatcher, Thomas H; Phipps, Richard P; Sime, Patricia J

    2015-12-01

    Myofibroblasts are one of the primary cell types responsible for the accumulation of extracellular matrix in fibrosing diseases, and targeting myofibroblast differentiation is an important therapeutic strategy for the treatment of pulmonary fibrosis. Transforming growth factor-β (TGF-β) has been shown to be an important inducer of myofibroblast differentiation. We previously demonstrated that lactate dehydrogenase and its metabolic product lactic acid are important mediators of myofibroblast differentiation, via acid-induced activation of latent TGF-β. Here we explore whether pharmacologic inhibition of LDH activity can prevent TGF-β-induced myofibroblast differentiation. Primary human lung fibroblasts from healthy patients and those with pulmonary fibrosis were treated with TGF-β and or gossypol, an LDH inhibitor. Protein and RNA were analyzed for markers of myofibroblast differentiation and extracellular matrix generation. Gossypol inhibited TGF-β-induced expression of the myofibroblast marker α-smooth muscle actin (α-SMA) in a dose-dependent manner in both healthy and fibrotic human lung fibroblasts. Gossypol also inhibited expression of collagen 1, collagen 3, and fibronectin. Gossypol inhibited LDH activity, the generation of extracellular lactic acid, and the rate of extracellular acidification in a dose-dependent manner. Furthermore, gossypol inhibited TGF-β bioactivity in a dose-dependent manner. Concurrent treatment with an LDH siRNA increased the ability of gossypol to inhibit TGF-β-induced myofibroblast differentiation. Gossypol inhibits TGF-β-induced myofibroblast differentiation through inhibition of LDH, inhibition of extracellular accumulation of lactic acid, and inhibition of TGF-β bioactivity. These data support the hypothesis that pharmacologic inhibition of LDH may play an important role in the treatment of pulmonary fibrosis.

  16. The grapevine polygalacturonase-inhibiting protein (VvPGIP1) reduces Botrytis cinerea susceptibility in transgenic tobacco and differentially inhibits fungal polygalacturonases

    NARCIS (Netherlands)

    Joubert, D.A.; Slaughter, A.R.; Kemp, G.; Becker, J.V.W.; Krooshof, G.H.; Bergmann, C.; Benen, J.A.E.; Pretorius, I.S.; Vivier, M.A.

    2006-01-01

    Polygalacturonase-inhibiting proteins (PGIPs) selectively inhibit polygalacturonases (PGs) secreted by invading plant pathogenic fungi. PGIPs display differential inhibition towards PGs from different fungi, also towards different isoforms of PGs originating from a specific pathogen. Recently, a PGI

  17. Inhibition of foodborne pathogens by pomegranate juice.

    Science.gov (United States)

    Haghayeghi, Koorosh; Shetty, Kalidas; Labbé, Ronald

    2013-05-01

    Pomegranates have health-promoting benefits because of their polyphenol constituents. Previous studies have demonstrated the antimicrobial activity of aqueous and organic extracts of pomegranate components and by-products. We sought to determine the antimicrobial activity against 40 foodborne pathogens representing eight bacterial species using juice itself. In addition, we sought to determine the synergistic antimicrobial activity between pomegranate juice and other plant products displaying antimicrobial activity. The antimicrobial activity of pomegranate juice was dependent on the test organism, which varied to highly susceptible (four Gram-positive species) to unaffected (Salmonella and Escherichia coli O157:H7). Two Gram-negative species, which were inhibited were Helicobacter pylori and Vibrio parahemolyticus. No synergistic antimicrobial activity was seen between pomegranate and either barberry, oregano, or cranberry. The antimicrobial activity of pomegranate juice is dependent on the test organism and extraction method. The sensitivity of H. pylori suggests that pomegranate juice may be an alternative or supplemental treatment for gastric ulcers caused by this organism.

  18. Say it with me: stuttering inhibited.

    Science.gov (United States)

    Saltuklaroglu, Tim; Dayalu, Vikram N; Kalinowski, Joseph; Stuart, Andrew; Rastatter, Michael P

    2004-04-01

    This study examined fluency enhancement in people who stutter via the concomitant presentation of silently mouthed visual speech. Ten adults who stutter recited memorized text while watching another speaker silently mouth linguistically equivalent and linguistically different material. Relative to a control condition, in which no concomitant stimulus was provided, stuttering was reduced by 71% in the linguistically equivalent condition versus only 35% in the linguistically different condition. Despite being an 'incomplete' second speech signal, visual speech possesses the capacity to immediately and substantially enhance fluency when it is linguistically equivalent to the intended utterance. It is suggested that fluency enhancement via concomitantly presented external speech is achieved through the extraction of relevant speech gestures from the external speech signal that compliment the intended production, thereby compensating for possible internal inconsistencies in the matching of speech codes in people who stutter. As visual speech perception relies on fewer redundant cues to demarcate the intended gestures, when used as an external stuttering inhibitor, higher degrees of linguistic equivalence seem to be necessary for optimal stuttering inhibition.

  19. Aspirin, cyclooxygenase inhibition and colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Carlos; Sostres; Carla; Jerusalen; Gargallo; Angel; Lanas

    2014-01-01

    Colorectal cancer(CRC)is the third most common type of cancer worldwide.Screening measures are far from adequate and not widely available in resourcepoor settings.Primary prevention strategies therefore remain necessary to reduce the risk of developing CRC.Increasing evidence from epidemiological studies,randomized clinical trials and basic science supports the effectiveness of aspirin,as well as other non-steroidal anti-inflammatory drugs,for chemoprevention of several types of cancer,including CRC.This includes the prevention of adenoma recurrence and reduction of CRC incidence and mortality.The detectable benefit of daily low-dose aspirin(at least 75 mg),as used to prevent cardiovascular disease events,strongly suggests that its antiplatelet action is central to explaining its antitumor efficacy.Daily low-dose aspirin achieves complete and persistent inhibition of cyclooxygenase(COX)-1 in platelets(in pre-systemic circulation)while causing alimited and rapidly reversible inhibitory effect on COX-2and/or COX-1 expressed in nucleated cells.Aspirin has a short half-life in human circulation(about 20 minutes);nucleated cells have the ability to resynthesize acetylated COX isozymes within a few hours,while platelets do not.COX-independent mechanisms of aspirin have been suggested to explain its chemopreventive effects but this concept remains to be demonstrated in vivo at clinical doses.

  20. Stathmin potentiates vinflunine and inhibits Paclitaxel activity.

    Science.gov (United States)

    Malesinski, Soazig; Tsvetkov, Philipp O; Kruczynski, Anna; Peyrot, Vincent; Devred, François

    2015-01-01

    Cell biology and crystallographic studies have suggested a functional link between stathmin and microtubule targeting agents (MTAs). In a previous study we showed that stathmin increases vinblastine (VLB) binding to tubulin, and that conversely VLB increases stathmin binding to tubulin. This constituted the first biochemical evidence of the direct relationship between stathmin and an antimitotic drug, and revealed a new mechanism of action for VLB. The question remained if the observed interaction was specific for this drug or represented a general phenomenon for all MTAs. In the present study we investigated the binding of recombinant stathmin to purified tubulin in the presence of paclitaxel or another Vinca alkaloid, vinflunine, using Isothermal Titration Calorimetry (ITC). These experiments revealed that stathmin binding to tubulin is increased in the presence of vinflunine, whereas no signal is observed in the presence of paclitaxel. Further investigation using turbidity and co-sedimentation showed that stathmin inhibited paclitaxel microtubule-stabilizing activity. Taken together with the previous study using vinblastine, our results suggest that stathmin can be seen as a modulator of MTA activity and binding to tubulin, providing molecular explanation for multiple previous cellular and in vivo studies showing that stathmin expression level affects MTAs efficiency.

  1. Dihydroxyoctadecamonoenoate esters inhibit the neutrophil respiratory burst

    Indian Academy of Sciences (India)

    David Alan Thompson; Bruce D Hammock

    2007-03-01

    The leukotoxins [9(10)- and 12(13)-EpOME] are produced by activated inflammatory leukocytes such as neutrophils. High EpOME levels are observed in disorders such as acute respiratory distress syndrome and in patients with extensive burns. Although the physiological significance of the EpOMEs remains poorly understood, in some systems, the EpOMEs act as a protoxin, with their corresponding epoxide hydrolase metabolites, 9,10- and 12,13-DiHOME, specifically exerting toxicity. Both the EpOMEs and the DiHOMEs were also recently shown to have neutrophil chemotactic activity. We evaluated whether the neutrophil respiratory burst, a surge of oxidant production thought to play an important role in limiting certain bacterial and fungal infections, is modulated by members of the EpOME metabolic pathway. We present evidence that the DiHOMEs suppress the neutrophil respiratory burst by a mechanism distinct from that of respiratory burst inhibitors such as cyclosporin H or lipoxin A4, which inhibit multiple aspects of neutrophil activation.

  2. Inhibition of Complement Retards Ankylosing Spondylitis Progression

    Science.gov (United States)

    Yang, Chaoqun; Ding, Peipei; Wang, Qingkai; Zhang, Long; Zhang, Xin; Zhao, Jianquan; Xu, Enjie; Wang, Na; Chen, Jianfeng; Yang, Guang; Hu, Weiguo; Zhou, Xuhui

    2016-01-01

    Ankylosing spondylitis (AS) is a chronic axial spondyloarthritis (SpA) resulting in back pain and progressive spinal ankyloses. Currently, there are no effective therapeutics targeting AS largely due to elusive pathogenesis mechanisms, even as potential candidates such as HLA-B27 autoantigen have been identified. Herein, we employed a proteoglycan (PG)-induced AS mouse model together with clinical specimens, and found that the complement system was substantially activated in the spinal bone marrow, accompanied by a remarkable proportion alteration of neutrophils and macrophage in bone marrow and spleen, and by the significant increase of TGF-β1 in serum. The combined treatment with a bacteria-derived complement inhibitor Efb-C (C-terminal of extracellular fibrinogen-binding protein of Staphylococcus aureus) remarkably retarded the progression of mouse AS by reducing osteoblast differentiation. Furthermore, we demonstrated that two important modulators involved in AS disease, TGF-β1 and RANKL, were elevated upon in vitro complement attack in osteoblast and/or osteoclast cells. These findings further unravel that complement activation is closely related with the pathogenesis of AS, and suggest that complement inhibition may hold great potential for AS therapy. PMID:27698377

  3. Efficacy of ALK5 inhibition in myelofibrosis

    Science.gov (United States)

    Zhao, Wanke; Ho, Wanting Tina; Han, Ying; Murdun, Cem; Mailloux, Adam W.; Zhang, Ling; Wang, Xuefeng; Budhathoki, Anjali; Pradhan, Kith; Rapaport, Franck; Wang, Huaquan; Shao, Zonghong; Ren, Xiubao; Steidl, Ulrich; Levine, Ross L.; Zhao, Zhizhuang Joe; Verma, Amit; Epling-Burnette, Pearlie K.

    2017-01-01

    Myelofibrosis (MF) is a bone marrow disorder characterized by clonal myeloproliferation, aberrant cytokine production, extramedullary hematopoiesis, and bone marrow fibrosis. Although somatic mutations in JAK2, MPL, and CALR have been identified in the pathogenesis of these diseases, inhibitors of the Jak2 pathway have not demonstrated efficacy in ameliorating MF in patients. TGF-β family members are profibrotic cytokines and we observed significant TGF-β1 isoform overexpression in a large cohort of primary MF patient samples. Significant overexpression of TGF-β1 was also observed in murine clonal MPLW515L megakaryocytic cells. TGF-β1 stimulated the deposition of excessive collagen by mesenchymal stromal cells (MSCs) by activating the TGF-β receptor I kinase (ALK5)/Smad3 pathway. MSCs derived from MPLW515L mice demonstrated sustained overproduction of both collagen I and collagen III, effects that were abrogated by ALK5 inhibition in vitro and in vivo. Importantly, use of galunisertib, a clinically active ALK5 inhibitor, significantly improved MF in both MPLW515L and JAK2V617F mouse models. These data demonstrate the role of malignant hematopoietic stem cell (HSC)/TGF-β/MSC axis in the pathogenesis of MF, and provide a preclinical rationale for ALK5 blockade as a therapeutic strategy in MF.

  4. Hsp90 inhibition decreases mitochondrial protein turnover.

    Directory of Open Access Journals (Sweden)

    Daciana H Margineantu

    Full Text Available BACKGROUND: Cells treated with hsp90 inhibitors exhibit pleiotropic changes, including an expansion of the mitochondrial compartment, accompanied by mitochondrial fragmentation and condensed mitochondrial morphology, with ultimate compromise of mitochondrial integrity and apoptosis. FINDINGS: We identified several mitochondrial oxidative phosphorylation complex subunits, including several encoded by mtDNA, that are upregulated by hsp90 inhibitors, without corresponding changes in mRNA abundance. Post-transcriptional accumulation of mitochondrial proteins observed with hsp90 inhibitors is also seen in cells treated with proteasome inhibitors. Detailed studies of the OSCP subunit of mitochondrial F1F0-ATPase revealed the presence of mono- and polyubiquitinated OSCP in mitochondrial fractions. We demonstrate that processed OSCP undergoes retrotranslocation to a trypsin-sensitive form associated with the outer mitochondrial membrane. Inhibition of proteasome or hsp90 function results in accumulation of both correctly targeted and retrotranslocated mitochondrial OSCP. CONCLUSIONS: Cytosolic turnover of mitochondrial proteins demonstrates a novel connection between mitochondrial and cytosolic compartments through the ubiquitin-proteasome system. Analogous to defective protein folding in the endoplasmic reticulum, a mitochondrial unfolded protein response may play a role in the apoptotic effects of hsp90 and proteasome inhibitors.

  5. Effects of fencamfamine on latent inhibition.

    Science.gov (United States)

    Alves, Cilene R R; Delucia, Roberto; Silva, M Teresa A

    2002-10-01

    The effects of fencamfamine (FCF), an indirect dopamine (DA) agent, were investigated using the latent inhibition (LI) model of schizophrenia. In the LI procedure, rats preexposed (PE) to an unreinforced stimulus show difficulty in subsequent learning of an association in which that stimulus is predictive of an unconditioned stimulus (US). FCF (1.75, 3.5 and 7.0 mg/kg i.p.) yielded an inverse dose-response relationship regarding LI. At 3.5 mg/kg, LI was abolished and no effect was observed at 1.75 and 7.0 mg/kg. The effect of FCF (3.5 mg/kg) on LI was blocked by the antipsychotic risperidone (RIS; 4.0 mg/kg), a D2/5HT2 antagonist. These results confirm the similarity of the behavioral profile of FCF and amphetamine (AMPH). In addition, they provide a further validation of the LI model for psychosis, since RIS was shown to prevent a psychostimulant-induced disruption of LI.

  6. Inhibition of Midkine Augments Osteoporotic Fracture Healing.

    Directory of Open Access Journals (Sweden)

    Melanie Haffner-Luntzer

    Full Text Available The heparin-binding growth and differentiation factor midkine (Mdk is proposed to negatively regulate osteoblast activity and bone formation in the adult skeleton. As Mdk-deficient mice were protected from ovariectomy (OVX-induced bone loss, this factor may also play a role in the pathogenesis of postmenopausal osteoporosis. We have previously demonstrated that Mdk negatively influences bone regeneration during fracture healing. Here, we investigated whether the inhibition of Mdk using an Mdk-antibody (Mdk-Ab improves compromised bone healing in osteoporotic OVX-mice. Using a standardized femur osteotomy model, we demonstrated that Mdk serum levels were significantly enhanced after fracture in both non-OVX and OVX-mice, however, the increase was considerably greater in osteoporotic mice. Systemic treatment with the Mdk-Ab significantly improved bone healing in osteoporotic mice by increasing bone formation in the fracture callus. On the molecular level, we demonstrated that the OVX-induced reduction of the osteoanabolic beta-catenin signaling in the bony callus was abolished by Mdk-Ab treatment. Furthermore, the injection of the Mdk-Ab increased trabecular bone mass in the skeleton of the osteoporotic mice. These results implicate that antagonizing Mdk may be useful for the therapy of osteoporosis and osteoporotic fracture-healing complications.

  7. Bromodomains: Structure, function and pharmacology of inhibition.

    Science.gov (United States)

    Ferri, Elena; Petosa, Carlo; McKenna, Charles E

    2016-04-15

    Bromodomains are epigenetic readers of histone acetylation involved in chromatin remodeling and transcriptional regulation. The human proteome comprises 46 bromodomain-containing proteins with a total of 61 bromodomains, which, despite highly conserved structural features, recognize a wide array of natural peptide ligands. Over the past five years, bromodomains have attracted great interest as promising new epigenetic targets for diverse human diseases, including inflammation, cancer, and cardiovascular disease. The demonstration in 2010 that two small molecule compounds, JQ1 and I-BET762, potently inhibit proteins of the bromodomain and extra-terminal (BET) family with translational potential for cancer and inflammatory disease sparked intense efforts in academia and pharmaceutical industry to develop novel bromodomain antagonists for therapeutic applications. Several BET inhibitors are already in clinical trials for hematological malignancies, solid tumors and cardiovascular disease. Currently, the field faces the challenge of single-target selectivity, especially within the BET family, and of overcoming problems related to the development of drug resistance. At the same time, new trends in bromodomain inhibitor research are emerging, including an increased interest in non-BET bromodomains and a focus on drug synergy with established antitumor agents to improve chemotherapeutic efficacy. This review presents an updated view of the structure and function of bromodomains, traces the development of bromodomain inhibitors and their potential therapeutic applications, and surveys the current challenges and future directions of this vibrant new field in drug discovery. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Collagen hydrolysate inhibits zymosan-induced inflammation.

    Science.gov (United States)

    Hartog, Anita; Cozijnsen, Miranda; de Vrij, Gerrit; Garssen, Johan

    2013-07-01

    During the past years, evidence accumulated showing that glycine comprises anti-inflammatory activities. These effects occur, at least in part, via the activation of glycine-gated chloride channels (GlyR). Glycine is one of the major structural units of collagen, making up about 30% of the amino acids. This study aims to investigate the anti-inflammatory potential of collagen hydrolysate (CH) using the zymosan-induced ear-skin inflammation mouse model. After oral intake of 12.5, 25 or 50 mg CH the plasma levels of glycine increased in a concentration-dependent manner. CH was able to counteract zymosan-induced ear-skin inflammation locally (ear swelling) as well as systemically (IL-6 production by lipopolysaccharide (LPS)-stimulated whole blood cells). The LPS-stimulated IL-6 production in whole blood correlated positively with the ear swelling response. This correlation was abolished by strychnine (a glycine receptor antagonist), indicating the involvement of GlyR. Collectively, these data show that CH is able to modulate inflammatory responses both locally as well as systemically. This effect might be constituted by inhibiting pro-inflammatory cytokine production via GlyR.

  9. Mortalin inhibition in experimental Parkinson's disease.

    Science.gov (United States)

    Chiasserini, Davide; Tozzi, Alessandro; de Iure, Antonio; Tantucci, Michela; Susta, Federica; Orvietani, Pier Luigi; Koya, Keizo; Binaglia, Luciano; Calabresi, Paolo

    2011-08-01

    Among heat shock proteins, mortalin has been linked to the pathogenesis of Parkinson's disease. In the present work a rat model of Parkinson's disease was used to analyze the expression of striatal proteins and, more specifically, mortalin expression. The possible involvement of mortalin in Parkinson's disease pathogenesis was further investigated by utilizing an electrophysiological approach and pharmacological inhibition of mortalin in both the physiological and the parkinsonian states. Proteomic analysis was used to investigate changes in striatal protein expression in the 6-hydroxydopamine rat model of Parkinson's disease. The electrophysiological effects of MKT-077, a rhodamine-123 analogue acting as an inhibitor of mortalin, were measured by field potential recordings from corticostriatal brain slices obtained from control, sham-operated, and 6-hydroxydopamine-denervated animals. Slices in the presence of rotenone, an inhibitor of mitochondrial complex I, were also analyzed. Proteomic analysis revealed downregulation of mortalin in the striata of 6-hydroxydopamine-treated rats in comparison with sham-operated animals. MKT-077 reduced corticostriatal field potential amplitude in physiological conditions, inducing membrane depolarization and inward current in striatal medium spiny neurons. In addition, we observed that concentrations of MKT-077 not inducing any electrophysiological effect in physiological conditions caused significant changes in striatal slices from parkinsonian animals as well as in slices treated with a submaximal concentration of rotenone. These findings suggest a critical link between mortalin function and mitochondrial activity in both physiological and pathological conditions mimicking Parkinson's disease.

  10. Obesity inhibits lymphangiogenesis in prostate tumors.

    Science.gov (United States)

    Moreira, Ângela; Pereira, Sofia S; Machado, Christiane L; Morais, Tiago; Costa, Madalena; Monteiro, Mariana P

    2014-01-01

    Lymphangiogenesis is the process that leads to new lymphatic vessels formation from preexisting blood vessels in the presence of appropriate inducing signals, which in pathologic conditions such as cancer, may contribute to tumor cells dissemination. The aim of the present study was to study the role of obesity, leptin and insulin in tumor lymphangiogenesis. For that, we have quantified the lymphatic vessels in prostate tumors through their immunohistochemistry staining by Lyve-1 in RM1 prostate tumors induced in different obese mice models (ob/ob, db/db and diet induced obese (DIO) and in normal weight C57BL/6J mice (control). Lymph vessels density was determined by Lyve-1 immunohistochemistry of prostate adenocarcinomas, while the percentage of the Lyve-1 stained area and lymphatic vessels number were obtained using a morphometric computerized tool. Obese ob/ob and DIO mice presented prostate tumors that were significantly larger (pprostate tumors of DIO mice compared to tumors of db/db mice (pobesity may have a protective effect against prostate cancer dissemination by inhibiting lymphangiogenesis through a still unidentified mechanism that appears not to involve leptin or insulin.

  11. Vagus nerve stimulation inhibits cortical spreading depression.

    Science.gov (United States)

    Chen, Shih-Pin; Ay, Ilknur; de Morais, Andreia Lopes; Qin, Tao; Zheng, Yi; Sadeghian, Homa; Oka, Fumiaki; Simon, Bruce; Eikermann-Haerter, Katharina; Ayata, Cenk

    2016-04-01

    Vagus nerve stimulation has recently been reported to improve symptoms of migraine. Cortical spreading depression is the electrophysiological event underlying migraine aura and is a trigger for headache. We tested whether vagus nerve stimulation inhibits cortical spreading depression to explain its antimigraine effect. Unilateral vagus nerve stimulation was delivered either noninvasively through the skin or directly by electrodes placed around the nerve. Systemic physiology was monitored throughout the study. Both noninvasive transcutaneous and invasive direct vagus nerve stimulations significantly suppressed spreading depression susceptibility in the occipital cortex in rats. The electrical stimulation threshold to evoke a spreading depression was elevated by more than 2-fold, the frequency of spreading depressions during continuous topical 1 M KCl was reduced by ∼40%, and propagation speed of spreading depression was reduced by ∼15%. This effect developed within 30 minutes after vagus nerve stimulation and persisted for more than 3 hours. Noninvasive transcutaneous vagus nerve stimulation was as efficacious as direct invasive vagus nerve stimulation, and the efficacy did not differ between the ipsilateral and contralateral hemispheres. Our findings provide a potential mechanism by which vagus nerve stimulation may be efficacious in migraine and suggest that susceptibility to spreading depression is a suitable platform to optimize its efficacy.

  12. Inhibition of carcinogenesis by retinoids. [Review

    Energy Technology Data Exchange (ETDEWEB)

    Nettesheim, P.

    1979-01-01

    Progress made in recent years in the search for retinoids with anticarcinogenic activity is reviewed. There are many studies to be found in the literature which show no substantial effect of retinoids on carcinogenesis or tumor growth. Some of these negative findings may be related to the carcinogen dose used, the type of retinoid used, the dose, dose schedule or mode of administration of the retinoid. Others may indicate that the particular type of tumor or tumor system is, indeed, refractory to retinoids in general or to those retinoids that were tested. A great gap still exists in our knowledge concerning the pharmake-kinetics of most retinoids their availability to various normal and cancerous tissues, and the role and existence of transport and binding proteins. There are studies which indicate that under certain conditions, particularly conditions of topical application, some retinoids may even enhance carcinogenesis. It seems, however, indisputable by now that some retinoids are effective inhibitors of carcinogenesis in some organ systems and can even inhibit the growth of some established tumors. While the mechanisms of these inhibitory effects are presently not understood, it does seem clear that they are not mediated via the cytotoxic mechanisms typical of chemotherapeutic agents. The hope that retinoids might become an effective tool to halt the progression of some neoplastic diseases, seems to be justified.

  13. Inhibition of Oxidation in Nuclear Graphite

    Energy Technology Data Exchange (ETDEWEB)

    Phil Winston; James W. Sterbentz; William E. Windes

    2013-10-01

    Graphite is a fundamental material of high temperature gas cooled nuclear reactors, providing both structure and neutron moderation. Its high thermal conductivity, chemical inertness, thermal heat capacity, and high thermal structural stability under normal and off normal conditions contribute to the inherent safety of these reactor designs. One of the primary safety issues for a high temperature graphite reactor core is the possibility of rapid oxidation of the carbon structure during an off normal design basis event where an oxidizing atmosphere (air ingress) can be introduced to the hot core. Although the current Generation IV high temperature reactor designs attempt to mitigate any damage caused by a postualed air ingress event, the use of graphite components that inhibit oxidation is a logical step to increase the safety of these reactors. Recent experimental studies of graphite containing between 5.5 and 7 wt% boron carbide (B4C) indicate that oxidation is dramatically reduced even at prolonged exposures at temperatures up to 900°C. The proposed addition of B4C to graphite components in the nuclear core would necessarily be enriched in B-11 isotope in order to minimize B-10 neutron absorption and graphite swelling. The enriched boron can be added to the graphite during billet fabrication. Experimental oxidation rate results and potential applications for borated graphite in nuclear reactor components will be discussed.

  14. Simvastatin inhibits CD44 fragmentation in chondrocytes.

    Science.gov (United States)

    Terabe, Kenya; Takahashi, Nobunori; Takemoto, Toki; Knudson, Warren; Ishiguro, Naoki; Kojima, Toshihisa

    2016-08-15

    In human osteoarthritic chondrocytes, the hyaluronan receptor CD44 undergoes proteolytic cleavage at the cell surface. CD44 cleavage is thought to require transit of CD44 into cholesterol-rich lipid rafts. The purpose of this study was to investigate whether statins exert a protective effect on articular chondrocytes due to diminution of cholesterol. Three model systems of chondrocytes were examined including human HCS-2/8 chondrosarcoma cells, human osteoarthritic chondrocytes and normal bovine articular chondrocytes. Treatment with IL-1β + Oncostatin M resulted in a substantial increase in CD44 fragmentation in each of the three chondrocyte models. Pre-incubation with simvastatin prior to treatment with IL-1β + Oncostatin M decreased the level of CD44 fragmentation, decreased the proportion of CD44 that transits into the lipid raft fractions, decreased ADAM10 activity and diminished the interaction between CD44 and ADAM10. In HCS-2/8 cells and bovine articular chondrocytes, fragmentation of CD44 was blocked by the knockdown of ADAM10. Inhibition of CD44 fragmentation by simvastatin also resulted in improved retention of pericellular matrix. Addition of cholesterol and farnesyl-pyrophosphate reversed the protective effects of simvastatin. Thus, the addition of simvastatin exerts positive effects on chondrocytes including reduced CD44 fragmentation and enhanced the retention of pericellular matrix. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Rational drug design applied to myeloperoxidase inhibition.

    Science.gov (United States)

    Van Antwerpen, P; Zouaoui Boudjeltia, K

    2015-06-01

    Rational drug design is a general approach using protein-structure technique in which the discovery of a ligand can be driven either by chance, screening, or rational theory. Myeloperoxidase (MPO) was rapidly identified as a therapeutical target because of its involvement in chronic inflammatory syndromes. In this context, the research of MPO inhibitors was intensified and development of new chemical entities was rationally driven by the research of ligands that enter into the MPO catalytic pocket. Actually, as soon as crystallography data of MPO have become available and its structure was virtually designed, the rational drug design has been applied to this peroxidase. Pharmaceutical industries and academic laboratories apply rational drug design on MPO by either optimizing known inhibitors or searching new molecules by high-throughput virtual screening. By these ways, they were able to find efficient MPO inhibitors and understand their interactions with the enzyme. During this quest of MPO inhibition, it appears that Glu268 is a crucial residue in order to optimize ligand-target interaction. This amino acid should be carefully considered by medicinal chemist when they design inhibitors interfering with MPO activity.

  16. Aspirin, cyclooxygenase inhibition and colorectal cancer.

    Science.gov (United States)

    Sostres, Carlos; Gargallo, Carla Jerusalen; Lanas, Angel

    2014-02-01

    Colorectal cancer (CRC) is the third most common type of cancer worldwide. Screening measures are far from adequate and not widely available in resource-poor settings. Primary prevention strategies therefore remain necessary to reduce the risk of developing CRC. Increasing evidence from epidemiological studies, randomized clinical trials and basic science supports the effectiveness of aspirin, as well as other non-steroidal anti-inflammatory drugs, for chemoprevention of several types of cancer, including CRC. This includes the prevention of adenoma recurrence and reduction of CRC incidence and mortality. The detectable benefit of daily low-dose aspirin (at least 75 mg), as used to prevent cardiovascular disease events, strongly suggests that its antiplatelet action is central to explaining its antitumor efficacy. Daily low-dose aspirin achieves complete and persistent inhibition of cyclooxygenase (COX)-1 in platelets (in pre-systemic circulation) while causing a limited and rapidly reversible inhibitory effect on COX-2 and/or COX-1 expressed in nucleated cells. Aspirin has a short half-life in human circulation (about 20 minutes); nucleated cells have the ability to resynthesize acetylated COX isozymes within a few hours, while platelets do not. COX-independent mechanisms of aspirin have been suggested to explain its chemopreventive effects but this concept remains to be demonstrated in vivo at clinical doses.

  17. Stathmin potentiates vinflunine and inhibits Paclitaxel activity.

    Directory of Open Access Journals (Sweden)

    Soazig Malesinski

    Full Text Available Cell biology and crystallographic studies have suggested a functional link between stathmin and microtubule targeting agents (MTAs. In a previous study we showed that stathmin increases vinblastine (VLB binding to tubulin, and that conversely VLB increases stathmin binding to tubulin. This constituted the first biochemical evidence of the direct relationship between stathmin and an antimitotic drug, and revealed a new mechanism of action for VLB. The question remained if the observed interaction was specific for this drug or represented a general phenomenon for all MTAs. In the present study we investigated the binding of recombinant stathmin to purified tubulin in the presence of paclitaxel or another Vinca alkaloid, vinflunine, using Isothermal Titration Calorimetry (ITC. These experiments revealed that stathmin binding to tubulin is increased in the presence of vinflunine, whereas no signal is observed in the presence of paclitaxel. Further investigation using turbidity and co-sedimentation showed that stathmin inhibited paclitaxel microtubule-stabilizing activity. Taken together with the previous study using vinblastine, our results suggest that stathmin can be seen as a modulator of MTA activity and binding to tubulin, providing molecular explanation for multiple previous cellular and in vivo studies showing that stathmin expression level affects MTAs efficiency.

  18. Decoupled echo state networks with lateral inhibition.

    Science.gov (United States)

    Xue, Yanbo; Yang, Le; Haykin, Simon

    2007-04-01

    Building on some prior work, in this paper we describe a novel structure termed the decoupled echo state network (DESN) involving the use of lateral inhibition. Two low-complexity implementation schemes, namely, the DESN with reservoir prediction (DESN + RP) and DESN with maximum available information (DESN + MaxInfo), are developed: (1) In the multiple superimposed oscillator (MSO) problem, DESN + MaxInfo exhibits three important attributes: lower generalization mean-square error (MSE), better robustness with respect to the random generation of reservoir weight matrix and feedback connections, and robustness to variations in the sparseness of reservoir weight matrix, compared to DESN + RP. (2) For a noiseless nonlinear prediction task, DESN + RP outperforms the DESN + MaxInfo and single reservoir-based ESN approach in terms of lower prediction MSE and better robustness to a change in the number of inputs and sparsity of the reservoir weight matrix. Finally, in a real-life prediction task using noisy sea clutter data, both schemes exhibit higher prediction accuracy and successful design ratio than a conventional ESN with a single reservoir.

  19. The Role of Test Context in Latent Inhibition of Conditioned Inhibition: Part of a Search for General Principles of Associative Interference

    OpenAIRE

    Miguez, Gonzalo; Soares, Julia S.; Miller, Ralph R.

    2015-01-01

    Two lick-suppression experiments with rats assessed interference with behavior indicative of conditioned inhibition by a latent inhibition treatment as a function of test context. We asked what effect the test context has, given identical latent inhibition treatment in Phase 1 and identical conditioned inhibition training in Phase 2. In Experiment 1, an AAA vs. AAB context-shift design determined that latent inhibition treatment in Phase 1 attenuated behavior indicative of conditioned inhibit...

  20. Attention Inhibition Training Can Reduce Betel-Nut Chewing Time

    Directory of Open Access Journals (Sweden)

    Ming-Chou Ho

    2011-05-01

    Full Text Available Betel nut (or areca is the fourth most commonly used drug worldwide after tobacco, alcohol, and caffeine. Many chemical ingredients of betel nut are carcinogenic. We examined whether the manipulation of attentional inhibition toward the areca-related stimuli could affect betel-nut chewing time. Three matched groups of habitual chewers were recruited: inhibit-areca, inhibit-non-areca, and control. This study consisted of a Go/No-Go task for inhibition training, followed by a taste test for observing chewing behavior. The Go/No-Go task constituted three phases (pretest, training and posttest. In the taste test, the habitual chewers were asked to rate the flavors of one betel nut and one gum. The purpose (blind to the chewers of this taste test was to observe whether their picking order and chewing time were affected by experimental manipulation. Results from the Go/No-Go task showed successful training. Further, the training groups (the inhibit-areca and inhibit-non-areca groups showed a significant reduction in betel nut chewing time, in comparison to the control group. Since both training groups showed reduced chewing time, the inhibition training may affect general control ability, in regardless of the stimulus (areca or not to be inhibited. Reduced chewing time is important for reducing areca-related diseases.

  1. Forgetting the Literal: The Role of Inhibition in Metaphor Comprehension

    Science.gov (United States)

    George, Tim; Wiley, Jennifer

    2016-01-01

    In order for a person to comprehend metaphoric expressions, do metaphor-irrelevant aspects of literal information need to be inhibited? Previous research using sentence-verification paradigms has found that literal associates take longer to process after reading metaphorical sentences; however, it is problematic to infer inhibition from this…

  2. An alternative inhibition method for determining cross-reactive allergens

    NARCIS (Netherlands)

    Schmidt-Hieltjes, Yvonne; Teodorowicz, Malgorzata; Jansen, Ad; Hartog, Den Gerco; Elfvering-Berendsen, Lisette; Jong, De Nicolette W.; Savelkoul, Huub F.J.; Ruinemans-Koerts, Janneke

    2017-01-01

    Inhibition assays are an useful tool to identify the allergen of primary sensitization of cross-reactive allergens. Classical ELISA-based inhibition assays are limited by both the availability of commercial standardized allergen extracts and the experience and knowledge needed for making home-made e

  3. Stuttering Inhibition via Altered Auditory Feedback during Scripted Telephone Conversations

    Science.gov (United States)

    Hudock, Daniel; Kalinowski, Joseph

    2014-01-01

    Background: Overt stuttering is inhibited by approximately 80% when people who stutter read aloud as they hear an altered form of their speech feedback to them. However, levels of stuttering inhibition vary from 60% to 100% depending on speaking situation and signal presentation. For example, binaural presentations of delayed auditory feedback…

  4. Cognitive Inhibition in Students with and without Dyslexia and Dyscalculia

    Science.gov (United States)

    Wang, Li-Chih; Tasi, Hung-Ju; Yang, Hsien-Ming

    2012-01-01

    The present study presents a comparison of the cognitive inhibition abilities of dyslexic, dyscalculic, and control students. The participants were 45 dyslexic students, 45 dyscalculic students, and 45 age-, gender-, and IQ-matched control students. The major evaluation tools included six cognitive inhibition tasks which were restructured during…

  5. Distractor Inhibition: Principles of Operation during Selective Attention

    Science.gov (United States)

    Wyatt, Natalie; Machado, Liana

    2013-01-01

    Research suggests that although target amplification acts as the main determinant of the efficacy of selective attention, distractor inhibition contributes under some circumstances. Here we aimed to gain insight into the operating principles that regulate the use of distractor inhibition during selective attention. The results suggest that, in…

  6. Effective inhibition of viral reproduction by hydrophobised antiviral antibodies.

    Science.gov (United States)

    Kabanov, A V; Ovcharenko, A V; Melik-Nubarov, N S; Bannikov, A I; Lisok, T P; Klyushnenkova, E V; Cherchenko, N G; Alakhov VYu; Levashov, A V; Kiselev, V I

    1990-01-01

    A method is proposed for the inhibition of viral reproduction in cells by means of fatty-acylated antiviral antibodies which, in contrast to the unmodified antibodies, have the ability to enter the cells. The potential of this technique is demonstrated in experiments involving inhibition of the reproduction of various strains of influenza virus and respiratory syncytial virus.

  7. Executive functioning in boys with ADHD: primarily an inhibition deficit?

    NARCIS (Netherlands)

    Scheres, A.P.J.; Oosterlaan, J.; Geurts, H.M.; Morein-Zamir, S.; Meiran, N.; Vlasveld, L.; Sergeant, J.A.

    2004-01-01

    This study was aimed at: (1) testing whether boys with Attention Deficit/Hyperactivity Disorder (ADHD) demonstrate a deficit in response inhibition and deficits in other executive functions (EF), or alternatively, demonstrate a deficit in only response inhibition; (2) investigating which role associ

  8. Stuttering Inhibition via Altered Auditory Feedback during Scripted Telephone Conversations

    Science.gov (United States)

    Hudock, Daniel; Kalinowski, Joseph

    2014-01-01

    Background: Overt stuttering is inhibited by approximately 80% when people who stutter read aloud as they hear an altered form of their speech feedback to them. However, levels of stuttering inhibition vary from 60% to 100% depending on speaking situation and signal presentation. For example, binaural presentations of delayed auditory feedback…

  9. A Subinhibitory Concentration of Clarithromycin Inhibits Mycobacterium avium Biofilm Formation

    OpenAIRE

    2004-01-01

    Mycobacterium avium causes disseminated infection in immunosuppressed individuals and lung infection in patients with chronic lung diseases. M. avium forms biofilm in the environment and possibly in human airways. Antibiotics with activity against the bacterium could inhibit biofilm formation. Clarithromycin inhibits biofilm formation but has no activity against established biofilm.

  10. 46 CFR 154.1740 - Vinyl chloride: Inhibiting and inerting.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Vinyl chloride: Inhibiting and inerting. 154.1740... Operating Requirements § 154.1740 Vinyl chloride: Inhibiting and inerting. When a vessel is carrying vinyl chloride, the master shall ensure that: (a) Section 154.1818 is met; or (b) Section 154.1710 is met,...

  11. The role of non-CRF inhibition in contour detection

    NARCIS (Netherlands)

    Grigorescu, Cosmin; Petkov, Nicolai; Westenberg, Michel A.; Skala,

    2003-01-01

    We propose a biologically motivated computational step, called non-classical receptive field (non-CRF) inhibition, to improve the performance of contour detectors. Non-CRF inhibition is exhibited by 80% of the orientation selective neurons in the primary visual cortex of macaque monkeys and has been

  12. Corrosion Inhibition of High Speed Steel by Biopolymer HPMC Derivatives

    OpenAIRE

    Shih-Chen Shi; Chieh-Chang Su

    2016-01-01

    The corrosion inhibition characteristics of the derivatives of biopolymer hydroxypropyl methylcellulose (HPMC), hydroxypropyl methylcellulose phthalate (HPMCP), and hydroxypropyl methylcellulose acetate succinate (HPMCAS) film are investigated. Based on electrochemical impedance spectroscopic measurements and potentiodynamic polarization, the corrosion inhibition performance of high speed steel coated with HPMC derivatives is evaluated. The Nyquist plot and Tafel polarization demonstrate prom...

  13. Corrosion Inhibition of Aluminium by Capparis deciduas in Acidic Media

    Directory of Open Access Journals (Sweden)

    P. Arora

    2007-01-01

    Full Text Available The inhibition efficiency of ethanolic extract of different parts of Capparis deciduas (Ker in acidic medium has been evaluated by mass loss and thermometric methods. Values of inhibition efficiency obtained from the two methods are in good agreement and are dependent upon the concentration of inhibitor and acid.

  14. Underlying Personality Characteristics of Behavioral Inhibition in Children

    Science.gov (United States)

    Muris, Peter; Dietvorst, Roeland

    2006-01-01

    Behavioral inhibition refers to the tendency of children to be unusually shy and to react with fear and withdrawal in situations that are novel and/or unfamiliar, and is generally regarded as a vulnerability factor for developing anxiety disorders. The present study investigated the hypothesis that behavioral inhibition is characterized by a…

  15. The Root-inhibiting Substance of Allium Cepa

    NARCIS (Netherlands)

    Stolk, Anth.

    1953-01-01

    Whereas scientific research on inhibiting substances has mainly occupied itself with the effect of these substances on the germination process, I was able to demonstrate the presence of a root-inhibiting agent during my studies on root formation in Fuchsia hybrida and Pelargonium zonale (Stolk, 1952

  16. The Affective Consequences of Cognitive Inhibition: Devaluation or Neutralization?

    Science.gov (United States)

    Frischen, Alexandra; Ferrey, Anne E.; Burt, Dustin H. R.; Pistchik, Meghan; Fenske, Mark J.

    2012-01-01

    Affective evaluations of previously ignored visual stimuli are more negative than those of novel items or prior targets of attention or response. This has been taken as evidence that inhibition has negative affective consequences. But inhibition could act instead to attenuate or "neutralize" preexisting affective salience, predicting opposite…

  17. Corrosion inhibition of carbon steel by sodium metavanadate

    Directory of Open Access Journals (Sweden)

    VIJAYA GOPAL SRIBHARATHY

    2012-08-01

    Full Text Available The inhibition efficiency of sodium metavanadate (SMV-adipic acid (AA system in controlling corrosion of carbon steel in an aqueous solution containing 60 ppm of Cl- has been evaluated by weight-loss method; 250 ppm of SMV exhibits inhibition efficiency of 56 %. Addition of adipic acid to SMV improves the inhibition efficiency of the system. The formulation consisting of 250 ppm of SMV and 250 ppm of adipic acid has inhibition efficiency of 98 %. A synergistic effect exists between SMV and adipic acid with the synergism parameters greater than 1. Mecha¬nistic aspects of corrosion inhibition have been studied by electrochemical methods like potentiodynamic polarization and electrochemical impedance spectroscopy. FTIR spectra reveal that the protective film consists of Fe2+-SMV complex and Fe2+-adipic acid complex. The protective film has been analyzed by fluorescence spectra, SEM and EDAX.

  18. Sulindac Sulfide, but Not Sulindac Sulfone, Inhibits Colorectal Cancer Growth

    Directory of Open Access Journals (Sweden)

    Christopher S. Williams

    1999-06-01

    Full Text Available Sulindac sulfide, a metabolite of the nonsteroidal antiinflammatory drug (NSAID sulindac sulfoxide, is effective at reducing tumor burden in both familial adenomatous polyposis patients and in animals with colorectal cancer. Another sulindac sulfoxide metabolite, sulindac sulfone, has been reported to have antitumor properties without inhibiting cyclooxygenase activity. Here we report the effect of sulindac sulfone treatment on the growth of colorectal carcinoma cells. We observed that sulindac sulfide or sulfone treatment of HCA-7 cells led to inhibition of prostaglandin E2 production. Both sulindac sulfide and sulfone inhibited HCA-7 and HCT-116 cell growth in vitro. Sulindac sulfone had no effect on the growth of either HCA-7 or HCT-116 xenografts, whereas the sulfide derivative inhibited HCA-7 growth in vivo. Both sulindac sulfide and sulfone inhibited colon carcinoma cell growth and prostaglandin production in vitro, but sulindac sulfone had no effect on the growth of colon cancer cell xenografts in nude mice.

  19. Thymoquinone Inhibits Escherichia coli ATP Synthase and Cell Growth.

    Directory of Open Access Journals (Sweden)

    Zulfiqar Ahmad

    Full Text Available We examined the thymoquinone induced inhibition of purified F1 or membrane bound F1FO E. coli ATP synthase. Both purified F1 and membrane bound F1FO were completely inhibited by thymoquinone with no residual ATPase activity. The process of inhibition was fully reversible and identical in both membrane bound F1Fo and purified F1 preparations. Moreover, thymoquinone induced inhibition of ATP synthase expressing wild-type E. coli cell growth and non-inhibition of ATPase gene deleted null control cells demonstrates that ATP synthase is a molecular target for thymoquinone. This also links the beneficial dietary based antimicrobial and anticancer effects of thymoquinone to its inhibitory action on ATP synthase.

  20. Thymoquinone Inhibits Escherichia coli ATP Synthase and Cell Growth.

    Science.gov (United States)

    Ahmad, Zulfiqar; Laughlin, Thomas F; Kady, Ismail O

    2015-01-01

    We examined the thymoquinone induced inhibition of purified F1 or membrane bound F1FO E. coli ATP synthase. Both purified F1 and membrane bound F1FO were completely inhibited by thymoquinone with no residual ATPase activity. The process of inhibition was fully reversible and identical in both membrane bound F1Fo and purified F1 preparations. Moreover, thymoquinone induced inhibition of ATP synthase expressing wild-type E. coli cell growth and non-inhibition of ATPase gene deleted null control cells demonstrates that ATP synthase is a molecular target for thymoquinone. This also links the beneficial dietary based antimicrobial and anticancer effects of thymoquinone to its inhibitory action on ATP synthase.

  1. Hypnosis and inhibition as viewed by Heidenhain and Pavlov.

    Science.gov (United States)

    Windholz, G

    1996-01-01

    About 1880, Rudolf Heidenhain, then Professor of Physiology and Histology at the University of Breslau, experimentally studied hypnotic phenomena. Heidenhain explained hypnosis physiologically, in terms of cortical inhibition. Subsequently, I.P. Pavlov, who in 1877 and again in 1884 was Heidenhain's student at Breslau, encountered hypnotic phenomena during conditional reflex experiments. In 1910, Pavlov described hypnotic states and explained them (as had Heidenhain three decades earlier), in terms of partial inhibition of the cortex. As the concepts of inhibition and excitation are cornerstones of Pavlov's theory of higher nervous activity, it is of historical interest to search for influences that led Pavlov to incorporate the concept of inhibition into his theory. It is most likely that Pavlov first encountered the concept of central inhibition in the 1860s when reading I.M. Sechenov's The Reflexes of the Brain (1863/1866) and that the importance of the concept was augmented by Heidenhain's use of it in explaining hypnotic phenomena.

  2. Study of electroplated silver-palladium biofouling inhibiting coating

    DEFF Research Database (Denmark)

    Chiang, Wen-Chi; Hilbert, Lisbeth Rischel; Schroll, Casper

    2008-01-01

    Biofouling can cause many undesirable effects in industrial and medical settings. In this study, a new biofouling inhibiting Ag-Pd surface was designed to form an inhibiting effect by itself. This design was based on silver combined with nobler palladium, both with catalytic properties. Owing...... to the potential difference between silver and palladium while contacting with an electrolyte, the surface can form numerous discrete anodic and cathodic areas, so that an inhibiting reaction can occur. In this paper, a series of electrochemical and biological investigations were conducted to study the properties...... and biofouling inhibiting mechanism of these surfaces. In this study, the evidence is presented that the inhibiting effect can be caused by the electrochemical interactions and/or electric field between Pd and Ag/AgCl combined with an organic environment....

  3. Pain inhibits pain; human brainstem mechanisms.

    Science.gov (United States)

    Youssef, A M; Macefield, V G; Henderson, L A

    2016-01-01

    Conditioned pain modulation is a powerful analgesic mechanism, occurring when a painful stimulus is inhibited by a second painful stimulus delivered at a different body location. Reduced conditioned pain modulation capacity is associated with the development of some chronic pain conditions and the effectiveness of some analgesic medications. Human lesion studies show that the circuitry responsible for conditioned pain modulation lies within the caudal brainstem, although the precise nuclei in humans remain unknown. We employed brain imaging to determine brainstem sites responsible for conditioned pain modulation in 54 healthy individuals. In all subjects, 8 noxious heat stimuli (test stimuli) were applied to the right side of the mouth and brain activity measured using functional magnetic resonance imaging. This paradigm was then repeated. However, following the fourth noxious stimulus, a separate noxious stimulus, consisting of an intramuscular injection of hypertonic saline into the leg, was delivered (conditioning stimulus). During this test and conditioning stimulus period, 23 subjects displayed conditioned pain modulation analgesia whereas 31 subjects did not. An individual's analgesic ability was not influenced by gender, pain intensity levels of the test or conditioning stimuli or by psychological variables such as pain catastrophizing or fear of pain. Brain images were processed using SPM8 and the brainstem isolated using the SUIT toolbox. Significant increases in signal intensity were determined during each test stimulus and compared between subjects that did and did not display CPM analgesia (ppain modulation circuitry provides a framework for the future investigations into the neural mechanisms responsible for the maintenance of persistent pain conditions thought to involve altered analgesic circuitry.

  4. Risedronate inhibits human osteosarcoma cell invasion

    Directory of Open Access Journals (Sweden)

    Jung Sung

    2009-07-01

    Full Text Available Abstract Background Osteosarcoma is a highly malignant bone tumor and is the most commonly encountered malignant bone tumor in children and adolescents. Furthermore, significant numbers of patients eventually develop pulmonary metastases and succumb to the disease even after conventional multi-agent chemotherapy and surgical excision. Several solid tumors display enhanced expression of matrix metalloproteinases (MMPs, and recently clinical trials have been initiated on MMP-inhibitors. On the other hand, bisphosphonates (BPs, which have a profound effect on bone resorption, are widely used to treat osteoclast-mediated bone diseases. BPs are also known to inhibit tumor growths and metastases in some tumors such as breast cancer, renal cell carcinoma, and prostate cancer. Methods Two osteosarcoma cell lines (SaOS-2 and U2OS were treated with risedronate (0, 0.1, 1, 10 μM for 48 hours. Cell viabilities were determined using MTT assay, the mRNA levels of MMP-2 and MMP-9 were analyzed by reverse-transcription polymerase chain reaction, the amount of MMP-2 and MMP-9 protein were analyzed by Westernblot, the activities of MMP-2 and MMP-9 were observed by Gelatin zymography, and Matrigel invasion assays were used to investigate the invasive potential of osteosarcoma cell lines before and after risedronate treatment. Results The invasiveness of osteosarcoma cell lines (SaOS-2, U2OS were reduced in a dose dependent manner follow 48 hour treatment of up to 10 μM of the risedronate at which concentration no cytotoxicity occurred. Furthermore, the gelatinolytic activities and protein and mRNA levels of MMP-2 and MMP-9 were also suppressed by increasing risedronate concentrations. Conclusion Given that MMP-2 and MMP-9 are instrumental in tumor cell invasion, our results suggest the risedronate could reduce osteosarcoma cell invasion.

  5. Volatile hydrocarbons inhibit methanogenic crude oil degradation

    Directory of Open Access Journals (Sweden)

    Angela eSherry

    2014-04-01

    Full Text Available Methanogenic degradation of crude oil in subsurface sediments occurs slowly, but without the need for exogenous electron acceptors, is sustained for long periods and has enormous economic and environmental consequences. Here we show that volatile hydrocarbons are inhibitory to methanogenic oil biodegradation by comparing degradation of an artificially weathered crude oil with volatile hydrocarbons removed, with the same oil that was not weathered. Volatile hydrocarbons (nC5-nC10, methylcyclohexane, benzene, toluene and xylenes were quantified in the headspace of microcosms. Aliphatic (n-alkanes nC12-nC34 and aromatic hydrocarbons (4-methylbiphenyl, 3-methylbiphenyl, 2-methylnaphthalene, 1-methylnaphthalene were quantified in the total hydrocarbon fraction extracted from the microcosms. 16S rRNA genes from key microorganisms known to play an important role in methanogenic alkane degradation (Smithella and Methanomicrobiales were quantified by quantitative PCR. Methane production from degradation of weathered oil in microcosms was rapid (1.1 ± 0.1 µmol CH4/g sediment/day with stoichiometric yields consistent with degradation of heavier n-alkanes (nC12-nC34. For non-weathered oil, degradation rates in microcosms were significantly lower (0.4 ± 0.3 µmol CH4/g sediment/day. This indicated that volatile hydrocarbons present in the non-weathered oil inhibit, but do not completely halt, methanogenic alkane biodegradation. These findings are significant with respect to rates of biodegradation of crude oils with abundant volatile hydrocarbons in anoxic, sulphate-depleted subsurface environments, such as contaminated marine sediments which have been entrained below the sulfate-reduction zone, as well as crude oil biodegradation in petroleum reservoirs and contaminated aquifers.

  6. Inhibition of inflammatory arthritis using fullerene nanomaterials.

    Directory of Open Access Journals (Sweden)

    Anthony L Dellinger

    Full Text Available Inflammatory arthritis (e.g. rheumatoid arthritis; RA is a complex disease driven by the interplay of multiple cellular lineages. Fullerene derivatives have previously been shown to have anti-inflammatory capabilities mediated, in part, by their ability to prevent inflammatory mediator release by mast cells (MC. Recognizing that MC can serve as a cellular link between autoantibodies, soluble mediators, and other effector populations in inflammatory arthritis, it was hypothesized that fullerene derivatives might be used to target this inflammatory disease. A panel of fullerene derivatives was tested for their ability to affect the function of human skin-derived MC as well as other lineages implicated in arthritis, synovial fibroblasts and osteoclasts. It is shown that certain fullerene derivatives blocked FcγR- and TNF-α-induced mediator release from MC; TNF-α-induced mediator release from RA synovial fibroblasts; and maturation of human osteoclasts. MC inhibition by fullerene derivatives was mediated through the reduction of mitochondrial membrane potential and FcγR-mediated increases in cellular reactive oxygen species and NF-κB activation. Based on these in vitro data, two fullerene derivatives (ALM and TGA were selected for in vivo studies using K/BxN serum transfer arthritis in C57BL/6 mice and collagen-induced arthritis (CIA in DBA/1 mice. Dye-conjugated fullerenes confirmed localization to affected joints in arthritic animals but not in healthy controls. In the K/BxN moldel, fullerenes attenuated arthritis, an effect accompanied by reduced histologic inflammation, cartilage/bone erosion, and serum levels of TNF-α. Fullerenes remained capable of attenuating K/BxN arthritis in mast cell-deficient mice Cre-Master mice, suggesting that lineages beyond the MC represent relevant targets in this system. These studies suggest that fullerene derivatives may hold promise both as an assessment tool and as anti-inflammatory therapy of arthritis.

  7. Inhibition of inflammatory arthritis using fullerene nanomaterials.

    Science.gov (United States)

    Dellinger, Anthony L; Cunin, Pierre; Lee, David; Kung, Andrew L; Brooks, D Bradford; Zhou, Zhiguo; Nigrovic, Peter A; Kepley, Christopher L

    2015-01-01

    Inflammatory arthritis (e.g. rheumatoid arthritis; RA) is a complex disease driven by the interplay of multiple cellular lineages. Fullerene derivatives have previously been shown to have anti-inflammatory capabilities mediated, in part, by their ability to prevent inflammatory mediator release by mast cells (MC). Recognizing that MC can serve as a cellular link between autoantibodies, soluble mediators, and other effector populations in inflammatory arthritis, it was hypothesized that fullerene derivatives might be used to target this inflammatory disease. A panel of fullerene derivatives was tested for their ability to affect the function of human skin-derived MC as well as other lineages implicated in arthritis, synovial fibroblasts and osteoclasts. It is shown that certain fullerene derivatives blocked FcγR- and TNF-α-induced mediator release from MC; TNF-α-induced mediator release from RA synovial fibroblasts; and maturation of human osteoclasts. MC inhibition by fullerene derivatives was mediated through the reduction of mitochondrial membrane potential and FcγR-mediated increases in cellular reactive oxygen species and NF-κB activation. Based on these in vitro data, two fullerene derivatives (ALM and TGA) were selected for in vivo studies using K/BxN serum transfer arthritis in C57BL/6 mice and collagen-induced arthritis (CIA) in DBA/1 mice. Dye-conjugated fullerenes confirmed localization to affected joints in arthritic animals but not in healthy controls. In the K/BxN moldel, fullerenes attenuated arthritis, an effect accompanied by reduced histologic inflammation, cartilage/bone erosion, and serum levels of TNF-α. Fullerenes remained capable of attenuating K/BxN arthritis in mast cell-deficient mice Cre-Master mice, suggesting that lineages beyond the MC represent relevant targets in this system. These studies suggest that fullerene derivatives may hold promise both as an assessment tool and as anti-inflammatory therapy of arthritis.

  8. Combined Angiotensin Receptor Antagonism and Neprilysin Inhibition.

    Science.gov (United States)

    Hubers, Scott A; Brown, Nancy J

    2016-03-15

    Heart failure affects ≈5.7 million people in the United States alone. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and aldosterone antagonists have improved mortality in patients with heart failure and reduced ejection fraction, but mortality remains high. In July 2015, the US Food and Drug Administration approved the first of a new class of drugs for the treatment of heart failure: Valsartan/sacubitril (formerly known as LCZ696 and currently marketed by Novartis as Entresto) combines the angiotensin receptor blocker valsartan and the neprilysin inhibitor prodrug sacubitril in a 1:1 ratio in a sodium supramolecular complex. Sacubitril is converted by esterases to LBQ657, which inhibits neprilysin, the enzyme responsible for the degradation of the natriuretic peptides and many other vasoactive peptides. Thus, this combined angiotensin receptor antagonist and neprilysin inhibitor addresses 2 of the pathophysiological mechanisms of heart failure: activation of the renin-angiotensin-aldosterone system and decreased sensitivity to natriuretic peptides. In the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, valsartan/sacubitril significantly reduced mortality and hospitalization for heart failure, as well as blood pressure, compared with enalapril in patients with heart failure, reduced ejection fraction, and an elevated circulating level of brain natriuretic peptide or N-terminal pro-brain natriuretic peptide. Ongoing clinical trials are evaluating the role of valsartan/sacubitril in the treatment of heart failure with preserved ejection fraction and hypertension. We review here the mechanisms of action of valsartan/sacubitril, the pharmacological properties of the drug, and its efficacy and safety in the treatment of heart failure and hypertension.

  9. Arginine deiminase inhibits Porphyromonas gingivalis surface attachment.

    Science.gov (United States)

    Cugini, Carla; Stephens, Danielle N; Nguyen, Daniel; Kantarci, Alpdogan; Davey, Mary E

    2013-02-01

    The oral cavity is host to a complex microbial community whose maintenance depends on an array of cell-to-cell interactions and communication networks, with little known regarding the nature of the signals or mechanisms by which they are sensed and transmitted. Determining the signals that control attachment, biofilm development and outgrowth of oral pathogens is fundamental to understanding pathogenic biofilm development. We have previously identified a secreted arginine deiminase (ADI) produced by Streptococcus intermedius that inhibited biofilm development of the commensal pathogen Porphyromonas gingivalis through downregulation of genes encoding the major (fimA) and minor (mfa1) fimbriae, both of which are required for proper biofilm development. Here we report that this inhibitory effect is dependent on enzymic activity. We have successfully cloned, expressed and defined the conditions to ensure that ADI from S. intermedius is enzymically active. Along with the cloning of the wild-type allele, we have created a catalytic mutant (ADIC399S), in which the resulting protein is not able to catalyse the hydrolysis of l-arginine to l-citrulline. P. gingivalis is insensitive to the ADIC399S catalytic mutant, demonstrating that enzymic activity is required for the effects of ADI on biofilm formation. Biofilm formation is absent under l-arginine-deplete conditions, and can be recovered by the addition of the amino acid. Taken together, the results indicate that arginine is an important signal that directs biofilm formation by this anaerobe. Based on our findings, we postulate that ADI functions to reduce arginine levels and, by a yet to be identified mechanism, signals P. gingivalis to alter biofilm development. ADI release from the streptococcal cell and its cross-genera effects are important findings in understanding the nature of inter-bacterial signalling and biofilm-mediated diseases of the oral cavity.

  10. Inositol pyrophosphates inhibit synaptotagmin-dependent exocytosis.

    Science.gov (United States)

    Lee, Tae-Sun; Lee, Joo-Young; Kyung, Jae Won; Yang, Yoosoo; Park, Seung Ju; Lee, Seulgi; Pavlovic, Igor; Kong, Byoungjae; Jho, Yong Seok; Jessen, Henning J; Kweon, Dae-Hyuk; Shin, Yeon-Kyun; Kim, Sung Hyun; Yoon, Tae-Young; Kim, Seyun

    2016-07-19

    Inositol pyrophosphates such as 5-diphosphoinositol pentakisphosphate (5-IP7) are highly energetic inositol metabolites containing phosphoanhydride bonds. Although inositol pyrophosphates are known to regulate various biological events, including growth, survival, and metabolism, the molecular sites of 5-IP7 action in vesicle trafficking have remained largely elusive. We report here that elevated 5-IP7 levels, caused by overexpression of inositol hexakisphosphate (IP6) kinase 1 (IP6K1), suppressed depolarization-induced neurotransmitter release from PC12 cells. Conversely, IP6K1 depletion decreased intracellular 5-IP7 concentrations, leading to increased neurotransmitter release. Consistently, knockdown of IP6K1 in cultured hippocampal neurons augmented action potential-driven synaptic vesicle exocytosis at synapses. Using a FRET-based in vitro vesicle fusion assay, we found that 5-IP7, but not 1-IP7, exhibited significantly higher inhibitory activity toward synaptic vesicle exocytosis than IP6 Synaptotagmin 1 (Syt1), a Ca(2+) sensor essential for synaptic membrane fusion, was identified as a molecular target of 5-IP7 Notably, 5-IP7 showed a 45-fold higher binding affinity for Syt1 compared with IP6 In addition, 5-IP7-dependent inhibition of synaptic vesicle fusion was abolished by increasing Ca(2+) levels. Thus, 5-IP7 appears to act through Syt1 binding to interfere with the fusogenic activity of Ca(2+) These findings reveal a role of 5-IP7 as a potent inhibitor of Syt1 in controlling the synaptic exocytotic pathway and expand our understanding of the signaling mechanisms of inositol pyrophosphates.

  11. . Psychological predictors of inhibition development in educational environments

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    Symanyuk, Elvira E.

    2016-09-01

    Full Text Available This article examines psychological predictors of inhibition in educational environments as well as various aspects of pedagogical communication, including facilitation, which is aimed at enhancing educational effectiveness and developing students by means of using a particular communication style and the teacher’s personality. The need to study inhibition (the deterioration of teacher-children interactions; the negation of a student’s individuality; the inability to understand and accept students’ viewpoints; teacher-provoked conflicts; and emotional callousness is substantiated. The essence of psychological predictors as independent variables, changes in which lead to changes in other dependent variables, allowing the prediction of inhibition development, is explained. The research objective was to identify psychological predictors of the development of inhibition in pedagogical communication. An empirical study was conducted using standardized techniques for diagnosing communicative attitudes (V. Boyko, developing general communicative tolerance (V. Boyko, identifying aggressiveness (A. Asinger, identifying the level of empathy (V. Boyko, and identifying the degree of pedagogical inhibition (L. Polosova. The sample contained 375 teachers from Yekaterinburg educational institutions, with participant selection made using stratified sampling. The teacher’s personality features (a negative communicative attitude, low communicative tolerance and empathy, and higher levels of aggression were shown to be key predictors of inhibition, which itself was found to depend on the length of teaching experience. At the beginning of one’s professional teaching career, the level of inhibition is minimal. However, the level of inhibition reaches its maximum level after 5-10 years of teaching, and after 20 years, there is a sharp decrease in the level of inhibition. The conclusion of this study stresses the importance of developing strategies to

  12. Inhibition of vascular permeability by antisense-mediated inhibition of plasma kallikrein and coagulation factor 12.

    Science.gov (United States)

    Bhattacharjee, Gourab; Revenko, Alexey S; Crosby, Jeffrey R; May, Chris; Gao, Dacao; Zhao, Chenguang; Monia, Brett P; MacLeod, A Robert

    2013-06-01

    Hereditary angioedema (HAE) is a rare disorder characterized by recurrent, acute, and painful episodes of swelling involving multiple tissues. Deficiency or malfunction of the serine protease inhibitor C1 esterase inhibitor (C1-INH) results in HAE types 1 and 2, respectively, whereas mutations in coagulation factor 12 (f12) have been associated with HAE type 3. C1-INH is the primary inhibitor of multiple plasma cascade pathways known to be altered in HAE patients, including the complement, fibrinolytic, coagulation, and kinin-kallikrein pathways. We have selectively inhibited several components of both the kinin-kallikrein system and the coagulation cascades with potent and selective antisense oligonucleotides (ASOs) to investigate their relative contributions to vascular permeability. We have also developed ASO inhibitors of C1-INH and characterized their effects on vascular permeability in mice as an inducible model of HAE. Our studies demonstrate that ASO-mediated reduction in C1-INH plasma levels results in increased vascular permeability and that inhibition of proteases of the kinin-kallikrein system, either f12 or prekallikrein (PKK) reverse the effects of C1-INH depletion with similar effects on both basal and angiotensin converting enzyme (ACE) inhibitor-induced permeability. In contrast, inhibition of coagulation factors 11 (f11) or 7 (f7) had no effect. These results suggest that the vascular defects observed in C1-INH deficiency are dependent on the kinin-kallikrein system proteases f12 and PKK, and not mediated through the coagulation pathways. In addition, our results highlight a novel therapeutic modality that can potentially be employed prophylactically to prevent attacks in HAE patients.

  13. Inhibition of Uterine Contractility by Thalidomide Analogs via Phosphodiesterase-4 Inhibition and Calcium Entry Blockade

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    Eduardo Fernández-Martínez

    2016-10-01

    Full Text Available Uterine relaxation is crucial during preterm labor. Phosphodiesterase-4 (PDE-4 inhibitors have been proposed as tocolytics. Some thalidomide analogs are PDE-4 inhibitors. The aim of this study was to assess the uterus-relaxant properties of two thalidomide analogs, methyl 3-(4-nitrophthalimido-3-(3,4-dimethoxyphenyl-propanoate (4NO2PDPMe and methyl 3-(4-aminophthalimido-3-(3,4-dimethoxyphenyl-propanoate (4APDPMe and were compared to rolipram in functional studies of spontaneous phasic, K+-induced tonic, and Ca2+-induced contractions in isolated pregnant human myometrial tissues. The accumulation of cAMP was quantified in HeLa cells. The presence of PDE-4B2 and phosphorylated myosin light-chain (pMLC, in addition to the effect of thalidomide analogs on oxytocin-induced pMLC, were assessed in human uterine myometrial cells (UtSMCs. Thalidomide analogs had concentration-dependent inhibitory effects on spontaneous and tonic contractions and inhibited Ca2+-induced responses. Tonic contraction was equipotently inhibited by 4APDPMe and rolipram (IC50 = 125 ± 13.72 and 98.45 ± 8.86 µM, respectively. Rolipram and the thalidomide analogs inhibited spontaneous and tonic contractions equieffectively. Both analogs increased cAMP accumulation in a concentration-dependent manner (p < 0.05 and induced changes in the subcellular localization of oxytocin-induced pMLC in UtSMCs. The inhibitory effects of thalidomide analogs on the contractions of pregnant human myometrium tissue may be due to their PDE-4 inhibitory effect and novel mechanism as calcium-channel blockers.

  14. On inhibition/disinhibition in developmental psychopathology: views from cognitive and personality psychology and a working inhibition taxonomy.

    Science.gov (United States)

    Nigg, J T

    2000-03-01

    Disinhibition is a common focus in psychopathology research. However, use of inhibition models often is piecemeal, lacking an overarching taxonomy of inhibitory processes. The author organizes key concepts and models pertaining to different kinds of inhibitory control from the cognitive and temperament/personality literatures. Within the rubrics of executive inhibitory processes, motivational inhibitory processes, and automatic attentional inhibition processes, 8 kinds of inhibition are distinguished. Three basic temperament traits may address key executive and motivational inhibitory processes. Future developmental psychopathology research should be based on a systematic conceptual taxonomy of the kinds of inhibitory function relevant to a given disorder. Such an approach can clarify which inhibition distinctions are correct and which inhibition deficits go with which disorders.

  15. Tim-3 inhibits macrophage control of Listeria monocytogenes by inhibiting Nrf2

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    Wang, Zhiding; Sun, Dejun; Chen, Guojiang; Li, Ge; Dou, Shuaijie; Wang, Renxi; Xiao, He; Hou, Chunmei; Li, Yan; Feng, Jiannan; Shen, Beifen; Han, Gencheng

    2017-01-01

    T cell immunoglobulin mucin-3 (Tim-3) is an immune checkpoint inhibitor and its dysregulation has been related to T cell tolerance and many immune disorders, such as tumors and infection tolerance. However, the physiopathology roles of Tim-3 in innate immunity remain elusive. Here, we demonstrate that Tim-3 inhibits macrophage phagocytosis of L. monocytogenes by inhibiting the nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway and increases bacterial burden. Tim-3 signaling promotes Nrf2 degradation by increasing its ubiquitination and, as a result, decreasing its nuclear translocation. CD36 and heme oxygenase-1 (HO-1), two downstream molecules in the Tim-3-Nrf2 signaling axis, are involved in the Tim-3- mediated immune evasion of L. monocytogenes both in vitro and in vivo. We here identified new mechanisms by which Tim-3 induces infection tolerance. By modulating the Tim-3 pathway, we demonstrate the feasibility of manipulating macrophage function as a potent tool for treating infectious diseases, such as Listeria infection. PMID:28205579

  16. Bryostatin I inhibits growth of breast cancer cells through the inhibition of synuclein-A expression

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    Jun-Xia Sun

    2016-09-01

    Full Text Available The present study was aimed to investigate the effect of bryostatin I on the expression of synuclein-A in breast cancer cells. Western blot analysis showed a significant (p<0.005 reduction in the expression of synuclein-A from a concentration of 20 µM in H3922 cells. The inhibitory effect of bryostatin I on synuclein-A expression was further confirmed by the treatment of H3922 cells with known synuclein-A inhibitor, cytokine oncostatin M. Bryostatin I treatment of H3922 cells also significantly increased their sensitivity to the taxol. Incubation of the cells with 25 µM concentration of bryostatin I followed by treatment with 0.5 μM concentration of taxol induced apoptosis in 89% cells compared to 9% cells in the taxol alone treated cultures. Treatment of the H3922 cells with bryostatin I at 25 µM concentration led to a significant increase in the activation of histone H1 protein. The results from MTT assay showed a significant decrease in the cell viability from 10 µM concentration of bryostatin I. Thus, bryostatin I inhibits the growth of breast cancer cells through inhibition of synuclein-A expression and can be used for breast cancer treatment.

  17. Inhibition of auxin movement from the shoot into the root inhibits lateral root development in Arabidopsis

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    Reed, R. C.; Brady, S. R.; Muday, G. K.

    1998-01-01

    In roots two distinct polar movements of auxin have been reported that may control different developmental and growth events. To test the hypothesis that auxin derived from the shoot and transported toward the root controls lateral root development, the two polarities of auxin transport were uncoupled in Arabidopsis. Local application of the auxin-transport inhibitor naphthylphthalamic acid (NPA) at the root-shoot junction decreased the number and density of lateral roots and reduced the free indoleacetic acid (IAA) levels in the root and [3H]IAA transport into the root. Application of NPA to the basal half of or at several positions along the root only reduced lateral root density in regions that were in contact with NPA or in regions apical to the site of application. Lateral root development was restored by application of IAA apical to NPA application. Lateral root development in Arabidopsis roots was also inhibited by excision of the shoot or dark growth and this inhibition was reversible by IAA. Together, these results are consistent with auxin transport from the shoot into the root controlling lateral root development.

  18. Presynaptic inhibition by kainate receptors converges mechanistically with presynaptic inhibition by adenosine and GABAB receptors.

    Science.gov (United States)

    Partovi, Dara; Frerking, Matthew

    2006-11-01

    Kainate receptors are widely reported to regulate the release of neurotransmitter in the CNS, but the mechanisms involved remain controversial. Previous studies have found that the kainate receptor agonist ATPA, which selectively activates Glu(K5)-containing kainate receptors, depresses glutamate release at Schaffer-collateral synapses in the hippocampus. In the present study, we provide pharmacological evidence that this depressant effect is mediated by Glu(K5)-containing heteromers, but is distinct from a similar depressant effect engaged by the kainate receptor agonist domoate. The depressant effect of ATPA is insensitive to antagonists for GABA(A), GABA(B), and adenosine receptors, and is also unaffected by lowering the release probability by reducing extracellular calcium. However, the effect of ATPA is partly occluded by prior activation of GABA(B) receptors and completely occluded by prior activation of adenosine receptors, suggesting a mechanistic convergence of heteromeric Glu(K5) kainate receptor signaling with GABA(B) receptors and adenosine receptors. The effects of domoate are partially occluded by both adenosine and GABA(B) receptor agonists, indicating at least a partial convergence of Glu(K5)-lacking kainate receptor signaling with these other pathways. The depressant effect of ATPA is not blocked by inhibition of serine/threonine protein kinases. These results suggest that ATPA and domoate inhibit glutamate release through mechanisms that converge with those of classical metabotropic receptor agonists, although they do so through different receptors.

  19. Resveratrol Inhibited Non-small Cell Lung Cancer Through Inhibiting STAT-3 Signaling.

    Science.gov (United States)

    Li, Xin; Wang, Dan; Zhao, Qing Chun; Shi, Tao; Chen, Jun

    2016-11-01

    Resveratrol has demonstrated many beneficial effects against cancers; however, the mechanism remains unclear. Non-small cell lung cancer accounts for 80% of lung cancers. The present study was designed to observe the effects and related mechanisms of resveratrol on non-small cell lung cancer in in vitro A549 cells. The anticancer effects of resveratrol were analyzed on cell viability, migration and invasion, proliferation and apoptosis. Cell viability was determined by sulphorhodamine B assays. Cell proliferation and apoptosis were determined by flow cytometry and migration and invasion by transwell chamber analysis. Expression of STAT-3 was examined by real-time polymerase chain reaction and western blot. Overexpressing vector of STAT-3 was also constructed and transfected into A549 cells to observe the effects of resveratrol on STAT-3 signaling. The results showed that resveratrol displayed a dose-dependent and time-dependent cytotoxicity action on A549 cell viability. Resveratrol also inhibited proliferation, migration and invasion and promoted apoptosis in a time-dependent manner from 0-72 hours. Further study showed that resveratrol inhibited the messenger RNA and protein expression of STAT-3, and overexpressed STAT-3 abolished the effects of resveratrol on proliferation, apoptosis, migration and invasion totally or in part. These results suggest that the anticancer effects of resveratrol are mediated by STAT-3 signaling. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  20. Nifuroxazide inhibits survival of multiple myeloma cells by directly inhibiting STAT3.

    Science.gov (United States)

    Nelson, Erik A; Walker, Sarah R; Kepich, Alicia; Gashin, Laurie B; Hideshima, Teru; Ikeda, Hiroshi; Chauhan, Dharminder; Anderson, Kenneth C; Frank, David A

    2008-12-15

    Constitutive activation of the transcription factor STAT3 contributes to the pathogenesis of many cancers, including multiple myeloma (MM). Since STAT3 is dispensable in most normal tissue, targeted inhibition of STAT3 is an attractive therapy for patients with these cancers. To identify STAT3 inhibitors, we developed a transcriptionally based assay and screened a library of compounds known to be safe in humans. We found the drug nifuroxazide to be an effective inhibitor of STAT3 function. Nifuroxazide inhibits the constitutive phosphorylation of STAT3 in MM cells by reducing Jak kinase autophosphorylation, and leads to down-regulation of the STAT3 target gene Mcl-1. Nifuroxazide causes a decrease in viability of primary myeloma cells and myeloma cell lines containing STAT3 activation, but not normal peripheral blood mononuclear cells. Although bone marrow stromal cells provide survival signals to myeloma cells, nifuroxazide can overcome this survival advantage. Reflecting the interaction of STAT3 with other cellular pathways, nifuroxazide shows enhanced cytotoxicity when combined with either the histone deacetylase inhibitor depsipeptide or the MEK inhibitor UO126. Therefore, using a mechanistic-based screen, we identified the clinically relevant drug nifuroxazide as a potent inhibitor of STAT signaling that shows cytotoxicity against myeloma cells that depend on STAT3 for survival.

  1. Inhibiting the inhibition: a neuronal network for sound localization in reverberant environments.

    Science.gov (United States)

    Pecka, Michael; Zahn, Thomas P; Saunier-Rebori, Bernadette; Siveke, Ida; Felmy, Felix; Wiegrebe, Lutz; Klug, Achim; Pollak, George D; Grothe, Benedikt

    2007-02-14

    The precedence effect describes the phenomenon whereby echoes are spatially fused to the location of an initial sound by selectively suppressing the directional information of lagging sounds (echo suppression). Echo suppression is a prerequisite for faithful sound localization in natural environments but can break down depending on the behavioral context. To date, the neural mechanisms that suppress echo directional information without suppressing the perception of echoes themselves are not understood. We performed in vivo recordings in Mongolian gerbils of neurons of the dorsal nucleus of the lateral lemniscus (DNLL), a GABAergic brainstem nucleus that targets the auditory midbrain, and show that these DNLL neurons exhibit inhibition that persists tens of milliseconds beyond the stimulus offset, so-called persistent inhibition (PI). Using in vitro recordings, we demonstrate that PI stems from GABAergic projections from the opposite DNLL. Furthermore, these recordings show that PI is attributable to intrinsic features of this GABAergic innervation. Implementation of these physiological findings into a neuronal model of the auditory brainstem demonstrates that, on a circuit level, PI creates an enhancement of responsiveness to lagging sounds in auditory midbrain cells. Moreover, the model revealed that such response enhancement is a sufficient cue for an ideal observer to identify echoes and to exhibit echo suppression, which agrees closely with the percepts of human subjects.

  2. Methylene Blue Inhibits Caspases by Oxidation of the Catalytic Cysteine.

    Science.gov (United States)

    Pakavathkumar, Prateep; Sharma, Gyanesh; Kaushal, Vikas; Foveau, Bénédicte; LeBlanc, Andrea C

    2015-09-24

    Methylene blue, currently in phase 3 clinical trials against Alzheimer Disease, disaggregates the Tau protein of neurofibrillary tangles by oxidizing specific cysteine residues. Here, we investigated if methylene blue can inhibit caspases via the oxidation of their active site cysteine. Methylene blue, and derivatives, azure A and azure B competitively inhibited recombinant Caspase-6 (Casp6), and inhibited Casp6 activity in transfected human colon carcinoma cells and in serum-deprived primary human neuron cultures. Methylene blue also inhibited recombinant Casp1 and Casp3. Furthermore, methylene blue inhibited Casp3 activity in an acute mouse model of liver toxicity. Mass spectrometry confirmed methylene blue and azure B oxidation of the catalytic Cys163 cysteine of Casp6. Together, these results show a novel inhibitory mechanism of caspases via sulfenation of the active site cysteine. These results indicate that methylene blue or its derivatives could (1) have an additional effect against Alzheimer Disease by inhibiting brain caspase activity, (2) be used as a drug to prevent caspase activation in other conditions, and (3) predispose chronically treated individuals to cancer via the inhibition of caspases.

  3. Executive control signals in orbitofrontal cortex during response inhibition.

    Science.gov (United States)

    Bryden, Daniel W; Roesch, Matthew R

    2015-03-04

    Orbitofrontal cortex (OFC) lesions produce deficits in response inhibition and imaging studies suggest that activity in OFC is stronger on trials that require suppression of behavior, yet few studies have examined neural correlates at the single-unit level in a behavioral task that probes response inhibition without varying other factors, such as anticipated outcomes. Here we recorded from single neurons in lateral OFC in a task that required animals in the minority of trials to STOP or inhibit an ongoing movement and respond in the opposite direction. We found that population and single-unit firing was modulated primarily by response direction and movement speed, and that very few OFC neurons exhibited a response independent inhibition signal. Remarkably, the strength of the directional signal was not diminished on STOP trials and was actually stronger on STOP trials during conflict adaptation. Finally, directional signals were stronger during sessions in which rats had the most difficulty inhibiting behavior. These results suggest that "inhibition" deficits observed with OFC interference studies reflect deficits unrelated to signaling the need to inhibit behavior, but instead support a role for OFC in executive functions related to dissociating between two perceptually similar actions during response conflict. Copyright © 2015 the authors 0270-6474/15/353903-12$15.00/0.

  4. Novel Bioactivity of Ellagic Acid in Inhibiting Human Platelet Activation

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    Yi Chang

    2013-01-01

    Full Text Available Pomegranates are widely consumed either as fresh fruit or in beverage form as juice and wine. Ellagic acid possesses potent antioxidative properties; it is known to be an effective phytotherapeutic agent with antimutagenic and anticarcinogenic qualities. Ellagic acid (20 to 80 μM exhibited a potent activity in inhibiting platelet aggregation stimulated by collagen; however, it did not inhibit platelet aggregation stimulated by thrombin, arachidonic acid, or U46619. Treatment with ellagic acid (50 and 80 μM significantly inhibited platelet activation stimulated by collagen; this alteration was accompanied by the inhibition of relative [Ca2+]i mobilization, and the phosphorylation of phospholipase C (PLCγ2, protein kinase C (PKC, mitogen-activated protein kinases (MAPKs, and Akt, as well as hydroxyl radical (OH● formation. In addition, ellagic acid also inhibited p38 MAPK and Akt phosphorylation stimulated by hydrogen peroxide. By contrast, ellagic acid did not significantly affect PKC activation and platelet aggregation stimulated by PDBu. This study is the first to show that, in addition to being considered a possible agent for preventing tumor growth, ellagic acid possesses potent antiplatelet properties. It appears to initially inhibit the PLCγ2-PKC cascade and/or hydroxyl radical formation, followed by decreased phosphorylation of MAPKs and Akt, ultimately inhibiting platelet aggregation.

  5. Desferrioxamine Inhibits Protein Tyrosine Nitration: Mechanisms and Implications

    Science.gov (United States)

    Adgent, Margaret A.; Squadrito, Giuseppe L.; Ballinger, Carol A.; Krzywanski, David M.; Lancaster, Jack R.; Postlethwait, Edward M.

    2012-01-01

    Tissues are exposed to exogenous and endogenous nitrogen dioxide (•NO2), which is the terminal agent in protein tyrosine nitration. Besides iron chelation, the hydroxamic acid (HA) desferrioxamine (DFO) shows multiple functionalities including nitration inhibition. To investigate mechanisms whereby DFO affects 3-nitrotyrosine (3-NT) formation, we utilized gas phase •NO2 exposures, to limit introduction of other reactive species, and a lung surface model wherein red cell membranes (RCM) were immobilized under a defined aqueous film. When RCM were exposed to •NO2 covered by +/− DFO: (i) DFO inhibited 3-NT formation more effectively than other HA and non-HA chelators; (ii) 3-NT inhibition occurred at very low [DFO] for prolonged times; and (iii) 3-NT formation was iron independent but inhibition required DFO present. DFO poorly reacted with •NO2 compared to ascorbate, assessed via •NO2 reactive absorption and aqueous phase oxidation rates, yet limited 3-NT formation at far lower concentrations. DFO also inhibited nitration under aqueous bulk phase conditions, and inhibited 3-NT generated by active myeloperoxidase “bound” to RCM. Per the above and kinetic analyses suggesting preferential DFO versus •NO2 reaction within membranes, we conclude that DFO inhibits 3-NT formation predominantly by facile repair of the tyrosyl radical intermediate, which prevents •NO2 addition, and thus nitration, and potentially influences biochemical functionalities. PMID:22705369

  6. Neural correlates of central inhibition during physical fatigue.

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    Masaaki Tanaka

    Full Text Available Central inhibition plays a pivotal role in determining physical performance during physical fatigue. Classical conditioning of central inhibition is believed to be associated with the pathophysiology of chronic fatigue. We tried to determine whether classical conditioning of central inhibition can really occur and to clarify the neural mechanisms of central inhibition related to classical conditioning during physical fatigue using magnetoencephalography (MEG. Eight right-handed volunteers participated in this study. We used metronome sounds as conditioned stimuli and maximum handgrip trials as unconditioned stimuli to cause central inhibition. Participants underwent MEG recording during imagery of maximum grips of the right hand guided by metronome sounds for 10 min. Thereafter, fatigue-inducing maximum handgrip trials were performed for 10 min; the metronome sounds were started 5 min after the beginning of the handgrip trials. The next day, neural activities during imagery of maximum grips of the right hand guided by metronome sounds were measured for 10 min. Levels of fatigue sensation and sympathetic nerve activity on the second day were significantly higher relative to those of the first day. Equivalent current dipoles (ECDs in the posterior cingulated cortex (PCC, with latencies of approximately 460 ms, were observed in all the participants on the second day, although ECDs were not identified in any of the participants on the first day. We demonstrated that classical conditioning of central inhibition can occur and that the PCC is involved in the neural substrates of central inhibition related to classical conditioning during physical fatigue.

  7. Australine, a pyrrolizidine alkaloid that inhibits amyloglucosidase and glycoprotein processing

    Energy Technology Data Exchange (ETDEWEB)

    Tropea, J.E.; Molyneux, R.J.; Kaushal, G.P.; Pan, Y.T.; Mitchell, M.; Elbein, A.D. (Univ. of Texas Health Science Center, San Antonio (USA))

    1989-03-07

    Australine is a polyhydroxylated pyrrolizidine alkaloid that was isolated from the seeds of the Australian tree Castanospermum australe and characterized by NMR and X-ray diffraction analysis. Since swainsonine and catanospermine are polyhydroxylated indolizidine alkaloids that inhibit specific glycosidases, the authors tested australine against a variety of exoglycosidases to determine whether it would inhibit any of these enzymes. This alkaloid proved to be a good inhibitor of the {alpha}-glucosidase amyloglucosidase (50% inhibition at 5.8 {mu}M), but it did not inhibit {beta}-glucosidase, {alpha}- or {beta}-mannosidase, or {alpha}- or {beta}-galactosidase. The inhibition of amyloglucosidase was of a competitive nature. Australine also inhibited the glycoprotein processing enzyme glucosidase I, but had only slight activity toward glucosidase II. When incubated with cultured cells, this alkaloid inhibited glycoprotein processing at the glucosidase I step and caused the accumulation of glycoproteins with Glc{sub 3}Man{sub 7-9}(GlcNAc){sub 2}-oligosaccharides.

  8. Malonate inhibits virulence gene expression in Vibrio cholerae.

    Science.gov (United States)

    Minato, Yusuke; Fassio, Sara R; Häse, Claudia C

    2013-01-01

    We previously found that inhibition of the TCA cycle, either through mutations or chemical inhibition, increased toxT transcription in Vibrio cholerae. In this study, we found that the addition of malonate, an inhibitor of succinate dehydrogenase (SDH), decreased toxT transcription in V. cholerae, an observation inconsistent with the previous pattern observed. Unlike another SDH inhibitor, 2-thenoyltrifluoroacetone (TTFA), which increased toxT transcription and slightly inhibited V. cholerae growth, malonate inhibited toxT transcription in both the wild-type strain and TCA cycle mutants, suggesting malonate-mediated inhibition of virulence gene expression is independent to TCA cycle activity. Addition of malonate also inhibited ctxB and tcpA expressions but did not affect aphA, aphB, tcpP and toxR expressions. Malonate inhibited cholera toxin (CT) production in both V. cholerae classical biotype strains O395N1 and CA401, and El Tor biotype strain, N16961. Consistent with previous reports, we confirmed that these strains of V. cholerae did not utilize malonate as a primary carbon source. However, we found that the addition of malonate to the growth medium stimulated V. cholerae growth. All together, these results suggest that metabolizing malonate as a nutrient source negatively affects virulence gene expression in V. cholerae.

  9. Lactobacillus acidophilus Probiotic Inhibits the Growth of Candida albicans

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    Sawitri D. Pertami

    2014-04-01

    Full Text Available Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4 Candida albicans is the most common organism causing oral candidiasis. Drug resistance to synthetic antifungal medication is becoming a problem in the treatment of oral candidiasis, especially in immunocompromised patients.Probiotic has been known for its health benefits. It produces lactic acid and bacteriocin that has antibacterial effect. Research focuses on antifungal effect of probiotic, escpecially for C. albicans is still needed. Objective: To determinethe inhibition effect of probiotic in the growth of C. albicans. Methods: Three concentrations of Lactobacillus acidophilus-containing probiotic (McFarland 6, 8, 10 were used to determine their inhibition effect on C. albicans (McFarland 0.5 growing in trypticase yeast-extract cystine (TYC agar. The inhibition effect of probiotic was determined by measuring the inhibition zone produced after 48 hours of culture. Difference in inhibition zone among experimental groups was analyzed using one-way ANOVA and LSD post-test. Results: Probiotic with McFarland 10 had the highest inhibition effect against C. albicans and the difference to other experimental groups was statistically significant (p<0.05. Conclusion: L. acidophilus probiotic has inhibition effect in the growth of C. albicans.DOI: 10.14693/jdi.v20i3.196

  10. Inhibition of Human Neutrophil Elastase by Pentacyclic Triterpenes

    Science.gov (United States)

    Feng, Li; Liu, Xiaoyu; Zhu, Weiliang; Guo, Fujiang; YingchunWu; Wang, Rui; Chen, Kaixian; Huang, Cheng; Li, Yiming

    2013-01-01

    Scope Inhibiting human neutrophil elastase (HNE) is a promising strategy for treating inflammatory lung diseases, such as H1N1 and SARS virus infections. The use of sivelestat, the only clinically registered synthesized HNE inhibitor, is largely limited by its risk of organ toxicity because it irreversibly inhibits HNE. Therefore, potent reversible HNE inhibitors are promising alternatives to sivelestat. Methods and Results An in vitro HNE inhibition assay was employed to screen a series of triterpenes. Six pentacyclic triterpenes, but not tetracyclic triterpenes, significantly inhibited HNE. Of these pentacyclic triterpenes, ursolic acid exhibited the highest inhibitory potency (IC50 = 5.51 µM). The HNE inhibitory activity of ursolic acid was further verified using a mouse model of acute smoke-induced lung inflammation. The results of nuclear magnetic resonance and HNE inhibition kinetic analysis showed that the pentacyclic triterpenes competitively and reversibly inhibited HNE. Molecular docking experiments indicated that the molecular scaffold, 28-COOH, and a double bond at an appropriate location in the pentacyclic triterpenes are important for their inhibitory activity. Conclusion Our results provide insights into the effects of pentacyclic triterpenes on lung inflammatory actions through reversible inhibition of HNE activity. PMID:24376583

  11. Inhibition of a plant sesquiterpene cyclase by mevinolin.

    Science.gov (United States)

    Vögeli, U; Chappell, J

    1991-07-01

    The specificity of mevinolin as an inhibitor of sterol and sesquiterpene metabolism in tobacco cell suspension cultures was examined. Exogenous mevinolin inhibited [14C]acetate, but not [3H]mevalonate incorporation into free sterols. In contrast, mevinolin inhibited the incorporation of both [14C]acetate and [3H]mevalonate into capsidiol, an extracellular sesquiterpene. Microsomal 3-hydroxy-3-methylglutaryl Coenzyme A reductase was inhibited greater than 90% by microM mevinolin, while squalene synthetase was insensitive to even 600 microM mevinolin. Sesquiterpene cyclase, the first branch point enzyme specific for sesquiterpene biosynthesis, was inhibited in a dose-dependent manner by mevinolin with a 50% reduction in activity at 100 microM. Kinetic analysis indicated that the mechanism for inhibition was complex with mevinolin acting as both a competitive and noncompetitive inhibitor. The results suggest that the mevinolin inhibition of [3H]mevalonate incorporation into extracellular sesquiterpenes can, in part, be attributed to a secondary, but specific, site of inhibition, the sesquiterpene cyclase.

  12. Curcumin inhibits amygdaloid kindled seizures in rats.

    Science.gov (United States)

    DU, Peng; Li, Xin; Lin, Hao-Jie; Peng, Wei-Feng; Liu, Jian-Ying; Ma, Yu; Fan, Wei; Wang, Xin

    2009-06-20

    Curcumin can reduce the severity of seizures induced by kainate acid (KA), but the role of curcumin in amygdaloid kindled models is still unknown. This study aimed to explore the effect of curcumin on the development of kindling in amygdaloid kindled rats. With an amygdaloid kindled Sprague-Dawley (SD) rat model and an electrophysiological method, different doses of curcumin (10 mgxkg(-1)xd(-1) and 30 mgxkg(-1)xd(-1) as low dose groups, 100 mgxkg(-1)xd(-1) and 300 mgxkg(-1)xd(-1) as high dose groups) were administrated intraperitoneally during the whole kindling days, by comparison with the course of kindling, afterdischarge (AD) thresholds and the number of ADs to reach the stages of class I to V seizures in the rats between control and experimental groups. One-way or two-way ANOVA and Fisher's least significant difference post hoc test were used for statistical analyses. Curcumin (both 100 mgxkg(-1)xd(-1) and 300 mgxkg(-1)xd(-1)) significantly inhibited the behavioral seizure development in the (19.80 +/- 2.25) and (21.70 +/- 2.21) stimulations respectively required to reach the kindled state. Rats treated with 100 mgxkg(-1)xd(-1) curcumin 30 minutes before kindling stimulation showed an obvious increase in the stimulation current intensity required to evoke AD from (703.3 +/- 85.9) microA to (960.0 +/- 116.5) microA during the progression to class V seizures. Rats treated with 300 mgxkg(-1)xd(-1) curcumin showed a significant increase in the stimulation current intensity required to evoke AD from (735.0 +/- 65.2) microA to (867.0 +/- 93.4) microA during the progression to class V seizures. Rats treated with 300 mgxkg(-1)xd(-1) curcumin required much more evoked ADs to reach the stage of class both IV (as (199.83 +/- 12.47) seconds) and V seizures (as (210.66 +/- 10.68) seconds). Rats treated with 100 mgxkg(-1)xd(-1) curcumin required much more evoked ADs to reach the stage of class V seizures (as (219.56 +/- 18.24) seconds). Our study suggests that curcumin has

  13. Inhibition of cellular respiration by endogenously produced carbon monoxide.

    Science.gov (United States)

    D'Amico, Gabriela; Lam, Francis; Hagen, Thilo; Moncada, Salvador

    2006-06-01

    Endogenously produced nitric oxide (NO) interacts with mitochondrial cytochrome c oxidase, leading to inhibition of cellular respiration. This interaction has been shown to have important physiological and pathophysiological consequences. Exogenous carbon monoxide (CO) is also known to inhibit cytochrome c oxidase in vitro; however, it is not clear whether endogenously produced CO can inhibit cellular respiration and, if so, what the significance of this might be. In this study, we show that exogenous CO inhibits respiration in a moderate but persistent manner in HEK293 cells under ambient (21%) oxygen concentrations (K(i) = 1.44 microM). This effect of CO was increased (K(i) = 0.35 microM) by incubation in hypoxic conditions (1% oxygen). Endogenous CO, generated by HEK293 cells transfected with the inducible isoform of haem oxygenase (haem oxygenase-1; HO-1), also inhibited cellular respiration moderately (by 12%) and this was accompanied by inhibition (23%) of cytochrome c oxidase activity. When the cells were incubated in hypoxic conditions during HO-1 induction, the inhibitory effect of CO on cell respiration was markedly increased to 70%. Furthermore, endogenously produced CO was found to be responsible for the respiratory inhibition that occurs in RAW264.7 cells activated in hypoxic conditions with lipopolysaccharide and interferon-gamma, in the presence of N-(iminoethyl)-L-ornithine to prevent the synthesis of NO. Our results indicate that CO contributes significantly to the respiratory inhibition in activated cells, particularly under hypoxic conditions. Inhibition of cell respiration by endogenous CO through its interaction with cytochrome c oxidase might have an important role in inflammatory and hypoxic conditions.

  14. Boric acid and boronic acids inhibition of pigeonpea urease.

    Science.gov (United States)

    Reddy, K Ravi Charan; Kayastha, Arvind M

    2006-08-01

    Urease from the seeds of pigeonpea was competitively inhibited by boric acid, butylboronic acid, phenylboronic acid, and 4-bromophenylboronic acid; 4-bromophenylboronic acid being the strongest inhibitor, followed by boric acid > butylboronic acid > phenylboronic acid, respectively. Urease inhibition by boric acid is maximal at acidic pH (5.0) and minimal at alkaline pH (10.0), i.e., the trigonal planar B(OH)3 form is a more effective inhibitor than the tetrahedral B(OH)4 -anionic form. Similarly, the anionic form of phenylboronic acid was least inhibiting in nature.

  15. INHIBITION OF RAT LENS ALDOSE REDUCTASE BY QUERCETAGETIN AND PATULETIN

    Institute of Scientific and Technical Information of China (English)

    1991-01-01

    In this paper the results of inhibition of the Aldose reductase(AR) activity on Wistar rat lens by Quercetagetin extracted from Tagetes erects Linn and by Patuletin extracted from Tagetes patula Linn are reported.Quercetagetin inhibited AR of the rat lens by 93.9% at 10~(-4)M, 76.0% at 10~(-5)M and 13.3% at 10~(-6)M. Patuletin inhibited AR of the rat lens by 100% at 10~(-1)M, 80% at 10~(-5)M and 22.7% at 10~(-6)M respectively. The results show that these two flavones are lens AR Inhibitors, but further ...

  16. Preference toward a polylysine enantiomer in inhibiting prions.

    Science.gov (United States)

    Jackson, Karen S; Yeom, Jihyun; Han, Youngmi; Bae, Younsoo; Ryou, Chongsuk

    2013-03-01

    Differential anti-prion activity of polylysine enantiomers was studied. Based on our recent discovery that poly-L-lysine (PLK) is a potent anti-prion agent, we investigated suppression of prions in cultured cells using poly-D-lysine (PDK). The results showed that PDK was more efficacious than PLK to inhibit prions. Protein misfolding cyclic amplification assay demonstrated improved efficacy of PDK in inhibiting plasminogen-mediated prion propagation, corresponding to the enantio-preference of PDK observed in cultured cells. Furthermore, our study demonstrated that polylysines formed a complex with plasminogen. These results propose to hypothesize a plausible mechanism that elicits prion inhibition by polylysine enantiomers.

  17. Endocannabinoids inhibit the growth of free-living amoebae.

    Science.gov (United States)

    Dey, Rafik; Pernin, Pierre; Bodennec, Jacques

    2010-07-01

    The cannabinoid Delta(9)-tetrahydrocannabinol inhibits the growth of some pathogenic amoebae in vitro and exacerbates amoebic encephalitis in animal models. However, the effects of endogenous cannabinoids on amoebae remain unknown. Therefore, we tested several endocannabinoids (N-acyl ethanolamines and 2-O-acyl glycerol) on different genera of amoebae. The results showed that all of the endocannabinoids tested inhibit amoebic growth at subpharmacological doses, with 50% inhibitory concentrations ranging from 15 to 20 microM. A nonhydrolyzable endocannabinoid had similar effects, showing that the inhibition seen results from endocannabinoids per se rather than from a catabolic product.

  18. Measuring Feedforward Inhibition and Its Impact on Local Circuit Function.

    Science.gov (United States)

    Hull, Court

    2017-05-01

    This protocol describes a series of approaches to measure feedforward inhibition in acute brain slices from the cerebellar cortex. Using whole-cell voltage and current clamp recordings from Purkinje cells in conjunction with electrical stimulation of the parallel fibers, these methods demonstrate how to measure the relationship between excitation and inhibition in a feedforward circuit. This protocol also describes how to measure the impact of feedforward inhibition on Purkinje cell excitability, with an emphasis on spike timing. © 2017 Cold Spring Harbor Laboratory Press.

  19. Complement inhibiting properties of dragon's blood from Croton draco.

    Science.gov (United States)

    Tsacheva, Ivanka; Rostan, Joerg; Iossifova, Tania; Vogler, Bernhard; Odjakova, Mariela; Navas, Hernan; Kostova, Ivanka; Kojouharova, Michaela; Kraus, Wolfgang

    2004-01-01

    The latex of Croton draco, its extracts and several latex components have been investigated for their influence on both classical (CP) and alternative (AP) activation pathways of the complement system using a hemolytic assay. The best inhibition was found for the classical pathway. The latex, ethyl acetate and ethyl ether extracts exhibited extremely high inhibition on the CP (94, 90 and 77%, respectively) at a concentration of 1 mg/ml. The flavonoid myricitrin, the alkaloid taspine and the cyclopeptides P1 and P2 showed high inhibition on CP (83, 91, 78 and 63%, respectively) at a concentration of 0.9 mM.

  20. Mechanism of acid corrosion inhibition using magnetic nanofluid

    Science.gov (United States)

    Parekh, Kinnari; Jauhari, Smita; Upadhyay, R. V.

    2016-12-01

    The inhibition effect of magnetic nanofluid on carbon steel in acid solutions was investigated using gravimetric, potentiodynamic and SEM measurement. The inhibition efficiency increases up to 95% and 75% for 51.7 mM concentration, respectively, in 1 M HCl and 1 M H2SO4 medium. The adsorption of nanoparticles to the steel surface forms a barrier between the metal and the aggressive environment, which is responsible for observed inhibition action. The adsorption of nanoparticles on steel surface is supported by the Langmuir and Freundlich adsorption isotherm and surface morphology scanned through SEM.

  1. Blue light does not inhibit nodulation in Sesbania rostrata.

    Science.gov (United States)

    Shimomura, Aya; Arima, Susumu; Hayashi, Makoto; Maymon, Maskit; Hirsch, Ann M; Suzuki, Akihiro

    2017-01-02

    Earlier, we reported that root nodulation was inhibited by blue light irradiation of Lotus japonicus. Because some legumes do not establish nodules exclusively on underground roots, we investigated whether nodule formation in Sesbania rostrata, which forms both root and "stem" nodules following inoculation with Azorhizobium caulinodans, is inhibited by blue light as are L. japonicus nodules. We found that neither S. rostrata nodulation nor nitrogen fixation was inhibited by blue light exposure. Moreover, although A. caulinodans proliferation was not affected by blue light irradiation, bacterial survival was decreased. Therefore, blue light appears to impose different responses depending on the legume-rhizobial symbiosis.

  2. Inhibition of cullin RING ligases by cycle inhibiting factor: evidence for interference with Nedd8-induced conformational control.

    Science.gov (United States)

    Boh, Boon Kim; Ng, Mei Ying; Leck, Yee Chin; Shaw, Barry; Long, Jed; Sun, Guang Wen; Gan, Yunn Hwen; Searle, Mark S; Layfield, Robert; Hagen, Thilo

    2011-10-21

    Cycle inhibiting factor (Cif) is produced by pathogenic intracellular bacteria and injected into the host cells via a type III secretion system. Cif is known to interfere with the eukaryotic cell cycle by inhibiting the function of cullin RING E3 ubiquitin ligases (CRLs). Cullin proteins form the scaffold protein of CRLs and are modified with the ubiquitin-like protein Nedd8, which exerts important conformational control required for CRL activity. Cif has recently been shown to catalyze the deamidation of Gln40 in Nedd8 to Glu. Here, we addressed how Nedd8 deamidation inhibits CRL activity. Our results indicate that Burkholderia pseudomallei Cif (also known as CHBP) inhibits the deconjugation of Nedd8 in vivo by inhibiting binding of the deneddylating COP9 signalosome (CSN) complex. We provide evidence that the reduced binding of CSN and the inhibition of CRL activity by Cif are due to interference with Nedd8-induced conformational control, which is dependent on the interaction between the Nedd8 hydrophobic patch and the cullin winged-helix B subdomain. Of note, mutation of Gln40 to Glu in ubiquitin, an additional target of Cif, inhibits the interaction between the hydrophobic surface of ubiquitin and the ubiquitin-binding protein p62/SQSTM1, showing conceptually that Cif activity can impair ubiquitin/ubiquitin-like protein non-covalent interactions. Our results also suggest that Cif may exert additional cellular effects by interfering with the association between ubiquitin and ubiquitin-binding proteins.

  3. MK615 inhibits pancreatic cancer cell growth by dual inhibition of Aurora A and B kinases

    Institute of Scientific and Technical Information of China (English)

    Toshie Okada; Tokihiko Sawada; Tatsushi Osawa; Masakazu Adachi; Keiichi Kubota

    2008-01-01

    AIM:To investigate the anti-neoplastic effect of MK615,an anti-neoplastic compound isolated from Japanese apricot,against human pancreatic cancer cells in vitro.METHODS:Three human pancreatic cancer cell lines PANC-1,PK-1,and PK45H were cultured with MK615 at concentrations of 600,300,150,and O μg/mL.Growth inhibition was evaluated by cell proliferation assay,and killing activity was determined by lactate dehydrogenase (LDH) assay.Expression of Aurora A and B kinases was detected by real-time polymerase chain reaction (PCR) and Western blotting.Cell cycle stages were evaluated by flow cytometry.RESULTS:The growth inhibitory rates of MK615 at 150,300,and 600 μg/mL were 2.3% ± 0.9%,8.9% ±3.2% and 67.1% ± 8.1% on PANC1 cells,1.3% ± 0.3%,8.7% ± 4.1% and 45.7 ± 7.6% on PK1 cells,and 1.2 ±0.8%,9.1% ± 2.1% and 52.1% ± 5.5% on PK45H cells,respectively (P<0.05).The percentage cytotoxicities of MK615 at 0,150,300,and 600 μg/mL were 19.6% ±1.3%,26.7% ± 1.8%,25.5% ± 0.9% and 26.4% ± 0.9%in PANC1 cells,19.7% ± 1.3%,24.7% ± 0.8%,25.9% ±0.9% and 29.9% ± 1.1% in PK1 cells,and 28.0% ± 0.9%,31.2% ± 0.9%,30.4% ± 1.1% and 35.3 ± 1.0% in PK45H cells,respectively (P<0.05).Real-time PCR and Western blotting showed that MK615 dually inhibited the expression of Aurora A and B kinases.Cell cycle analysis revealed that MK615 increased the population of cells in G2/M phase.CONCLUSION:MK615 exerts an anti-neoplastic effect on human pancreatic cancer cells in vitro by dual inhibition of Aurora A and B kinases.

  4. Beyond Behavioral Inhibition: Etiological Factors in Childhood Anxiety

    Science.gov (United States)

    Manassis, Katharina; Hudson, Jennifer L.; Webb, Alicia; Albano, Anne Marie

    2004-01-01

    Theoretical models of childhood anxiety have emphasized temperamental vulnerability, principally behavioral inhibition, and its interaction with various environmental factors promoting anxiety (for example, overprotective parenting, insecure attachment, life stress). Although clearly establishing the importance of both nature and nurture in…

  5. Chloroquinone Inhibits Cell Proliferation and Induces Apoptosis in ...

    African Journals Online (AJOL)

    Chloroquinone Inhibits Cell Proliferation and Induces Apoptosis in ... of cell proliferation while an inverted microscope was employed for the analysis of ... μΜ concentration of CQ without affecting normal human skin keratinocyte cell line, K38.

  6. Inhibition of HIV-1 lentiviral particles infectivity by Gynostemma ...

    African Journals Online (AJOL)

    Yomi

    2012-01-24

    Jan 24, 2012 ... study in which the inhibition of viral vector infectivity of HeLa cells was assessed flow cytometrically by measuring the expression .... plant Gynostemma pentaphyllum (Cucurbitaceae) for ..... sapogenins and differentiation from.

  7. Functional inhibition of UQCRB suppresses angiogenesis in zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Yoon Sun; Jung, Hye Jin [Chemical Genomics National Research Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Seok, Seung Hyeok [Department of Microbiology and Immunology, Institute for Experimental Animals, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Payumo, Alexander Y.; Chen, James K. [Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305 (United States); Kwon, Ho Jeong, E-mail: kwonhj@yonsei.ac.kr [Chemical Genomics National Research Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

    2013-04-19

    Highlights: ► This is the first functional characterization of UQCRB in vivo model. ► Angiogenesis is inhibited with UQCRB loss of function in zebrafish. ► UQCRB is introduced as a prognostic marker for mitochondria- and angiogenesis-related diseases. -- Abstract: As a subunit of mitochondrial complex III, UQCRB plays an important role in complex III stability, electron transport, and cellular oxygen sensing. Herein, we report UQCRB function regarding angiogenesis in vivo with the zebrafish (Danio rerio). UQCRB knockdown inhibited angiogenesis in zebrafish leading to the suppression of VEGF expression. Moreover, the UQCRB-targeting small molecule terpestacin also inhibited angiogenesis and VEGF levels in zebrafish, supporting the role of UQCRB in angiogenesis. Collectively, UQCRB loss of function by either genetic and pharmacological means inhibited angiogenesis, indicating that UQCRB plays a key role in this process and can be a prognostic marker of angiogenesis- and mitochondria-related diseases.

  8. Transcriptome dynamics of the microRNA inhibition response

    DEFF Research Database (Denmark)

    Wen, Jiayu; Leucci, Elenora; Vendramin, Roberto

    2015-01-01

    We report a high-resolution time series study of transcriptome dynamics following antimiR-mediated inhibition of miR-9 in a Hodgkin lymphoma cell-line-the first such dynamic study of the microRNA inhibition response-revealing both general and specific aspects of the physiological response. We show...... validate the key observations with independent time series qPCR and we experimentally validate key predicted miR-9 targets. Methodologically, we developed sensitive functional data analytic predictive methods to analyse the weak response inherent in microRNA inhibition experiments. The methods...... of this study will be applicable to similar high-resolution time series transcriptome analyses and provides the context for more accurate experimental design and interpretation of future microRNA inhibition studies....

  9. Cross inhibition improves activity selection when switching incurs time costs

    Institute of Scientific and Technical Information of China (English)

    James A.R.MARSHALL; Angélique FAVREAU-PEIGN(E); Lutz FROMHAGE; John M.MCNAMARA; Lianne F.S.MEAH; Alasdair I.HOUSTON

    2015-01-01

    We consider a behavioural model of an animal choosing between two activities,based on positive feedback,and examine the effect of introducing cross inhibition between the motivations for the two activities.While cross-inhibition has previously been included in models of decision making,the question of what benefit it may provide to an animal's activity selection behaviour has not previously been studied.In neuroscience and in collective behaviour cross-inhibition,and other equivalent means of coupling evidence-accumulating pathways,have been shown to approximate statistically-optimal decision-making and to adaptively break deadlock,thereby improving decision performance.Switching between activities is an ongoing decision process yet here we also find that cross-inhibition robustly improves its efficiency,by reducing the frequency of costly switches between behaviours [Current Zoology 61 (2):242-250,2015].

  10. Application of various water soluble polymers in gas hydrate inhibition

    DEFF Research Database (Denmark)

    Kamal, Muhammad Shahzad; Hussein, Ibnelwaleed A.; Sultan, Abdullah S.

    2016-01-01

    . This review presents the various types of water soluble polymers used for hydrate inhibition, including conventional and novel polymeric inhibitors along with their limitations. The review covers the relevant properties of vinyl lactam, amide, dendrimeric, fluorinated, and natural biodegradable polymers...

  11. Biological phosphorus removal inhibition by roxarsone in batch culture systems.

    Science.gov (United States)

    Guo, Qingfeng; Liu, Li; Hu, Zhenhu; Chen, Guowei

    2013-06-01

    Roxarsone has been extensively used in the feed of animals, which is usually excreted unchanged in the manure and eventually enter into animal wastewater, challenging the biological phosphorus removal processes. Knowledge of its inhibition effect is key for guiding treatment of roxarsone-contaminated wastewater, and is unfortunately keeping unclear. We study the inhibition of roxarsone on biological phosphorus removal processes for roxarsone-contaminated wastewater treatment, in terms of the removal and rates of chemical oxygen demand (COD), phosphate. Results showed that presence of roxarsone considerably limited the COD removals, especially at roxarsone concentration exceeding 40 mg L(-1). Additionally, roxarsone inhibited both phosphorus release and uptake processes, consistent with the phosphate profiles during the biological phosphorus removal processes; whereas, roxarsone is more toxic to phosphorus uptake process, than release function. The results indicated that it is roxarsone itself, rather than the inorganic arsenics, inhibit biological phosphorus removal processes within both aerobic and anaerobic roxarsone-contaminated wastewater treatment.

  12. IN VITRO STUDY ON INHIBITION OF GLYCOSYLATION OF ...

    African Journals Online (AJOL)

    Administrator

    extract inhibits the binding of glucose to hemoglobin, since at higher concentration of glucose ... nonenzymatic glycosylation also occur in nucleic acids. In the later reaction ..... Raphael, S. S. (1983). Lynch's Medical Laboratory Technology 4th.

  13. Aging and vigilance: who has the inhibition deficit?

    Science.gov (United States)

    Brache, Kristina; Scialfa, Charles; Hudson, Carl

    2010-04-01

    The present study compared 18 younger (M = 21.00 years) and 17 older adults (M = 64.29 years) in a modified vigilance task that required the inhibition of a routinized response. The task was a 50-min simulation of industrial inspection, wherein observers were presented with simple displays labeled "good" and "bad" parts. General linear modeling indicated that younger adults showed a doubling of inhibition failures over time (from 19% to 43%); older adults' inhibition failures held constant at approximately 17.5%. In both age groups, those who responded most quickly were also most error-prone. A control experiment, using the traditional vigilance task requiring a response to infrequent "bad" parts, found only small age differences in accuracy and these also favored older adults. This research suggests that younger adults may demonstrate larger inhibition failures when the routinized responses on simple tasks must be suppressed. There are several implications for theory, industrial design, and cognitive assessment.

  14. Inhibition of Fungal Aflatoxin B1 Biosynthesis by Diverse Botanically ...

    African Journals Online (AJOL)

    effects on A. flavus growth and AFB1 production. Fungal spores were cultured ... Keywords: Polyphenols, Quercetin, Aflatoxin B1, Inhibition, Antioxidation. Tropical Journal of ..... agents used in animal feed or food processing areas. However,.

  15. Spectroscopic analysis of urinary calculi and inhibition of their growth

    Science.gov (United States)

    Manciu, Felicia; Durrer, William; Govani, Jayesh; Reza, Layra; Pinales, Luis

    2009-10-01

    We present here a study of kidney stone formation and growth inhibition based on a traditional medicine approach with Aquatica Lour (RAL) herbal extracts. Kidney stone material systems were synthesized in vitro using a simplified single diffusion gel growth technique. With the objective of revealing the mechanism of inhibition of calculi formation by RAL extracts, samples prepared without the presence of extract, and with the presence of extract, were analyzed using Raman, photoluminescence, and XPS. The unexpected presence of Zn revealed by XPS in a sample prepared with RAL provides an explanation for the inhibition process, and also explains the dramatic reflectance of incident light observed in attempts to obtain infrared transmission data. Raman data are consistent with the binding of the inhibitor to the oxygen of the kidney stone. Photoluminescence data corroborate with the other results to provide additional evidence of Zn-related inhibition.

  16. A Broad Dynamical Model for Pattern Formation by Lateral Inhibition

    CERN Document Server

    Arcak, Murat

    2012-01-01

    Many patterning events in multi-cellular organisms rely on cell-to-cell contact signaling, such as the Notch pathway in metazoans. A particularly interesting phenomenon in this form of communication is lateral inhibition where a cell that adopts a particular fate inhibits its immediate neighbors from doing the same. Dynamical models are of great interest for understanding the circuit topologies involved in lateral inhibition and for predicting the associated patterns. Several simplified models have been employed for Notch signalling pathways in the literature. The objective of this paper is to present an abstract dynamical model that captures the essential features of lateral inhibition and to demonstrate with dynamical systems techniques that these features indeed lead to patterning.

  17. The neural basis of inhibition in cognitive control.

    Science.gov (United States)

    Aron, Adam R

    2007-06-01

    The concept of "inhibition" is widely used in synaptic, circuit, and systems neuroscience, where it has a clear meaning because it is clearly observable. The concept is also ubiquitous in psychology. One common use is to connote an active/willed process underlying cognitive control. Many authors claim that subjects execute cognitive control over unwanted stimuli, task sets, responses, memories, and emotions by inhibiting them, and that frontal lobe damage induces distractibility, impulsivity, and perseveration because of damage to an inhibitory mechanism. However, with the exception of the motor domain, the notion of an active inhibitory process underlying cognitive control has been heavily challenged. Alternative explanations have been provided that explain cognitive control without recourse to inhibition as concept, mechanism, or theory. This article examines the role that neuroscience can play when examining whether the psychological concept of active inhibition can be meaningfully applied in cognitive control research.

  18. Mildiomycin: a nucleoside antibiotic that inhibits protein synthesis.

    Science.gov (United States)

    Feduchi, E; Cosín, M; Carrasco, L

    1985-03-01

    Mildiomycin, a new nucleoside antibiotic, selectively inhibits protein synthesis in HeLa cells, and is less active in the inhibition of RNA or DNA synthesis. An increased inhibition of translation by mildiomycin is observed in cultured HeLa cells when they are permeabilized by encephalomyocarditis virus. This observation suggests that this antibiotic does not easily pass through the cell membrane, as occurs with other nucleoside and aminoglycoside antibiotics. The inhibition of translation is also observed in cell-free systems, such as endogenous protein synthesis in a rabbit reticulocyte lysate or the synthesis of polyphenylalanine directed by poly (U). Finally the mode of action of mildiomycin was investigated and the results suggest that the compound blocks the peptidyl-transferase center.

  19. A hammerhead ribozyme inhibits ADE1 gene expression in yeast.

    Science.gov (United States)

    Ferbeyre, G; Bratty, J; Chen, H; Cedergren, R

    1995-03-21

    To study factors that affect in vivo ribozyme (Rz) activity, a model system has been devised in Saccharomyces cerevisiae based on the inhibition of ADE1 gene expression. This gene was chosen because Rz action can be evaluated visually by the Red phenotype produced when the activity of the gene product is inhibited. Different plasmid constructs allowed the expression of the Rz either in cis or in trans with respect to ADE1. Rz-related inhibition of ADE1 expression was correlated with a Red phenotype and a diminution of ADE1 mRNA levels only when the Rz gene was linked 5' to ADE1. The presence of the expected 3' cleavage fragment was demonstrated using a technique combining RNA ligation and PCR. This yeast system and detection technique are suited to the investigation of general factors affecting Rz-catalyzed inhibition of gene expression under in vivo conditions.

  20. Noninvasive optical inhibition with a red-shifted microbial rhodopsin.

    Science.gov (United States)

    Chuong, Amy S; Miri, Mitra L; Busskamp, Volker; Matthews, Gillian A C; Acker, Leah C; Sørensen, Andreas T; Young, Andrew; Klapoetke, Nathan C; Henninger, Mike A; Kodandaramaiah, Suhasa B; Ogawa, Masaaki; Ramanlal, Shreshtha B; Bandler, Rachel C; Allen, Brian D; Forest, Craig R; Chow, Brian Y; Han, Xue; Lin, Yingxi; Tye, Kay M; Roska, Botond; Cardin, Jessica A; Boyden, Edward S

    2014-08-01

    Optogenetic inhibition of the electrical activity of neurons enables the causal assessment of their contributions to brain functions. Red light penetrates deeper into tissue than other visible wavelengths. We present a red-shifted cruxhalorhodopsin, Jaws, derived from Haloarcula (Halobacterium) salinarum (strain Shark) and engineered to result in red light-induced photocurrents three times those of earlier silencers. Jaws exhibits robust inhibition of sensory-evoked neural activity in the cortex and results in strong light responses when used in retinas of retinitis pigmentosa model mice. We also demonstrate that Jaws can noninvasively mediate transcranial optical inhibition of neurons deep in the brains of awake mice. The noninvasive optogenetic inhibition opened up by Jaws enables a variety of important neuroscience experiments and offers a powerful general-use chloride pump for basic and applied neuroscience.

  1. Effect of glycolysis inhibition on mitochondrial function in rat brain.

    Science.gov (United States)

    Cano-Ramírez, D; Torres-Vargas, C E; Guerrero-Castillo, S; Uribe-Carvajal, S; Hernández-Pando, R; Pedraza-Chaverri, J; Orozco-Ibarra, M

    2012-05-01

    Inhibition of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase enhances the neural vulnerability to excitotoxicity both in vivo and in vitro through an unknown mechanism possibly related to mitochondrial failure. However, as the effect of glycolysis inhibition on mitochondrial function in brain has not been studied, the aim of the present work was to evaluate the effect of glycolysis inhibition induced by iodoacetate on mitochondrial function and oxidative stress in brain. Mitochondria were isolated from brain cortex, striatum and cerebellum of rats treated systemically with iodoacetate (25 mg/kg/day for 3 days). Oxygen consumption, ATP synthesis, transmembrane potential, reactive oxygen species production, lipoperoxidation, glutathione levels, and aconitase activity were assessed. Oxygen consumption and aconitase activity decreased in the brain cortex and striatum, showing that glycolysis inhibition did not trigger severe mitochondrial impairment, but a slight mitochondrial malfunction and oxidative stress were present.

  2. Motivating inhibition - reward prospect speeds up response cancellation.

    Science.gov (United States)

    Boehler, Carsten N; Hopf, Jens-Max; Stoppel, Christian M; Krebs, Ruth M

    2012-12-01

    Reward prospect has been demonstrated to facilitate various cognitive and behavioral operations, particularly by enhancing the speed and vigor of processes linked to approaching reward. Studies in this domain typically employed task regimes in which participants' overt responses are facilitated by prospective rewards. In contrast, we demonstrate here that even the cancellation of a motor response can be accelerated by reward prospect, thus signifying reward-related benefits on restraint rather than approach behavior. Importantly, this facilitation occurred independent of strategy-related adjustments of response speed, which are known to systematically distort the estimation of response-cancellation speed. The fact that motivational factors can indeed facilitate response inhibition is not only relevant for understanding how motivation and response inhibition interact in healthy participants but also for work on various patient groups that display response-inhibition deficits, suggesting that core differences in the ability to inhibit motor responses have to be differentiated from motivational factors.

  3. Glycinergic inhibition tunes coincidence detection in the auditory brainstem.

    Science.gov (United States)

    Myoga, Michael H; Lehnert, Simon; Leibold, Christian; Felmy, Felix; Grothe, Benedikt

    2014-05-07

    Neurons in the medial superior olive (MSO) detect microsecond differences in the arrival time of sounds between the ears (interaural time differences or ITDs), a crucial binaural cue for sound localization. Synaptic inhibition has been implicated in tuning ITD sensitivity, but the cellular mechanisms underlying its influence on coincidence detection are debated. Here we determine the impact of inhibition on coincidence detection in adult Mongolian gerbil MSO brain slices by testing precise temporal integration of measured synaptic responses using conductance-clamp. We find that inhibition dynamically shifts the peak timing of excitation, depending on its relative arrival time, which in turn modulates the timing of best coincidence detection. Inhibitory control of coincidence detection timing is consistent with the diversity of ITD functions observed in vivo and is robust under physiologically relevant conditions. Our results provide strong evidence that temporal interactions between excitation and inhibition on microsecond timescales are critical for binaural processing.

  4. What about inhibition in the Wisconsin Card Sorting Test?

    Science.gov (United States)

    Steinmetz, Jean-Paul; Houssemand, Claude

    2011-05-01

    The commercially available Wisconsin Card Sorting Test (WCST) is one of the most commonly used tests for assessing executive functions within clinical settings. Importantly, however, it remains relatively unclear exactly what processes are assessed by the test. Conceptually, increased perseverative errors in sorting cards are usually related to deficient inhibition processes. Empirically, evidence supporting this conclusion is limited. In a sample of 38 healthy adults we addressed the question to what extent inhibition mechanisms assessed by the go/no-go and the stop-signal paradigm are related to WCST performances. Inhibition-related scores were found to predict non-perseverative errors better than perseverative errors. Consequently we conclude that the non-perseverative errors score reflects processes that are partly dependent on inhibition functions.

  5. Inhibition of phage infection in capsule-producing Streptococcus ...

    African Journals Online (AJOL)

    SERVER

    2007-10-04

    Oct 4, 2007 ... Acid production by capsule-producing Streptococcus thermophilus was inhibited less ... lactic acid bacteria (LAB) are of similar size to fat globules ..... Characterization of new virulent phage (MLC-A) of Lactobacillus paracasei.

  6. Corrosion Inhibition of a Green Scale Inhibitor Polyepoxysuccinic Acid

    Institute of Scientific and Technical Information of China (English)

    Rong Chun XIONG; Qing ZHOU; Gang WEI

    2003-01-01

    The corrosion inhibition of a green scale inhibitor, polyepoxysuccinic acid (PESA) wasstudied based on dynamic tests. It is found that when PESA is used alone, it had good corrosioninhibition. So, PESA should be included in the category of corrosion inhibitors. It is not only akind of green scale inhibitor, but also a green corrosion inhibitor. The synergistic effect betweenPESA and Zn2+ or sodium gluconate is poor. However, the synergistic effect among PESA, Zn2+and sodium gluconate is excellent, and the corrosion inhibition efficiency for carbon steel is higherthan 99%. Further study of corrosion inhibition mechanism reveals that corrosion inhibition ofPESA is not affected by carboxyl group, but by the oxygen atom inserted The existence ofoxygen atom in PESA molecular structure makes it easy to form stable chelate with pentacyclicstructure.

  7. Protection from latent inhibition provided by a conditioned inhibitor.

    Science.gov (United States)

    McConnell, Bridget L; Wheeler, Daniel S; Urcelay, Gonzalo P; Miller, Ralph R

    2009-10-01

    Two conditioned suppression experiments with rats investigated the influence on latent inhibition of compounding a Pavlovian conditioned inhibitor with the target cue during preexposure treatment. Results were compared with those of subjects that received conventional latent inhibition training, no preexposure, or preexposure to the target cue in compound with a neutral stimulus. In Experiment 1, greater attenuation of the latent inhibition effect was observed in subjects that received target preexposure in compound with a Pavlovian conditioned inhibitor relative to subjects that received preexposure with a neutral stimulus or to the target alone. In Experiment 2, this protection from latent inhibition was attenuated if the excitor that was used to train the conditioned inhibitor was extinguished between preexposure and target training. The results are consistent with an account offered by the extended comparator hypothesis.

  8. Motivational control of latent inhibition in flavor preference conditioning.

    Science.gov (United States)

    Garcia-Burgos, David; González, Felisa; Hall, Geoffrey

    2013-09-01

    In three experiments, rats given pairings of a neutral flavor with sucrose showed a preference for that flavor when subsequently allowed to choose between it and water. Preexposure to the flavor produced a latent inhibition effect (reduced the size of the preference) when the rats were hungry during the test (Experiments 1 and 2). Rats that were not hungry during the test failed to show latent inhibition (Experiments 1-3). Experiment 3 confirmed that sucrose-flavor pairings were capable of producing a preference even in nonhungry rats. It is argued that the preference shown by rats that are hungry on test depends on a flavor-nutrient association, a form of learning that is susceptible to latent inhibition in the same way as standard conditioning procedures are. The failure to obtain latent inhibition in nonhungry rats suggests that the preference obtained in these conditions depends on a different form of learning that is less susceptible to the effects of stimulus exposure.

  9. Inhibition of Porcine Small Intestinal Sucrase by Validamine

    Institute of Scientific and Technical Information of China (English)

    郑裕国; 申屠旭萍; 沈寅初

    2005-01-01

    As an important medicinal intermediate with broad uses, validamine, an aminocyclitol, isolated from the enzymolysis broth of validamycins, has gained more and more attention. The absolute configuration of validamine is similar to that of α-D-glucose, and it demonstrates powerful inhibition activity on glycosidase. In this paper, the inhibitory effect of validamine on porcine small intestinal sucrase was investigated. Validamine was found to be a potent, competitive inhibitor to porcine small intestinal sucrase in vitro with an IC50 value of 6.85 × 10-4 mol·L-1. Validamine exhibited a dose-dependent inhibition effect on porcine small intestinal sucrase, whereby the inhibition interaction of validamine and porcine small intestinal sucrase was a fast binding process. The inhibition of validamine on porcine small intestinal sucrase was pH-dependent.

  10. Impaired face recognition is associated with social inhibition.

    Science.gov (United States)

    Avery, Suzanne N; VanDerKlok, Ross M; Heckers, Stephan; Blackford, Jennifer U

    2016-02-28

    Face recognition is fundamental to successful social interaction. Individuals with deficits in face recognition are likely to have social functioning impairments that may lead to heightened risk for social anxiety. A critical component of social interaction is how quickly a face is learned during initial exposure to a new individual. Here, we used a novel Repeated Faces task to assess how quickly memory for faces is established. Face recognition was measured over multiple exposures in 52 young adults ranging from low to high in social inhibition, a core dimension of social anxiety. High social inhibition was associated with a smaller slope of change in recognition memory over repeated face exposure, indicating participants with higher social inhibition showed smaller improvements in recognition memory after seeing faces multiple times. We propose that impaired face learning is an important mechanism underlying social inhibition and may contribute to, or maintain, social anxiety.

  11. Electrochemical impedance spectroscopy study on corrosion inhibition of benzyltriethylammonium chloride

    Science.gov (United States)

    Idris, Mohd Nazri; Daud, Abdul Razak; Othman, Norinsan Kamil

    2013-11-01

    Electrochemical Impedance Spectroscopy (EIS) was employed to study the corrosion inhibition behavior of benzyltriethylammonium chloride (BTC) for carbon steel corrosion. The inhibition efficiency was investigated in 1.0 M HCl solution at room temperature (25°C) by varying the BTC concentration. EIS results indicated that the double layer capacitance of electrolyte/carbon steel interface decreases with the increasing of BTC concentration and consequently enhances the polarization resistance of equivalence Randles circuit. The results indicated that inhibition efficiency of as high as 65% could be achieved when 10mM BTC was present in 1.0 M HCl solution as compared to inhibitor-free solution. The inhibition process of BTC on the carbon steel corrosion was found to obey Langmuir adsorption isotherm. This study revealed that BTC is suitable to be used as a corrosion inhibitor in acid media.

  12. DMSO inhibits human platelet activation through cyclooxygenase-1 inhibition. A novel agent for drug eluting stents?

    Energy Technology Data Exchange (ETDEWEB)

    Asmis, Lars [Institute for Clinical Hematology, University Hospital Zuerich, Zuerich (Switzerland); Tanner, Felix C. [Cardiovascular Research, Physiology Institute, University of Zuerich, Zuerich (Switzerland); Center for Integrative Human Physiology, University of Zuerich, Zuerich (Switzerland); Cardiology, Cardiovascular Center, University Hospital Zuerich, Zuerich (Switzerland); Sudano, Isabella [Cardiology, Cardiovascular Center, University Hospital Zuerich, Zuerich (Switzerland); Luescher, Thomas F. [Cardiovascular Research, Physiology Institute, University of Zuerich, Zuerich (Switzerland); Center for Integrative Human Physiology, University of Zuerich, Zuerich (Switzerland); Cardiology, Cardiovascular Center, University Hospital Zuerich, Zuerich (Switzerland); Camici, Giovanni G., E-mail: giovannic@access.uzh.ch [Cardiovascular Research, Physiology Institute, University of Zuerich, Zuerich (Switzerland); Center for Integrative Human Physiology, University of Zuerich, Zuerich (Switzerland)

    2010-01-22

    Background: DMSO is routinely infused together with hematopoietic cells in patients undergoing myeloablative therapy and was recently found to inhibit smooth muscle cells proliferation and arterial thrombus formation in the mouse by preventing tissue factor (TF), a key activator of the coagulation cascade. This study was designed to investigate whether DMSO prevents platelet activation and thus, whether it may represent an interesting agent to be used on drug eluting stents. Methods and results: Human venous blood from healthy volunteers was collected in citrated tubes and platelet activation was studied by cone and platelet analyzer (CPA) and rapid-platelet-function-assay (RPFA). CPA analysis showed that DMSO-treated platelets exhibit a lower adherence in response to shear stress (-15.54 {+-} 0.9427%, n = 5, P < 0.0001 versus control). Additionally, aggregometry studies revealed that DMSO-treated, arachidonate-stimulated platelets had an increased lag phase (18.0% {+-} 4.031, n = 9, P = 0.0004 versus control) as well as a decreased maximal aggregation (-6.388 {+-} 2.212%, n = 6, P = 0.0162 versus control). Inhibitory action of DMSO could be rescued by exogenous thromboxane A2 and was mediated, at least in part, by COX-1 inhibition. Conclusions: Clinically relevant concentrations of DMSO impair platelet activation by a thromboxane A2-dependent, COX-1-mediated effect. This finding may be crucial for the previously reported anti-thrombotic property displayed by DMSO. Our findings support a role for DMSO as a novel drug to prevent not only proliferation, but also thrombotic complications of drug eluting stents.

  13. Combined MET inhibition and topoisomerase I inhibition block cell growth of small cell lung cancer.

    Science.gov (United States)

    Rolle, Cleo E; Kanteti, Rajani; Surati, Mosmi; Nandi, Suvobroto; Dhanasingh, Immanuel; Yala, Soheil; Tretiakova, Maria; Arif, Qudsia; Hembrough, Todd; Brand, Toni M; Wheeler, Deric L; Husain, Aliya N; Vokes, Everett E; Bharti, Ajit; Salgia, Ravi

    2014-03-01

    Small cell lung cancer (SCLC) is a devastating disease, and current therapies have not greatly improved the 5-year survival rates. Topoisomerase (Top) inhibition is a treatment modality for SCLC; however, the response is short lived. Consequently, our research has focused on improving SCLC therapeutics through the identification of novel targets. Previously, we identified MNNG HOS transforming gene (MET) to be overexpressed and functional in SCLC. Herein, we investigated the therapeutic potential of combinatorial targeting of MET using SU11274 and Top1 using 7-ethyl-10-hydroxycamptothecin (SN-38). MET and TOP1 gene copy numbers and protein expression were determined in 29 patients with limited (n = 11) and extensive (n = 18) disease. MET gene copy number was significantly increased (>6 copies) in extensive disease compared with limited disease (P = 0.015). Similar TOP1 gene copy numbers were detected in limited and extensive disease. Immunohistochemical staining revealed a significantly higher Top1 nuclear expression in extensive (0.93) versus limited (0.15) disease (P = 0.04). Interestingly, a significant positive correlation was detected between MET gene copy number and Top1 nuclear expression (r = 0.5). In vitro stimulation of H82 cells revealed hepatocyte growth factor (HGF)-induced nuclear colocalization of p-MET and Top1. Furthermore, activation of the HGF/MET axis enhanced Top1 activity, which was abrogated by SU11274. Combination of SN-38 with SU11274 dramatically decreased SCLC growth as compared with either drug alone. Collectively, these findings suggest that the combinatorial inhibition of MET and Top1 is a potentially efficacious treatment strategy for SCLC. ©2013 AACR.

  14. Delta-Notch Lateral Inhibition within the Organ of Corti

    Science.gov (United States)

    Summers, R.; Abdulla, T.; Luff, R.

    2013-09-01

    Lateral inhibition is described as an emergent property of the Delta-Notch signalling network. Two separate model representations of lateral inhibition are proposed for different purposes. One provides information about bioenergetics while the other has the capability to produce a physical representation. It is proposed that both can be used in further studies of the sensory pathways in the human connectome model of brain function.

  15. Neurosteroids Reverse Tonic Inhibition Deficits in Fragile X Syndrome

    Science.gov (United States)

    2016-08-01

    model of the human syndrome. In addition, we propose an innovative way of reversing the reduced tonic inhibition by boosting GABAAR trafficking to...showed that phosphorylation of these residues changes the trafficking of the subunits so the changes observed in Fmr1 KO mice would predictably have...consequences for trafficking of these essential inhibitory subunits. We noted that there was a significant decrease in tonic inhibition in dentate

  16. Aspirin inhibits hepatitis C virus entry by downregulating claudin-1.

    Science.gov (United States)

    Yin, P; Zhang, L

    2016-01-01

    Aspirin has previously been reported to inhibit hepatitis C virus (HCV) replication. The aim of this study was to investigate whether aspirin is involved in blocking HCV entry. We found that aspirin inhibits the entry of HCVpp and infectious HCV. The level of claudin-1, an HCV receptor, is reduced by aspirin. Our results extend the anti-HCV effect of aspirin to the HCV entry step and further reinforce the anti-HCV role of aspirin.

  17. Anger inhibition and pain: conceptualizations, evidence and new directions.

    Science.gov (United States)

    Burns, John W; Quartana, Phillip J; Bruehl, Stephen

    2008-06-01

    Anger and how anger is regulated appear to affect acute and chronic pain intensity. The inhibition of anger (anger-in), in particular, has received much attention, and it is widely believed that suppressing or inhibiting the verbal or physical expression of anger is related to increased pain severity. We examine theoretical accounts for expecting that anger inhibition should affect pain, and review evidence for this claim. We suggest that the evidence for a link between trait anger-in (the self-reported tendency to inhibit anger expression when angry) and acute and chronic pain severity is quite limited owing to a number of factors including a inadequate definition of trait anger-in embodied in the popular anger-in subscale of Spielberger's Anger Expression Inventory, and a strong overlap between trait anger-in scores and measures of general negative affect (NA). We argue that in order to determine whether something unique to the process of anger inhibition exerts direct effects on subsequent pain intensity, new conceptualizations and approaches are needed that go beyond self-report assessments of trait anger-in. We present one model of anger inhibition and pain that adopts elements of Wegner's ironic process theory of thought suppression. Findings from this emerging research paradigm indicate that state anger suppression (suppression manipulated in the laboratory) may indeed affect sensitivity to subsequent painful stimuli, and we outline potentially productive avenues of future inquiry that build on this model. We conclude that although studies employing correlational designs and self-reports of trait anger-in have not upheld the claim that anger inhibition affects pain severity, evidence from studies using new models suggests that actually inhibiting anger expression during a provocative event may increase perceived pain at a later time.

  18. Inhibition of influenza A virus replication by rifampicin and selenocystamine

    Energy Technology Data Exchange (ETDEWEB)

    Hamzehei, M.; Ledinko, N.

    1980-01-01

    The effects of selenocystamine, an inhibitor of influenza virus RNA-dependent RNA polymerase in vitro activity, in the antibiotic rifampicin were studied on influenza A/PR/8/34 (HON1) infection in embryonated eggs. Both drugs completely inhibited hemagglutinating and infective virus yields when added at relatively early times postinfection. Maximal inhibition was produced by apparently noncytotoxic concentrations of 50 microgram of selenocystamine, or of 400 microgram of rifampicin, per egg.

  19. Inhibition and impulsivity: behavioral and neural basis of response control.

    Science.gov (United States)

    Bari, Andrea; Robbins, Trevor W

    2013-09-01

    In many circumstances alternative courses of action and thoughts have to be inhibited to allow the emergence of goal-directed behavior. However, this has not been the accepted view in the past and only recently has inhibition earned its own place in the neurosciences as a fundamental cognitive function. In this review we first introduce the concept of inhibition from early psychological speculations based on philosophical theories of the human mind. The broad construct of inhibition is then reduced to its most readily observable component which necessarily is its behavioral manifestation. The study of 'response inhibition' has the advantage of dealing with a relatively simple and straightforward process, the overriding of a planned or already initiated action. Deficient inhibitory processes profoundly affect everyday life, causing impulsive conduct which is generally detrimental for the individual. Impulsivity has been consistently linked to several types of addiction, attention deficit/hyperactivity disorder, mania and other psychiatric conditions. Our discussion of the behavioral assessment of impulsivity will focus on objective laboratory tasks of response inhibition that have been implemented in parallel for humans and other species with relatively few qualitative differences. The translational potential of these measures has greatly improved our knowledge of the neurobiological basis of behavioral inhibition and impulsivity. We will then review the current models of behavioral inhibition along with their expression via underlying brain regions, including those involved in the activation of the brain's emergency 'brake' operation, those engaged in more controlled and sustained inhibitory processes and other ancillary executive functions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. LATENT INHIBITION AND PSYCHOMETRICALLY DEFINED SCHIZOTYPY: AN EXPERIMENTAL INVESTIGATION

    OpenAIRE

    Tsakanikos, Elias

    2003-01-01

    The review of the literature suggests that the interpretation of the disruption of latent inhibition within the schizophrenia continuum remains elusive due to a number of methodological and theoretical problems. This thesis adopted a personality-based approach to experimental psychopathology testing alternative interpretations of latent inhibition deficits as a function of psychotic-like features in non-clinical participants. Results from 12 Experiments are discussed in terms of a two-compone...

  1. Common neural substrates for inhibition of spoken and manual responses.

    Science.gov (United States)

    Xue, Gui; Aron, Adam R; Poldrack, Russell A

    2008-08-01

    The inhibition of speech acts is a critical aspect of human executive control over thought and action, but its neural underpinnings are poorly understood. Using functional magnetic resonance imaging and the stop-signal paradigm, we examined the neural correlates of speech control in comparison to manual motor control. Initiation of a verbal response activated left inferior frontal cortex (IFC: Broca's area). Successful inhibition of speech (naming of letters or pseudowords) engaged a region of right IFC (including pars opercularis and anterior insular cortex) as well as presupplementary motor area (pre-SMA); these regions were also activated by successful inhibition of a hand response (i.e., a button press). Moreover, the speed with which subjects inhibited their responses, stop-signal reaction time, was significantly correlated between speech and manual inhibition tasks. These findings suggest a functional dissociation of left and right IFC in initiating versus inhibiting vocal responses, and that manual responses and speech acts share a common inhibitory mechanism localized in the right IFC and pre-SMA.

  2. Lupine protein hydrolysates inhibit enzymes involved in the inflammatory pathway.

    Science.gov (United States)

    Millán-Linares, María del Carmen; Yust, María del Mar; Alcaide-Hidalgo, Juan María; Millán, Francisco; Pedroche, Justo

    2014-05-15

    Lupine protein hydrolysates (LPHs) were obtained from a lupine protein isolate (LPI) by enzymatic hydrolysis using two proteases, Izyme AL and Alcalase 2.4 L, and their potential anti-inflammatory capacities were studied by determining their in vitro inhibition of the following enzymes that are involved in the inflammatory process: phospholipase A2 (PLA2), cyclooxygenase 2 (COX-2), thrombin, and transglutaminase (TG). The strongest inhibitory activities toward PLA2 and TG were found in the hydrolysates obtained by hydrolysis with Izyme and subsequently with Alcalase, with more than 70% inhibition obtained in some cases. All of the hydrolysates tested inhibited more than 60% of the COX-2 activity. In no case did the percentage of thrombin activity inhibition exceed 40%. The best inhibitory activities were found in the LPH obtained after 15 min of hydrolysis with Alcalase and in the LPH obtained after 60 min of hydrolysis with Izyme followed by 15 min of hydrolysis with Alcalase. Enzyme kinetic analyses were conducted to determine the Km and Vmax parameters of these two hydrolysates using the Lineweaver-Burk equation. Both hydrolysates competitively inhibited the thrombin and PLA2 activities. In the case of COX-2 and TG, the inhibition appeared to be the mixed type. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Aggregated IgG inhibits the differentiation of human fibrocytes.

    Science.gov (United States)

    Pilling, Darrell; Tucker, Nancy M; Gomer, Richard H

    2006-06-01

    Fibrocytes are fibroblast-like cells, which appear to participate in wound healing and are present in pathological lesions associated with asthma, pulmonary fibrosis, and scleroderma. Fibrocytes differentiate from CD14+ peripheral blood monocytes, and the presence of serum delays this process dramatically. We previously purified the factor in serum, which inhibits fibrocyte differentiation, and identified it as serum amyloid P (SAP). As SAP binds to Fc receptors for immunoglobulin G (IgG; Fc gammaRs), Fc gammaR activation may be an inhibitory signal for fibrocyte differentiation. Fc gammaR are activated by aggregated IgG, and we find aggregated but not monomeric, human IgG inhibits human fibrocyte differentiation. Monoclonal antibodies that bind to Fc gammaRI (CD64) or Fc gammaRII (CD32) also inhibit fibrocyte differentiation. Aggregated IgG lacking Fc domains or aggregated IgA, IgE, or IgM do not inhibit fibrocyte differentiation. Incubation of monocytes with SAP or aggregated IgG inhibited fibrocyte differentiation. Using inhibitors of protein kinase enzymes, we show that Syk- and Src-related tyrosine kinases participate in the inhibition of fibrocyte differentiation. These observations suggest that fibrocyte differentiation can occur in situations where SAP and aggregated IgG levels are low, such as the resolution phase of inflammation.

  4. Inhibition of in vitro cholesterol synthesis by fatty acids.

    Science.gov (United States)

    Kuroda, M; Endo, A

    1976-01-18

    Inhibitory effect of 44 species of fatty acids on cholesterol synthesis has been examined with a rat liver enzyme system. In the case of saturated fatty acids, the inhibitory activity increased with chain length to a maximum at 11 to 14 carbons, after which activity decreased rapidly. The inhibition increased with the degree of unsaturation of fatty acids. Introduction of a hydroxy group at the alpha-position of fatty acids abolished the inhibition, while the inhibition was enhanced by the presence of a hydroxy group located in an intermediate position of the chain. Branched chain fatty acids having a methyl group at the terminal showed much higher activity than the corresponding saturated straight chain fatty acids with the same number of carbons. With respect to the mechanism for inhibition, tridecanoate was found to inhibit acetoacetyl-CoA thiolase specifically without affecting the other reaction steps in the cholesterol synthetic pathway. The highly unsaturated fatty acids, arachidonate and linoleate, were specific inhibitors of 3-hydroxy-3-methyl-glutaryl-CoA synthase. On the other hand, ricinoleate (hydroxy acid) and phytanate (branched-chain acid) diminished the conversion of mevalonate to sterols by inhibiting a step or steps between squalene and lanosterol.

  5. Inhibition of apple polyphenol oxidase activity by sodium chlorite.

    Science.gov (United States)

    Lu, Shengmin; Luo, Yaguang; Feng, Hao

    2006-05-17

    Sodium chlorite (SC) was shown to have strong efficacy both as a sanitizer to reduce microbial growth on produce and as a browning inhibitor on fresh-cut apples in previous experiments. This study was undertaken to investigate the inhibitory effect of SC on polyphenol oxidase (PPO) and the associated mechanisms. The experiment showed that SC had a strong inhibition of apple PPO. The extent of inhibition was influenced by SC concentration and pH. Inhibition was most prominent at pH 4.5, at which approximately 30% of enzyme activity was lost in the presence of 10 mM SC, followed closely by that at pH 4.0 with a 26% reduction in PPO activity. The inhibition mode was determined using Dixon and Lineweaver-Burk plots, which established SC to be a mixed inhibitor of apple PPO for the oxidation of catechol. Preincubation of PPO with 8 mM SC for 8 min caused a maximum of 46% activity reduction compared to noninhibited control. However, preincubation of SC with catechol for 8 min resulted in no additional loss of PPO activity. These findings provide further evidence that the inhibition of PPO activity by SC is due to the inhibition of the enzyme itself rather than removal of the substrate.

  6. Posterior insular cortex is necessary for conditioned inhibition of fear.

    Science.gov (United States)

    Foilb, Allison R; Flyer-Adams, Johanna G; Maier, Steven F; Christianson, John P

    2016-10-01

    Veridical detection of safety versus danger is critical to survival. Learned signals for safety inhibit fear, and so when presented, reduce fear responses produced by danger signals. This phenomenon is termed conditioned inhibition of fear. Here, we report that CS+/CS- fear discrimination conditioning over 5 days in rats leads the CS- to become a conditioned inhibitor of fear, as measured by the classic tests of conditioned inhibition: summation and retardation of subsequent fear acquisition. We then show that NMDA-receptor antagonist AP5 injected to posterior insular cortex (IC) before training completely prevented the acquisition of a conditioned fear inhibitor, while intra-AP5 to anterior and medial IC had no effect. To determine if the IC contributes to the recall of learned fear inhibition, injections of the GABAA agonist muscimol were made to posterior IC before a summation test. This resulted in fear inhibition per se, which obscured inference to the effect of IC inactivation with recall of the safety cue. Control experiments sought to determine if the role of the IC in conditioned inhibition learning could be reduced to simpler fear discrimination function, but fear discrimination and recall were unaffected by AP5 or muscimol, respectively, in the posterior IC. These data implicate a role of posterior IC in the learning of conditioned fear inhibitors.

  7. Comparing the context specificity of extinction and latent inhibition.

    Science.gov (United States)

    Miller, Ralph R; Laborda, Mario A; Polack, Cody W; Miguez, Gonzalo

    2015-12-01

    Exposure to a cue alone either before (i.e., latent inhibition treatment) or after (i.e., extinction) the cue is paired with an unconditioned stimulus results in attenuated conditioned responding to the cue. Here we report two experiments in which potential parallels between the context specificity of the effects of extinction and latent inhibition treatments were directly compared in a lick suppression preparation with rats. The reversed ordering of conditioning and nonreinforcement in extinction and latent inhibition designs allowed us to examine the effect of training order on the context specificity of what is learned given phasic reinforcement and nonreinforcement of a target cue. Experiment 1 revealed that when conditioned-stimulus (CS) conditioning and CS nonreinforcement were administered in the same context, both extinction and latent inhibition treatments had reduced impacts on test performance, relative to excitatory conditioning when testing occurred outside the treatment context. Similarly, Experiment 2 showed that when conditioning was administered in one context and nonreinforcement was administered in a second context, the effects of both extinction and latent inhibition treatments were attenuated when testing occurred in a neutral context, relative to the context in which the CS was nonreinforced. The observed context specificity of extinction and latent inhibition treatments has been previously reported in both cases, but not in a single experiment under otherwise identical conditions. The results of the two experiments convergently suggest that memory of nonreinforcement becomes context dependent after a cue is both reinforced and nonreinforced, independent of the order of training.

  8. Inhibition of Bacillus subtilis growth and sporulation by threonine.

    Science.gov (United States)

    Lamb, D H; Bott, K F

    1979-01-01

    A 1-mg/ml amount of threonine (8.4 mM) inhibited growth and sporulation of Bacillus subtilis 168. Inhibition of sporulation was efficiently reversed by valine and less efficiently by pyruvate, arginine, glutamine, and isoleucine. Inhibition of vegetative growth was reversed by asparate and glutamate as well as by valine, arginine, or glutamine. Cells in minimal growth medium were inhibited only transiently by very high concentrations of threonine, whereas inhibition of sporulation was permanent. Addition of threonine prevented the normal increase in alkaline phosphatase and reduced the production of extracellular protease by about 50%, suggesting that threonine blocked the sporulation process relatively early. 2-Ketobutyrate was able to mimic the effect of threonine on sporulation. Sporulation in a strain selected for resistance to azaleucine was partially resistant. Seventy-five percent of the mutants selected for the ability to grow vegetatively in the presence of high threonine concentrations were found to be simultaneously isoleucine auxotrophs. In at least one of these mutants, the threonine resistance phenotpye could not be dissociated from the isoleucine requirement by transformation. This mutation was closely linked to a known ilvA mutation (recombination index, 0.16). This strain also had reduced intracellular threonine deaminase activity. These results suggest that threonine inhibits B. subtilis by causing valine starvation.

  9. Proteasome inhibition as a novel therapeutic target in human cancer.

    Science.gov (United States)

    Rajkumar, S Vincent; Richardson, Paul G; Hideshima, Teru; Anderson, Kenneth C

    2005-01-20

    The 26S proteasome is a large intracellular adenosine 5'-triphosphate-dependent protease that identifies and degrades proteins tagged for destruction by the ubiquitin system. The orderly degradation of cellular proteins is critical for normal cell cycling and function, and inhibition of the proteasome pathway results in cell-cycle arrest and apoptosis. Dysregulation of this enzymatic system may also play a role in tumor progression, drug resistance, and altered immune surveillance, making the proteasome an appropriate and novel therapeutic target in cancer. Bortezomib (formerly known as PS-341) is the first proteasome inhibitor to enter clinical practice. It is a boronic aid dipeptide that binds directly with and inhibits the enzymatic complex. Bortezomib has recently shown significant preclinical and clinical activity in several cancers, confirming the therapeutic value of proteasome inhibition in human malignancy. It was approved in 2003 for the treatment of advanced multiple myeloma (MM), with approximately one third of patients with relapsed and refractory MM showing significant clinical benefit in a large clinical trial. Its mechanism of action is partly mediated through nuclear factor-kappa B inhibition, resulting in apoptosis, decreased angiogenic cytokine expression, and inhibition of tumor cell adhesion to stroma. Additional mechanisms include c-Jun N-terminal kinase activation and effects on growth factor expression. Several clinical trials are currently ongoing in MM as well as several other malignancies. This article discusses proteasome inhibition as a novel therapeutic target in cancer and focuses on the development, mechanism of action, and current clinical experience with bortezomib.

  10. Inhibition by streptovaricins of Rauscher leukemia virus splenomegaly.

    Science.gov (United States)

    Borden, E C; Carter, W A; Sensenbrenner, L L; Owens, A H; Lichtenstein, J; Gray, G D; Neil, G L; Nichol, F R; Li, L H

    1974-12-15

    Streptovaricins (Sv), ansa macrolide antibiotics, inhibited Rauscher leukemia virus (RLV) splenomegaly by 25-50%. All streptovaricins tested were effective when administered orally either by diet ad lib or by intubation from infection to time of killing. When delivered by intubation, Sv was measurable in plasma for up to 6 h. SvC, at 300 mg/kg/day, reduced mean spleen weight of infected mice from 478 plus or minus 51 (SE) mg to 300 plus or minus 55 (SE) mg. Rifampicin, at 250 mg/kg/day, had no similar activity. Decrease in caloric intake and in body-weight gain also resulted in an inhibition of RLV splenomegaly; although Sv-treated mice gained weight, the increase was usually slightly less than controls. However, mice treated with a Sv diet for a week prior to infection, after an initial period of weight loss, gained at a rate equivalent to control group, and when killed had a marked reduction in splenomegaly. The selectivity of streptovaricins and specificity for viral events was suggested by several observations: (1) Splenomegaly and mortality, induced by L1210 or a non-infective transplantable tumor of RLV origin, was not inhibited. (2) No inhibition of normal hematopoietic spleen colonies was observed. (3) Host immune responses, including cellular and humoral immunity and interferon production and action, were not inhibited. Thus, although the effect of slightly decreased weight and intake could not be unequivocally established, the findings were most compatible with a selective inhibition of RLV splenomegaly by Sv.

  11. Alpha oscillatory correlates of motor inhibition in the aged brain

    Directory of Open Access Journals (Sweden)

    Marlene eBoenstrup

    2015-10-01

    Full Text Available Exerting inhibitory control is a cognitive ability mediated by functions known to decline with age. The goal of this study is to add to the mechanistic understanding of cortical inhibition during motor control in aged brains. Based on behavioral findings of impaired inhibitory control with age we hypothesized that elderly will show a reduced or a lack of EEG alpha-power increase during tasks that require motor inhibition. Since inhibitory control over movements has been shown to rely on prior motor memory formation, we investigated cortical inhibitory processes at two points in time - early after learning and after an overnight consolidation phase and hypothesized an overnight increase of inhibitory capacities. Young and elderly participants acquired a complex finger movement sequence and in each experimental session brain activity during execution and inhibition of the sequence was recorded with multi-channel EEG. We assessed cortical processes of sustained inhibition by means of task-induced changes of alpha oscillatory power. During inhibition of the learned movement, young participants showed a significant alpha power increase at the sensorimotor cortices whereas elderly did not. Interestingly, for both groups, the overnight consolidation phase improved up-regulation of alpha power during sustained inhibition. This points to deficits in the generation and enhancement of local inhibitory mechanisms at the sensorimotor cortices in aged brains. However, the alpha power increase in both groups implies neuroplastic changes that strengthen the network of alpha power generation over time in young as well as elderly brains.

  12. Unconsciously triggered response inhibition requires an executive setting.

    Science.gov (United States)

    Chiu, Yu-Chin; Aron, Adam R

    2014-02-01

    Much research on response inhibition has focused on a consciously triggered variety (i.e., outright stopping of action). However, recent studies have shown that response inhibition can also be triggered unconsciously. For example, van Gaal, Ridderinkhof, Scholte, and Lamme (2010) showed that an unconscious no-go prime slowed down ongoing behavior, at least when outright stopping was sometimes required (i.e., in an executive setting). Here we replicated that result but also went further by including a condition with no executive setting. Then there was no slowing following a no-go prime. These results support the hypothesis that an executive setting is necessary for unconsciously triggered inhibition. We speculate that this arises from the fact that when the context includes outright stopping, the brain network for response inhibition is primed, and it can be triggered by the unconscious prime. The result has theoretical implications for the distinction between conscious and unconscious response inhibition and also clinical implications for how to train response inhibition so that it is instantiated automatically.

  13. Magnetoencephalographic signatures of right prefrontal cortex involvement in response inhibition.

    Science.gov (United States)

    Hege, Maike A; Preissl, Hubert; Stingl, Krunoslav T

    2014-10-01

    The prefrontal cortex has a pivotal role in top-down control of cognitive and sensory functions. In complex go-nogo tasks, the right dorsolateral prefrontal cortex is considered to be important for guiding the response inhibition. However, little is known about the temporal dynamics and neurophysiological nature of this activity. To address this issue, we recorded magnetoencephalographic brain activity in 20 women during a visual go-nogo task. The right dorsolateral prefrontal cortex showed an increase for the amplitude of the event-related fields and an increase in induced alpha frequency band activity for nogo in comparison to go trials. The peak of this prefrontal activity preceded the mean reaction time of around 360 ms for go trials, and thus supports the proposed role of right dorsolateral prefrontal cortex in gating the response inhibition and further suggests that right prefrontal alpha band activity might be involved in this gating. However, the results in right dorsolateral prefrontal cortex were similar for both successful and unsuccessful response inhibition. In these conditions, we instead observed pre- and poststimulus differences in alpha band activity in occipital and central areas. Thus, successful response inhibition seemed to additionally depend on prestimulus anticipatory alpha desynchronization in sensory areas as it was reduced prior to unsuccessful response inhibition. In conclusion, we suggest a role for functional inhibition by alpha synchronization not only in sensory, but also in prefrontal areas.

  14. The Inhibition of Lipase and Glucosidase Activities by Acacia Polyphenol

    Directory of Open Access Journals (Sweden)

    Nobutomo Ikarashi

    2011-01-01

    Full Text Available Acacia polyphenol (AP extracted from the bark of the black wattle tree (Acacia mearnsii is rich in unique catechin-like flavan-3-ols, such as robinetinidol and fisetinidol. In an in vitro study, we measured the inhibitory activity of AP on lipase and glucosidase. In addition, we evaluated the effects of AP on absorption of orally administered olive oil, glucose, maltose, sucrose and starch solution in mice. We found that AP concentration-dependently inhibited the activity of lipase, maltase and sucrase with an IC50 of 0.95, 0.22 and 0.60 mg ml−1, respectively. In ICR mice, olive oil was administered orally immediately after oral administration of AP solution, and plasma triglyceride concentration was measured. We found that AP significantly inhibited the rise in plasma triglyceride concentration after olive oil loading. AP also significantly inhibited the rise in plasma glucose concentration after maltose and sucrose loading, and this effect was more potent against maltose. AP also inhibited the rise in plasma glucose concentration after glucose loading and slightly inhibited it after starch loading. Our results suggest that AP inhibits lipase and glucosidase activities, which leads to a reduction in the intestinal absorption of lipids and carbohydrates.

  15. Inhibition properties of propolis extracts to some clinically important enzymes.

    Science.gov (United States)

    Baltas, Nimet; Yildiz, Oktay; Kolayli, Sevgi

    2016-01-01

    The present study was conducted to envisage inhibition effects of propolis on the crucial enzymes, urease, xanthine oxidase (XO) and acetylcholinesterase (AChE). Some of the antioxidant properties of the propolis samples were determined using the total phenolic content (TPE) and total flavonoids in the eight different ethanolic propolis extracts (EPE) samples. Inhibition values of the enzymes were expressed as inhibition concentration (IC50; mg/mL or μg/mL) causing 50% inhibition of the enzymes with donepezil, acetohydroxamic acid and allopurinol as reference inhibitors. All the propolis extracts exhibited variable inhibition effects on these enzymes, but the higher the phenolic contents the lower the inhibitions values (IC50 = 0.074 to 1.560 mg/mL). IC50 values of the P5 propolis sample having the highest TPE, obtained from Zonguldak, for AChE, urease and XO were 0.081 ± 0.009, 0.080 ± 0.006 and 0.074 ± 0.011 μg/mL, respectively. The EPE proved to be a good source of inhibitor agents that can be used as natural inhibitors to serve human health.

  16. Targeted Inhibition of Multiple Receptor Tyrosine Kinases in Mesothelioma

    Directory of Open Access Journals (Sweden)

    Wen-Bin Ou

    2011-01-01

    Full Text Available The receptor tyrosine kinases (RTKs epidermal growth factor receptor (EGFR and MET are activated in subsets of mesothelioma, suggesting that these kinases might represent novel therapeutic targets in this notoriously chemotherapy-resistant cancer. However, clinical trials have shown little activity for EGFR inhibitors in mesothelioma. Despite the evidence for RTK activation in mesothelioma pathogenesis, it is unclear whether transforming activity is dependent on an individual kinase oncoprotein or the coordinated activity of multiple kinases. Using phospho-RTK and immunoblot assays, we herein demonstrate activation of multiple RTKs (EGFR, MET, AXL, and ERBB3 in individual mesothelioma cell lines but not in normal mesothelioma cells. Inhibition of mesothelioma multi-RTK signaling was accomplished using combinations of RTK direct inhibitors or by inhibition of the RTK chaperone, heat shock protein 90 (HSP90. Multi-RTK inhibition by the HSP90 inhibitor 17-allyloamino-17demethoxygeldanamycin (17-AAG had a substantially greater effect on mesothelioma proliferation and survival compared with inhibition of individual activated RTKs. HSP90 inhibition also suppressed phosphorylation of down-stream signaling intermediates (AKT, mitogen-activated protein kinase, and S6; upregulated the p53, p21, and p27 cell cycle checkpoints; induced G2 phase arrest; induced caspase 3/7 activity; and led to an increase in the sub-G1 apoptotic population. These compelling proapoptotic and antiproliferative responses indicate that HSP90 inhibition warrants clinical evaluation as a novel therapeutic strategy in mesothelioma.

  17. Palmitoylethanolamide Inhibits Glutamate Release in Rat Cerebrocortical Nerve Terminals

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    Tzu-Yu Lin

    2015-03-01

    Full Text Available The effect of palmitoylethanolamide (PEA, an endogenous fatty acid amide displaying neuroprotective actions, on glutamate release from rat cerebrocortical nerve terminals (synaptosomes was investigated. PEA inhibited the Ca2+-dependent release of glutamate, which was triggered by exposing synaptosomes to the potassium channel blocker 4-aminopyridine. This release inhibition was concentration dependent, associated with a reduction in cytosolic Ca2+ concentration, and not due to a change in synaptosomal membrane potential. The glutamate release-inhibiting effect of PEA was prevented by the Cav2.1 (P/Q-type channel blocker ω-agatoxin IVA or the protein kinase A inhibitor H89, not affected by the intracellular Ca2+ release inhibitors dantrolene and CGP37157, and partially antagonized by the cannabinoid CB1 receptor antagonist AM281. Based on these results, we suggest that PEA exerts its presynaptic inhibition, likely through a reduction in the Ca2+ influx mediated by Cav2.1 (P/Q-type channels, thereby inhibiting the release of glutamate from rat cortical nerve terminals. This release inhibition might be linked to the activation of presynaptic cannabinoid CB1 receptors and the suppression of the protein kinase A pathway.

  18. Highly reflective reasoners show no signs of belief inhibition.

    Science.gov (United States)

    Svedholm-Häkkinen, Annika M

    2015-01-01

    The processes underlying individual differences in reasoning performance are not entirely understood. What do people who do well on reasoning tasks where beliefs and logic conflict do differently from other people? Because abundant evidence shows that even poorer reasoners detect these conflicts, it has been suggested that individual differences in reasoning performance arise from inhibition failures later in the reasoning process. The present paper argues that a minority of highly skilled reasoners may deviate from this general reasoning process from an early stage. Two studies investigated signs of belief inhibition using a lexical access paradigm (Study 1) and a negative priming paradigm (Study 2). Study 1 showed that while other people exhibited signs of belief inhibition following a belief-logic conflict, people with the highest disposition for cognitive reflection did not. In Study 2, this finding was replicated and similar results were also obtained when comparing groups with higher and lower general cognitive ability. Two possible explanations are discussed. The reasoners with a highly reflective cognitive style or high general cognitive ability may have engaged and inhibited belief processing but if so, they may have been exceptionally efficient at recovering from it, wherefore no belief inhibition effects were found. An alternative account is that these reasoners started Type 2 processing directly, without first engaging in and then inhibiting belief-based processing. Under either explanation, the results indicate that individual differences in reasoning may partly arise from differences that occur early in the reasoning process.

  19. Inhibition of Chlorination in Streptomyces aureofaciens by Nitriles and Related Compounds

    Science.gov (United States)

    Goodman, Joseph J.; Matrishin, Mary

    1973-01-01

    A number of nitriles and cyano compounds inhibited chlorination by Streptomyces aureofaciens. In most cases, this inhibition was enhanced by bromide. Methylene blue and p-amino-propiophenone reversed the inhibition to some extent. PMID:4208277

  20. Substrate and product inhibition of hydrogen production by the extreme thermophile, Caldicellulosiruptor saccharolyticus

    NARCIS (Netherlands)

    Niel, van E.W.J.; Claassen, P.A.M.; Stams, A.J.M.

    2003-01-01

    Substrate and product inhibition of hydrogen production during sucrose fermentation by the extremely thermophilic bacterium Caldicellulosiruptor saccharolyticus was studied. The inhibition kinetics were analyzed with a noncompetitive, nonlinear inhibition model. Hydrogen was the most severe inhibito

  1. Cantharidin biosynthesis in a blister beetle: inhibition by 6-fluoromevalonate causes chemical disarmament.

    Science.gov (United States)

    Carrel, J E; Doom, J P; McCormick, J P

    1986-07-15

    Biosynthesis of cantharidin in a blister beetle, Lytta polita, is effectively inhibited by 6-fluoromevalonate. Inhibition is attributed specifically to the fluorine substituent. Biochemical inhibition has not been demonstrated previously for an arthropod's defensive substance.

  2. Reactor design for minimizing product inhibition during enzymatic lignocellulose hydrolysis II. Quantification of inhibition and suitability of membrane reactors

    DEFF Research Database (Denmark)

    Andric, Pavle; Meyer, Anne S.; Jensen, Peter Arendt;

    2010-01-01

    hydrolysis rates and higher enzyme usage efficiency (kg(product/)kg(enzyme)). Current membrane reactor designs are however not feasible for large scale operations. The report emphasizes that the industrial realization of cellulosic ethanol requires more focus on the operational feasibility within......Product inhibition of cellulolytic enzymes affects the efficiency of the biocatalytic conversion of lignocellulosic biomass to ethanol and other valuable products. New strategies that focus on reactor designs encompassing product removal, notably glucose removal, during enzymatic cellulose...... conversion are required for alleviation of glucose product inhibition. Supported by numerous calculations this review assesses the quantitative aspects of glucose product inhibition on enzyme-catalyzed cellulose degradation rates. The significance of glucose product inhibition on dimensioning of different...

  3. Gingival tissue-produced inhibition of platelet aggregation and the loss of inhibition in streptozotocin-induced diabetic rats

    Energy Technology Data Exchange (ETDEWEB)

    Kawamura, Keiichiroh; Tamai, Kazuharu; Shirakawa, Masaharu; Okamoto, Hiroshi; Dohi, Toshihiro; Tsujimoto, Akira

    1988-01-01

    Addition of medium incubated with normal rat gingival tissue to platelet-rich plasma inhibited ADP-induced platelet aggregation. The ability of rat gingiva to produce activity inhibiting platelet aggregation was enhanced by the addition of arachidonic acid. Diabetic rat gingiva failed to inhibit platelet aggregation but did produce the anti-platelet aggregating activity in the presence of arachidonic acid. Indomethacin blocked the production of anti-platelet aggregating activity. There was no difference in conversion of (1-/sup 14/C)arachidonic acid to prostaglandins by normal and diabetic rat gingiva. These results suggest that an arachidonic acid metabolite released from gingiva during incubation inhibits platelet aggregation, and the synthesis of the metabolite is impaired in diabetic rat gingiva. A decrease in availability of arachidonic acid may be a causal factor of the defect in diabetic rat gingiva.

  4. The Effect of Oxidation on Berberine-Mediated CYP1 Inhibition: Oxidation Behavior and Metabolite-Mediated Inhibition.

    Science.gov (United States)

    Lo, Sheng-Nan; Shen, Chien-Chang; Chang, Chia-Yu; Tsai, Keng-Chang; Huang, Chiung-Chiao; Wu, Tian-Shung; Ueng, Yune-Fang

    2015-07-01

    The protoberberine alkaloid berberine carries methylenedioxy moiety and exerts a variety of pharmacological effects, such as anti-inflammation and lipid-lowering effects. Berberine causes potent CYP1B1 inhibition, whereas CYP1A2 shows resistance to the inhibition. To reveal the influence of oxidative metabolism on CYP1 inhibition by berberine, berberine oxidation and the metabolite-mediated inhibition were determined. After NADPH-fortified preincubation of berberine with P450, the inhibition of CYP1A1 and CYP1B1 variants (CYP1B1.1, CYP1B1.3, and CYP1B1.4) by berberine was not enhanced, and CYP1A2 remained resistant. Demethyleneberberine was identified as the most abundant metabolite of CYP1A1- and CYP1B1-catalyzed oxidations, and thalifendine was generated at a relatively low rate. CYP1A1-catalyzed berberine oxidation had the highest maximal velocity (V max) and exhibited positive cooperativity, suggesting the assistance of substrate binding when the first substrate was present. In contrast, the demethylenation by CYP1B1 showed the property of substrate inhibition. CYP1B1-catalyzed berberine oxidation had low K m values, but it had V max values less than 8% of those of CYP1A1. The dissociation constants generated from the binding spectrum and fluorescence quenching suggested that the low K m values of CYP1B1-catalyzed oxidation might include more than the rate constants describing berberine binding. The natural protoberberine/berberine fmetabolites with methylenedioxy ring-opening (palmatine, jatrorrhizine, and demethyleneberberine) and the demethylation (thalifendine and berberrubine) caused weak CYP1 inhibition. These results demonstrated that berberine was not efficiently oxidized by CYP1B1, and metabolism-dependent irreversible inactivation was minimal. Metabolites of berberine caused a relatively weak inhibition of CYP1.

  5. Tumour growth inhibition and anti-angiogenic effects using curcumin correspond to combined PDE2 and PDE4 inhibition.

    Science.gov (United States)

    Abusnina, Abdurazzag; Keravis, Thérèse; Zhou, Qingwei; Justiniano, Hélène; Lobstein, Annelise; Lugnier, Claire

    2015-02-01

    Vascular endothelial growth factor (VEGF) plays a major role in angiogenesis by stimulating endothelial cells. Increase in cyclic AMP (cAMP) level inhibits VEGF-induced endothelial cell proliferation and migration. Cyclic nucleotide phosphodiesterases (PDEs), which specifically hydrolyse cyclic nucleotides, are critical in the regulation of this signal transduction. We have previously reported that PDE2 and PDE4 up-regulations in human umbilical vein endothelial cells (HUVECs) are implicated in VEGF-induced angiogenesis and that inhibition of PDE2 and PDE4 activities prevents the development of the in vitro angiogenesis by increasing cAMP level, as well as the in vivo chicken embryo angiogenesis. We have also shown that polyphenols are able to inhibit PDEs. The curcumin having anti-cancer properties, the present study investigated whether PDE2 and PDE4 inhibitors and curcumin could have similar in vivo anti-tumour properties and whether the anti-angiogenic effects of curcumin are mediated by PDEs. Both PDE2/PDE4 inhibitor association and curcumin significantly inhibited in vivo tumour growth in C57BL/6N mice. In vitro, curcumin inhibited basal and VEGF-stimulated HUVEC proliferation and migration and delayed cell cycle progression at G0/G1, similarly to the combination of selective PDE2 and PDE4 inhibitors. cAMP levels in HUVECs were significantly increased by curcumin, similarly to rolipram (PDE4 inhibitor) and BAY-60-550 (PDE2 inhibitor) association, indicating cAMP-PDE inhibitions. Moreover, curcumin was able to inhibit VEGF-induced cAMP-PDE activity without acting on cGMP-PDE activity and to modulate PDE2 and PDE4 expressions in HUVECs. The present results suggest that curcumin exerts its in vitro anti-angiogenic and in vivo anti-tumour properties through combined PDE2 and PDE4 inhibition.

  6. Evidence that neomycin inhibits human cytomegalovirus infection of fibroblasts.

    Science.gov (United States)

    Lobert, P E; Hober, D; Delannoy, A S; Wattré, P

    1996-01-01

    The effect of phosphoinositide-binding aminoglycosides, such as neomycin, gentamicin and streptomycin, on human cytomegalovirus (HCMV) infection of human fibroblasts MRC-5 was studied. The inhibition of HCMV infection was obtained with all of these molecules but neomycin was more effective than the others. We showed that the inoculation of the cells with cell-free viral suspension in presence of neomycin concentrations above 5 mM at 37 degrees C, inhibited more than 98% the HCMV infection. However, the preincubation of the fibroblasts with neomycin at 4 degrees C, before the removal of the drug and the inoculation of the cells, induced only a 30% decrease in the number of infected cells. Addition of neomycin after the HCMV-binding at 4 degrees C or the infection of the cells was less efficient to inhibit HCMV infection than the standard incubation of neomycin during inoculation of the fibroblasts. Indeed, 1 hour after the inoculation of the cells at 37 degrees C, neomycin still inhibited HCMV infection, but 4 hours after the inoculation, this drug had no effect on HCMV infection. Our findings demonstrated that neomycin must be present at the time of infection in order to exert a full inhibiting effect. The effect of neomycin on the HCMV infection was almost immediate upon the addition of the drug (binding and/or internalization) and after the virus internalization (inhibition of immediate-early events). We suggest that neomycin and other aminoglycoside antibiotics may interact with HCMV glycoproteins for binding to similar structural features of cell surface heparan sulfate proteoglycans and may inhibit HCMV infection in fibroblasts by disrupting phosphoinositide-mediated events in the cells.

  7. Task Dominance Determines Backward Inhibition in Task Switching

    Directory of Open Access Journals (Sweden)

    Kerstin Jost

    2017-05-01

    Full Text Available Switching between tasks is assumed to be accompanied by inhibiting currently irrelevant, but competing tasks. A dominant task that strongly interferes with performing a weaker task may receive especially strong inhibition. We tested this prediction by letting participants switch among three tasks that differ in dominance: a location discrimination task with strong stimulus–response bindings (responding with left-hand and right-hand button presses to stimuli presented left or right to the fixation cross was combined with a color/pattern and a shape discrimination task, for which stimulus–response mappings were arbitrary (e.g., left-hand button press mapped to a red stimulus. Across three experiments, the dominance of the location task was documented by faster and more accurate responses than in the other tasks. This even held for incompatible stimulus–response mappings (i.e., right-hand response to a left-presented stimulus and vice versa, indicating that set-level compatibility (i.e., “dimension overlap” was sufficient for making this location task dominant. As a behavioral marker for backward inhibition, we utilized n-2 repetition costs that are defined by higher reaction times for a switch back to a just abandoned and thus just inhibited task (ABA sequence than for a switch to a less recently inhibited task (CBA, n-2 non-repetition. Reliable n-2 task repetition costs were obtained for all three tasks. Importantly, these costs were largest for the location task, suggesting that inhibition indeed was stronger for the dominant task. This finding adds to other evidence that the amount of inhibition is adjusted in a context-sensitive way.

  8. Curcumin directly inhibits the transport activity of GLUT1.

    Science.gov (United States)

    Gunnink, Leesha K; Alabi, Ola D; Kuiper, Benjamin D; Gunnink, Stephen M; Schuiteman, Sam J; Strohbehn, Lauren E; Hamilton, Kathryn E; Wrobel, Kathryn E; Louters, Larry L

    2016-06-01

    Curcumin, a major ingredient in turmeric, has a long history of medicinal applications in a wide array of maladies including treatment for diabetes and cancer. Seemingly counterintuitive to the documented hypoglycemic effects of curcumin, however, a recent report indicates that curcumin directly inhibits glucose uptake in adipocytes. The major glucose transporter in adipocytes is GLUT4. Therefore, this study investigates the effects of curcumin in cell lines where the major transporter is GLUT1. We report that curcumin has an immediate inhibitory effect on basal glucose uptake in L929 fibroblast cells with a maximum inhibition of 80% achieved at 75 μM curcumin. Curcumin also blocks activation of glucose uptake by azide, glucose deprivation, hydroxylamine, or phenylarsine oxide. Inhibition does not increase with exposure time and the inhibitory effects reverse within an hour. Inhibition does not appear to involve a reaction between curcumin and the thiol side chain of a cysteine residue since neither prior treatment of cells with iodoacetamide nor curcumin with cysteine alters curcumin's inhibitory effects. Curcumin is a mixed inhibitor reducing the Vmax of 2DG transport by about half with little effect on the Km. The inhibitory effects of curcumin are not additive to the effects of cytochalasin B and 75 μM curcumin actually reduces specific cytochalasin B binding by 80%. Taken together, the data suggest that curcumin binds directly to GLUT1 at a site that overlaps with the cytochalasin B binding site and thereby inhibits glucose transport. A direct inhibition of GLUT proteins in intestinal epithelial cells would likely reduce absorption of dietary glucose and contribute to a hypoglycemic effect of curcumin. Also, inhibition of GLUT1 activity might compromise cancer cells that overexpress GLUT1 and be another possible mechanism for the documented anticancer effects of curcumin. Copyright © 2016. Published by Elsevier B.V.

  9. Suicidal behaviours in affective disorders: a deficit of cognitive inhibition?

    Science.gov (United States)

    Richard-Devantoy, Stéphane; Gorwood, Philip; Annweiler, Cédric; Olié, Jean-Pierre; Le Gall, Didier; Beauchet, Olivier

    2012-04-01

    Suicide has been related to affective disorders. We hypothesized that suicide could be associated with cognitive inhibition deficit. Our study aimed to systematically review all published articles that examined the relation between cognitive inhibition deficit and suicidal behaviours (that is, suicide attempt or suicidal ideation) in patients with affective disorders. We performed an English and French MEDLINE and EMBASE search, ranging from 1970 to 2010, indexed under the MeSH terms of suicide, neuropsychology, neuropsychological tests, and executive function, combined with the following title and abstract terms: neuropsychological functions, executive functioning, and executive performance. Among the 164 selected studies, 9 observational studies met the selection criteria and were included in the final analysis. The number of participants ranged from 57 to 244 (28% to 66%, respectively, were men). Executive dysfunction was more frequently found among patients with suicidal behaviours. In particular, higher cognitive inhibition deficit was observed in depressed subjects with suicide behaviours, compared with depressed subjects without any suicidal behaviour. The results of the meta-analysis showed a higher impairment in inhibition score, according to the number of perseverations in the Wisconsin Card Sorting Test (Cohen d = 0.68) than in inhibition according to the time needed to perform the Trail-Making Test part B (d = 0.01) among patients with suicidal behaviour, compared with patients with no suicidal behaviour. This systematic review and meta-analysis showed a positive association between cognitive inhibition deficit and suicide attempts in patients with affective disorders. Future research should examine whether cognitive inhibition deficit precedes the suicidal behaviour.

  10. Toll-like receptor 2 agonists inhibit human fibrocyte differentiation

    Directory of Open Access Journals (Sweden)

    Maharjan Anu S

    2010-11-01

    Full Text Available Abstract Background In healing wounds, some monocytes enter the wound and differentiate into fibroblast-like cells called fibrocytes. Since Toll-like receptors (TLRs are present on monocytes, and pathogens that can infect a wound have and/or release TLR agonists, we examined whether TLR agonists affect fibrocyte differentiation. Results When human peripheral blood mononuclear cells (PBMCs were cultured with TLR3, TLR4, TLR5, TLR7, TLR8 or TLR9 agonists, there was no significant effect on fibrocyte differentiation, even though enhanced extracellular tumor necrosis factor (TNF-α accumulation and/or increased cell surface CD86 or major histocompatibility complex (MHC class II levels were observed. However, all TLR2 agonists tested inhibited fibrocyte differentiation without any significant effect on cell survival. Adding TLR2 agonists to purified monocytes had no effect on fibrocyte differentiation. However, some TLR2 agonists caused PBMCs to secrete a factor that inhibits the differentiation of purified monocytes into fibrocytes. This factor is not interferon (IFN-α, IFN-γ, interleukin (IL-12, aggregated immunoglobulin G (IgG or serum amyloid P (SAP, factors known to inhibit fibrocyte differentiation. TLR2 agonist-treated PBMCs secrete low levels of IL-6, TNF-α, IFN-γ, granulocyte colony-stimulating factor and tumor growth factor β1, but combinations of these factors had no effect on fibrocyte differentiation from purified monocytes. Conclusions Our results indicate that TLR2 agonists indirectly inhibit fibrocyte differentiation and that, for some TLR2 agonists, this inhibition involves other cell types in the PBMC population secreting an unknown factor that inhibits fibrocyte differentiation. Together, these data suggest that the presence of some bacterial signals can inhibit fibrocyte differentiation and may thus slow wound closure.

  11. Opsin-mediated inhibition of bacterioruberin synthesis in halophilic Archaea.

    Science.gov (United States)

    Peck, Ronald F; Pleşa, Alexandru M; Graham, Serena M; Angelini, David R; Shaw, Emily L

    2017-08-07

    Halophilic Archaea often inhabit environments with limited oxygen, and many produce ion-pumping rhodopsin complexes that allow them to maintain electrochemical gradients when aerobic respiration is inhibited. Rhodopsins require a protein, opsin, and an organic cofactor, retinal. We have previously demonstrated that, in Halobacterium salinarum, bacterioopsin (BO), when not bound by retinal, inhibits the production of bacterioruberin, a biochemical pathway that shares intermediates with retinal biosynthesis. In this work, we use heterologous expression in a related halophilic Archaeon, Haloferax volcanii, to demonstrate that BO is sufficient to inhibit bacterioruberin synthesis catalyzed by the H. salinarum lycopene elongase (Lye) enzyme. This inhibition was observed both in liquid cultures and in a novel colorimetric assay to quantify bacterioruberin abundance based on the colony color. Addition of retinal to convert BO to the bacteriorhodopsin complex resulted in a partial rescue of bacterioruberin production. To explore if this regulatory mechanism occurs in other organisms, we expressed a Lye homolog and an opsin from Haloarcula vallismortis in H. volcaniiH. vallismortis cruxopsin expression inhibited bacterioruberin synthesis catalyzed by H. vallismortis Lye, but had no effect when bacterioruberin synthesis was catalyzed by H. salinarum or H. volcanii Lye. Conversely, H. salinarum BO did not inhibit H. vallismortis Lye activity. Together, our data suggest that opsin-mediated inhibition of Lye is potentially widespread and represents an elegant regulatory mechanism that allows organisms to efficiently utilize ion-pumping rhodopsins obtained through lateral gene transfer.Importance Many enzymes are complexes of proteins and non-protein organic molecules called cofactors. To ensure efficient formation of functional complexes, organisms must regulate the production of proteins and cofactors. To study this regulation, we use bacteriorhodopsin from the Archaeon

  12. Inhibition of proliferation, migration and proteolysis contribute to corticosterone-mediated inhibition of angiogenesis.

    Directory of Open Access Journals (Sweden)

    Eric A Shikatani

    Full Text Available The angiostatic nature of pharmacological doses of glucocorticoid steroids is well known. However, the consequences of pathophysiological elevation of endogenous glucocorticoids are not well established. In the current study, we hypothesized that the angiostatic effect of corticosterone, an endogenous glucocorticoid in rodents, occurs through multi-faceted alterations in skeletal muscle microvascular endothelial cell proliferation, migration, and proteolysis. Chronic corticosterone treatment significantly reduced the capillary to fiber ratio in the tibialis anterior muscle compared to that of placebo-treated rats. Corticosterone inhibited endothelial cell sprouting from capillary segments ex vivo. Similarly, 3-dimensional endothelial cell spheroids treated with corticosterone for 48 hours showed evidence of sprout regression and reduced sprout length. Endothelial cell proliferation was reduced in corticosterone treated cells, coinciding with elevated FoxO1 and reduced VEGF production. Corticosterone treated endothelial cells exhibited reduced migration, which correlated with a reduction in RhoA activity. Furthermore, corticosterone treated endothelial cells in both 3-dimensional and monolayer cultures had decreased MMP-2 production and activation resulting in decreased proteolysis by endothelial cells, limiting their angiogenic potential. Promoter assays revealed that corticosterone treatment transcriptionally repressed MMP-2, which may map to a predicted GRE between -1510 and -1386 bp of the MMP-2 promoter. Additionally, Sp1, a known transcriptional activator of MMP-2 was decreased following corticosterone treatment. This study provides new insights into the mechanisms by which pathophysiological levels of endogenous glucocorticoids may exert angiostatic effects.

  13. Inhibition of 5-Lipoxygenase Pathway Attenuates Acute Liver Failure by Inhibiting Macrophage Activation

    Directory of Open Access Journals (Sweden)

    Lu Li

    2014-01-01

    Full Text Available This study aimed to investigate the role of 5-lipoxygenase (5-LO in acute liver failure (ALF and changes in macrophage activation by blocking it. ALF was induced in rats by administration of D-galactosamine (D-GalN/lipopolysaccharide (LPS. Rats were injected intraperitoneally with AA-861 (a specific 5-LO inhibitor, 24 hr before D-GalN/LPS administration. After D-GalN/LPS injection, the liver tissue was collected for assessment of histology, macrophage microstructure, macrophage counts, 5-LO mRNA formation, protein expression, and concentration of leukotrienes. Serum was collected for detecting alanine aminotransferase (ALT, aspartate transaminase (AST, total bilirubin (Tbil, and tumor necrosis factor- (TNF-α. Twenty-four hours after injection, compared with controls, ALF rats were characterized by widespread hepatocyte necrosis and elevated ALT, AST, and Tbil, and 5-LO protein expression reached a peak. Liver leukotriene B4 was also significantly elevated. However, 5-LO mRNA reached a peak 8 hr after D-GalN/LPS injection. Simultaneously, the microstructure of macrophages was changed most significantly and macrophages counts were increased significantly. Moreover, serum TNF-α was also elevated. By contrast, AA-861 pretreatment significantly decreased liver necrosis as well as all of the parameters compared with the rats without pretreatment. Macrophages, via the 5-LO pathway, play a critical role in ALF, and 5-LO inhibitor significantly alleviates ALF, possibly related to macrophage inhibition.

  14. Recruitment of Perisomatic Inhibition during Spontaneous Hippocampal Activity In Vitro.

    Directory of Open Access Journals (Sweden)

    Anna Beyeler

    Full Text Available It was recently shown that perisomatic GABAergic inhibitory postsynaptic potentials (IPSPs originating from basket and chandelier cells can be recorded as population IPSPs from the hippocampal pyramidal layer using extracellular electrodes (eIPSPs. Taking advantage of this approach, we have investigated the recruitment of perisomatic inhibition during spontaneous hippocampal activity in vitro. Combining intracellular and extracellular recordings from pyramidal cells and interneurons, we confirm that inhibitory signals generated by basket cells can be recorded extracellularly, but our results suggest that, during spontaneous activity, eIPSPs are mostly confined to the CA3 rather than CA1 region. CA3 eIPSPs produced the powerful time-locked inhibition of multi-unit activity expected from perisomatic inhibition. Analysis of the temporal dynamics of spike discharges relative to eIPSPs suggests significant but moderate recruitment of excitatory and inhibitory neurons within the CA3 network on a 10 ms time scale, within which neurons recruit each other through recurrent collaterals and trigger powerful feedback inhibition. Such quantified parameters of neuronal interactions in the hippocampal network may serve as a basis for future characterisation of pathological conditions potentially affecting the interactions between excitation and inhibition in this circuit.

  15. Mechanism of Arsenic Trioxide Inhibiting Angiogenesis in Multiple Myeloma

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In order to explore the molecular mechanism of arsenic trioxide treating multiple myeloma (MM) via inhibition of angiogenesis, the expression of brain derived neurotrophic factor (BD-NF) and its specific receptor TrkB in human MM cell line KM3 and endothelial cell line ECV304 was detected by Western blotting. The angiogenic activity was evaluated by wound migration assay and tubule formation assay in vitro. The results showed that BDNF was detected in the MM cells and TrkB in the endothelial cells. Furthermore, 100 ng/mL BDNF could significantly induced endo thelial cell tubule formation and wound migration. As2 O3 depressed the expression of BDNF and TrkB in the dose- and time-dependent manner. As2O3 inhibited BDNF-induced wound migration and capillary tube formation. It was concluded that BDNF is a novel angiogenic protein as well as VEGF and has a relation with the pathogenesis of MM. As2O3 interrupts a paracrine loop between MM cells and endothelial cells by down-regulating the TrkB expression in endothelial cells and inhibiting BDNF production in MM cells, finally resulting in inhibition of MM angiogenesis. This is probably one part of the mechanisms of the As2O3 treating MM via the inhibition of angiogenesis.

  16. Inhibition potentiates the synchronizing action of electrical synapses

    Directory of Open Access Journals (Sweden)

    Benjamin Pfeuty

    2007-11-01

    Full Text Available In vivo and in vitro experimental studies have found that blocking electrical interactions connecting GABAergic interneurons reduces oscillatory activity in the µ range in cortex. However, recent theoretical works have shown that the ability of electrical synapses to promote or impede synchrony, when alone, depends on their location on the dendritic tree of the neurons, the intrinsic properties of the neurons and the connectivity of the network. The goal of the present paper is to show that this versatility in the synchronizing ability of electrical synapses is greatly reduced when the neurons also interact via inhibition. To this end, we study a model network comprising two-compartment conductance-based neurons interacting with both types of synapses. We investigate the effect of electrical synapses on the dynamical state of the network as a function of the strength of the inhibition. We find that for weak inhibition, electrical synapses reinforce inhibition-generated synchrony only if they promote synchrony when they are alone. In contrast, when inhibition is sufficiently strong, electrical synapses improve synchrony even if when acting alone they would stabilize asynchronous firing. We clarify the mechanism underlying this cooperative interplay between electrical and inhibitory synapses. We show that it is relevant in two physiologically observed regimes: spike-to-spike synchrony, where neurons fire at almost every cycle of the population oscillations, and stochastic synchrony, where neurons fire irregularly and at a rate which is substantially lower than the frequency of the global population rhythm.

  17. Menthol binding and inhibition of α7-nicotinic acetylcholine receptors.

    Science.gov (United States)

    Ashoor, Abrar; Nordman, Jacob C; Veltri, Daniel; Yang, Keun-Hang Susan; Al Kury, Lina; Shuba, Yaroslav; Mahgoub, Mohamed; Howarth, Frank C; Sadek, Bassem; Shehu, Amarda; Kabbani, Nadine; Oz, Murat

    2013-01-01

    Menthol is a common compound in pharmaceutical and commercial products and a popular additive to cigarettes. The molecular targets of menthol remain poorly defined. In this study we show an effect of menthol on the α7 subunit of the nicotinic acetylcholine (nACh) receptor function. Using a two-electrode voltage-clamp technique, menthol was found to reversibly inhibit α7-nACh receptors heterologously expressed in Xenopus oocytes. Inhibition by menthol was not dependent on the membrane potential and did not involve endogenous Ca(2+)-dependent Cl(-) channels, since menthol inhibition remained unchanged by intracellular injection of the Ca(2+) chelator BAPTA and perfusion with Ca(2+)-free bathing solution containing Ba(2+). Furthermore, increasing ACh concentrations did not reverse menthol inhibition and the specific binding of [(125)I] α-bungarotoxin was not attenuated by menthol. Studies of α7- nACh receptors endogenously expressed in neural cells demonstrate that menthol attenuates α7 mediated Ca(2+) transients in the cell body and neurite. In conclusion, our results suggest that menthol inhibits α7-nACh receptors in a noncompetitive manner.

  18. IGF-1 receptor inhibition by picropodophyllin in medulloblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Ohshima-Hosoyama, Sachiko; Hosoyama, Tohru; Nelon, Laura D. [Greehey Children' s Cancer Research Institute, University of Texas Health Science Center, San Antonio, TX 78229 (United States); Keller, Charles, E-mail: keller@ohsu.edu [Greehey Children' s Cancer Research Institute, University of Texas Health Science Center, San Antonio, TX 78229 (United States); Department of Pediatrics, University of Texas Health Science Center, San Antonio, TX 78229 (United States); Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229 (United States)

    2010-09-03

    Research highlights: {yields} Igf1r is overexpressed and activated in a Sonic Hedgehog driven model of medulloblastoma. {yields} Picropodophyllin targets and abrogates IGF signaling in medulloblastoma. {yields} Picropodophyllin inhibits medulloblastoma tumor cell growth by induction of apoptosis. -- Abstract: The insulin-like growth factor-1 receptor (Igf1r) is a multifunctional membrane-associated tyrosine kinase associated with regulation of transformation, proliferation, differentiation and apoptosis. Increased IGF pathway activity has been reported in human and murine medulloblastoma. Tumors from our genetically-engineered medulloblastoma mouse model over-express Igf1r, and thus this mouse model is a good platform with which to study the role of Igf1r in tumor progression. We hypothesize that inhibition of IGF pathway in medulloblastoma can slow or inhibit tumor growth and metastasis. To test our hypothesis, we tested the role of IGF in tumor growth in vitro by treatment with the tyrosine kinase small molecule inhibitor, picropodophyllin (PPP), which strongly inhibits the IGF pathway. Our results demonstrate that PPP-mediated downregulation of the IGF pathway inhibits mouse tumor cell growth and induces apoptotic cell death in vitro in primary medulloblastoma cultures that are most reflective of tumor cell behavior in vivo.

  19. IGFBP-3, hypoxia and TNF-{alpha} inhibit adiponectin transcription

    Energy Technology Data Exchange (ETDEWEB)

    Zappala, Giovanna, E-mail: zappalag@mail.nih.gov [Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (United States); Rechler, Matthew M. [Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (United States); Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (United States)

    2009-05-15

    The thiazolidinedione rosiglitazone, an agonist ligand for the nuclear receptor PPAR-{gamma}, improves insulin sensitivity in part by stimulating transcription of the insulin-sensitizing adipokine adiponectin. It activates PPAR-{gamma}-RXR-{alpha} heterodimers bound to PPAR-{gamma} response elements in the adiponectin promoter. Rosiglitazone-stimulated adiponectin protein synthesis in 3T3-L1 mouse adipocytes has been shown to be inhibited by IGFBP-3, which can be induced by hypoxia and the proinflammatory cytokine, TNF-{alpha}, two inhibitors of adiponectin transcription. The present study demonstrates that IGFBP-3, the hypoxia-mimetic agent cobalt chloride, and TNF-{alpha} inhibit rosiglitazone-induced adiponectin transcription in mouse embryo fibroblasts that stably express PPAR-{gamma}2. Native IGFBP-3 can bind RXR-{alpha} and inhibited rosiglitazone stimulated promoter activity, whereas an IGFBP-3 mutant that does not bind RXR-{alpha} did not. These results suggest that IGFBP-3 may mediate the inhibition of adiponectin transcription by hypoxia and TNF-{alpha}, and that IGFBP-3 binding to RXR-{alpha} may be required for the observed inhibition.

  20. Menthol binding and inhibition of α7-nicotinic acetylcholine receptors.

    Directory of Open Access Journals (Sweden)

    Abrar Ashoor

    Full Text Available Menthol is a common compound in pharmaceutical and commercial products and a popular additive to cigarettes. The molecular targets of menthol remain poorly defined. In this study we show an effect of menthol on the α7 subunit of the nicotinic acetylcholine (nACh receptor function. Using a two-electrode voltage-clamp technique, menthol was found to reversibly inhibit α7-nACh receptors heterologously expressed in Xenopus oocytes. Inhibition by menthol was not dependent on the membrane potential and did not involve endogenous Ca(2+-dependent Cl(- channels, since menthol inhibition remained unchanged by intracellular injection of the Ca(2+ chelator BAPTA and perfusion with Ca(2+-free bathing solution containing Ba(2+. Furthermore, increasing ACh concentrations did not reverse menthol inhibition and the specific binding of [(125I] α-bungarotoxin was not attenuated by menthol. Studies of α7- nACh receptors endogenously expressed in neural cells demonstrate that menthol attenuates α7 mediated Ca(2+ transients in the cell body and neurite. In conclusion, our results suggest that menthol inhibits α7-nACh receptors in a noncompetitive manner.

  1. Mutant p53 protein localized in the cytoplasm inhibits autophagy.

    Science.gov (United States)

    Morselli, Eugenia; Tasdemir, Ezgi; Maiuri, Maria Chiara; Galluzzi, Lorenzo; Kepp, Oliver; Criollo, Alfredo; Vicencio, José Miguel; Soussi, Thierry; Kroemer, Guido

    2008-10-01

    The knockout, knockdown or chemical inhibition of p53 stimulates autophagy. Moreover, autophagy-inducing stimuli such as nutrient depletion, rapamycin or lithium cause the depletion of cytoplasmic p53, which in turn is required for the induction of autophagy. Here, we show that retransfection of p53(-/-) HCT 116 colon carcinoma cells with wild type p53 decreases autophagy down to baseline levels. Surprisingly, one third among a panel of 22 cancer-associated p53 single amino acid mutants also inhibited autophagy when transfected into p53(-/-) cells. Those variants of p53 that preferentially localize to the cytoplasm effectively repressed autophagy, whereas p53 mutants that display a prominently nuclear distribution failed to inhibit autophagy. The investigation of a series of deletion mutants revealed that removal of the DNA-binding domain from p53 fails to interfere with its role in the regulation of autophagy. Altogether, these results identify the cytoplasmic localization of p53 as the most important feature for p53-mediated autophagy inhibition. Moreover, the structural requirements for the two biological activities of extranuclear p53, namely induction of apoptosis and inhibition of autophagy, are manifestly different.

  2. In vino veritas? Alcohol, response inhibition and lying.

    Science.gov (United States)

    Suchotzki, Kristina; Crombez, Geert; Debey, Evelyne; van Oorsouw, Kim; Verschuere, Bruno

    2015-01-01

    Despite the widespread belief that alcohol makes the truth come out more easily, we know very little on how alcohol impacts deception. Given that alcohol impairs response inhibition, and that response inhibition may be critically involved in deception, we expected that alcohol intake would hamper lying. In total, 104 volunteers were tested at a science festival, where they had the opportunity to drink alcohol. Stop-Signal Reaction Times (SSRTs) served as operationalization of response inhibition. Differences in error rates and reaction times (RTs) between lying and truth telling served as indicators of the cognitive cost of lying. Higher blood alcohol concentration was related to longer SSRTs, but unrelated to the cognitive costs of lying. This study validates previous laboratory research on alcohol and response inhibition in a realistic drinking environment, yet failed to find an effect of alcohol on lying. Implications of these findings and for the role of response inhibition in lying are discussed. © The Author 2014. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  3. Paeoniflorin inhibits macrophage-mediated lung cancer metastasis.

    Science.gov (United States)

    Wu, Qi; Chen, Gang-Ling; Li, Ya-Juan; Chen, Yang; Lin, Fang-Zhen

    2015-12-01

    Alternatively activated macrophages are more frequently involved in tumor growth, angiogenesis, and immunosuppression. A previous study showed that paeoniflorin, the major active constituent of Paeonia lactiflora Pallas, can inhibit tumor growth and lung metastases of Lewis lung tumor-bearing mice. This study tried to investigate whether paeoniflorin inhibited lung cancer metastasis by inhibiting the alternative activation of macrophages (M2 macrophage). Using a viability assay, the cytotoxicity of paeoniflorin on Lewis lung cancer cells and peritoneal macrophages were investigated. In vitro scratch wound and in vivo lung metastasis experiments were used to test the ability to inhibit the migration of paeoniflorin and the function of M2 macrophages. Flow cytometry was performed to test the cell cycle of Lewis lung cancer cells, and to test the M2 macrophages in peritoneal macrophages and subcutaneous transplantable tumor. It was found that paeoniflorin showed no inhibitory effect on the growth of Lewis lung cancer cells and peritoneal macrophages of mouse in vitro. Paeoniflorin could attenuate the migration of LLC stimulated by alternatively activated macrophages (stimulated for 24 h and 48 h, paeoniflorin 1, 3, 10, 30, 100 μmol·L(-1), P lung cancer cells (paeoniflorin 100 μmol·L(-1), P lung metastasis of Lewis lung cancer cells xenograft and decrease the numbers of M2 macrophages in subcutaneous xenograft tumour in vivo (paeoniflorin 20, 40 mg·kg(-1), P lung metastasis of Lewis lung cancer cells xenograft partly through inhibiting the alternative activation of macrophages.

  4. Prox1 regulates the notch1-mediated inhibition of neurogenesis.

    Directory of Open Access Journals (Sweden)

    Valeria Kaltezioti

    Full Text Available Activation of Notch1 signaling in neural progenitor cells (NPCs induces self-renewal and inhibits neurogenesis. Upon neuronal differentiation, NPCs overcome this inhibition, express proneural genes to induce Notch ligands, and activate Notch1 in neighboring NPCs. The molecular mechanism that coordinates Notch1 inactivation with initiation of neurogenesis remains elusive. Here, we provide evidence that Prox1, a transcription repressor and downstream target of proneural genes, counteracts Notch1 signaling via direct suppression of Notch1 gene expression. By expression studies in the developing spinal cord of chick and mouse embryo, we showed that Prox1 is limited to neuronal precursors residing between the Notch1+ NPCs and post-mitotic neurons. Physiological levels of Prox1 in this tissue are sufficient to allow binding at Notch1 promoter and they are critical for proper Notch1 transcriptional regulation in vivo. Gain-of-function studies in the chick neural tube and mouse NPCs suggest that Prox1-mediated suppression of Notch1 relieves its inhibition on neurogenesis and allows NPCs to exit the cell cycle and differentiate. Moreover, loss-of-function in the chick neural tube shows that Prox1 is necessary for suppression of Notch1 outside the ventricular zone, inhibition of active Notch signaling, down-regulation of NPC markers, and completion of neuronal differentiation program. Together these data suggest that Prox1 inhibits Notch1 gene expression to control the balance between NPC self-renewal and neuronal differentiation.

  5. Interneuron-mediated inhibition synchronizes neuronal activity during slow oscillation

    Science.gov (United States)

    Chen, Jen-Yung; Chauvette, Sylvain; Skorheim, Steven; Timofeev, Igor; Bazhenov, Maxim

    2012-01-01

    The signature of slow-wave sleep in the electroencephalogram (EEG) is large-amplitude fluctuation of the field potential, which reflects synchronous alternation of activity and silence across cortical neurons. While initiation of the active cortical states during sleep slow oscillation has been intensively studied, the biological mechanisms which drive the network transition from an active state to silence remain poorly understood. In the current study, using a combination of in vivo electrophysiology and thalamocortical network simulation, we explored the impact of intrinsic and synaptic inhibition on state transition during sleep slow oscillation. We found that in normal physiological conditions, synaptic inhibition controls the duration and the synchrony of active state termination. The decline of interneuron-mediated inhibition led to asynchronous downward transition across the cortical network and broke the regular slow oscillation pattern. Furthermore, in both in vivo experiment and computational modelling, we revealed that when the level of synaptic inhibition was reduced significantly, it led to a recovery of synchronized oscillations in the form of seizure-like bursting activity. In this condition, the fast active state termination was mediated by intrinsic hyperpolarizing conductances. Our study highlights the significance of both intrinsic and synaptic inhibition in manipulating sleep slow rhythms. PMID:22641778

  6. Organo-selenium-containing dental sealant inhibits bacterial biofilm.

    Science.gov (United States)

    Tran, P; Hamood, A; Mosley, T; Gray, T; Jarvis, C; Webster, D; Amaechi, B; Enos, T; Reid, T

    2013-05-01

    Oral bacteria, including Streptococcus mutans and Streptococcus salivarius, contribute to tooth decay and plaque formation; therefore, it is essential to develop strategies to prevent dental caries and plaque formation. We recently showed that organo-selenium compounds covalently attached to different biomaterials inhibited bacterial biofilms. Our current study investigates the efficacy of an organo-selenium dental sealant (SeLECT-Defense(TM) sealant) in inhibiting S. mutans and S. salivarius biofilm formation in vitro. The organo-selenium was synthesized and covalently attached to dental sealant material via standard polymer chemistry. By colony-forming unit (CFU) assay and confocal microscopy, SeLECT-Defense(TM) sealant was found to completely inhibit the development of S. mutans and S. salivarius biofilms. To assess the durability of the anti-biofilm effect, we soaked the SeLECT-Defense(TM) sealant in PBS for 2 mos at 37°C and found that the biofilm-inhibitory effect was not diminished after soaking. To determine if organo-selenium inhibits bacterial growth under the sealant, we placed SeLECT-Defense sealant over a lawn of S. mutans. In contrast to a control sealant, SeLECT-Defense(TM) sealant completely inhibited the growth of S. mutans. These results suggest that the inhibitory effect of SeLECT-Defense(TM) sealant against S. mutans and S. salivarius biofilms is very effective and durable.

  7. Potent inhibition of microRNA in vivo without degradation.

    Science.gov (United States)

    Davis, Scott; Propp, Stephanie; Freier, Susan M; Jones, Laura E; Serra, Martin J; Kinberger, Garth; Bhat, Balkrishen; Swayze, Eric E; Bennett, C Frank; Esau, Christine

    2009-01-01

    Chemically modified antisense oligonucleotides (ASOs) are widely used as a tool to functionalize microRNAs (miRNAs). Reduction of miRNA level after ASO inhibition is commonly reported to show efficacy. Whether this is the most relevant endpoint for measuring miRNA inhibition has not been adequately addressed in the field although it has important implications for evaluating miRNA targeting studies. Using a novel approach to quantitate miRNA levels in the presence of excess ASO, we have discovered that the outcome of miRNA inhibition can vary depending on the chemical modification of the ASO. Although some miRNA inhibitors cause a decrease in mature miRNA levels, we have identified a novel 2'-fluoro/2'-methoxyethyl modified ASO motif with dramatically improved in vivo potency which does not. These studies show there are multiple mechanisms of miRNA inhibition by ASOs and that evaluation of secondary endpoints is crucial for interpreting miRNA inhibition studies.

  8. Thyroid peroxidase activity is inhibited by amino acids

    Directory of Open Access Journals (Sweden)

    D.P. Carvalho

    2000-03-01

    Full Text Available Normal in vitro thyroid peroxidase (TPO iodide oxidation activity was completely inhibited by a hydrolyzed TPO preparation (0.15 mg/ml or hydrolyzed bovine serum albumin (BSA, 0.2 mg/ml. A pancreatic hydrolysate of casein (trypticase peptone, 0.1 mg/ml and some amino acids (cysteine, tryptophan and methionine, 50 µM each also inhibited the TPO iodide oxidation reaction completely, whereas casamino acids (0.1 mg/ml, and tyrosine, phenylalanine and histidine (50 µM each inhibited the TPO reaction by 54% or less. A pancreatic digest of gelatin (0.1 mg/ml or any other amino acid (50 µM tested did not significantly decrease TPO activity. The amino acids that impair iodide oxidation also inhibit the TPO albumin iodination activity. The inhibitory amino acids contain side chains with either sulfur atoms (cysteine and methionine or aromatic rings (tyrosine, tryptophan, histidine and phenylalanine. Among the amino acids tested, only cysteine affected the TPO guaiacol oxidation reaction, producing a transient inhibition at 25 or 50 µM. The iodide oxidation inhibitory activity of cysteine, methionine and tryptophan was reversed by increasing iodide concentrations from 12 to 18 mM, while no such effect was observed when the cofactor (H2O2 concentration was increased. The inhibitory substances might interfere with the enzyme activity by competing with its normal substrates for their binding sites, binding to the free substrates or reducing their oxidized form.

  9. Decavanadate induces mitochondrial membrane depolarization and inhibits oxygen consumption.

    Science.gov (United States)

    Soares, S S; Gutiérrez-Merino, C; Aureliano, M

    2007-05-01

    Decavanadate induced rat liver mitochondrial depolarization at very low concentrations, half-depolarization with 39 nM decavanadate, while it was needed a 130-fold higher concentration of monomeric vanadate (5 microM) to induce the same effect. Decavanadate also inhibits mitochondrial repolarization induced by reduced glutathione in vitro, with an inhibition constant of 1 microM, whereas no effect was observed up to 100 microM of monomeric vanadate. The oxygen consumption by mitochondria is also inhibited by lower decavanadate than monomeric vanadate concentrations, i.e. 50% inhibition is attained with 99 M decavanadate and 10 microM monomeric vanadate. Thus, decavanadate is stronger as mitochondrial depolarization agent than as inhibitor of mitochondrial oxygen consumption. Up to 5 microM, decavanadate does not alter mitochondrial NADH levels nor inhibit neither F(O)F(1)-ATPase nor cytochrome c oxidase activity, but it induces changes in the redox steady-state of mitochondrial b-type cytochromes (complex III). NMR spectra showed that decameric vanadate is the predominant vanadate species in decavanadate solutions. It is concluded that decavanadate is much more potent mitochondrial depolarization agent and a more potent inhibitor of mitochondrial oxygen consumption than monomeric vanadate, pointing out the importance to take into account the contribution of higher oligomeric species of vanadium for the biological effects of vanadate solutions.

  10. Gamma irradiation inhibits wound induced browning in shredded cabbage.

    Science.gov (United States)

    Banerjee, Aparajita; Suprasanna, Penna; Variyar, Prasad S; Sharma, Arun

    2015-04-15

    Gamma-radiation induced browning inhibition in minimally processed shredded cabbage stored (10 °C) for up to 8 days was investigated. γ-irradiation (2 kGy) resulted in inhibition of browning as a result of down-regulation (1.4-fold) in phenylalanine ammonia lyase (PAL) gene expression and a consequent decrease in phenylalanine ammonia lyase (PAL) activity. Activity of polyphenol oxidase and peroxidase, total and individual phenolic content as well as o-quinone concentration were, however, unaffected. In the non-irradiated samples, PAL activity increased as a consequence of up-regulation of PAL gene expression after 24 and 48 h by 1.2 and 7.7-fold, respectively, during storage that could be linearly correlated with enhanced quinone formation and browning. Browning inhibition in radiation processed shredded cabbage as a result of inhibition of PAL activity was thus clearly demonstrated. The present work provides an insight for the first time on the mechanism of browning inhibition at both biochemical and genetic level. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Molecular mechanism of viomycin inhibition of peptide elongation in bacteria.

    Science.gov (United States)

    Holm, Mikael; Borg, Anneli; Ehrenberg, Måns; Sanyal, Suparna

    2016-01-26

    Viomycin is a tuberactinomycin antibiotic essential for treating multidrug-resistant tuberculosis. It inhibits bacterial protein synthesis by blocking elongation factor G (EF-G) catalyzed translocation of messenger RNA on the ribosome. Here we have clarified the molecular aspects of viomycin inhibition of the elongating ribosome using pre-steady-state kinetics. We found that the probability of ribosome inhibition by viomycin depends on competition between viomycin and EF-G for binding to the pretranslocation ribosome, and that stable viomycin binding requires an A-site bound tRNA. Once bound, viomycin stalls the ribosome in a pretranslocation state for a minimum of ∼ 45 s. This stalling time increases linearly with viomycin concentration. Viomycin inhibition also promotes futile cycles of GTP hydrolysis by EF-G. Finally, we have constructed a kinetic model for viomycin inhibition of EF-G catalyzed translocation, allowing for testable predictions of tuberactinomycin action in vivo and facilitating in-depth understanding of resistance development against this important class of antibiotics.

  12. Rolipram attenuates MK-801-induced deficits in latent inhibition.

    Science.gov (United States)

    Davis, Jennifer A; Gould, Thomas J

    2005-04-01

    Latent inhibition is used to examine attention and study cognitive deficits associated with schizophrenia. Research using MK-801, an N-methyl-D-aspartate (NMDA) open channel blocker, implicates glutamate receptors in acquisition of latent inhibition of cued fear conditioning. Evidence suggests an important relationship between NMDA-induced increases in cyclic adenosine monophosphate (cAMP) and learning and memory. The authors examine whether amplification of the cAMP signaling pathway by rolipram, a selective Type 4 cAMP phosphodiesterase inhibitor, reverses MK-801-induced impairments in latent inhibition. One day before training, mice were injected with MK-801, rolipram, MK-801 and rolipram, or vehicle and received 20 preexposures or no preexposures to an auditory conditioned stimulus (CS). Training consisted of 2 CS-footshock unconditioned stimulus pairings. Rolipram attenuated the disruptive effect of MK-801 on latent inhibition, which suggests a role for the cAMP signaling pathway in the task and implicates phosphodiesterase inhibition as a target for treating cognitive impairments associated with schizophrenia.

  13. Selection and inhibition mechanisms for human voluntary action decisions.

    Science.gov (United States)

    Zhang, Jiaxiang; Hughes, Laura E; Rowe, James B

    2012-10-15

    One can choose between action alternatives that have no apparent difference in their outcomes. Such voluntary action decisions are associated with widespread frontal-parietal activation, and a tendency to inhibit the repetition of a previous action. However, the mechanism of initiating voluntary actions and the functions of different brain regions during this process remains largely unknown. Here, we combine computational modeling and functional magnetic resonance imaging to test the selection and inhibition mechanisms that mediate trial-to-trial voluntary action decisions. We fitted an optimized accumulator model to behavioral responses in a finger-tapping task in which participants were instructed to make chosen actions or specified actions. Model parameters derived from each individual were then applied to estimate the expected accumulated metabolic activity (EAA) engaged in every single trial. The EAA was associated with blood oxygenation level-dependent responses in a decision work that was maximal in the supplementary motor area and the caudal anterior cingulate cortex, consistent with a competitive accumulation-to-threshold mechanism for action decision by these regions. Furthermore, specific inhibition of the previous action's accumulator was related to the suppression of response repetition. This action-specific inhibition correlated with the activity of the right inferior frontal gyrus, when the option to repeat existed. Our findings suggest that human voluntary action decisions are mediated by complementary processes of intentional selection and inhibition.

  14. AI-2 of Aggregatibacter actinomycetemcomitans Inhibits Candida albicans Biofilm Formation

    Directory of Open Access Journals (Sweden)

    Endang W. Bachtiar

    2014-07-01

    Full Text Available Aggregatibacter actinomycetemcomitans, a Gram-negative bacterium, and Candida albicans, a polymorphic fungus, are both commensals of the oral cavity but both are opportunistic pathogens that can cause oral diseases. A. actinomycetemcomitans produces a quorum-sensing molecule called autoinducer-2 (AI-2, synthesized by LuxS, that plays an important role in expression of virulence factors, in intra- but also in interspecies communication. The aim of this study was to investigate the role of AI-2 based signaling in the interactions between C. albicans and A. actinomycetemcomitans. A. actinomycetemcomitans adhered to C. albicans and inhibited biofilm formation by means of a molecule that was secreted during growth. C. albicans biofilm formation increased significantly when co-cultured with A. actinomycetemcomitans luxS, lacking AI-2 production. Addition of wild-type-derived spent medium or synthetic AI-2 to spent medium of the luxS strain, restored inhibition of C. albicans biofilm formation to wild-type levels. Addition of synthetic AI-2 significantly inhibited hypha formation of C. albicans possibly explaining the inhibition of biofilm formation. AI-2 of A. actinomycetemcomitans is synthesized by LuxS, accumulates during growth and inhibits C. albicans hypha- and biofilm formation. Identifying the molecular mechanisms underlying the interaction between bacteria and fungi may provide important insight into the balance within complex oral microbial communities.

  15. Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles

    Energy Technology Data Exchange (ETDEWEB)

    Hannon, Patrick R., E-mail: phannon2@illinois.edu; Brannick, Katherine E., E-mail: kbran@illinois.edu; Wang, Wei, E-mail: Wei.Wang2@covance.com; Gupta, Rupesh K., E-mail: drrupesh@yahoo.com; Flaws, Jodi A., E-mail: jflaws@illinois.edu

    2015-04-01

    Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1–100 μg/ml) for 24–96 h to establish the temporal effects of DEHP on the follicle. Following 24–96 h of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17α-hydroxylase-17,20-desmolase, 17β-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis. - Highlights: • DEHP inhibits antral follicle growth by dysregulating cell cycle regulators. • DEHP induces antral follicle atresia by dysregulating apoptosis regulators. • DEHP

  16. Group remembering: does social loafing underlie collaborative inhibition?

    Science.gov (United States)

    Weldon, M S; Blair, C; Huebsch, P D

    2000-11-01

    When people collaborate to recall information, they experience collaborative inhibition, a deficit in recall relative to nominal groups (the pooled, nonredundant recall of individuals working alone). That is, people recalling in groups do not perform up to their potential. Collaborative inhibition may be due to retrieval interference (e.g., B. H. Basden, D. R. Basden, S. Bryner, & R. L. Thomas, 1997) or to motivational factors such as social loafing in the group situation. Five experiments examined the role of motivational factors by varying monetary incentives, recall criterion, personal accountability, group cohesion, and group gender. Increasing motivation sometimes increased the overall level of recall but failed to eliminate the collaborative inhibition effect. The results suggest that collaboration interferes with an individual's ability to reconstruct his or her knowledge.

  17. Natural Product Polyamines That Inhibit Human Carbonic Anhydrases

    Directory of Open Access Journals (Sweden)

    Rohan A. Davis

    2014-01-01

    Full Text Available Natural product compound collections have proven an effective way to access chemical diversity and recent findings have identified phenolic, coumarin, and polyamine natural products as atypical chemotypes that inhibit carbonic anhydrases (CAs. CA enzymes are implicated as targets of variable drug therapeutic classes and the discovery of selective, drug-like CA inhibitors is essential. Just two natural product polyamines, spermine and spermidine, have until now been investigated as CA inhibitors. In this study, five more complex natural product polyamines 1–5, derived from either marine sponge or fungi, were considered for inhibition of six different human CA isozymes of interest in therapeutic drug development. All compounds share a simple polyamine core fragment, either spermine or spermidine, yet display substantially different structure activity relationships for CA inhibition. Notably, polyamines 1–5 were submicromolar inhibitors of the cancer drug target CA IX, this is more potent than either spermine or spermidine.

  18. Ribavirin Inhibits Parrot Bornavirus 4 Replication in Cell Culture.

    Science.gov (United States)

    Musser, Jeffrey M B; Heatley, J Jill; Koinis, Anastasia V; Suchodolski, Paulette F; Guo, Jianhua; Escandon, Paulina; Tizard, Ian R

    2015-01-01

    Parrot bornavirus 4 is an etiological agent of proventricular dilatation disease, a fatal neurologic and gastrointestinal disease of psittacines and other birds. We tested the ability of ribavirin, an antiviral nucleoside analog with antiviral activity against a range of RNA and DNA viruses, to inhibit parrot bornavirus 4 replication in duck embryonic fibroblast cells. Two analytical methods that evaluate different products of viral replication, indirect immunocytochemistry for viral specific nucleoprotein and qRT-PCR for viral specific phosphoprotein gene mRNA, were used. Ribavirin at concentrations between 2.5 and 25 μg/mL inhibited parrot bornavirus 4 replication, decreasing viral mRNA and viral protein load, in infected duck embryonic fibroblast cells. The addition of guanosine diminished the antiviral activity of ribavirin suggesting that one possible mechanism of action against parrot bornavirus 4 may likely be through inosine monophosphate dehydrogenase inhibition. This study demonstrates parrot bornavirus 4 susceptibility to ribavirin in cell culture.

  19. Ribavirin Inhibits Parrot Bornavirus 4 Replication in Cell Culture.

    Directory of Open Access Journals (Sweden)

    Jeffrey M B Musser

    Full Text Available Parrot bornavirus 4 is an etiological agent of proventricular dilatation disease, a fatal neurologic and gastrointestinal disease of psittacines and other birds. We tested the ability of ribavirin, an antiviral nucleoside analog with antiviral activity against a range of RNA and DNA viruses, to inhibit parrot bornavirus 4 replication in duck embryonic fibroblast cells. Two analytical methods that evaluate different products of viral replication, indirect immunocytochemistry for viral specific nucleoprotein and qRT-PCR for viral specific phosphoprotein gene mRNA, were used. Ribavirin at concentrations between 2.5 and 25 μg/mL inhibited parrot bornavirus 4 replication, decreasing viral mRNA and viral protein load, in infected duck embryonic fibroblast cells. The addition of guanosine diminished the antiviral activity of ribavirin suggesting that one possible mechanism of action against parrot bornavirus 4 may likely be through inosine monophosphate dehydrogenase inhibition. This study demonstrates parrot bornavirus 4 susceptibility to ribavirin in cell culture.

  20. Do motivational incentives reduce the inhibition deficit in ADHD?

    Science.gov (United States)

    Shanahan, Michelle A; Pennington, Bruce F; Willcutt, Erik W

    2008-01-01

    The primary goal of this study was to test three competing theories of ADHD: the inhibition theory, the motivational theory, and a dual deficit theory. Previous studies have produced conflicting findings about the effects of incentives on executive processes in ADHD. In the present study of 25 children with ADHD and 30 typically developing controls, motivation was manipulated within the Stop Task. Stop signal reaction time was examined, as well as reaction time, its variability, and the number of errors in the primary choice reaction time task. Overall, the pattern of results supported the inhibition theory over the motivational or dual deficit hypotheses, as main effects of group were found for most key variables (ADHD group was worse), whereas the group by reward interaction predicted by the motivational and dual deficit accounts was not found. Hence, as predicted by the inhibition theory, children with ADHD performed worse than controls irrespective of incentives.

  1. Investigation on inhibition of biological effects of endothelin

    Institute of Scientific and Technical Information of China (English)

    田青; 赵东; 张继峰; 高连如; 刘胜昔; 杨军; 苏静怡; 张肇康; 汤健; 唐朝枢

    1996-01-01

    The effects of a series of substances on the biological function of endothelin (ET) are reported. The substances used are: synthetic inhibitors of endothelium derived relaxing factors (EDRFs), inhibitor of big-endothelin converting enzyme phosphoramidon, antiserum of endothelin, antagonists of endothelin A receptor BQ123 and JKC301, and two Chinese anti-snake venom herb medicines Lobelia radians Thumb and Taris polyphylla Smith var. chinensis (Franch) Hara. The results showed that inhibiting the production of nitric oxide (NO) could stimulate ET release from vascular endothelium, elevate plasma ET and increase blood pressure. These changes could be reversed by L-arginine (L-Arg), the substrate of nitric oxide synthase (NOS). The amount of ET released by arterial endothelium could be increased or inhibited by inhibiting or stimulating the synthesis of prostacyclin (PGI2). The plasma ET level and blood pressure in both SHR and WKY rats could be decreased by giving phosphoramidon (PhR). The above results i

  2. Inhibition of mouse liver respiration by Chelidonium majus isoquinoline alkaloids.

    Science.gov (United States)

    Barreto, M Carmo; Pinto, Ruy E; Arrabaça, João D; Pavão, M Leonor

    2003-12-15

    The alkaloids from Chelidonium majus L. which had a significant inhibitory effect in mitochondrial respiration were those which contain a positive charge due to a quaternary nitrogen atom, i.e., chelerythrine, sanguinarine, berberine and coptisine, both with malate+glutamate or with succinate as substrates. When malate+glutamate was used as substrate, chelerythrine and berberine, which contain methoxy groups, were particularly more active, since they had a strong effect even at low concentrations. In submitochondrial particles, berberine and coptisine had a marked inhibitory effect on NADH dehydrogenase activity but practically no effect on succinate dehydrogenase activity, whereas chelerythrine and sanguinarine inhibited more strongly succinate dehydrogenase than NADH dehydrogenase, which is in agreement with the results found for mitochondrial respiration. Protopine and allocryptopine, which did not inhibit mitochondrial respiration, strongly inhibited NADH dehydrogenase in submitochondrial particles, but had no effect on succinate dehydrogenase activity.

  3. The clinically approved antiviral drug sofosbuvir inhibits Zika virus replication

    Science.gov (United States)

    Sacramento, Carolina Q.; de Melo, Gabrielle R.; de Freitas, Caroline S.; Rocha, Natasha; Hoelz, Lucas Villas Bôas; Miranda, Milene; Fintelman-Rodrigues, Natalia; Marttorelli, Andressa; Ferreira, André C.; Barbosa-Lima, Giselle; Abrantes, Juliana L.; Vieira, Yasmine Rangel; Bastos, Mônica M.; de Mello Volotão, Eduardo; Nunes, Estevão Portela; Tschoeke, Diogo A.; Leomil, Luciana; Loiola, Erick Correia; Trindade, Pablo; Rehen, Stevens K.; Bozza, Fernando A.; Bozza, Patrícia T.; Boechat, Nubia; Thompson, Fabiano L.; de Filippis, Ana M. B.; Brüning, Karin; Souza, Thiago Moreno L.

    2017-01-01

    Zika virus (ZIKV) is a member of the Flaviviridae family, along with other agents of clinical significance such as dengue (DENV) and hepatitis C (HCV) viruses. Since ZIKV causes neurological disorders during fetal development and in adulthood, antiviral drugs are necessary. Sofosbuvir is clinically approved for use against HCV and targets the protein that is most conserved among the members of the Flaviviridae family, the viral RNA polymerase. Indeed, we found that sofosbuvir inhibits ZIKV RNA polymerase, targeting conserved amino acid residues. Sofosbuvir inhibited ZIKV replication in different cellular systems, such as hepatoma (Huh-7) cells, neuroblastoma (SH-Sy5y) cells, neural stem cells (NSC) and brain organoids. In addition to the direct inhibition of the viral RNA polymerase, we observed that sofosbuvir also induced an increase in A-to-G mutations in the viral genome. Together, our data highlight a potential secondary use of sofosbuvir, an anti-HCV drug, against ZIKV. PMID:28098253

  4. Gold Nanoparticles and Microwave Irradiation Inhibit Beta-Amyloid Amyloidogenesis

    Directory of Open Access Journals (Sweden)

    Bastus Neus

    2008-01-01

    Full Text Available Abstract Peptide-Gold nanoparticles selectively attached to β-amyloid protein (Aβ amyloidogenic aggregates were irradiated with microwave. This treatment produces dramatic effects on the Aβ aggregates, inhibiting both the amyloidogenesis and the restoration of the amyloidogenic potential. This novel approach offers a new strategy to inhibit, locally and remotely, the amyloidogenic process, which could have application in Alzheimer’s disease therapy. We have studied the irradiation effect on the amyloidogenic process in the presence of conjugates peptide-nanoparticle by transmission electronic microscopy observations and by Thioflavine T assays to quantify the amount of fibrils in suspension. The amyloidogenic aggregates rather than the amyloid fibrils seem to be better targets for the treatment of the disease. Our results could contribute to the development of a new therapeutic strategy to inhibit the amyloidogenic process in Alzheimer’s disease.

  5. Inhibition of Bacterial RNase P RNA by Phenothiazine Derivatives

    Directory of Open Access Journals (Sweden)

    Shiying Wu

    2016-09-01

    Full Text Available There is a need to identify novel scaffolds and targets to develop new antibiotics. Methylene blue is a phenothiazine derivative, and it has been shown to possess anti-malarial and anti-trypanosomal activities. Here, we show that different phenothiazine derivatives and pyronine G inhibited the activities of three structurally different bacterial RNase P RNAs (RPRs, including that from Mycobacterium tuberculosis, with Ki values in the lower μM range. Interestingly, three antipsychotic phenothiazines (chlorpromazine, thioridazine, and trifluoperazine, which are known to have antibacterial activities, also inhibited the activity of bacterial RPRs, albeit with higher Ki values than methylene blue. Phenothiazines also affected lead(II-induced cleavage of bacterial RPR and inhibited yeast tRNAPhe, indicating binding of these drugs to functionally important regions. Collectively, our findings provide the first experimental data showing that long, noncoding RNAs could be targeted by different phenothiazine derivatives.

  6. Corrosion inhibition performance of a ionic liquid surfactant Br

    Directory of Open Access Journals (Sweden)

    Jing LIU

    2016-02-01

    Full Text Available In order to study the novel green organic mercury-substituting inhibitors, the ionic liquid surfactant 1-methyl-3-dodecyl imidazole bromide ( Br is synthesized with N-methyl imidazole and 1-bromodecane as raw materials. The corrosion inhibition of Br for zinc in zinc-manganese batteries is investigated using electrochemical methods and weight loss methods. The results show that corrosion inhibition efficiency increases with the increase of the concentration of Br, and when the concentration is higher than 8×10-3 mol/L, the inhibition efficiency tends to be stable. The polarization curve shows that Br belongs to mixed-type corrosion inhibitor. The thermodynamic parameters show that Br is spontaneously adsorbed on the zinc surface, forming a monomolecular adsorption layer, which fits with Langmuir adsorption isotherm with physical and chemical adsorption mechanism.

  7. Inhibition of cathepsin K for treatment of osteoporosis.

    Science.gov (United States)

    Boonen, Steven; Rosenberg, Elizabeth; Claessens, Frank; Vanderschueren, Dirk; Papapoulos, Socrates

    2012-03-01

    Cathepsin K is the protease that is primarily responsible for the degradation of bone matrix by osteoclasts. Inhibitors of cathepsin K are in development for treatment of osteoporosis. Currently available antiresorptive drugs interfere with osteoclast function. They inhibit both bone resorption and formation, due to the coupling between these processes. Cathepsin K inhibitors, conversely, target the resorption process itself and may not interfere with osteoclast stimulation of bone formation. In fact, when cathepsin K is absent or inhibited in mice, rabbits, or monkeys, bone formation is maintained or increased. In humans, inhibition of cathepsin K is associated with sustained reductions in bone resorption markers but with smaller and transient reductions in bone formation markers. The usefulness of cathepsin K inhibitors in osteoporosis is now being examined in phase 2 and phase 3 clinical trials of postmenopausal osteoporotic women.

  8. Ketamine protects acetylcholinesterase against inhibition by propoxur and phoxim.

    Science.gov (United States)

    Koutsoviti-Papadopoulou, M; Kounenis, G; Elezoglou, V

    1994-01-01

    In the present study the effect of ketamine on the contractions caused by propoxur and phoxim on the isolated guinea pig ileum was investigated. Ketamine was found able to inhibit in a concentration-dependent manner the contractile responses of the ileum to propoxur and phoxim, while it did not significantly modify the contractions induced by acetylcholine. Propoxur and phoxim augmented the contractile responses induced by acetylcholine in the presence of acetylcholinesterase. This augmentation was prevented by ketamine, in a concentration-dependent manner. These findings suggest that ketamine inhibits the contractile effect of propoxur and phoxim on the guinea pig ileum and this inhibition seems to be associated with the protection of acetylcholinesterase against the action of these two compounds.

  9. Inhibition of coagulation factors by recombinant barley serpin BSZx

    DEFF Research Database (Denmark)

    Dahl, Søren Weis; Rasmussen, S.K.; Petersen, L..C.;

    1996-01-01

    Barley serpin BSZx is a potent inhibitor of trypsin and chymotrypsin at overlapping reactive sites (Dahl, S.W., Rasmussen, S.K. and Hejgaard, J. (1996) J. Biol, Chem., in press), We have now investigated the interactions of BSZx with a range of serine proteinases from human plasma, pancreas...... as substrate, Complexes of these proteinase with BSZx resisted boiling in SDS, and amino acid sequencing showed that cleavage in the reactive center loop only occurred after P-1 Arg. Activated protein C and leukocyte elastase were slowly inhibited by BSZx (k(ass) = 1-2 x 10(2) M(-1) s(-1)) whereas factor XIIa......, urokinase and tissue type plasminogen activator, plasmin and pancreas kallikrein and elastase were not or only weakly affected, The inhibition pattern with mammalian proteinases reveal a specificity of BSZx similar to that of antithrombin III. Trypsin from Fusarium was not inhibited while interaction...

  10. Somatosensory integration controlled by dynamic thalamocortical feed-forward inhibition.

    Science.gov (United States)

    Gabernet, Laetitia; Jadhav, Shantanu P; Feldman, Daniel E; Carandini, Matteo; Scanziani, Massimo

    2005-10-20

    The temporal features of tactile stimuli are faithfully represented by the activity of neurons in the somatosensory cortex. However, the cellular mechanisms that enable cortical neurons to report accurate temporal information are not known. Here, we show that in the rodent barrel cortex, the temporal window for integration of thalamic inputs is under the control of thalamocortical feed-forward inhibition and can vary from 1 to 10 ms. A single thalamic fiber can trigger feed-forward inhibition and contacts both excitatory and inhibitory cortical neurons. The dynamics of feed-forward inhibition exceed those of each individual synapse in the circuit and are captured by a simple disynaptic model of the thalamocortical projection. The variations in the integration window produce changes in the temporal precision of cortical responses to whisker stimulation. Hence, feed-forward inhibitory circuits, classically known to sharpen spatial contrast of tactile inputs, also increase the temporal resolution in the somatosensory cortex.

  11. Quantum Chemical Study on the Corrosion Inhibition of Some Oxadiazoles

    Directory of Open Access Journals (Sweden)

    Hong Ju

    2015-01-01

    Full Text Available Quantum chemical calculations based on DFT method were performed on three nitrogen-bearing heterocyclic compounds used as corrosion inhibitors for the mild steel in acid media to determine the relationship between the molecular structure of inhibitors and inhibition efficiency. The structural parameters, such as energy and distribution of highest occupied molecular orbital (HOMO and lowest unoccupied molecular orbital (LUMO, the charge distribution of the studied inhibitors, the absolute electronegativity (χ values, and the fraction of electrons (ΔN transfer from inhibitors to mild steel were also calculated and correlated with inhibition efficiencies. The results showed that the inhibition efficiency of inhibitors increased with the increase in energy of HOMO and decrease in energy gap of frontier molecular orbital, and the areas containing N and O atoms are most possible sites for bonding the steel surface by donating electrons to the mild steel.

  12. Corrosion Inhibition of High Speed Steel by Biopolymer HPMC Derivatives

    Directory of Open Access Journals (Sweden)

    Shih-Chen Shi

    2016-07-01

    Full Text Available The corrosion inhibition characteristics of the derivatives of biopolymer hydroxypropyl methylcellulose (HPMC, hydroxypropyl methylcellulose phthalate (HPMCP, and hydroxypropyl methylcellulose acetate succinate (HPMCAS film are investigated. Based on electrochemical impedance spectroscopic measurements and potentiodynamic polarization, the corrosion inhibition performance of high speed steel coated with HPMC derivatives is evaluated. The Nyquist plot and Tafel polarization demonstrate promising anti-corrosion performance of HPMC and HPMCP. With increasing film thickness, both materials reveal improvement in corrosion inhibition. Moreover, because of a hydrophobic surface and lower moisture content, HPMCP shows better anti-corrosion performance than HPMCAS. The study is of certain importance for designing green corrosion inhibitors of high speed steel surfaces by the use of biopolymer derivatives.

  13. Repellents Inhibit P450 Enzymes in Stegomyia (Aedes) aegypti

    Science.gov (United States)

    Jaramillo Ramirez, Gloria Isabel; Logan, James G.; Loza-Reyes, Elisa; Stashenko, Elena; Moores, Graham D.

    2012-01-01

    The primary defence against mosquitoes and other disease vectors is often the application of a repellent. Despite their common use, the mechanism(s) underlying the activity of repellents is not fully understood, with even the mode of action of DEET having been reported to be via different mechanisms; e.g. interference with olfactory receptor neurones or actively detected by olfactory receptor neurones on the antennae or maxillary palps. In this study, we discuss a novel mechanism for repellence, one of P450 inhibition. Thirteen essential oil extracts from Colombian plants were assayed for potency as P450 inhibitors, using a kinetic fluorometric assay, and for repellency using a modified World Health Organisation Pesticide Evaluations Scheme (WHOPES) arm-in cage assay with Stegomyia (Aedes) aegypti mosquitoes. Bootstrap analysis on the inhibition analysis revealed a significant correlation between P450-inhibition and repellent activity of the oils. PMID:23152795

  14. Genetic influences on the acquisition and inhibition of fear.

    Science.gov (United States)

    Wendt, Julia; Neubert, Jörg; Lindner, Katja; Ernst, Florian D; Homuth, Georg; Weike, Almut I; Hamm, Alfons O

    2015-12-01

    As a variant of the Pavlovian fear conditioning paradigm the conditional discrimination design allows for a detailed investigation of fear acquisition and fear inhibition. Measuring fear-potentiated startle responses, we investigated the influence of two genetic polymorphisms (5-HTTLPR and COMT Val(158)Met) on fear acquisition and fear inhibition which are considered to be critical mechanisms for the etiology and maintenance of anxiety disorders. 5-HTTLPR s-allele carriers showed a more stable potentiation of the startle response during fear acquisition. Homozygous COMT Met-allele carriers, which had demonstrated delayed extinction in previous investigations, show deficient fear inhibition in presence of a learned safety signal. Thus, our results provide further evidence that 5-HTTLPR and COMT Val(158)Met genotypes influence the vulnerability for the development of anxiety disorders via different mechanisms.

  15. Inhibition of placenta growth factor with TB-403

    DEFF Research Database (Denmark)

    Nielsen, Dorte Lisbet; Sengeløv, Lisa

    2012-01-01

    targeting angiogenesis. AREAS COVERED: The data are obtained by searching in the PubMed database. The search terms used included antiangiogenic therapy, TB-403 (RO5323441), placenta growth factor (PlGF) and VEGFR-1 (Flt-1). We review preclinical data concerning the function and inhibition of Pl......GF and summarize data on expression of PlGF in cancer patients. Data from early-phase clinical trials of TB-403 (RO5323441), a monoclonal antibody inhibiting PlGF, are discussed. Future development strategies, therapeutic potentials and limitations of TB-403 are further evaluated. EXPERT OPINION: There are some...... conflicting data on the function of PlGF and the importance of its role in primary tumor growth. Data from some preclinical models of PlGF inhibition and early-phase clinical trials with TB-403 are, however, promising, although the true potential of the drug is yet to be determined. Further clinical...

  16. Biofilms: strategies for metal corrosion inhibition employing microorganisms.

    Science.gov (United States)

    Zuo, Rongjun

    2007-10-01

    Corrosion causes dramatic economic loss. Currently widely used corrosion control strategies have disadvantages of being expensive, subject to environmental restrictions, and sometimes inefficient. Studies show that microbial corrosion inhibition is actually a common phenomenon. The present review summarizes recent progress in this novel strategy: corrosion control using beneficial bacteria biofilms. The possible mechanisms may involve: (1) removal of corrosive agents (such as oxygen) by bacterial physiological activities (e.g., aerobic respiration), (2) growth inhibition of corrosion-causing bacteria by antimicrobials generated within biofilms [e.g., sulfate-reducing bacteria (SRB) corrosion inhibition by gramicidin S-producing Bacillus brevis biofilm], (3) generation of protective layer by biofilms (e.g., Bacillus licheniformis biofilm produces on aluminum surface a sticky protective layer of gamma-polyglutamate). Successful utilization of this novel strategy relies on advances in study at the interface of corrosion engineering and biofilm biology.

  17. Blockade of p38 MAPK inhibits chronic allograft vasculopathy.

    Science.gov (United States)

    Ollinger, Robert; Thomas, Michael; Kogler, Pamela; Hermann, Martin; Weiss, Helmut; Mark, Walter; Bilban, Martin; Troppmair, Jakob; Bach, Fritz H; Margreiter, Raimund

    2008-01-27

    Long-term survival after solid-organ transplantation is hampered by chronic changes in the arteries of the grafts, called chronic allograft vasculopathy (CAV). The lesions consist mainly of proliferating vascular smooth muscle cells that cause narrowing of the vessels; these lesions can develop within a few months. There is no effective treatment to prevent CAV. We previously noted that the pharmacological inhibition of p38 mitogen-activated protein kinase (MAPK) suppresses the proliferation of vascular smooth muscle cells. We hypothesized that in vivo inhibition of p38 MAPK in mice bearing allogeneic aortic allografts would prevent CAV. We here report that blockade of p38 MAPK, a signaling molecule involved in cell division, apoptosis, and cell death, markedly suppresses CAV. Given recent data indicating that inhibition of p38 MAPK is a promising approach for the treatment of autoimmune diseases plus our present findings, p38 MAPK blockade for CAV seems a reasonable approach to consider for clinical application.

  18. Electrochemical and Corrosion Inhibition Studies of Cucurbita Maxima

    Directory of Open Access Journals (Sweden)

    K. Anbarasi

    2016-08-01

    Full Text Available The influence of the acid extract of peel of Cucurbita maxima (PCM on the corrosion of mild steel in 1N H2SO4 was investigated by weight loss, polarization and impedance methods and SEM analysis. The inhibition efficiency increases with extract concentration and immersion period. Weight loss and corrosion rates of mild steel decreased as the concentration of inhibitor increased. The results showed that PCM was potential corrosion inhibitor and maximum inhibition efficiency (IE % obtained was 98% for 3%PCM at 1h. Impedance measurement results an increase in charge transfer resistance (Rct, which also confirms the corrosion inhibitive nature of the plant extract. Potentiodynamic study showed that PCM acts as a mixed type of inhibitor, which controls both the anodic and cathodic reactions. Scanning electron microscopic studies provided the evidence of improved surface condition for the corrosion protection, due to the adsorption.

  19. Adsorption, inhibition, and biotransformation of ciprofloxacin under aerobic conditions.

    Science.gov (United States)

    Liu, Zhanguang; Sun, Peizhe; Pavlostathis, Spyros G; Zhou, Xuefei; Zhang, Yalei

    2013-09-01

    The adsorption, inhibition, and biotransformation of the fluoroquinolone antibiotic ciprofloxacin (CIP) under aerobic conditions were investigated in this study. The maximum adsorption capacity and the Langmuir constant were 37.9 mg CIP/g VSS and 37 L/g, respectively. A glucose-fed aerobic culture was inhibited by CIP at 10mg/L or higher and the degree of inhibition increased with increasing CIP concentration. However, the microbial activity recovered to some extent with prolonged incubation under a semi-continuous feeding mode. A low extent of CIP biotransformation was observed in an aerobic, glucose-fed culture derived from poultry litter extract. LC/UV/MS analysis of the biotransformation product showed that only the piperazine ring was oxidized, while the antibiotic quinolone part of CIP was intact. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Inhibitive Effects of Quercetin on Rabbit Tenon Capsule Fibroblasts Proliferation

    Institute of Scientific and Technical Information of China (English)

    Su Liu; Lin Chen

    2005-01-01

    Purpose:To study the inhibitive effects of quercetin (QU) on the fibroblasts proliferation of rabbit Tenon's capsule and its mechanism.Methods: Cultured fibroblasts were exposed to different concentrations of QU solution and investigated by microculture tetrazolium (MTT) assay. The effect of QU was obser ved on cells cycle using the flow cytometer. Besults: QU can suppress the proliferation of rabbit Tenon's capsule fibroblasts in vitro and show a dose-time dependent tendency.Flow cytometer results showed 26.92% cell increase in G1 phase, 23.50% decrease in S phase and 3.42% decrease in G2 phase.Conclusions: QU can suppress the proliferation of rabbit Tenon's capsule fibroblasts in vitro and show a dose-time dependent tendency. QU may effect all phase of cell cycle and inhibit cell proliferation by inhibiting G1 phase transitting to S phase and G2 phase.

  1. Repellents inhibit P450 enzymes in Stegomyia (Aedes aegypti.

    Directory of Open Access Journals (Sweden)

    Gloria Isabel Jaramillo Ramirez

    Full Text Available The primary defence against mosquitoes and other disease vectors is often the application of a repellent. Despite their common use, the mechanism(s underlying the activity of repellents is not fully understood, with even the mode of action of DEET having been reported to be via different mechanisms; e.g. interference with olfactory receptor neurones or actively detected by olfactory receptor neurones on the antennae or maxillary palps. In this study, we discuss a novel mechanism for repellence, one of P450 inhibition. Thirteen essential oil extracts from Colombian plants were assayed for potency as P450 inhibitors, using a kinetic fluorometric assay, and for repellency using a modified World Health Organisation Pesticide Evaluations Scheme (WHOPES arm-in cage assay with Stegomyia (Aedes aegypti mosquitoes. Bootstrap analysis on the inhibition analysis revealed a significant correlation between P450-inhibition and repellent activity of the oils.

  2. Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection

    Science.gov (United States)

    Conway, Michael J.; Londono-Renteria, Berlin; Troupin, Andrea; Watson, Alan M.; Klimstra, William B.; Fikrig, Erol; Colpitts, Tonya M.

    2016-01-01

    Aedes aegypti is the primary vector of several medically relevant arboviruses including dengue virus (DENV) types 1–4. Ae. aegypti transmits DENV by inoculating virus-infected saliva into host skin during probing and feeding. Ae. aegypti saliva contains over one hundred unique proteins and these proteins have diverse functions, including facilitating blood feeding. Previously, we showed that Ae. aegypti salivary gland extracts (SGEs) enhanced dissemination of DENV to draining lymph nodes. In contrast, HPLC-fractionation revealed that some SGE components inhibited infection. Here, we show that D7 proteins are enriched in HPLC fractions that are inhibitory to DENV infection, and that recombinant D7 protein can inhibit DENV infection in vitro and in vivo. Further, binding assays indicate that D7 protein can directly interact with DENV virions and recombinant DENV envelope protein. These data reveal a novel role for D7 proteins, which inhibits arbovirus transmission to vertebrates through a direct interaction with virions. PMID:27632170

  3. Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection.

    Directory of Open Access Journals (Sweden)

    Michael J Conway

    2016-09-01

    Full Text Available Aedes aegypti is the primary vector of several medically relevant arboviruses including dengue virus (DENV types 1-4. Ae. aegypti transmits DENV by inoculating virus-infected saliva into host skin during probing and feeding. Ae. aegypti saliva contains over one hundred unique proteins and these proteins have diverse functions, including facilitating blood feeding. Previously, we showed that Ae. aegypti salivary gland extracts (SGEs enhanced dissemination of DENV to draining lymph nodes. In contrast, HPLC-fractionation revealed that some SGE components inhibited infection. Here, we show that D7 proteins are enriched in HPLC fractions that are inhibitory to DENV infection, and that recombinant D7 protein can inhibit DENV infection in vitro and in vivo. Further, binding assays indicate that D7 protein can directly interact with DENV virions and recombinant DENV envelope protein. These data reveal a novel role for D7 proteins, which inhibits arbovirus transmission to vertebrates through a direct interaction with virions.

  4. Study of electroplated silver-palladium biofouling inhibiting coating

    DEFF Research Database (Denmark)

    Chiang, Wen-Chi; Hilbert, Lisbeth Rischel; Møller, Per

    , a new coating has been designed to form an inhibiting effect on the surface by itself. In this way, it is desired that the release of any matter will be in low concentration. This design is based on silver combined with nobler palladium, both with catalytic properties. Due to the potential difference......The undesired microbial and biofilm adhesions on the surfaces of food industrial facilities, water supply systems and etc. are so called as “biofouling”. Biofouling can cause many undesirable effects. Until now for solving biofouling, there are few non-toxic inhibiting treatments. In this study...... between silver and palladium while contacting with an electrolyte, the surface can form numerous discrete anodic and cathodic areas, so that an inhibiting reaction can be formed. In this paper, a series of electrochemical and biological tests were conducted to study the properties of these surfaces...

  5. Verapamil inhibits scar formation after peripheral nerve repairin vivo

    Institute of Scientific and Technical Information of China (English)

    A-chao Han; Jing-xiu Deng; Qi-shun Huang; Huai-yuan Zheng; Pan Zhou; Zhi-wei Liu; Zhen-bing Chen

    2016-01-01

    The calcium channel blocker, verapamil, has been shown to reduce scar formation by inhibiting ifbroblast adhesion and proliferationin vitro. It was not clear whether topical application of verapamil after surgical repair of the nerve in vivo could inhibit the formation of ex-cessive scar tissue. In this study, the right sciatic nerve of adult Sprague-Dawley rats was transected and sutured with No. 10-0 suture. The stoma was wrapped with gelfoam soaked with verapamil solution for 4 weeks. Compared with the control group (stoma wrapped with gelfoam soaked with physiological saline), the verapamil application inhibited the secretion of extracellular matrix from ifbroblasts in vivo, suppressed type I and III collagen secretion and increased the total number of axons and the number of myelinated axons. These ifndings suggest that verapamil could reduce the formation of scar tissue and promote axon growth after peripheral nerve repair.

  6. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase

    DEFF Research Database (Denmark)

    Madiraju, Anila K; Erion, Derek M; Rahimi, Yasmeen

    2014-01-01

    prescribed to patients with type 2 diabetes worldwide, yet the underlying mechanism by which metformin inhibits hepatic gluconeogenesis remains unknown. Here we show that metformin non-competitively inhibits the redox shuttle enzyme mitochondrial glycerophosphate dehydrogenase, resulting in an altered...... hepatocellular redox state, reduced conversion of lactate and glycerol to glucose, and decreased hepatic gluconeogenesis. Acute and chronic low-dose metformin treatment effectively reduced endogenous glucose production, while increasing cytosolic redox and decreasing mitochondrial redox states. Antisense...... oligonucleotide knockdown of hepatic mitochondrial glycerophosphate dehydrogenase in rats resulted in a phenotype akin to chronic metformin treatment, and abrogated metformin-mediated increases in cytosolic redox state, decreases in plasma glucose concentrations, and inhibition of endogenous glucose production...

  7. Corrosion inhibition of aluminum 6063 using some pharmaceutical compounds

    Energy Technology Data Exchange (ETDEWEB)

    Fouda, A.S. [Department of Chemistry, Faculty of Science, El-Mansoura University, El-Mansoura 35516 (Egypt)], E-mail: asfouda@mans.edu.eg; Al-Sarawy, A.A. [Department of Chemistry, Faculty of Engineering, El-Mansoura University, El-Mansoura (Egypt); Ahmed, F.Sh. [Department of Chemistry, Faculty of Science (Demitta), El-Mansoura University, El-Mansoura (Egypt); El-Abbasy, H.M. [Department of Chemistry, Faculty of Science, El-Mansoura University, El-Mansoura 35516 (Egypt)

    2009-03-15

    The corrosion inhibition characteristics of some pharmaceutical compounds on aluminum 6063 in 0.5 mol l{sup -1} H{sub 3}PO{sub 4} has been studied using weight loss and galvanostatic polarization techniques. Results showed that the inhibition occurs through adsorption of the inhibitor molecules on the metal surface. The inhibition efficiency increased with increasing inhibitor concentration, but decreased with increasing temperature. The adsorption of first group pharmaceutical compounds on the metal surface is found to obey Frumkin's adsorption isotherm, but the adsorption of second group pharmaceutical compounds is found to obey Temkin's adsorption isotherm. Thermodynamic parameters for adsorption process were determined. Galvanostatic polarization studies showed that first and second groups' pharmaceutical compounds are mixed-type inhibitors and the results obtained from the two techniques are in good agreement.

  8. Response inhibition signals and miscoding of direction in dorsomedial striatum

    Directory of Open Access Journals (Sweden)

    Daniel W Bryden

    2012-09-01

    Full Text Available The ability to inhibit action is critical for everyday behavior and is affected by a variety of disorders. Behavioral control and response inhibition is thought to depend on a neural circuit that includes the dorsal striatum, yet the neural signals that lead to response inhibition and its failure are unclear. To address this issue, we recorded from neurons in rat dorsomedial striatum (mDS in a novel task in which rats responded to a spatial cue that signaled that reward would be delivered either to the left or to the right. On 80% of trials rats were instructed to respond in the direction cued by the light (GO. On 20% of trials a second light illuminated instructing the rat to refrain from making the cued movement and move in the opposite direction (STOP. Many neurons in mDS encoded direction, firing more or less strongly for GO movements made ipsilateral or contralateral to the recording electrode. Neurons that fired more strongly for contralateral GO responses were more active when rats were faster, showed reduced activity on STOP trials, and miscoded direction on errors, suggesting that when these neurons were overly active, response inhibition failed. Neurons that decreased firing for contralateral movement were excited during trials in which the rat was required to stop the ipsilateral movement. For these neurons activity was reduced when errors were made and was negatively correlated with movement time suggesting that when these neurons were less active on STOP trials, response inhibition failed. Finally, the activity of a significant number of neurons represented a global inhibitory signal, firing more strongly during response inhibition regardless of response direction. Breakdown by cell type suggests that putative medium spiny neurons tended to fire more strongly under STOP trials, whereas putative interneurons exhibited both activity patterns. 

  9. Response inhibition signals and miscoding of direction in dorsomedial striatum

    Science.gov (United States)

    Bryden, Daniel W.; Burton, Amanda C.; Kashtelyan, Vadim; Barnett, Brian R.; Roesch, Matthew R.

    2012-01-01

    The ability to inhibit action is critical for everyday behavior and is affected by a variety of disorders. Behavioral control and response inhibition is thought to depend on a neural circuit that includes the dorsal striatum, yet the neural signals that lead to response inhibition and its failure are unclear. To address this issue, we recorded from neurons in rat dorsomedial striatum (mDS) in a novel task in which rats responded to a spatial cue that signaled that reward would be delivered either to the left or to the right. On 80% of trials rats were instructed to respond in the direction cued by the light (GO). On 20% of trials a second light illuminated instructing the rat to refrain from making the cued movement and move in the opposite direction (STOP). Many neurons in mDS encoded direction, firing more or less strongly for GO movements made ipsilateral or contralateral to the recording electrode. Neurons that fired more strongly for contralateral GO responses were more active when rats were faster, showed reduced activity on STOP trials, and miscoded direction on errors, suggesting that when these neurons were overly active, response inhibition failed. Neurons that decreased firing for contralateral movement were excited during trials in which the rat was required to stop the ipsilateral movement. For these neurons activity was reduced when errors were made and was negatively correlated with movement time suggesting that when these neurons were less active on STOP trials, response inhibition failed. Finally, the activity of a significant number of neurons represented a global inhibitory signal, firing more strongly during response inhibition regardless of response direction. Breakdown by cell type suggests that putative medium spiny neurons (MSNs) tended to fire more strongly under STOP trials, whereas putative interneurons exhibited both activity patterns. PMID:22973206

  10. S-layer proteins of Lactobacillus acidophilus inhibits JUNV infection.

    Science.gov (United States)

    Martínez, María Guadalupe; Prado Acosta, Mariano; Candurra, Nélida A; Ruzal, Sandra M

    2012-06-15

    It has been previously described that S-layer binds to the C-type lectin DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN, CD209). It was also shown that DC-SIGN is a cell-surface adhesion factor that enhances viral entry of several virus families. Among those, Junin virus (JUNV) entry is enhanced in cells expressing DC-SIGN and for that reason surface-layer protein (S-layer) of Lactobacillus acidophilus ATCC 4365 was evaluated as a possible JUNV inhibitor. Experiments using 3T3 cells stably expressing DC-SIGN, showed an almost complete inhibition of JUNV infection when they were treated with S-layer in a similar extend as the inhibition shown by mannan. However no inhibition effect was observed in 3T3 wild type cells or in 3T3 cells expressing liver/lymph node-specific ICAM-3 grabbing nonintegrin (L-SIGN or DC-SIGNR or CD209L). Treatments with S-layer during different times in the infection demonstrated that inhibition was only observed when S-layer was presented in early stages of the viral infection. This inhibition does not involve the classic recognition of mannose by this C-type lectin as the S-layer showed no evidence to be glycosylated. In fact, the highly basic nature of the S-layer (pI>9.5) seems to be involved in electrostatic interactions between DC-SIGN and S-layer, since high pH abolished the inhibitory effect on infection cause by the S-layer. In silico analysis predicts a Ca(2+)-dependant carbohydrate recognition domain in the SlpA protein. This novel characteristic of the S-layer, a GRAS status protein, contribute to the pathogen exclusion reported for this probiotic strain and may be applied as an antiviral agent to inhibit several kinds of viruses.

  11. Nesfatin-1 inhibits ovarian epithelial carcinoma cell proliferation in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yang; Pang, Xiaoyan; Dong, Mei; Wen, Fang, E-mail: wenfang64@hotmail.com; Zhang, Yi, E-mail: syzi960@yahoo.com

    2013-11-01

    Highlights: •Nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest. •Nesfatin-1 enhances HO-8910 cell apoptosis. •Nesfatin-1 inhibits HO-8910 cell proliferation via mTOR and RhoA/ROCK signaling pathway. •The first report of nesfatin-1-mediated proliferation in ovarian epithelial carcinoma. -- Abstract: Nesfatin-1, an 82-amino-acid peptide derived from a 396-amino-acid precursor protein nucleobindin 2 (NUCB2), was originally identified in hypothalamic nuclei involved in the regulation of food intake. It was recently reported that nesfatin-1 is a novel depot specific adipokine preferentially produced by subcutaneous tissue, with obesity- and food deprivation-regulated expression. Although a relation between ovarian cancer mortality and obesity has been previously established, a role of nesfatin-1 in ovarian epithelial carcinoma remains unknown. The aim of the present study is to examine the effect of nesfatin-1 on ovary carcinoma cells proliferation. We found that nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest, this inhibition could be abolished by nesfatin-1 neutralizing antibody. Nesfatin-1 enhances HO-8910 cell apoptosis, activation of mammalian target of rapamycin (mTOR) and RhoA/ROCK signaling pathway block the effects of nesfatin-1-induced apoptosis, therefore reverses the inhibition of HO-8910 cell proliferation by nesfatin-1. In conclusion, the present study demonstrated that nesfatin-1 can inhibit the proliferation in human ovarian epithelial carcinoma cell line HO-8910 cells through inducing apoptosis via mTOR and RhoA/ROCK signaling pathway. This study provides a novel regulatory signaling pathway of nesfatin-1-regulated ovarian epithelial carcinoma growth and may contribute to ovarian cancer prevention and therapy, especially in obese patients.

  12. Calcium inhibits bap-dependent multicellular behavior in Staphylococcus aureus.

    Science.gov (United States)

    Arrizubieta, María Jesús; Toledo-Arana, Alejandro; Amorena, Beatriz; Penadés, José R; Lasa, Iñigo

    2004-11-01

    Bap (biofilm-associated protein) is a 254-kDa staphylococcal surface protein implicated in formation of biofilms by staphylococci isolated from chronic mastitis infections. The presence of potential EF-hand motifs in the amino acid sequence of Bap prompted us to investigate the effect of calcium on the multicellular behavior of Bap-expressing staphylococci. We found that addition of millimolar amounts of calcium to the growth media inhibited intercellular adhesion of and biofilm formation by Bap-positive strain V329. Addition of manganese, but not addition of magnesium, also inhibited biofilm formation, whereas bacterial aggregation in liquid media was greatly enhanced by metal-chelating agents. In contrast, calcium or chelating agents had virtually no effect on the aggregation of Bap-deficient strain M556. The biofilm elicited by insertion of bap into the chromosome of a biofilm-negative strain exhibited a similar dependence on the calcium concentration, indicating that the observed calcium inhibition was an inherent property of the Bap-mediated biofilms. Site-directed mutagenesis of two of the putative EF-hand domains resulted in a mutant strain that was capable of forming a biofilm but whose biofilm was not inhibited by calcium. Our results indicate that Bap binds Ca2+ with low affinity and that Ca2+ binding renders the protein noncompetent for biofilm formation and for intercellular adhesion. The fact that calcium inhibition of Bap-mediated multicellular behavior takes place in vitro at concentrations similar to those found in milk serum supports the possibility that this inhibition is relevant to the pathogenesis and/or epidemiology of the bacteria in the mastitis process.

  13. R-lipoic acid inhibits mammalian pyruvate dehydrogenase kinase.

    Science.gov (United States)

    Korotchkina, Lioubov G; Sidhu, Sukhdeep; Patel, Mulchand S

    2004-10-01

    The four pyruvate dehydrogenase kinase (PDK) and two pyruvate dehydrogenase phosphatase (PDP) isoenzymes that are present in mammalian tissues regulate activity of the pyruvate dehydrogenase complex (PDC) by phosphorylation/dephosphorylation of its pyruvate dehydrogenase (E1) component. The effect of lipoic acids on the activity of PDKs and PDPs was investigated in purified proteins system. R-lipoic acid, S-lipoic acid and R-dihydrolipoic acid did not significantly affect activities of PDPs and at the same time inhibited PDKs to different extents (PDK1>PDK4 approximately PDK2>PDK3 for R-LA). Since lipoic acids inhibited PDKs activity both when reconstituted in PDC and in the presence of E1 alone, dissociation of PDK from the lipoyl domains of dihydrolipoamide acetyltransferase in the presence of lipoic acids is not a likely explanation for inhibition. The activity of PDK1 towards phosphorylation sites 1, 2 and 3 of E1 was decreased to the same extent in the presence of R-lipoic acid, thus excluding protection of the E1 active site by lipoic acid from phosphorylation. R-lipoic acid inhibited autophosphorylation of PDK2 indicating that it exerted its effect on PDKs directly. Inhibition of PDK1 by R-lipoic acid was not altered by ADP but was decreased in the presence of pyruvate which itself inhibits PDKs. An inhibitory effect of lipoic acid on PDKs would result in less phosphorylation of E1 and hence increased PDC activity. This finding provides a possible mechanism for a glucose (and lactate) lowering effect of R-lipoic acid in diabetic subjects.

  14. Fatty acid amide hydrolase inhibition by neurotoxic organophosphorus pesticides.

    Science.gov (United States)

    Quistad, G B; Sparks, S E; Casida, J E

    2001-05-15

    Organophosphorus (OP) compound-induced inhibition of acetylcholinesterase (AChE) and neuropathy target esterase explains the rapid onset and delayed neurotoxic effects, respectively, for OP insecticides and related compounds but apparently not a third or intermediate syndrome with delayed onset and reduced limb mobility. This investigation tests the hypothesis that fatty acid amide hydrolase (FAAH), a modulator of endogenous signaling compounds affecting sleep (oleamide) and analgesia (anandamide), is a sensitive target for OP pesticides with possible secondary neurotoxicity. Chlorpyrifos oxon inhibits 50% of the FAAH activity (IC50 at 15 min, 25 degrees C, pH 9.0) in vitro at 40--56 nM for mouse brain and liver, whereas methyl arachidonyl phosphonofluoridate, ethyl octylphosphonofluoridate (EOPF), oleyl-4H-1,3,2-benzodioxaphosphorin 2-oxide (oleyl-BDPO), and dodecyl-BDPO give IC50s of 0.08--1.1 nM. These BDPOs and EOPF inhibit mouse brain FAAH in vitro with > or =200-fold higher potency than for AChE. Five OP pesticides inhibit 50% of the brain FAAH activity (ED50) at diazinon, and methamidophos occurs near acutely toxic levels, profenofos and tribufos are effective at asymptomatic doses. Two BDPOs (dodecyl and phenyl) and EOPF are potent inhibitors of FAAH in vivo (ED50 0.5--6 mg/kg). FAAH inhibition of > or =76% in brain depresses movement of mice administered anandamide at 30 mg/kg ip, often leading to limb recumbency. Thus, OP pesticides and related inhibitors of FAAH potentiate the cannabinoid activity of anandamide in mice. More generally, OP compound-induced FAAH inhibition and the associated anandamide accumulation may lead to reduced limb mobility as a secondary neurotoxic effect.

  15. Fcγ receptor-mediated inflammation inhibits axon regeneration.

    Directory of Open Access Journals (Sweden)

    Gang Zhang

    Full Text Available Anti-glycan/ganglioside antibodies are the most common immune effectors found in patients with Guillain-Barré Syndrome, which is a peripheral autoimmune neuropathy. We previously reported that disease-relevant anti-glycan autoantibodies inhibited axon regeneration, which echo the clinical association of these antibodies and poor recovery in Guillain-Barré Syndrome. However, the specific molecular and cellular elements involved in this antibody-mediated inhibition of axon regeneration are not previously defined. This study examined the role of Fcγ receptors and macrophages in the antibody-mediated inhibition of axon regeneration. A well characterized antibody passive transfer sciatic nerve crush and transplant models were used to study the anti-ganglioside antibody-mediated inhibition of axon regeneration in wild type and various mutant and transgenic mice with altered expression of specific Fcγ receptors and macrophage/microglia populations. Outcome measures included behavior, electrophysiology, morphometry, immunocytochemistry, quantitative real-time PCR, and western blotting. We demonstrate that the presence of autoantibodies, directed against neuronal/axonal cell surface gangliosides, in the injured mammalian peripheral nerves switch the proregenerative inflammatory environment to growth inhibitory milieu by engaging specific activating Fcγ receptors on recruited monocyte-derived macrophages to cause severe inhibition of axon regeneration. Our data demonstrate that the antibody orchestrated Fcγ receptor-mediated switch in inflammation is one mechanism underlying inhibition of axon regeneration. These findings have clinical implications for nerve repair and recovery in antibody-mediated immune neuropathies. Our results add to the complexity of axon regeneration in injured peripheral and central nervous systems as adverse effects of B cells and autoantibodies on neural injury and repair are increasingly recognized.

  16. Inhibitive effects of three compositae plants on Microcystis aeruginosa

    Institute of Scientific and Technical Information of China (English)

    Weihao ZHANG; Fuqing XU; Wei HE; Xing ZHENG; Chen YANG

    2009-01-01

    Based on common phenomena of biochemical interaction between plants and microorganisms, the inhi-bitive effects of three common terrestrial compositae plants, namely Artemisia lavandulaefolia DC., Conyza canadensis (L.) Cronq., and Kalimeris indica (L.) Sch.-Bip. on the blue algae Microcystis aeruginosa was studied.Live compositae plants are co-cultivated with algae in two different inoculation doses for 10 days in 5-pools incuba-tors, in order to exclude the influence of bacteria and nutri-ents. The results show that Artemisia lavandulaefolia DC has the most inhibitive potential among the three plants as evidenced by the most drastic decrease in optical density (OD680) of the algae. The inhibition rate is 93.3% (with initial inoculation dose of 2.0 × l06 Cells/mL) and 89.3% (with initial inoculation dose of 4.0 × 106 Cells/mL)respectively on the 10th day of cultivation. The average inhibition rate during the later half of the experiment is 0.76 (with initial inoculation dose of 2.0 × 106 Cells/mL) and 0.71 (with initial inoculation dose of 4.0 × 106 Cells/ mL), respectively. Logistic model analysis shows that com-positae plants such as A. lavandulaefolia DC. causes the reduction of the habitat's carrying capacity of algae.ANOVA analysis is used to determine the similarity and differences between every experimental group and an aver-age inhibitive rate model is used to evaluate the inhibition effects. The results show that A. lavandulaefolia DC., which grow well in the aquatic environment, may have a great potential in controlling algae bloom in eutrophic water.

  17. Neural signature of behavioural inhibition in women with bulimia nervosa.

    Science.gov (United States)

    Skunde, Mandy; Walther, Stephan; Simon, Joe J; Wu, Mudan; Bendszus, Martin; Herzog, Wolfgang; Friederich, Hans-Christoph

    2016-08-01

    Impaired inhibitory control is considered a behavioural phenotype in patients with bulimia nervosa. However, the underlying neural correlates of impaired general and food-specific behavioural inhibition are largely unknown. Therefore, we investigated brain activation during the performance of behavioural inhibition to general and food-related stimuli in adults with bulimia nervosa. Women with bulimia and healthy control women underwent event-related fMRI while performing a general and a food-specific no-go task. We included 28 women with bulimia nervosa and 29 healthy control women in our study. On a neuronal level, we observed significant group differences in response to general no-go stimuli in women with bulimia nervosa with high symptom severity; compared with healthy controls, the patients showed reduced activation in the right sensorimotor area (postcentral gyrus, precentral gyrus) and right dorsal striatum (caudate nucleus, putamen). The present results are limited to adult women with bulimia nervosa. Furthermore, it remains unclear whether impaired behavioural inhibition in patients with this disorder are a cause or consequence of chronic illness. Our findings suggest that diminished frontostriatal brain activation in patients with bulimia nervosa contribute to the severity of binge eating symptoms. Gaining further insight into the neural mechanisms of behavioural inhibition problems in individuals with this disorder may inform brain-directed treatment approaches and the development of response inhibition training approaches to improve inhibitory control in patients with bulimia nervosa. The present study does not support greater behavioural and neural impairments to food-specific behavioural inhibition in these patients.

  18. Kinetic properties and inhibition of Acinetobacter glutaminase-asparaginase.

    Science.gov (United States)

    Steckel, J; Roberts, J; Philips, F S; Chou, T C

    1983-03-15

    Kinetic parameters, substrate specificity and exclusivity of ligands at binding sites of L-glutaminase-L-asparaginase purified from Acinetobacter glutaminasificans were studied in order to gain knowledge about the dual activities of this enzyme and its inhibition by structural analogs. Both L-glutamine and L-asparagine, which showed similar Km (4 approximately 7 X 10(-5) M) and Vmax (molecular activity 1.0 min-1) values, were competitive with each other for the substrate binding site. The products, L-glutamic acid and L-aspartic acid, showed competitive inhibition with respect to either L-glutamine or L-asparagine as substrates. Multiple inhibition of the glutaminase activity by L-glutamic acid and L-aspartic acid indicated that these ligands are mutually exclusive at the product-releasing site. The initial rates of both of the enzyme's activities were competitively inhibited by the following inhibitors (in rates of both of the enzyme's activities were competitively inhibited by the following inhibitors (in decreasing order of activity): 6-diazo-5-oxo-L-norleucine (DON), L-methionine sulfoximine, azaserine, and Acivicin. DON and azaserine inhibited both the asparaginase and glutaminase activities in a time-dependent and irreversible manner. The kinetic data suggest an ordered mechanism with glutamine or asparagine as the first substrate and glutamic acid or aspartic acid, respectively, as the last product. These results also suggest that a single mechanism and a single set of binding sites are responsible for catalyzing both of the enzyme's activities. The data also showed that succinylated enzyme, which has a 10-fold increase of plasma half-life in animals and humans and, thus, has benefit as a cancer chemotherapeutic agent, retained its catalytic activity and maintained Km and Vmax values similar to the native enzyme.

  19. Celastrol inhibits TGF-β1-induced epithelial-mesenchymal transition by inhibiting Snail and regulating E-cadherin expression.

    Science.gov (United States)

    Kang, Hyereen; Lee, Minjae; Jang, Sung-Wuk

    2013-08-09

    The epithelial-mesenchymal transition (EMT) is a pivotal event in the invasive and metastatic potentials of cancer progression. Celastrol inhibits the proliferation of a variety of tumor cells including leukemia, glioma, prostate, and breast cancer; however, the possible role of celastrol in the EMT is unclear. We investigated the effect of celastrol on the EMT. Transforming growth factor-beta 1 (TGF-β1) induced EMT-like morphologic changes and upregulation of Snail expression. The downregulation of E-cadherin expression and upregulation of Snail in Madin-Darby Canine Kidney (MDCK) and A549 cell lines show that TGF-β1-mediated the EMT in epithelial cells; however, celastrol markedly inhibited TGF-β1-induced morphologic changes, Snail upregulation, and E-cadherin expression. Migration and invasion assays revealed that celastrol completely inhibited TGF-β1-mediated cellular migration in both cell lines. These findings indicate that celastrol downregulates Snail expression, thereby inhibiting TGF-β1-induced EMT in MDCK and A549 cells. Thus, our findings provide new evidence that celastrol suppresses lung cancer invasion and migration by inhibiting TGF-β1-induced EMT. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Inhibition of Adipogenesis by Oligonol through Akt-mTOR Inhibition in 3T3-L1 Adipocytes

    Directory of Open Access Journals (Sweden)

    Jae-Yeo Park

    2014-01-01

    Full Text Available Polyphenols have recently become an important focus of study in obesity research. Oligonol is an oligomerized polyphenol, typically comprised of catechin-type polyphenols from a variety of fruits, which has been found to exhibit better bioavailability and bioreactivity than natural polyphenol compounds. Here, we demonstrated that Oligonol inhibits 3T3-L1 adipocyte differentiation by reducing adipogenic gene expression. During adipogenesis, Oligonol downregulated the mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ, CCAAT/enhancer binding proteins α (C/EBPα, and δ (C/EBPδ in a dose-dependent manner and the expression of genes involved in lipid biosynthesis. The antiadipogenic effect of Oligonol appears to originate from its ability to inhibit the Akt and mammalian target of rapamycin (mTOR signaling pathway by diminishing the phosphorylation of ribosomal protein S6 kinase (p70S6K, a downstream target of mTOR and forkhead box protein O1 (Foxo1. These results suggest that Oligonol may be a potent regulator of obesity by repressing major adipogenic genes through inhibition of the Akt signaling pathway, which induces the inhibition of lipid accumulation, ultimately inhibiting adipogenesis.