WorldWideScience

Sample records for differentially activate natural

  1. Lactobacilli Differentially Activate Natural Killer Cells

    DEFF Research Database (Denmark)

    Fink, Lisbeth Nielsen; Christensen, Hanne Risager; Frøkiær, Hanne

    bacteria on regulatory functions of NK-cells. Here, we have investigated how human gut flora-derived non-pathogenic lactobacilli affect NK cells in vitro, by measuring proliferation and IFN-gamma production of human peripheral blood NK cells upon bacterial stimulation. CD3-CD56+ NK cells were isolated from...... having engulfed bacteria, stimulated the growth of the NK cells. In contrast, a Lactobacillus paracasei strain caused the NK cells to proliferate only in the presence of monocytes. These results demonstrate that various lactobacilli have the capacity to activate NK cells in vitro, in a monocyte dependent...

  2. Lactic Acid Bacteria Differentially Activate Natural Killer Cells

    DEFF Research Database (Denmark)

    Fink, Lisbeth Nielsen; Christensen, Hanne Risager; Frøkiær, Hanne

    antigen presenting cells and T-cells. Bacteria translocating across the gastrointestinal mucosa are presumed to gain access to NK cell compartments, as consumption of certain strains of lactic acid bacteria has been shown to increase in vivo NK cytotoxic activity. On-going research in our lab aims...

  3. Natural Product Vibsanin A Induces Differentiation of Myeloid Leukemia Cells through PKC Activation.

    Science.gov (United States)

    Yu, Zu-Yin; Xiao, He; Wang, Li-Mei; Shen, Xing; Jing, Yu; Wang, Lin; Sun, Wen-Feng; Zhang, Yan-Feng; Cui, Yu; Shan, Ya-Jun; Zhou, Wen-Bing; Xing, Shuang; Xiong, Guo-Lin; Liu, Xiao-Lan; Dong, Bo; Feng, Jian-Nan; Wang, Li-Sheng; Luo, Qing-Liang; Zhao, Qin-Shi; Cong, Yu-Wen

    2016-05-01

    All-trans retinoic acid (ATRA)-based cell differentiation therapy has been successful in treating acute promyelocytic leukemia, a unique subtype of acute myeloid leukemia (AML). However, other subtypes of AML display resistance to ATRA-based treatment. In this study, we screened natural, plant-derived vibsane-type diterpenoids for their ability to induce differentiation of myeloid leukemia cells, discovering that vibsanin A potently induced differentiation of AML cell lines and primary blasts. The differentiation-inducing activity of vibsanin A was mediated through direct interaction with and activation of protein kinase C (PKC). Consistent with these findings, pharmacological blockade of PKC activity suppressed vibsanin A-induced differentiation. Mechanistically, vibsanin A-mediated activation of PKC led to induction of the ERK pathway and decreased c-Myc expression. In mouse xenograft models of AML, vibsanin A administration prolonged host survival and inhibited PKC-mediated inflammatory responses correlated with promotion of skin tumors in mice. Collectively, our results offer a preclinical proof of concept for vibsanin A as a myeloid differentiation-inducing compound, with potential application as an antileukemic agent. Cancer Res; 76(9); 2698-709. ©2016 AACR. ©2016 American Association for Cancer Research.

  4. Natural cytolytic activity in mice with natural or induced cellular defects. I. Differential ability of in vitro interleukin-2 addition to augment natural cytolytic function

    International Nuclear Information System (INIS)

    Ades, E.W.; Hinson, A.; Butler, L.D.

    1986-01-01

    The ability of in vitro addition of recombinant interleukin 2 (rIL-2) to differentially enhance natural cytotoxicity was assessed using cells from mice with natural and induced cellular defects. In vivo treatment with most immunosuppressive or cytoreductive agents, anti-asialo-GM1 antibody, or gamma irradiation dramatically reduced in vitro cytotoxicity against natural killer (NK) sensitive targets by direct reduction in either percentage specific lysis or lytic units per spleen. In most cases, in vitro addition of rIL-2 (at concentrations causing augmented NK function in cells from naive Balb/C mice) enhanced cytotoxic activity of cells from treatment groups to a normal value but not within the rIL-2-enhanced range of nontreated animals. Additionally, cytotoxic activity of cells from animals treated with certain drugs or gamma irradiation could be augmented by rIL-2 when measured by percentage lysis but not lytic units per spleen. In vivo treatment with cyclosporin A did not affect natural cytotoxic activity and addition of rIL-2 augmented the NK activity in a similar fashion to the profile of naive cells. In experiments using cells from beige (C57Bl/6-bg) mice which have a natural defect in NK activity against YAC-1 targets, addition of rIL-2 (at concentrations causing augmented natural cytotoxic function in cells from C57Bl/6 mice) could not effectively enhance in vitro natural cytotoxic function

  5. Natural cytolytic activity in mice with natural or induced cellular defects. I. Differential ability of in vitro interleukin-2 addition to augment natural cytolytic function

    Energy Technology Data Exchange (ETDEWEB)

    Ades, E.W.; Hinson, A.; Butler, L.D.

    1986-08-01

    The ability of in vitro addition of recombinant interleukin 2 (rIL-2) to differentially enhance natural cytotoxicity was assessed using cells from mice with natural and induced cellular defects. In vivo treatment with most immunosuppressive or cytoreductive agents, anti-asialo-GM1 antibody, or gamma irradiation dramatically reduced in vitro cytotoxicity against natural killer (NK) sensitive targets by direct reduction in either percentage specific lysis or lytic units per spleen. In most cases, in vitro addition of rIL-2 (at concentrations causing augmented NK function in cells from naive Balb/C mice) enhanced cytotoxic activity of cells from treatment groups to a normal value but not within the rIL-2-enhanced range of nontreated animals. Additionally, cytotoxic activity of cells from animals treated with certain drugs or gamma irradiation could be augmented by rIL-2 when measured by percentage lysis but not lytic units per spleen. In vivo treatment with cyclosporin A did not affect natural cytotoxic activity and addition of rIL-2 augmented the NK activity in a similar fashion to the profile of naive cells. In experiments using cells from beige (C57Bl/6-bg) mice which have a natural defect in NK activity against YAC-1 targets, addition of rIL-2 (at concentrations causing augmented natural cytotoxic function in cells from C57Bl/6 mice) could not effectively enhance in vitro natural cytotoxic function.

  6. A natural diarylheptanoid promotes neuronal differentiation via activating ERK and PI3K-Akt dependent pathways.

    Science.gov (United States)

    Tang, G; Dong, X; Huang, X; Huang, X-J; Liu, H; Wang, Y; Ye, W-C; Shi, L

    2015-09-10

    Neuronal differentiation is a critical developmental process that determines accurate synaptic connection and circuit wiring. A wide variety of naturally occurring compounds have been shown as promising drug leads for the generation and differentiation of neurons. Here we report that a diarylheptanoid from the plant Alpinia officinarum, 7-(4-hydroxyphenyl)-1-phenyl-4E-hepten-3-one (Cpd 1), exhibited potent activities in neuronal differentiation and neurite outgrowth. Cpd 1 induced differentiation of neuroblastoma Neuro-2a cells into a neuron-like morphology, and accelerated the establishment of axon-dendrite polarization of cultured hippocampal neurons. Moreover, Cpd 1 promoted neurite extension in both Neuro-2a cells and neurons. We showed that the effects of Cpd 1 on neuronal differentiation and neurite growth were specifically dependent on the activation of extracellular signal-regulated kinases (ERKs) and phosphoinositide 3-kinase (PI3K)-Akt signaling pathways. Importantly, intraperitoneal administration of Cpd 1 promoted the differentiation of new-born progenitor cells into mature neurons in the adult hippocampal dentate gyrus. Collectively, this study identifies a naturally occurring diarylheptanoid with beneficial effects on neuronal differentiation and neurite outgrowth in vitro and in vivo. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Differential loss of natural killer cell activity in patients with acute myocardial infarction and stable angina pectoris.

    Science.gov (United States)

    Yan, Wenwen; Zhou, Lin; Wen, Siwan; Duan, Qianglin; Huang, Feifei; Tang, Yu; Liu, Xiaohong; Chai, Yongyan; Wang, Lemin

    2015-01-01

    To evaluate the activity of natural killer cells through their inhibitory and activating receptors and quantity in peripheral blood mononuclear cells extracted from patients with acute myocardial infarction, stable angina pectoris and the controls. 100 patients with myocardial infarction, 100 with stable angina, and 20 healthy volunteers were recruited into the study. 20 randomly chosen people per group were examined for the whole human genome microarray analysis to detect the gene expressions of all 40 inhibitory and activating natural killer cell receptors. Flow cytometry analysis was applied to all 200 patients to measure the quantity of natural killer cells. In myocardial infarction group, the mRNA expressions of six inhibitory receptors KIR2DL2, KIR3DL3, CD94, NKG2A, KLRB1, KLRG1, and eight activating receptors KIR2DS3, KIR2DS5, NKp30, NTB-A, CRACC, CD2, CD7 and CD96 were significantly down-regulated (Pangina patients and the controls. There was no statistical difference in receptor expressions between angina patients and control group. The quantity of natural killer cells was significantly decreased in both infarction and angina patients compared with normal range (Pangina patients showed a quantitative loss and dysfunction of natural killer cells in myocardial infarction patients.

  8. Curtailed T-cell activation curbs effector differentiation and generates CD8+ T cells with a naturally-occurring memory stem cell phenotype.

    Science.gov (United States)

    Zanon, Veronica; Pilipow, Karolina; Scamardella, Eloise; De Paoli, Federica; De Simone, Gabriele; Price, David A; Martinez Usatorre, Amaia; Romero, Pedro; Mavilio, Domenico; Roberto, Alessandra; Lugli, Enrico

    2017-09-01

    Human T memory stem (T SCM ) cells with superior persistence capacity and effector functions are emerging as important players in the maintenance of long-lived T-cell memory and are thus considered an attractive population to be used in adoptive transfer-based immunotherapy of cancer. However, the molecular signals regulating their generation remain poorly defined. Here we show that curtailed T-cell receptor stimulation curbs human effector CD8 + T-cell differentiation and allows the generation of CD45RO - CD45RA + CCR7 + CD27 + CD95 + -phenotype cells from highly purified naïve T-cell precursors, resembling naturally-occurring human T SCM . These cells proliferate extensively in vitro and in vivo, express low amounts of effector-associated genes and transcription factors and undergo considerable self-renewal in response to IL-15 while retaining effector differentiation potential. Such a phenotype is associated with a lower number of mitochondria compared to highly-activated effector T cells committed to terminal differentiation. These results shed light on the molecular signals that are required to generate long-lived memory T cells with potential application in adoptive cell transfer immunotherapy. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co.KGaA, Weinheim.

  9. Psoriasis: epidemiology, natural history, and differential diagnosis

    Directory of Open Access Journals (Sweden)

    Basko-Plluska JL

    2012-09-01

    Full Text Available Juliana L Basko-Plluska, Vesna Petronic-RosicDepartment of Medicine, Section of Dermatology, University of Chicago, Chicago, IL, USAAbstract: Psoriasis is a chronic, immune-mediated, inflammatory disease which affects primarily the skin and joints. It occurs worldwide, but its prevalence varies considerably between different regions of the world. Genetic susceptibility as well as environmental factors play an important role in determining the development and prognosis of psoriasis. Genome-wide association studies have identified many genetic loci as potential psoriasis susceptibility regions, including PSORS1 through PSORS7. Histocompatibility antigen (HLA studies have also identified several HLA antigens, with HLA-Cw6 being the most frequently associated antigen. Epidemiological studies identified several modifiable risk factors that may predispose individuals to developing psoriasis or exacerbate pre-existing disease. These include smoking, obesity, alcohol consumption, diet, infections, medications and stressful life events. The exact mechanism by which they trigger psoriasis remains to be elucidated; however, existing data suggest that they are linked through Th1-mediated immunological pathways. The natural history of psoriasis varies depending on the clinical subtype as well as special circumstances, including pregnancy and HIV infection. In general, psoriasis is a chronic disease with intermittent remissions and exacerbations. The differential diagnosis is vast and includes many other immune-mediated, inflammatory disorders.Keywords: psoriasis, epidemiology, natural history, differential diagnosis

  10. NATURAL SCIENCE AT SCHOOL: MODERN APPROACHES TO THE DIFFERENTIATED STUDY

    Directory of Open Access Journals (Sweden)

    Dechtyarenko S.G.

    2015-08-01

    Full Text Available The article analyzes the possibility of differentiated study natural science at school on the basis of ecological educational process. Natural science is the science about nature as a single unity or totality of the natural sciences, which constituting a single unit. The main aim of the course is to develop student’s natural science competence through integrated mastering system knowledge about nature and man, the basics of environmental knowledge, ways of improving teaching and learning activities, development of value orientations in relation to the nature. There is strong need to review approaches to teaching nature science at schools, taking into account the general trend of greening of the educational process. The aim of the work is to analyze the possibility of practical application of modern approaches to differentiated teaching of the nature science at school greening within the educational process. In our view, the environmental component may be a basis to the formation and differentiated teaching in general. The environmental component of the educational sector has been aimed to the student’s environmental consciousness and compliance with rules of environmentally safe behavior in the environment. The learning of the integrated knowledge about nature and man can be submitted through the prism of action of the environmental factors according classic approach to their classification: abiotic, biotic and anthropogenic factors. In parallel, it is reasonable to raise the issues of practical importance as some natural objects and actions of each of these factors. The new degree of the studying of the environment has been provided by the beginning of the systematization of knowledge about natural objects and structure of the universe, by the formation of primary concepts about the relationship between the world of the living and inanimate nature, between organisms and between human activities and changes that has been occurred in the

  11. Differential activity of autochthonous bacteria in controlling drought stress in native Lavandula and Salvia plants species under drought conditions in natural arid soil.

    Science.gov (United States)

    Armada, Elisabeth; Roldán, Antonio; Azcon, Rosario

    2014-02-01

    The effectiveness of autochthonous plant growth-promoting rhizobacteria was studied in Lavandula dentata and Salvia officinalis growing in a natural arid Mediterranean soil under drought conditions. These bacteria identified as Bacillus megaterium (Bm), Enterobacter sp. (E), Bacillus thuringiensis (Bt), and Bacillus sp. (Bsp). Each bacteria has different potential to meliorate water limitation and alleviating drought stress in these two plant species. B. thuringiensis promoted growth and drought avoidance in Lavandula by increasing K content, by depressing stomatal conductance, and it controlled shoot proline accumulation. This bacterial effect on increasing drought tolerance was related to the decrease of glutathione reductase (GR) and ascorbate peroxidase (APX) that resulted sensitive indexes of lower cellular oxidative damage involved in the adaptative drought response in B. thuringiensis-inoculated Lavandula plants. In contrast, in Salvia, having intrinsic lower shoot/root ratio, higher stomatal conductance and lower APX and GR activities than Lavandula, the bacterial effects on nutritional, physiological and antioxidant enzymatic systems were lower. The benefit of bacteria depended on intrinsic stress tolerance of plant involved. Lavadula demonstrated a greater benefit than Salvia to control drought stress when inoculated with B. thuringiensis. The bacterial drought tolerance assessed as survival, proline, and indolacetic acid production showed the potential of this bacteria to help plants to grow under drought conditions. B. thuringiensis may be used for Lavandula plant establishment in arid environments. Particular characteristic of the plant species as low shoot/root ratio and high stomatal conductance are important factors controlling the bacterial effectiveness improving nutritional, physiological, and metabolic plant activities.

  12. Overcoming natural replication barriers: differential helicase requirements.

    Science.gov (United States)

    Anand, Ranjith P; Shah, Kartik A; Niu, Hengyao; Sung, Patrick; Mirkin, Sergei M; Freudenreich, Catherine H

    2012-02-01

    DNA sequences that form secondary structures or bind protein complexes are known barriers to replication and potential inducers of genome instability. In order to determine which helicases facilitate DNA replication across these barriers, we analyzed fork progression through them in wild-type and mutant yeast cells, using 2-dimensional gel-electrophoretic analysis of the replication intermediates. We show that the Srs2 protein facilitates replication of hairpin-forming CGG/CCG repeats and prevents chromosome fragility at the repeat, whereas it does not affect replication of G-quadruplex forming sequences or a protein-bound repeat. Srs2 helicase activity is required for hairpin unwinding and fork progression. Also, the PCNA binding domain of Srs2 is required for its in vivo role of replication through hairpins. In contrast, the absence of Sgs1 or Pif1 helicases did not inhibit replication through structural barriers, though Pif1 did facilitate replication of a telomeric protein barrier. Interestingly, replication through a protein barrier but not a DNA structure barrier was modulated by nucleotide pool levels, illuminating a different mechanism by which cells can regulate fork progression through protein-mediated stall sites. Our analyses reveal fundamental differences in the replication of DNA structural versus protein barriers, with Srs2 helicase activity exclusively required for fork progression through hairpin structures.

  13. Natural differential operations on manifolds: an algebraic approach

    International Nuclear Information System (INIS)

    Katsylo, P I; Timashev, D A

    2008-01-01

    Natural algebraic differential operations on geometric quantities on smooth manifolds are considered. A method for the investigation and classification of such operations is described, the method of IT-reduction. With it the investigation of natural operations reduces to the analysis of rational maps between k-jet spaces, which are equivariant with respect to certain algebraic groups. On the basis of the method of IT-reduction a finite generation theorem is proved: for tensor bundles V,W→M all the natural differential operations D:Γ(V)→Γ(W) of degree at most d can be algebraically constructed from some finite set of such operations. Conceptual proofs of known results on the classification of natural linear operations on arbitrary and symplectic manifolds are presented. A non-existence theorem is proved for natural deformation quantizations on Poisson manifolds and symplectic manifolds. Bibliography: 21 titles.

  14. Radon activities in natural gases

    International Nuclear Information System (INIS)

    Sajo, B.L.; Palfalvi, J.

    1995-01-01

    Radon activities have been measured in gas samples used for residential heading, in Venezuela and in Hungary. Gas bottles were selected randomly in different regions, and radon activities were monitored with ionization clambers and solid stoke track detections. Radon concentrations in household natural gas are presented for regions in Venezuela and in Budapest, Hungary. The latter was found to be in the range of 88-135 Bq/m 3 . (R.P.)

  15. Naturally-occurring alpha activity

    Energy Technology Data Exchange (ETDEWEB)

    Mayneord, W V

    1960-12-01

    In view of the difficulties of assessing the significance of man-made radioactivity it is important to study for comparison the background of natural radioactivity against which the human race has evolved and lives. It is also important to define the present levels of activity so that it will be possible to detect and study as quickly as possible any changes which may occur owing to the release into the environment of new radioactive materials. Moreover, by the study of the behaviour of natural radioactivity light may be shed upon that of the artificially produced isotopes and a number of analogies traced between the two groups. These concepts have led to studies of naturally-occurring radioactive materials alongside a programme of research into fission products in food, water and air, as well as studies of the metabolism of both sets of materials in the human body. Since the last report there has been a useful increase in our knowledge of natural radioactivity in the biosphere, and its levels relative to the new man-made activities. These studies have necessitated technical developments, particularly in the methods of measuring and identifying alpha-ray emitters, to which group many of the more important natural radioactive materials belong.

  16. Different amounts of ejaculatory activity, a natural rewarding behavior, induce differential mu and delta opioid receptor internalization in the rat's ventral tegmental area.

    Science.gov (United States)

    Garduño-Gutiérrez, René; León-Olea, Martha; Rodríguez-Manzo, Gabriela

    2013-12-06

    Opioid receptors internalize upon specific agonist stimulation. The in vivo significance of receptor internalization is not well established, partly due to the limited in vivo models used to study this phenomenon. Ejaculation promotes endogenous opioid release which activates opioid receptors at the brain, including the mesolimbic system and medial preoptic area. The objective of the present work was to analyze if there was a correlation between the degree of in vivo mu (MOR) and delta opioid receptor (DOR) internalization in the ventral tegmental area and the execution of different amounts of ejaculatory behavior of male rats. To this aim, we analyzed the brains of rats that ejaculated once or six successive times and of sexually exhausted rats with an established sexual inhibition, using immunofluorescence and confocal microscopy. Results showed that MOR and DOR internalization increased as a consequence of ejaculation. There was a relationship between the amount of sexual activity executed and the degree of internalization for MOR, but not for DOR. MOR internalization was larger in rats that ejaculated repeatedly than in animals ejaculating only once. Significant DOR internalization was found only in animals ejaculating once. Changes in MOR, DOR and beta arrestin2 detection, associated to sexual activity, were also found. It is suggested that copulation to satiety might be useful as a model system to study the biological significance of receptor internalization. © 2013 Published by Elsevier B.V.

  17. Natural compounds with herbicidal activity

    Directory of Open Access Journals (Sweden)

    Mariano Fracchiolla

    2007-12-01

    Full Text Available Research about phytotoxic activity of natural compounds could lead both to find new herbicidal active ingredients and to plan environmental friendly weed control strategies. Particularly, living organisms could be a source of compounds that are impossible, for their complexity, to synthesize artificially. More over, they could have alternative sites of action respect to the known chemical herbicides and, due to their origin, they should be more environmental safe. Many living organism, such as bacteria, fungi, insects, lichens and plants, are able to produce bioactive compounds. They generally are secondary metabolites or simply waste molecules. In this paper we make a review about these compounds, highlighting potential and constraints.

  18. Natural compounds with herbicidal activity

    Directory of Open Access Journals (Sweden)

    Pasquale Montemurro

    2011-02-01

    Full Text Available Research about phytotoxic activity of natural compounds could lead both to find new herbicidal active ingredients and to plan environmental friendly weed control strategies. Particularly, living organisms could be a source of compounds that are impossible, for their complexity, to synthesize artificially. More over, they could have alternative sites of action respect to the known chemical herbicides and, due to their origin, they should be more environmental safe. Many living organism, such as bacteria, fungi, insects, lichens and plants, are able to produce bioactive compounds. They generally are secondary metabolites or simply waste molecules. In this paper we make a review about these compounds, highlighting potential and constraints.

  19. PREREQUISITES FOR CREATING A COMPETITIVE ADVANTAGE IN NATURE PARKS THROUGH DIFFERENTIATION

    Directory of Open Access Journals (Sweden)

    Vesna Vučemilović

    2017-01-01

    Full Text Available Differentiation is a way for gaining a sustainable competitive advantage or achieving a market position which enables companies to satisfy customers’ needs better than the competition. Differentiation can manifest itself through four dimensions: product, services, personnel and image. Nature parks, national parks, strict reserves and special reserves are categories of protected areas of national importance. Nature parks and national parks have exceptional potential for visiting system development, but are also responsible for the management of these activities. There are numerous nature protection restrictions arising from legislation and management documents. The principal task is to protect and preserve the natural and landscape values and ecological characteristics. Creating and realizing visiting activities as a part of tourist services supplied trough Public institutions are also specific. These services must be differentiated on the market in relation to the competition. Income generated from tourist services in the income structure of nature parks, will be even more important in the future, because of self-financing development and central budget dependency reduction. It must be emphasized that nature parks help the larger community through development of complementary economic activities. This paper is based on market research conducted in the period from 16 May to 10 June 2016 in Nature Park Kopački rit, which is one of the most visited nature parks in the Republic of Croatia. A poll survey was carried out among 300 randomly selected visitors. The research results may be used for policy suggestions for how to create adequate products, services and promotional activities, ensure quality education for visitors about natural, historical and cultural protected area values and minimize visitors’ impact on natural resources.

  20. Sequence learning in differentially activated dendrites

    DEFF Research Database (Denmark)

    Nielsen, Bjørn Gilbert

    2003-01-01

    . It is proposed that the neural machinery required in such a learning/retrieval mechanism could involve the NMDA receptor, in conjunction with the ability of dendrites to maintain differentially activated regions. In particular, it is suggested that such a parcellation of the dendrite allows the neuron......Differentially activated areas of a dendrite permit the existence of zones with distinct rates of synaptic modification, and such areas can be individually accessed using a reference signal which localizes synaptic plasticity and memory trace retrieval to certain subregions of the dendrite...... to participate in multiple sequences, which can be learned without suffering from the 'wash-out' of synaptic efficacy associated with superimposition of training patterns. This is a biologically plausible solution to the stability-plasticity dilemma of learning in neural networks....

  1. Adjoint optimization of natural convection problems: differentially heated cavity

    Science.gov (United States)

    Saglietti, Clio; Schlatter, Philipp; Monokrousos, Antonios; Henningson, Dan S.

    2017-12-01

    Optimization of natural convection-driven flows may provide significant improvements to the performance of cooling devices, but a theoretical investigation of such flows has been rarely done. The present paper illustrates an efficient gradient-based optimization method for analyzing such systems. We consider numerically the natural convection-driven flow in a differentially heated cavity with three Prandtl numbers (Pr=0.15{-}7) at super-critical conditions. All results and implementations were done with the spectral element code Nek5000. The flow is analyzed using linear direct and adjoint computations about a nonlinear base flow, extracting in particular optimal initial conditions using power iteration and the solution of the full adjoint direct eigenproblem. The cost function for both temperature and velocity is based on the kinetic energy and the concept of entransy, which yields a quadratic functional. Results are presented as a function of Prandtl number, time horizons and weights between kinetic energy and entransy. In particular, it is shown that the maximum transient growth is achieved at time horizons on the order of 5 time units for all cases, whereas for larger time horizons the adjoint mode is recovered as optimal initial condition. For smaller time horizons, the influence of the weights leads either to a concentric temperature distribution or to an initial condition pattern that opposes the mean shear and grows according to the Orr mechanism. For specific cases, it could also been shown that the computation of optimal initial conditions leads to a degenerate problem, with a potential loss of symmetry. In these situations, it turns out that any initial condition lying in a specific span of the eigenfunctions will yield exactly the same transient amplification. As a consequence, the power iteration converges very slowly and fails to extract all possible optimal initial conditions. According to the authors' knowledge, this behavior is illustrated here for

  2. Radionuclides incorporation in activated natural nanotubes

    International Nuclear Information System (INIS)

    Silva, Jose Parra

    2016-01-01

    Natural palygorskite nanotubes show suitable physical and chemical properties and characteristics to be use as potential nanosorbent and immobilization matrix for the concentration and solidification of radionuclides present in nuclear wastes. In the development process of materials with sorption properties for the incorporation and subsequent immobilization of radionuclides, the most important steps are related with the generation of active sites simultaneously to the increase of the specific surface area and suitable heat treatment to producing the structural folding. This study evaluated the determining parameters and conditions for the activation process of the natural palygorskite nanotubes aiming at the sorption of radionuclides in the nanotubes structure and subsequent evaluation of the parameters involve in the structural folding by heat treatments. The optimized results about the maximum sorption capacity of nickel in activated natural nanotubes show that these structures are apt and suitable for incorporation of radionuclides similar to nickel. By this study is verified that the optimization of the acid activation process is fundamental to improve the sorption capacities for specifics radionuclides by activated natural nanotubes. Acid activation condition optimized maintaining structural integrity was able to remove around 33.3 wt.% of magnesium cations, equivalent to 6.30·10 -4 g·mol -1 , increasing in 42.8% the specific surface area and incorporating the same molar concentration of nickel present in the liquid radioactive waste at 80 min. (author)

  3. Irregular activity arises as a natural consequence of synaptic inhibition

    International Nuclear Information System (INIS)

    Terman, D.; Rubin, J. E.; Diekman, C. O.

    2013-01-01

    Irregular neuronal activity is observed in a variety of brain regions and states. This work illustrates a novel mechanism by which irregular activity naturally emerges in two-cell neuronal networks featuring coupling by synaptic inhibition. We introduce a one-dimensional map that captures the irregular activity occurring in our simulations of conductance-based differential equations and mathematically analyze the instability of fixed points corresponding to synchronous and antiphase spiking for this map. We find that the irregular solutions that arise exhibit expansion, contraction, and folding in phase space, as expected in chaotic dynamics. Our analysis shows that these features are produced from the interplay of synaptic inhibition with sodium, potassium, and leak currents in a conductance-based framework and provides precise conditions on parameters that ensure that irregular activity will occur. In particular, the temporal details of spiking dynamics must be present for a model to exhibit this irregularity mechanism and must be considered analytically to capture these effects

  4. Irregular activity arises as a natural consequence of synaptic inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Terman, D., E-mail: terman@math.ohio-state.edu [Department of Mathematics, The Ohio State University, Columbus, Ohio 43210 (United States); Rubin, J. E., E-mail: jonrubin@pitt.edu [Department of Mathematics, University of Pittsburgh, Pittsburgh, Pennsylvania 15260 (United States); Diekman, C. O., E-mail: diekman@njit.edu [Department of Mathematical Sciences, New Jersey Institute of Technology, Newark, New Jersey 07102 (United States)

    2013-12-15

    Irregular neuronal activity is observed in a variety of brain regions and states. This work illustrates a novel mechanism by which irregular activity naturally emerges in two-cell neuronal networks featuring coupling by synaptic inhibition. We introduce a one-dimensional map that captures the irregular activity occurring in our simulations of conductance-based differential equations and mathematically analyze the instability of fixed points corresponding to synchronous and antiphase spiking for this map. We find that the irregular solutions that arise exhibit expansion, contraction, and folding in phase space, as expected in chaotic dynamics. Our analysis shows that these features are produced from the interplay of synaptic inhibition with sodium, potassium, and leak currents in a conductance-based framework and provides precise conditions on parameters that ensure that irregular activity will occur. In particular, the temporal details of spiking dynamics must be present for a model to exhibit this irregularity mechanism and must be considered analytically to capture these effects.

  5. Ecological and Genetic Barriers Differentiate Natural Populations of Saccharomyces cerevisiae.

    Science.gov (United States)

    Clowers, Katie J; Heilberger, Justin; Piotrowski, Jeff S; Will, Jessica L; Gasch, Audrey P

    2015-09-01

    How populations that inhabit the same geographical area become genetically differentiated is not clear. To investigate this, we characterized phenotypic and genetic differences between two populations of Saccharomyces cerevisiae that in some cases inhabit the same environment but show relatively little gene flow. We profiled stress sensitivity in a group of vineyard isolates and a group of oak-soil strains and found several niche-related phenotypes that distinguish the populations. We performed bulk-segregant mapping on two of the distinguishing traits: The vineyard-specific ability to grow in grape juice and oak-specific tolerance to the cell wall damaging drug Congo red. To implicate causal genes, we also performed a chemical genomic screen in the lab-strain deletion collection and identified many important genes that fell under quantitative trait loci peaks. One gene important for growth in grape juice and identified by both the mapping and the screen was SSU1, a sulfite-nitrite pump implicated in wine fermentations. The beneficial allele is generated by a known translocation that we reasoned may also serve as a genetic barrier. We found that the translocation is prevalent in vineyard strains, but absent in oak strains, and presents a postzygotic barrier to spore viability. Furthermore, the translocation was associated with a fitness cost to the rapid growth rate seen in oak-soil strains. Our results reveal the translocation as a dual-function locus that enforces ecological differentiation while producing a genetic barrier to gene flow in these sympatric populations. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  6. Natural radiation exposure modified by human activities

    International Nuclear Information System (INIS)

    Fujimoto, Kenzo

    1995-01-01

    We are now living in the radiation environment modified by our technology. It is usually called 'Technologically Enhanced Natural Radiation' and have been discussed in the UNSCEAR Reports as an important source of exposure. The terrestrial radionuclide concentrations as well as the intensity of cosmic rays are considered to have been constant after our ancestors came down from trees and started walking on their two feet. However, we have been changing our environment to be more comfortable for our life and consequently ambient radiation levels are nomore what used to be. In this paper exposures due to natural radiation modified by our following activities are discussed: housing, balneology, cave excursion, mountain climbing, skiing, swimming, smoking and usage of mineral water, well water, coal, natural gas, phosphate rocks and minerals. In the ICRP Publication No. 39, it is clearly mentioned that even natural radiation should be controlled as far as it is controllable. We have to pay more attention to our activities not to enhance the exposure due to unnecessary, avoidable radiation. (author)

  7. Viral Evasion of Natural Killer Cell Activation.

    Science.gov (United States)

    Ma, Yi; Li, Xiaojuan; Kuang, Ersheng

    2016-04-12

    Natural killer (NK) cells play a key role in antiviral innate defenses because of their abilities to kill infected cells and secrete regulatory cytokines. Additionally, NK cells exhibit adaptive memory-like antigen-specific responses, which represent a novel antiviral NK cell defense mechanism. Viruses have evolved various strategies to evade the recognition and destruction by NK cells through the downregulation of the NK cell activating receptors. Here, we review the recent findings on viral evasion of NK cells via the impairment of NK cell-activating receptors and ligands, which provide new insights on the relationship between NK cells and viral actions during persistent viral infections.

  8. Viral Evasion of Natural Killer Cell Activation

    Directory of Open Access Journals (Sweden)

    Yi Ma

    2016-04-01

    Full Text Available Natural killer (NK cells play a key role in antiviral innate defenses because of their abilities to kill infected cells and secrete regulatory cytokines. Additionally, NK cells exhibit adaptive memory-like antigen-specific responses, which represent a novel antiviral NK cell defense mechanism. Viruses have evolved various strategies to evade the recognition and destruction by NK cells through the downregulation of the NK cell activating receptors. Here, we review the recent findings on viral evasion of NK cells via the impairment of NK cell-activating receptors and ligands, which provide new insights on the relationship between NK cells and viral actions during persistent viral infections.

  9. A laboratory activity for teaching natural radioactivity

    Science.gov (United States)

    Pilakouta, M.; Savidou, A.; Vasileiadou, S.

    2017-01-01

    This paper presents an educational approach for teaching natural radioactivity using commercial granite samples. A laboratory activity focusing on the topic of natural radioactivity is designed to develop the knowledge and understanding of undergraduate university students on the topic of radioactivity, to appreciate the importance of environmental radioactivity and familiarize them with the basic technology used in radioactivity measurements. The laboratory activity is divided into three parts: (i) measurements of the count rate with a Geiger-Muller counter of some granite samples and the ambient background radiation rate, (ii) measurement of one of the samples using gamma ray spectrometry with a NaI detector and identification of the radioactive elements of the sample, (iii) using already recorded 24 h gamma ray spectra of the samples from the first part (from the Granite Gamma-Ray Spectrum Library (GGRSL) of our laboratory) and analyzing selected peaks in the spectrum, students estimate the contribution of each radioactive element to the total specific activity of each sample. A brief description of the activity as well as some results and their interpretation are presented.

  10. The Nature of Crisis in Enterprise Activities

    Directory of Open Access Journals (Sweden)

    Kozachenko Ganna V.

    2017-09-01

    Full Text Available It is shown that the concept of enterprise anti-crisis management and its components should be based on the nature of crisis in enterprise activities, the idea of which is the fundamental basis of enterprise anti-crisis management and determines its object, subject, tasks, main guidelines and vectors. Examples of defining the concept “crisis in enterprise activities”, which testify to the lack of unity of views on its content, are given. There revealed the attributive nature of crisis in enterprise activities, according to which a crisis, being an attribute of the system “enterprise”, begins intensifying under the influence of driving forces and individual factors, which is identified by presence of disruptions in the performance by the enterprise of its functions. There substantiated the expediency of singling out manifestations of crisis in enterprise activities (crisis phenomena, crisis situation and crisis state depending on the level of disruptions in the performance by the enterprise of its functions, which is of great importance for determining the tasks of enterprise anti-crisis management. The crisis cycle in enterprise activities in any of its manifestations is analysed, features of the cycle are considered.

  11. Marketing activities of a natural gas company

    Energy Technology Data Exchange (ETDEWEB)

    Goldammer, D [Thyssengas G.m.b.H., Duisburg (Germany, F.R.)

    1978-01-01

    The last 10 years have produced an extra ordinary upswing in the gas industry. Natural gas could, in part, satisfy the demands in fields previously reserved for heating oil. However, after these successes it seems necessary to analyze the new initial situation for future marketing activities and to find a new strategy. This investigation is concerned with those tasks. Crucial points are dealt with that represent interesting of activities for gas-supply initiatures, and the author tries to show by what means these efforts can be crowned with success. All important sectors of the market are discussed, new technological developments are dealt with briefly, and finally the special case of opening up new areas for natural gas-supply is examined. It is regarded as an absolute necessity that marketing information for new activities should be appreciably improved by market surveys. The whole article describes the activites that have arisen from the co-operation between Thyssen gas and the gas supply undertakings supplied by Thyssen gas.

  12. Research of the Nature of Leadership Activities

    Directory of Open Access Journals (Sweden)

    Andrea Jankurová

    2017-06-01

    Full Text Available Professional literature on leadership mostly states that a leader should be like (personality traits and describes different leadership styles and types. However, very little is known about what leaders do in their everyday practice, or how they do it. Leadership should be seen more widely and should be explored along the characteristics and style of leadership and how leaders are manifested externally through their work, which means to explore the nature of leadership work. The aim of the research project was to gain more knowledge about the activities undertaken by leaders to answer a simple, but yet not too clearly answered question: „What does a leader really do?“ This finding will help reveal important activities on which best leaders focus and determine which elements are really important for leadership. The research project was managed as a combination of interviews conducted with leaders, people on senior management positions along with a questionnaire survey.

  13. Marine natural flavonoids: chemistry and biological activities.

    Science.gov (United States)

    Martins, Beatriz T; Correia da Silva, Marta; Pinto, Madalena; Cidade, Honorina; Kijjoa, Anake

    2018-05-04

    As more than 70% of the world's surface is covered by oceans, marine organisms offer a rich and unlimited resource of structurally diverse bioactive compounds. These organisms have developed unique properties and bioactive compounds that are, in majority of them, unparalleled by their terrestrial counterparts due to the different surrounding ecological systems. Marine flavonoids have been extensively studied in the last decades due to a growing interest concerning their promising biological/pharmacological activities. The most common classes of marine flavonoids are flavones and flavonols, which are mostly isolated from marine plants. Although most of flavonoids are hydroxylated and methoxylated, some marine flavonoids possess an unusual substitution pattern, not commonly found in terrestrial organisms, namely the presence of sulphate, chlorine, and amino groups. This review presents, for the first time in a systematic way, the structure, natural occurrence, and biological activities of marine flavonoids.

  14. Dynamics differentiate between active and inactive inteins.

    Science.gov (United States)

    Cronin, Melissa; Coolbaugh, Michael J; Nellis, David; Zhu, Jianwei; Wood, David W; Nussinov, Ruth; Ma, Buyong

    2015-02-16

    The balance between stability and dynamics for active enzymes can be somewhat quantified by studies of intein splicing and cleaving reactions. Inteins catalyze the ligation of flanking host exteins while excising themselves. The potential for applications led to engineering of a mini-intein splicing domain, where the homing endonuclease domain of the Mycobacterium tuberculosis RecA (Mtu recA) intein was removed. The remaining domains were linked by several short peptides, but splicing activity in all was substantially lower than the full-length intein. Native splicing activity was restored in some cases by a V67L mutation. Using computations and experiments, we examine the impact of this mutation on the stability and conformational dynamics of the mini-intein splicing domain. Molecular dynamics simulations were used to delineate the factors that determine the active state, including the V67L mini-intein mutant, and peptide linker. We found that (1) the V67L mutation lowers the global fluctuations in all modeled mini-inteins, stabilizing the mini-intein constructs; (2) the connecting linker length affects intein dynamics; and (3) the flexibilities of the linker and intein core are higher in the active structure. We have observed that the interaction of the linker region and a turn region around residues 35-41 provides the pathway for the allostery interaction. Our experiments reveal that intein catalysis is characterized by non-linear Arrhenius plot, confirming the significant contribution of protein conformational dynamics to intein function. We conclude that while the V67L mutation stabilizes the global structure, cooperative dynamics of all intein regions appear more important for intein function than high stability. Our studies suggest that effectively quenching the conformational dynamics of an intein through engineered allosteric interactions could deactivate intein splicing or cleaving. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  15. Optimal Extraction and Taxation of Strategic Natural Resources: A Differential Game Approach

    OpenAIRE

    Pemy, Moustapha

    2016-01-01

    This paper studies the optimal extraction and taxation of nonrenewable natural resources. It is well known the market values of the main strategic resources such as oil, natural gas, uranium, copper,...,etc, fluctuate randomly following global and seasonal macro-economic parameters, these values are modeled using Markov switching L\\'evy processes. We formulate this problem as a differential game where the two players are the mining company whose aim is to maximize the revenues generated from ...

  16. Differential sensitivity to natural ultraviolet radiation among phytoplankton species in Arctic lakes (Spitsbergen, Norway)

    NARCIS (Netherlands)

    Donk, van E.; Faafeng, B.A.; Lange, de H.J.

    2001-01-01

    Incubation experiments demonstrated a differential sensitivity to natural UV-radiation among the dominant phytoplankton species from three Arctic lakes, situated near Ny-Ålesund, Spitsbergen (79° N). The growth of small chlorophytes, diatoms and picocyanobacteria from two oligotrophic lakes was

  17. Differential gene expression in Pyropia columbina (Bangiales, Rhodophyta under natural hydration and desiccation conditions

    Directory of Open Access Journals (Sweden)

    Loretto Contreras-Porcia

    2013-11-01

    Full Text Available In rocky shores, desiccation is triggered by daily tide changes, and experimental evidence suggests that local distribution of algal species across the intertidal rocky zone is related to their capacity to tolerate desiccation. In this context, the permanence of Pyropia columbina in the high intertidal rocky zone is explained by its exceptional physiological tolerance to desiccation. This study explored the metabolic pathways involved in tolerance to desiccation in the Chilean P. columbina, by characterizing its transcriptome under contrasting conditions of hydration. We obtained 1,410 ESTs from two subtracted cDNA libraries in naturally hydrated and desiccated fronds. Results indicate that transcriptome from both libraries contain transcripts from diverse metabolic pathways related to tolerance. Among the transcripts differentially expressed, 15% appears involved in protein synthesis, processing and degradation, 14.4% are related to photosynthesis and chloroplast, 13.1% to respiration and mitochondrial function (NADH dehydrogenase and cytochrome c oxidase proteins, 10.6% to cell wall metabolism, and 7.5% are involved in antioxidant activity, chaperone and defense factors (catalase, thioredoxin, heat shock proteins, cytochrome P450. Both libraries highlight the presence of genes/proteins never described before in algae. This information provides the first molecular work regarding desiccation tolerance in P. columbina, and helps, to some extent, explaining the classical patterns of ecological distribution described for algae across the intertidal zone.

  18. KIC 9451096: Magnetic Activity, Flares and Differential Rotation

    Science.gov (United States)

    Özdarcan, O.; Yoldaş, E.; Dal, H. A.

    2018-04-01

    We present a spectroscopic and photometric analysis of KIC 9451096. The combined spectroscopic and photometric modelling shows that the system is a detached eclipsing binary in a circular orbit and composed of F5V + K2V components. Subtracting the best-fitting light curve model from the whole long cadence data reveals additional low (mmag) amplitude light variations in time and occasional flares, suggesting a low, but still remarkable level of magnetic spot activity on the K2V component. Analyzing the rotational modulation of the light curve residuals enables us to estimate the differential rotation coefficient of the K2V component as k = 0.069 ± 0.008, which is 3 times weaker compared with the solar value of k = 0.19, assuming a solar type differential rotation. We find the stellar flare activity frequency for the K2V component as 0.000368411 h-1 indicating a low magnetic activity level.

  19. Antifouling Activity of Marine Natural Products

    KAUST Repository

    Qian, Pei-Yuan; Xu, Sharon Ying

    2012-01-01

    for marine industries. Marine natural products have been considered as one of the most promising sources of antifouling compounds in recent years. In antifouling compound screening processes, bioassay systems often play most critical/vital roles in screening

  20. Direct numerical simulation and modeling of turbulent natural convection in a vertical differentially heated slot

    International Nuclear Information System (INIS)

    Boudjemadi, R.

    1996-03-01

    The main objectives of this thesis are the direct numerical simulation of natural convection in a vertical differentially heated slot and the improvements of second-order turbulence modelling. A three-dimensional direct numerical simulation code has been developed in order to gain a better understanding of turbulence properties in natural convection flows. This code has been validated in several physical configurations: non-stratified natural convection flows (conduction solution), stratified natural convection flows (double boundary layer solution), transitional and turbulent Poiseuille flows. For the conduction solution, the turbulent regime was reached at a Rayleigh number of 1*10 5 and 5.4*10 5 . A detailed analysis of these results has revealed the principal qualities of the available models but has also pointed our their shortcomings. This data base has been used in order to improve the triple correlations transport models and to select the turbulent time scales suitable for such flows. (author). 122 refs., figs., tabs., 4 appends

  1. Differential Dynamic Evolutionary Model of Emergency Financial Service Supply Chain in Natural Disaster Risk Management

    Directory of Open Access Journals (Sweden)

    Shujian Ma

    2016-01-01

    Full Text Available A government-market-public partnership (GMPP could be a feasible arrangement for providing insurance coverage for natural disaster. Firstly, we put forward GMPP management mode. Secondly, the emergency financial service supply chain for natural disaster risk is built from the view of supply chain. Finally, the objective of this paper is to obtain insights into the cooperative and competitive relationship in GMPP system. We establish the cooperative and competitive differential dynamic evolutionary models and prove the existence of equilibrium solutions in order to solve the coordination problems. In conclusion, the equilibrium solutions can be achieved among the insurers, the operating governments, and the public.

  2. Regulatory Activities to the Natural Hazard

    International Nuclear Information System (INIS)

    Choi, Kangryong; Jung, Raeyoung

    2008-01-01

    The safety of the Nuclear Power Plants(NPPs) against the natural hazards has been investigated focused on earthquake and tsunami. Since the mass media and general people have high interests on nuclear safety whenever the natural hazards occur, earthquake and tsunami are not only technical safety concern, but also psychological issues in terms of public acceptance of nuclear energy. The Korean peninsula has been considered as a safe zone compared to neighboring countries against natural hazard, but the historical documents which state severely damaged events due to the strong earthquake make US paying careful attention to assure the safety against natural phenomenon. The potential and characteristics of earthquake and tsunami have been examined, and the status of seismic and tsunami safety of the NPPs in Korea is described. the follow-up action after disastrous huge earthquake and tsunami occurred in neighboring countries is summarized as well. The assessment results show that the NPPs in Korea are well designed, constructed and maintained with certain amount of safety margin against natural hazards, and the utility and the regulatory body are continuously doing an effort to enhance the safety with consideration of lessons learned from big events in other countries

  3. Role for early-differentiated natural killer cells in infectious mononucleosis.

    Science.gov (United States)

    Azzi, Tarik; Lünemann, Anna; Murer, Anita; Ueda, Seigo; Béziat, Vivien; Malmberg, Karl-Johan; Staubli, Georg; Gysin, Claudine; Berger, Christoph; Münz, Christian; Chijioke, Obinna; Nadal, David

    2014-10-16

    A growing body of evidence suggests that the human natural killer (NK)-cell compartment is phenotypically and functionally heterogeneous and is composed of several differentiation stages. Moreover, NK-cell subsets have been shown to exhibit adaptive immune features during herpes virus infection in experimental mice and to expand preferentially during viral infections in humans. However, both phenotype and role of NK cells during acute symptomatic Epstein-Barr virus (EBV) infection, termed infectious mononucleosis (IM), remain unclear. Here, we longitudinally assessed the kinetics, the differentiation, and the proliferation of subsets of NK cells in pediatric IM patients. Our results indicate that acute IM is characterized by the preferential proliferation of early-differentiated CD56(dim) NKG2A(+) immunoglobulin-like receptor(-) NK cells. Moreover, this NK-cell subset exhibits features of terminal differentiation and persists at higher frequency during at least the first 6 months after acute IM. Finally, we demonstrate that this NK-cell subset preferentially degranulates and proliferates on exposure to EBV-infected B cells expressing lytic antigens. Thus, early-differentiated NK cells might play a key role in the immune control of primary infection with this persistent tumor-associated virus. © 2014 by The American Society of Hematology.

  4. Differential rotation of the Sun and the Maunder minimum of solar activity

    International Nuclear Information System (INIS)

    Ikhsanov, R.N.; Vitinskij, Yu.I.

    1980-01-01

    Nature of differential rotation of the Sun is discussed. Investigation of long term changes in differential rotation separately for two phase of 11 year cycle of the Sun activity is carried out. Data on heliographic coordinates for every day of all groups of the Sun spots for the years preceding the epoch of the minimum of the 11 year cycle and the Sun groups for the years of maximum from ''Greenwich Photoheliographic Results'' for 1875-1954 are used as initial material. It is shown that differential rotation of the Sun changes in time from one 11 year cycle of the Sun activity to another. This change is connected with the power of 11 year cycle. During the maximum phase of 11 year cycle differentiality of the rotation increases in the cycles where the cycle maximum is higher. Before the minimum of 11 year cycle rotation differentiability is lower in the cycles for which activity maximum is higher in the next 11 year cycle. Equatorial rate of the Sun rotation increases with the decrease in the cycle power when the maximum Wolf number is less than 110. The mentioned regularities took place both during Maunder minimum and before its beginning [ru

  5. Virtual nature environment with nature sound exposure induce stress recovery by enhanced parasympathetic activity

    DEFF Research Database (Denmark)

    Annerstedt, Matilda; Jönsson, Peter; Wallergård, Mattias

    2013-01-01

    . The group that recovered in virtual nature without sound and the control group displayed no particular autonomic activation or deactivation. The results demonstrate a potential mechanistic link between nature, the sounds of nature, and stress recovery, and suggest the potential importance of virtual reality......Experimental research on stress recovery in natural environments is limited, as is study of the effect of sounds of nature. After inducing stress by means of a virtual stress test, we explored physiological recovery in two different virtual natural environments (with and without exposure to sounds...... of nature) and in one control condition. Cardiovascular data and saliva cortisol were collected. Repeated ANOVA measurements indicated parasympathetic activation in the group subjected to sounds of nature in a virtual natural environment, suggesting enhanced stress recovery may occur in such surroundings...

  6. Glucose metabolism regulates T cell activation, differentiation and functions

    Directory of Open Access Journals (Sweden)

    Clovis Steve Palmer

    2015-01-01

    Full Text Available The adaptive immune system is equipped to eliminate both tumors and pathogenic microorganisms. It requires a series of complex and coordinated signals to drive the activation, proliferation and differentiation of appropriate T cell subsets. It is now established that changes in cellular activation are coupled to profound changes in cellular metabolism. In addition, emerging evidence now suggest that specific metabolic alterations associated with distinct T cell subsets may be ancillary to their differentiation and influential in their immune functions. The Warburg effect originally used to describe a phenomenon in which most cancer cells relied on aerobic glycolysis for their growth is a key process that sustain T cell activation and differentiation. Here we review how different aspects of metabolism in T cells influence their functions, focusing on the emerging role of key regulators of glucose metabolism such as HIF-1α. A thorough understanding of the role of metabolism in T cell function could provide insights into mechanisms involved in inflammatory-mediated conditions, with the potential for developing novel therapeutic approaches to treat these diseases.

  7. Measurement of natural activity in peat ashes

    International Nuclear Information System (INIS)

    Suomela, J.

    1985-01-01

    High proportions of radioactive materials in peat ashes may involve radiation hazards during handling and deposition of these waste materials. Measurements have been performed to determine the content of radioactive materials in ashes from peat burning. The activities in fly ash and ''solid'' ash in seven peat-fired power plants in Sweden are presented. The methods of analysing and measuring peat ashes for activity from different radionuclides are described. The activity levels in ash samples are given

  8. Differential Effects of Tacrolimus versus Sirolimus on the Proliferation, Activation and Differentiation of Human B Cells.

    Directory of Open Access Journals (Sweden)

    Opas Traitanon

    Full Text Available The direct effect of immunosuppressive drugs calcineurin inhibitor (Tacrolimus, TAC and mTOR inhibitor (Sirolimus, SRL on B cell activation, differentiation and proliferation is not well documented. Purified human B cells from healthy volunteers were stimulated through the B Cell Receptor with Anti-IgM + anti-CD40 + IL21 in the absence / presence of TAC or SRL. A variety of parameters of B cell activity including activation, differentiation, cytokine productions and proliferation were monitored by flow cytometry. SRL at clinically relevant concentrations (6 ng/ml profoundly inhibited CD19(+ B cell proliferation compared to controls whereas TAC at similar concentrations had a minimal effect. CD27(+ memory B cells were affected more by SRL than naïve CD27- B cells. SRL effectively blocked B cell differentiation into plasma cells (CD19(+CD138(+ and Blimp1(+/Pax5(low cells even at low dose (2 ng/ml, and totally eliminated them at 6 ng/ml. SRL decreased absolute B cell counts, but the residual responding cells acquired an activated phenotype (CD25(+/CD69(+ and increased the expression of HLA-DR. SRL-treated stimulated B cells on a per cell basis were able to enhance the proliferation of allogeneic CD4(+CD25(- T cells and induce a shift toward the Th1 phenotype. Thus, SRL and TAC have different effects on B lymphocytes. These data may provide insights into the clinical use of these two agents in recipients of solid organ transplants.

  9. Contemporary evolution during invasion: evidence for differentiation, natural selection, and local adaptation.

    Science.gov (United States)

    Colautti, Robert I; Lau, Jennifer A

    2015-05-01

    Biological invasions are 'natural' experiments that can improve our understanding of contemporary evolution. We evaluate evidence for population differentiation, natural selection and adaptive evolution of invading plants and animals at two nested spatial scales: (i) among introduced populations (ii) between native and introduced genotypes. Evolution during invasion is frequently inferred, but rarely confirmed as adaptive. In common garden studies, quantitative trait differentiation is only marginally lower (~3.5%) among introduced relative to native populations, despite genetic bottlenecks and shorter timescales (i.e. millennia vs. decades). However, differentiation between genotypes from the native vs. introduced range is less clear and confounded by nonrandom geographic sampling; simulations suggest this causes a high false-positive discovery rate (>50%) in geographically structured populations. Selection differentials (¦s¦) are stronger in introduced than in native species, although selection gradients (¦β¦) are not, consistent with introduced species experiencing weaker genetic constraints. This could facilitate rapid adaptation, but evidence is limited. For example, rapid phenotypic evolution often manifests as geographical clines, but simulations demonstrate that nonadaptive trait clines can evolve frequently during colonization (~two-thirds of simulations). Additionally, QST-FST studies may often misrepresent the strength and form of natural selection acting during invasion. Instead, classic approaches in evolutionary ecology (e.g. selection analysis, reciprocal transplant, artificial selection) are necessary to determine the frequency of adaptive evolution during invasion and its influence on establishment, spread and impact of invasive species. These studies are rare but crucial for managing biological invasions in the context of global change. © 2015 John Wiley & Sons Ltd.

  10. Profit, productivity, and price differential: an international performance comparison of the natural gas transportation industry

    International Nuclear Information System (INIS)

    Jeong-Dong Lee; Sung-Bae Park; Tai-Yoo Kim

    1999-01-01

    The objective of this paper is to evaluate the performance of natural gas transportation utilities, focusing on the three-key strategic performance measures of profit, productivity, and price differential. We propose a methodology that expresses the three performance measures in a unified single equation using the Edgeworth index. The proposed methodology is applied to an international comparison of the performance of 28 natural gas transportation utilities operating in eight countries in which the business environments differ greatly. The empirical results show the possible causes of performance differences and may shed some light on the direction of regulatory policy, especially for developing countries that have relatively short histories in the natural gas industry, such as Korea. (author)

  11. Investigation of Thermal Behavior for Natural Fibres Reinforced Epoxy using Thermogravimetric and Differential Scanning Calorimetric Analysis

    Directory of Open Access Journals (Sweden)

    Fauzi F.A.

    2016-01-01

    Full Text Available This paper presented the research works on the investigation of the thermal behavior of the natural fibres; i.e. pineapple leaf fibre, kenaf fibre and mengkuang fibres reinforced epoxy. The thermogravimetric analysis and differential scanning calorimetric analysis were used to measure the thermal behavior of the treated and untreated pineapple, kenaf and mengkuang fibres reinforced epoxy. The samples for both analysis were subjected to maximum temperature 600°C at the heating rate of 10°C/min. The results showed that the treated fibres show higher maximum peak temperature as compared to the untreated fibres. Additionally, the glass transition temperature showed a lower value for all treated fibre. It can be concluded that investigation of thermal properties of these natural fibres could improve the utilization of natural fibre composites in various applications i.e. sports applications.

  12. Research of the Nature of Leadership Activities

    OpenAIRE

    Andrea Jankurová; Ivana Ljudvigová; Klaudia Gubová

    2017-01-01

    Professional literature on leadership mostly states that a leader should be like (personality traits) and describes different leadership styles and types. However, very little is known about what leaders do in their everyday practice, or how they do it. Leadership should be seen more widely and should be explored along the characteristics and style of leadership and how leaders are manifested externally through their work, which means to explore the nature of leadership work. The aim of the...

  13. Epigenetic differentiation persists after male gametogenesis in natural populations of the perennial herb Helleborus foetidus (Ranunculaceae).

    Science.gov (United States)

    Herrera, Carlos M; Medrano, Mónica; Bazaga, Pilar

    2013-01-01

    Despite the importance of assessing the stability of epigenetic variation in non-model organisms living in real-world scenarios, no studies have been conducted on the transgenerational persistence of epigenetic structure in wild plant populations. This gap in knowledge is hindering progress in the interpretation of natural epigenetic variation. By applying the methylation-sensitive amplified fragment length polymorphism (MSAP) technique to paired plant-pollen (i.e., sporophyte-male gametophyte) DNA samples, and then comparing methylation patterns and epigenetic population differentiation in sporophytes and their descendant gametophytes, we investigated transgenerational constancy of epigenetic structure in three populations of the perennial herb Helleborus foetidus (Ranunculaceae). Single-locus and multilocus analyses revealed extensive epigenetic differentiation between sporophyte populations. Locus-by-locus comparisons of methylation status in individual sporophytes and descendant gametophytes showed that ~75% of epigenetic markers persisted unchanged through gametogenesis. In spite of some epigenetic reorganization taking place during gametogenesis, multilocus epigenetic differentiation between sporophyte populations was preserved in the subsequent gametophyte stage. In addition to illustrating the efficacy of applying the MSAP technique to paired plant-pollen DNA samples to investigate epigenetic gametic inheritance in wild plants, this paper suggests that epigenetic differentiation between adult plant populations of H. foetidus is likely to persist across generations.

  14. Epigenetic differentiation persists after male gametogenesis in natural populations of the perennial herb Helleborus foetidus (Ranunculaceae.

    Directory of Open Access Journals (Sweden)

    Carlos M Herrera

    Full Text Available Despite the importance of assessing the stability of epigenetic variation in non-model organisms living in real-world scenarios, no studies have been conducted on the transgenerational persistence of epigenetic structure in wild plant populations. This gap in knowledge is hindering progress in the interpretation of natural epigenetic variation. By applying the methylation-sensitive amplified fragment length polymorphism (MSAP technique to paired plant-pollen (i.e., sporophyte-male gametophyte DNA samples, and then comparing methylation patterns and epigenetic population differentiation in sporophytes and their descendant gametophytes, we investigated transgenerational constancy of epigenetic structure in three populations of the perennial herb Helleborus foetidus (Ranunculaceae. Single-locus and multilocus analyses revealed extensive epigenetic differentiation between sporophyte populations. Locus-by-locus comparisons of methylation status in individual sporophytes and descendant gametophytes showed that ~75% of epigenetic markers persisted unchanged through gametogenesis. In spite of some epigenetic reorganization taking place during gametogenesis, multilocus epigenetic differentiation between sporophyte populations was preserved in the subsequent gametophyte stage. In addition to illustrating the efficacy of applying the MSAP technique to paired plant-pollen DNA samples to investigate epigenetic gametic inheritance in wild plants, this paper suggests that epigenetic differentiation between adult plant populations of H. foetidus is likely to persist across generations.

  15. TAILORING ACTIVATED CARBONS FOR ENHANCED REMOVAL OF NATURAL ORGANIC MATTER FROM NATURAL WATERS. (R828157)

    Science.gov (United States)

    Several pathways have been employed to systematically modify two granular activated carbons (GACs), F400 (coal-based) and Macro (wood-based), for examining adsorption of dissolved natural organic matter (DOM) from natural waters. A total of 24 activated carbons with different ...

  16. Acerogenin A, a natural compound isolated from Acer nikoense Maxim, stimulates osteoblast differentiation through bone morphogenetic protein action

    International Nuclear Information System (INIS)

    Kihara, Tasuku; Ichikawa, Saki; Yonezawa, Takayuki; Lee, Ji-Won; Akihisa, Toshihiro; Woo, Je Tae; Michi, Yasuyuki; Amagasa, Teruo; Yamaguchi, Akira

    2011-01-01

    Research highlights: → Acerogenin A stimulated osteoblast differentiation in osteogenic cells. → Acerogenin A-induced osteoblast differentiation was inhibited by noggin. → Acerogenin A increased Bmp-2, Bmp-4 and Bmp-7 mRNA expression in MC3T3-E1 cells. → Acerogenin A is a candidate agent for stimulating bone formation. -- Abstract: We investigated the effects of acerogenin A, a natural compound isolated from Acer nikoense Maxim, on osteoblast differentiation by using osteoblastic cells. Acerogenin A stimulated the cell proliferation of MC3T3-E1 osteoblastic cells and RD-C6 osteoblastic cells (Runx2-deficient cell line). It also increased alkaline phosphatase activity in MC3T3-E1 and RD-C6 cells and calvarial osteoblastic cells isolated from the calvariae of newborn mice. Acerogenin A also increased the expression of mRNAs related to osteoblast differentiation, including Osteocalcin, Osterix and Runx2 in MC3T3-E1 cells and primary osteoblasts: it also stimulated Osteocalcin and Osterix mRNA expression in RD-C6 cells. The acerogenin A treatment for 3 days increased Bmp-2, Bmp-4, and Bmp-7 mRNA expression levels in MC3T3-E1 cells. Adding noggin, a BMP specific-antagonist, inhibited the acerogenin A-induced increase in the Osteocalcin, Osterix and Runx2 mRNA expression levels. These results indicated that acerogenin A stimulates osteoblast differentiation through BMP action, which is mediated by Runx2-dependent and Runx2-independent pathways.

  17. Anticancer and antiproliferative activity of natural brassinosteroids

    Czech Academy of Sciences Publication Activity Database

    Malíková, J.; Swaczynová, Jana; Kolář, Z.; Strnad, Miroslav

    2008-01-01

    Roč. 69, č. 2 (2008), s. 418-426 ISSN 0031-9422 Institutional research plan: CEZ:AV0Z50380511 Keywords : Brassinosteroids * Anticancer activity * Cell cycle Subject RIV: CE - Biochemistry Impact factor: 2.946, year: 2008

  18. Epidermis-type lipoxygenase 3 regulates adipocyte differentiation and peroxisome proliferator-activated receptor gamma activity

    DEFF Research Database (Denmark)

    Hallenborg, Philip; Jørgensen, Claus; Petersen, Rasmus K

    2010-01-01

    preadipocytes. Here, we show that forced expression of eLOX3 or addition of eLOX3 products stimulated adipogenesis under conditions that normally require an exogenous PPAR gamma ligand for differentiation. Hepoxilins, a group of oxidized arachidonic acid derivatives produced by eLOX3, bound to and activated...... PPAR gamma. Production of hepoxilins was increased transiently during the initial stages of adipogenesis. Furthermore, small interfering RNA-mediated or retroviral short hairpin RNA-mediated knockdown of eLOX3 expression abolished differentiation of 3T3-L1 preadipocytes. Finally, we demonstrate...... differentiation has remained enigmatic. Previously, we showed that lipoxygenase (LOX) activity is involved in activation of PPAR gamma during the early stages of adipocyte differentiation. Of the seven known murine LOXs, only the unconventional LOX epidermis-type lipoxygenase 3 (eLOX3) is expressed in 3T3-L1...

  19. Natural cytotoxicity in immunodeficiency diseases: preservation of natural killer activity and the in vivo appearance of radioresistant killing

    International Nuclear Information System (INIS)

    Pierce, G.F.; Polmar, S.H.; Schacter, B.Z.; Brovall, C.; Hornick, D.L.; Sorensen, R.U.

    1986-01-01

    We studied spontaneous natural killer (NK) cell activity and radiation-resistant NK mediated cytotoxicity in four patients with clinically documented severe combined immune deficiency disease (SCID), and in one subject each with intestinal lymphangiectasia and cartilage-hair hypoplasia. We observed the preservation of spontaneous NK activity in all patients despite the presence of profound B- and T-lymphocytopenia and clinical immunodeficiency. NK activity was associated with relatively normal circulating numbers of OKM1+ lymphocytes, a population known to contain NK effectors. Spontaneous NK activity resistant to 3000 rad was increased in all patients, indicating the presence of activated natural killer cells in vivo. The concept of a chronically activated immune system in these patients was further supported by the presence of increased Ia positive T cells in all subjects tested, suggesting that radioresistant NK activity may be a useful parameter to measure when assessing in vivo immune activation. Our data, as well as that of others, supports the hypothesis that at least one population of NK cells is a distinct lineage arising at the differentiation level of myeloid and lymphoid stem cells in the bone marrow

  20. Development of a differential infrared absorption method to measure the deuterium content of natural water

    International Nuclear Information System (INIS)

    D'Alessio, Enrique; Bonadeo, Hernan; Karaianev de Del Carril, Stiliana.

    1975-07-01

    A system to measure the deuterium content of natural water using differential infrared spectroscopy is described. Parameters conducing to an optimized design are analyzed, and the construction of the system is described. A Perkin Elmer 225 infrared spectrometer, to which a scale expansion system has been added, is used. Sample and reference waters are alternatively introduced by a pneumatical-mechanical system into a unique F Ca thermostatized infrared cell. Results and calibration curves shown prove that the system is capable of measuring deuterium content with a precision of 1 part per million. (author)

  1. Visualization of the Differential Transition State Stabilization within the Active Site Environment

    Directory of Open Access Journals (Sweden)

    Jerzy Leszczynski

    2004-05-01

    Full Text Available Abstract: Increasing interest in the enzymatic reaction mechanisms and in the nature of catalytic effects in enzymes causes the need of appropriate visualization methods. A new interactive method to investigate catalytic effects using differential transition state stabilization approach (DTSS [1, 2] is presented. The catalytic properties of the active site of cytidine deaminase (E.C. 3.5.4.5 is visualized in the form of differential electrostatic properties. The visualization was implemented using scripting interface of VMD [3]. Cumulative Atomic Multipole Moments (CAMM [4,5,6] were utilized for efficient yet accurate evaluation of the electrostatic properties. The implementation is efficient enough for interactive presentation of catalytic effects in the active site of the enzyme due to transition state or substrate movement. This system of visualization of DTTS approach can be potentially used to validate hypotheses regarding the catalytic mechanism or to study binding properties of transition state analogues.

  2. Striatal Activation Predicts Differential Therapeutic Responses to Methylphenidate and Atomoxetine.

    Science.gov (United States)

    Schulz, Kurt P; Bédard, Anne-Claude V; Fan, Jin; Hildebrandt, Thomas B; Stein, Mark A; Ivanov, Iliyan; Halperin, Jeffrey M; Newcorn, Jeffrey H

    2017-07-01

    Methylphenidate has prominent effects in the dopamine-rich striatum that are absent for the selective norepinephrine transporter inhibitor atomoxetine. This study tested whether baseline striatal activation would predict differential response to the two medications in youth with attention-deficit/hyperactivity disorder (ADHD). A total of 36 youth with ADHD performed a Go/No-Go test during functional magnetic resonance imaging at baseline and were treated with methylphenidate and atomoxetine using a randomized cross-over design. Whole-brain task-related activation was regressed on clinical response. Task-related activation in right caudate nucleus was predicted by an interaction of clinical responses to methylphenidate and atomoxetine (F 1,30  = 17.00; p atomoxetine. The rate of robust response was higher for methylphenidate than for atomoxetine in youth with high (94.4% vs. 38.8%; p = .003; number needed to treat = 2, 95% CI = 1.31-3.73) but not low (33.3% vs. 50.0%; p = .375) caudate activation. Furthermore, response to atomoxetine predicted motor cortex activation (F 1,30  = 14.99; p atomoxetine in youth with ADHD, purportedly reflecting the dopaminergic effects of methylphenidate but not atomoxetine in the striatum, whereas motor cortex activation may predict response to atomoxetine. These data do not yet translate directly to the clinical setting, but the approach is potentially important for informing future research and illustrates that it may be possible to predict differential treatment response using a biomarker-driven approach. Stimulant Versus Nonstimulant Medication for Attention Deficit Hyperactivity Disorder in Children; https://clinicaltrials.gov/; NCT00183391. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Antifouling Activity of Marine Natural Products

    KAUST Repository

    Qian, Pei-Yuan

    2012-01-01

    With the global ban of application of organotin-based marine coatings by International Maritime Organization in 2008, there is a practical and urgent need of identifying environmentally friendly low-toxic and nontoxic antifouling compounds for marine industries. Marine natural products have been considered as one of the most promising sources of antifouling compounds in recent years. In antifouling compound screening processes, bioassay systems often play most critical/vital roles in screening efforts. To meet various needs, a variety of bioassay systems have been developed and/or adopted in both research and commercial laboratories. In this chapter, we provide a brief outline of common bioassay procedures for both antimicrofouling and antimacrofouling assays, which can serve as a general guideline for setting up bioassay systems in laboratories engaged in antifouling compound screening. Some bioassay procedures currently practiced in various laboratories are not included in this book chapter for various reasons. Individual laboratories should modify bioassay protocols based on their research interests or needs. Nevertheless, we highly recommend the research laboratories to adapt high-throughput assays as much as possible for preliminary screening assays, followed by more complex bioassay processes using multiple target species. We argue strongly for studies in mode-of-action of antifouling compounds against settling propagules, which shall lead to discovery of molecular biomarkers (genes, proteins, receptors, or receptor system) and will allow us to design more targeted bioassay systems.

  4. Use of Natural Zeolite to Upgrade Activated Sludge Process

    Directory of Open Access Journals (Sweden)

    Hanife Büyükgüngör

    2003-01-01

    Full Text Available The objective of this study was to achieve better efficiency of phosphorus removal in an enhanced biological phosphorus removal process by upgrading the system with different amounts of natural zeolite addition. The system performance for synthetic wastewater containing different carbon sources applied at different initial concentrations of phosphorus, as well as for municipal wastewater, was investigated. Natural zeolite addition in the aerobic phase of the anaerobic/aerobic bioaugmented activated sludge system contributed to a significant improvement of phosphorus removal in systems with synthetic wastewater and fresh municipal wastewater. Improvement of phosphorus removal with regard to the control reactors was higher with the addition of 15 than with 5 g/L of natural zeolite. In reactors with natural zeolite addition with regard to the control reactors significantly decreased chemical oxygen demand, ammonium and nitrate, while higher increment and better-activated sludge settling were achieved, without changes in the pH-values of the medium. It was shown that the natural zeolite particles are suitable support material for the phosphate-accumulating bacteria Acinetobacter calcoaceticus (DSM 1532, which were adsorbed on the particle surface, resulting in increased biological activity of the system. The process of phosphorus removal in a system with bioaugmented activated sludge and natural zeolite addition consisted of: metabolic activity of activated sludge, phosphorus uptake by phosphate-accumulating bacteria adsorbed on the natural zeolite particles and suspended in solution, and phosphorus adsorption on the natural zeolite particles.

  5. Calpain expression and activity during lens fiber cell differentiation.

    Science.gov (United States)

    De Maria, Alicia; Shi, Yanrong; Kumar, Nalin M; Bassnett, Steven

    2009-05-15

    In animal models, the dysregulated activity of calcium-activated proteases, calpains, contributes directly to cataract formation. However, the physiological role of calpains in the healthy lens is not well defined. In this study, we examined the expression pattern of calpains in the mouse lens. Real time PCR and Western blotting data indicated that calpain 1, 2, 3, and 7 were expressed in lens fiber cells. Using controlled lysis, depth-dependent expression profiles for each calpain were obtained. These indicated that, unlike calpain 1, 2, and 7, which were most abundant in cells near the lens surface, calpain 3 expression was strongest in the deep cortical region of the lens. We detected calpain activities in vitro and showed that calpains were active in vivo by microinjecting fluorogenic calpain substrates into cortical fiber cells. To identify endogenous calpain substrates, membrane/cytoskeleton preparations were treated with recombinant calpain, and cleaved products were identified by two-dimensional difference electrophoresis/mass spectrometry. Among the calpain substrates identified by this approach was alphaII-spectrin. An antibody that specifically recognized calpain-cleaved spectrin was used to demonstrate that spectrin is cleaved in vivo, late in fiber cell differentiation, at or about the time that lens organelles are degraded. The generation of the calpain-specific spectrin cleavage product was not observed in lens tissue from calpain 3-null mice, indicating that calpain 3 is uniquely activated during lens fiber differentiation. Our data suggest a role for calpains in the remodeling of the membrane cytoskeleton that occurs with fiber cell maturation.

  6. Nouns referring to tools and natural objects differentially modulate the motor system.

    Science.gov (United States)

    Gough, Patricia M; Riggio, Lucia; Chersi, Fabian; Sato, Marc; Fogassi, Leonardo; Buccino, Giovanni

    2012-01-01

    While increasing evidence points to a critical role for the motor system in language processing, the focus of previous work has been on the linguistic category of verbs. Here we tested whether nouns are effective in modulating the motor system and further whether different kinds of nouns - those referring to artifacts or natural items, and items that are graspable or ungraspable - would differentially modulate the system. A Transcranial Magnetic Stimulation (TMS) study was carried out to compare modulation of the motor system when subjects read nouns referring to objects which are Artificial or Natural and which are Graspable or Ungraspable. TMS was applied to the primary motor cortex representation of the first dorsal interosseous (FDI) muscle of the right hand at 150 ms after noun presentation. Analyses of Motor Evoked Potentials (MEPs) revealed that across the duration of the task, nouns referring to graspable artifacts (tools) were associated with significantly greater MEP areas. Analyses of the initial presentation of items revealed a main effect of graspability. The findings are in line with an embodied view of nouns, with MEP measures modulated according to whether nouns referred to natural objects or artifacts (tools), confirming tools as a special class of items in motor terms. Additionally our data support a difference for graspable versus non graspable objects, an effect which for natural objects is restricted to initial presentation of items. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Capabilities of laser ablation mass spectrometry in the differentiation of natural and artificial opal gemstones.

    Science.gov (United States)

    Erel, Eric; Aubriet, Frédéric; Finqueneisel, Gisèle; Muller, Jean-François

    2003-12-01

    The potentialities of laser ablation coupled to ion cyclotron resonance Fourier transform mass spectrometry are evaluated to distinguish natural and artificial opals. The detection of specific species in both ion detection modes leads us to obtain relevant criteria of differentiation. In positive ions, species including hafnium and large amounts of zirconium atoms are found to be specific for artificial opal. In contrast, aluminum, titanium, iron, and rubidium are systematically detected in the study of natural opals. Moreover, some ions allow us to distinguish between natural opal from Australia and from Mexico. Australian gemstone includes specifically strontium, cesium, and barium. Moreover, it is also found that the yield of (H2O)0-1(SiO2)nX- (X- = O-, OH-, KO-, NaO-, SiO2-, AlO1-2-, FeO2-, ZrO2-, and ZrO3-) and (Al2O3)(SiO2)nAlO2- ions depends on the composition of the sample when opals are laser ablated. Ions, which include zirconium oxide species, are characteristics of artificial gem. In contrast, natural opals lead us, after laser ablation, to the production of ions including H2O, Al2O3 motifs and AlO-, KO-, NaO-, and FeO2- species.

  8. ADAPTIVE METHODS FOR STOCHASTIC DIFFERENTIAL EQUATIONS VIA NATURAL EMBEDDINGS AND REJECTION SAMPLING WITH MEMORY.

    Science.gov (United States)

    Rackauckas, Christopher; Nie, Qing

    2017-01-01

    Adaptive time-stepping with high-order embedded Runge-Kutta pairs and rejection sampling provides efficient approaches for solving differential equations. While many such methods exist for solving deterministic systems, little progress has been made for stochastic variants. One challenge in developing adaptive methods for stochastic differential equations (SDEs) is the construction of embedded schemes with direct error estimates. We present a new class of embedded stochastic Runge-Kutta (SRK) methods with strong order 1.5 which have a natural embedding of strong order 1.0 methods. This allows for the derivation of an error estimate which requires no additional function evaluations. Next we derive a general method to reject the time steps without losing information about the future Brownian path termed Rejection Sampling with Memory (RSwM). This method utilizes a stack data structure to do rejection sampling, costing only a few floating point calculations. We show numerically that the methods generate statistically-correct and tolerance-controlled solutions. Lastly, we show that this form of adaptivity can be applied to systems of equations, and demonstrate that it solves a stiff biological model 12.28x faster than common fixed timestep algorithms. Our approach only requires the solution to a bridging problem and thus lends itself to natural generalizations beyond SDEs.

  9. Naturally occurring cobalamins have antimalarial activity.

    Science.gov (United States)

    Chemaly, Susan M; Chen, Chien-Teng; van Zyl, Robyn L

    2007-05-01

    The acquisition of resistance by malaria parasites towards existing antimalarials has necessitated the development of new chemotherapeutic agents. The effect of vitamin B(12) derivatives on the formation of beta-haematin (synthetic haemozoin) was determined under conditions similar to those in the parasitic food vacuole (using chloroquine, a known inhibitor of haemozoin formation for comparison). Adenosylcobalamin (Ado-cbl), methylcobalamin (CH(3)-cbl) and aquocobalamin (H(2)O-cbl) were approximately forty times more effective inhibitors of beta-haematin formation than chloroquine, cyanocobalamin (CN-cbl) was slightly more inhibitory than chloroquine, while dicyanocobinamide had no effect. It is proposed that the cobalamins exert their inhibitory effect on beta-haematin formation by pi-interactions of their corrin ring with the Fe(III)-protoporphyrin ring and by hydrogen-bonding using their 5,6-dimethylbenzimidazole/ribose/sugar side-chain. The antimalarial activity for the cobalamins (Ado-cbl>CH(3)-cbl>H(2)O-cbl>CN-cbl) was found to be less than that for chloroquine or quinine. Ado-cbl, CH(3)-cbl and CN-cbl do not accumulate in the parasite food vacuole by pH trapping, but H(2)O-cbl does. Unlike humans, the malaria parasite has only one enzyme that uses cobalamin as a cofactor, namely methionine synthase, which is important for growth and metabolism. Thus cobalamins in very small amounts are necessary for Plasmodium falciparum growth but in larger amounts they display antimalarial properties.

  10. Pathway data concerning differentiation and activation of macrophage - DMPD | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available List Contact us DMPD Pathway data concerning differentiation and activation of macrophage Data detail Data name Pathway data concern...scription of data contents Pathways concerning differentiation and activation of macrophage extracted from t...tory of This Database Site Policy | Contact Us Pathway data concerning differentiation and activation of macrophage - DMPD | LSDB Archive ...

  11. Differential actigraphy for monitoring asymmetry in upper limb motor activities.

    Science.gov (United States)

    Rabuffetti, M; Meriggi, P; Pagliari, C; Bartolomeo, P; Ferrarin, M

    2016-09-21

    Most applications of accelerometry-based actigraphy require a single sensor, properly located onto the body, to estimate, for example, the level of activity or the energy expenditure. Some approaches adopt a multi-sensor setup to improve those analyses or to classify different types of activity. The specific case of two symmetrically placed actigraphs allowing, by some kind of differential analysis, for the assessment of asymmetric motor behaviors, has been considered in relatively few studies. This article presents a novel method for differential actigraphy, which requires the synchronized measurements of two triaxial accelerometers (programmable eZ430-Chronos, Texas Instruments, USA) placed symmetrically on both wrists. The method involved the definition of a robust epoch-related activity index and its implementation on-board the adopted programmable platform. Finally, the activity recordings from both sensors allowed us to define a novel asymmetry index AR 24 h ranging from  -100% (only the left arm moves) to  +100% (only the right arm moves) with null value marking a perfect symmetrical behavior. The accuracy of the AR 24 h index was 1.3%. Round-the-clock monitoring on 31 healthy participants (20-79 years old, 10 left handed) provided for the AR 24 h reference data (range  -5% to 21%) and a fairly good correlation to the clinical handedness index (r  =  0.66, p  <  0.001). A subset of 20 participants repeated the monitoring one week apart evidencing an excellent test-retest reliability (r  =  0.70, p  <  0.001). Such figures support future applications of the methodology for the study of pathologies involving motor asymmetries, such as in patients with motor hemisyndromes and, in general, for those subjects for whom a quantification of the asymmetry in daily motor performances is required to complement laboratory tests.

  12. Bringing Nature to Schools to Promote Children's Physical Activity.

    Science.gov (United States)

    Sharma-Brymer, Vinathe; Bland, Derek

    2016-07-01

    Physical activity (PA) is essential for human health and wellbeing across all age, socioeconomic, and ethnic groups. Engagement with the natural world is a new defining criterion for enhancing the benefits of PA, particularly for children and young people. Interacting with nature benefits children's social and emotional wellbeing, develops resilience, and reduces the risk of obesity and type 2 diabetes mellitus across all population groups. Governments around the world are now recognizing the importance of children spending more active time outdoors. However, children's outdoor activities, free play, and nature-related exploration are often structured and supervised by adults due to safety concerns and risks. In this context, schools become more accessible and safe options for children to engage in PA outdoors with the presence of nature features. Research on school designs involving young children has revealed that children prefer nature-related features in school environments. Affordances in nature may increase children's interest in physically active behaviors. Given that present school campuses are designed for operational efficiency and economic reasons, there is a need to re-design schools responding to the positive role of nature on human health. If schools were re-designed to incorporate diverse natural features, children's PA and consequent health and wellbeing would likely improve markedly.

  13. Natural gold composition studied by proton activation analysis (PAA)

    International Nuclear Information System (INIS)

    Cojocaru, V.; Badica, T.; Popescu, I.V.

    2003-01-01

    The minor and trace element concentration of natural gold is essential for provenance studies of gold archaeological artifacts. In this work proton activation analysis is used in order to find what elements can be put into evidence in natural gold. For that purpose some gold nuggets from Romania were used. It was found that PAA is a good supplemental method to neutron activation analysis. (authors)

  14. MDS G(N) fast differentiation between natural and artificial gamma radiation with a new class of mobile instruments

    International Nuclear Information System (INIS)

    Katzung, W.; Bottcher, J.

    2009-01-01

    A State-of-the-Art tool used for detecting and tracking artificial gamma radiation out of a helicopter or a vehicle is the MDS G(N) - Mobile Detection System. A highly sensitive scintillation detector detects a significant artificial gamma radiation on the ground even if the helicopter is travelling at high speed. The GPS-aided system visualizes the measured values on a moveable map displayed on the screen of a notebook every second. The colours of the continuously entered points do represent adjustable alarm thresholds. This way, location and intensity of an unknown radioactive source or a radioactive contamination can be determined very quickly. The NBR-technology (Natural Background Rejection) which is used here leads to expressive measurement results differentiating between artificial and natural gamma radiation. Additional He-3 detectors allow simultaneously the detection of neutrons. The NBR principle - developed by Thermo Scientific - stands out for its very short response times. Thus, artificial radiation can be detected reliably within seconds - even when the unit is operated by untrained staff. Unlike traditional analytic measuring techniques, the NBR method is able to detect artificial radiation sources hidden or strongly shielded gamma sources clearly from the natural background radiation. The measuring range from 1 nSv/h to 20 ?Sv/h and is extended to 1 Sv/h with a Geiger Mueller counting tube. The sensitivity amounts to max. 20000 cps (referred to 1 ?Sv/h for Cs-137). The NBR- technique is well-proven and tested for: tracking hidden radiation sources, even such ones with low activity or which are shielded, detection of artificial radiation portions in the range of the natural background, reliably measuring the ambient equivalent dose rate in the range of the natural background, fast detection of artificial radioactivity out of helicopters and vehicles.(author)

  15. Epigenetic Differentiation of Natural Populations of Lilium bosniacum Associated with Contrasting Habitat Conditions.

    Science.gov (United States)

    Zoldoš, Vlatka; Biruš, Ivan; Muratovic, Edina; Šatovic, Zlatko; Vojta, Aleksandar; Robin, Odile; Pustahija, Fatima; Bogunic, Faruk; Vicic Bockor, Vedrana; Siljak-Yakovlev, Sonja

    2018-01-01

    Epigenetic variation in natural populations with contrasting habitats might be an important element, in addition to the genetic variation, in plant adaptation to environmental stress. Here, we assessed genetic, epigenetic, and cytogenetic structure of the three Lilium bosniacum populations growing on distinct habitats. One population was growing under habitual ecological conditions for this species and the other two were growing under stress associated with high altitude and serpentine soil. Amplified fragment length polymorphism and methylation-sensitive amplification polymorphism analyses revealed that the three populations did not differentiate genetically, but were clearly separated in three distinct clusters according to DNA methylation profiles. Principal coordinate analysis showed that overall epigenetic variation was closely related to habitat conditions. A new methylation-sensitive amplification polymorphism scoring approach allowed identification of mainly unmethylated (φST = 0.190) and fully CpG methylated (φST = 0.118) subepiloci playing a role in overall population differentiation, in comparison with hemimethylated sites (φST = 0.073). In addition, unusual rDNA repatterning and the presence of B chromosomes bearing 5S rDNA loci were recorded in the population growing on serpentine soil, suggesting dynamic chromosome rearrangements probably linked to global genome demethylation, which might have reactivated some mobile elements. We discuss our results considering our earlier data on morphology and leaf anatomy of several L. bosniacum populations, and suggest a possible role of epigenetics as a key element in population differentiation associated with environmental stress in these particular lily populations. © The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  16. AHR prevents human IL-1R1hi ILC3 differentiation to natural killer cells

    Science.gov (United States)

    Hughes, Tiffany; Briercheck, Edward L.; Freud, Aharon G.; Trotta, Rossana; McClory, Susan; Scoville, Steven D.; Keller, Karen; Deng, Youcai; Cole, Jordan; Harrison, Nicholas; Mao, Charlene; Zhang, Jianying; Benson, Don M.; Yu, Jianhua; Caligiuri, Michael A.

    2014-01-01

    SUMMARY Accumulating evidence indicates that human natural killer (NK) cells develop in secondary lymphoid tissue (SLT) through a so-called “stage 3” developmental intermediate minimally characterized by a CD34-CD117+CD94- immunophenotype that lacks mature NK cell function. This stage 3 population is heterogeneous, potentially composed of functionally distinct innate lymphoid cell (ILC) types that includes interleukin-1 receptor (IL-1R1) positive, IL-22-producing ILC3s. Whether human ILC3s are developmentally related to NK cells is a subject of ongoing investigation. Here we show that antagonism of the aryl hydrocarbon receptor (AHR) or silencing of AHR gene expression promotes differentiation of tonsillar IL-22-producing IL-1R1hi human ILC3s to CD56brightCD94+ IFN-gamma-producing cytolytic mature NK cells expressing eomesodermin (EOMES) and T-Box Protein 21 (TBX21 or TBET). Hence, AHR is a transcription factor that prevents human IL-1R1hi ILC3s from differentiating into NK cells. PMID:24953655

  17. THE ACTIVATION OF MATRIX METALLOPROTEINASES AND CHONDROCYTE DIFFERENTIATION, WHICH ACCOMPANIES THE INDUCTION OF COLLAGEN DECOMPOSITION UNDER THE ACTION OF COLLAGEN PEPTIDE IN THE CARTILAGE OFHEALTHY INDIVIDUALS

    Directory of Open Access Journals (Sweden)

    Elena Vasil'evna Chetina

    2010-01-01

    Conclusion. This study has shown that the induction of collagenase activity by CB12-2 in the human articular cartilage chondrocytes is attended by terminal differentiation/hypertrophy of these cells. The terminal differentiation of chondrocytes may be one of the mechanisms of chondrolysis in osteoarthrosis since it naturally occurs not only in endochondrial ossification, but also in the development of pathology.

  18. Appropriation of common access natural resources through exploration: A differential game of a claiming rush

    Energy Technology Data Exchange (ETDEWEB)

    Mohr, E

    1985-10-01

    This paper provides a model of natural resource exploration, where the sole motivation to explore arises from a strategic incentive to preempt competitors. It is assumed that private ownership rights over a finite unexplored and commonly held resource stock can be established through a costly deterministic exploration process. The open-loop and the feedback Nash equilibrium is analysed. It is shown that in between intervals of soaring exploratory activities there may be an interval where exploration is declining over time.

  19. Complementary effect of natural and sexual selection against immigrants maintains differentiation between locally adapted fish

    Science.gov (United States)

    Plath, Martin; Riesch, Rüdiger; Oranth, Alexandra; Dzienko, Justina; Karau, Nora; Schießl, Angela; Stadler, Stefan; Wigh, Adriana; Zimmer, Claudia; Arias-Rodriguez, Lenin; Schlupp, Ingo; Tobler, Michael

    2010-08-01

    Adaptation to ecologically heterogeneous environments can drive speciation. But what mechanisms maintain reproductive isolation among locally adapted populations? Using poeciliid fishes in a system with naturally occurring toxic hydrogen sulfide, we show that (a) fish from non-sulfidic sites ( Poecilia mexicana) show high mortality (95 %) after 24 h when exposed to the toxicant, while locally adapted fish from sulfidic sites ( Poecilia sulphuraria) experience low mortality (13 %) when transferred to non-sulfidic water. (b) Mate choice tests revealed that P. mexicana females exhibit a preference for conspecific males in non-sulfidic water, but not in sulfidic water, whereas P. sulphuraria females never showed a preference. Increased costs of mate choice in sulfidic, hypoxic water, and the lack of selection for reinforcement due to the low survival of P. mexicana may explain the absence of a preference in P. sulphuraria females. Taken together, our study may be the first to demonstrate independent—but complementary—effects of natural and sexual selection against immigrants maintaining differentiation between locally adapted fish populations.

  20. Differential radioprotection and free radical scavenging activity of Caesalpinia digyna extracts and the active constituent

    International Nuclear Information System (INIS)

    Singh, Umang; Kunwar, A.; Barik, A.; Priyadarsini, K.I.; Mula, S.; Srinivasan, R.

    2008-01-01

    Differential free radical activity of the fractionated extracts (F1: methanolic fraction, F2: acetone soluble fraction and F3: acetone insoluble fraction) of a medicinal plant Caesalpinia digyna, has been studied employing DPPH, superoxide radical and in vitro radioprotecting activity by following their effect on radiation induced protein carbonylation and DNA damage in pBR322. The activity for these fractions is in the order of F1>F2>F3. HPLC analysis indicated that all fractions contain high amount of bergenin, a polyhydroxy isocoumarin derivative and the fractions are more active than isolated bergenin. (author)

  1. Differential radioprotection and free radical scavenging activity of Caesalpinia digyna extracts and the active constituent

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Umang; Kunwar, A; Barik, A; Priyadarsini, K I [Radiation and Photochemistry Div., Bhabha Atomic Research Centre, Mumbai (India); Mula, S [Bio-Organic Div., Bhabha Atomic Research Centre, Mumbai (India); Srinivasan, R [JSS College of Pharmacy, Ootacamund (India)

    2008-01-15

    Differential free radical activity of the fractionated extracts (F1: methanolic fraction, F2: acetone soluble fraction and F3: acetone insoluble fraction) of a medicinal plant Caesalpinia digyna, has been studied employing DPPH, superoxide radical and in vitro radioprotecting activity by following their effect on radiation induced protein carbonylation and DNA damage in pBR322. The activity for these fractions is in the order of F1>F2>F3. HPLC analysis indicated that all fractions contain high amount of bergenin, a polyhydroxy isocoumarin derivative and the fractions are more active than isolated bergenin. (author)

  2. Influence of natural and recombinant interferons on development of antiviral condition and activity of natural killers

    International Nuclear Information System (INIS)

    Kuznetsov, V.P.; Avdeev, G.I.; Vyadro, M.M.; Leikin, Yu.D.; Frolova, I.S.

    1986-01-01

    For the purpose of a preliminary estimate of the therapeutic potential of domestic recombinant alpha 2 -component of human leukocytic interferon (rl) in vitro tests, the authors studied its ability to induce development of antiviral condition in diploid culture of human embryo fibroblasts and to activate the cytolytic effect of natural killers in relation to tumor cells, of the K-562 leukemia line and cells of lung adenocarcinoma. The authors used a medicinal form of rL which was derived by expression of a reconstructed gene in Escherichia coli cells. Part of the tests were conducted with an analogous preparation synthesized using another producer, Pseudomonas sp). The biological effect of both preparations was the same. For comparison, a natural preparation was used in all tests: human leukocytic interferon for injection, II(le). The authors studied activity of natural killers in a fraction of mononuclears isolated from blood of essentially healthy donors and from cancer patients. Cells were incubated for 2 h with various concentrations of interferons, then combined in a ratio of 25-50:1 with target cells labeled with 51 Cr. Cytotoxic reaction was conducted for 4 (4-CTR) or 18 h (18-CTR) at 37 0 C. Natural killers could thus be divided into two subpopulations: killer (4-CTR) and cytotoxic (18-CTR) cells. In preliminary tests, both preparations possessed the ability to active natural killers. The effective concentration for rL was within the limits of 1000-2000 IU/ml, and 50-200 Iu/ml for Le. The data on activation of natural killers in 16 oncological patients (primarily with lung cancer), the authors established that both rL and Le induced activation of natural killers in the overwhelming majority of cases in relation to K-562 target cells and adenocarcinomas of the lung

  3. Granivory of invasive, naturalized, and native plants in communities differentially susceptible to invasion.

    Science.gov (United States)

    Connolly, B M; Pearson, D E; Mack, R N

    2014-07-01

    Seed predation is an important biotic filter that can influence abundance and spatial distributions of native species through differential effects on recruitment. This filter may also influence the relative abundance of nonnative plants within habitats and the communities' susceptibility to invasion via differences in granivore identity, abundance, and food preference. We evaluated the effect of postdispersal seed predators on the establishment of invasive, naturalized, and native species within and between adjacent forest and steppe communities of eastern Washington, USA that differ in severity of plant invasion. Seed removal from trays placed within guild-specific exclosures revealed that small mammals were the dominant seed predators in both forest and steppe. Seeds of invasive species (Bromus tectorum, Cirsium arvense) were removed significantly less than the seeds of native (Pseudoroegneria spicata, Balsamorhiza sagittata) and naturalized (Secale cereale, Centaurea cyanus) species. Seed predation limited seedling emergence and establishment in both communities in the absence of competition in a pattern reflecting natural plant abundance: S. cereale was most suppressed, B. tectorum was least suppressed, and P. spicata was suppressed at an intermediate level. Furthermore, seed predation reduced the residual seed bank for all species. Seed mass correlated with seed removal rates in the forest and their subsequent effects on plant recruitment; larger seeds were removed at higher rates than smaller seeds. Our vegetation surveys indicate higher densities and canopy cover of nonnative species occur in the steppe compared with the forest understory, suggesting the steppe may be more susceptible to invasion. Seed predation alone, however, did not result in significant differences in establishment for any species between these communities, presumably due to similar total small-mammal abundance between communities. Consequently, preferential seed predation by small

  4. Transcription control and neuronal differentiation by agents that activate the LXR nuclear receptor family.

    Science.gov (United States)

    Schmidt, A; Vogel, R; Holloway, M K; Rutledge, S J; Friedman, O; Yang, Z; Rodan, G A; Friedman, E

    1999-09-10

    LXR and PPAR receptors belong to the nuclear receptor superfamily of transcriptional activating factors. Using ligand-dependent transcription assays, we found that 5-tetradecyloxy-2-furancarboxylic acid (TOFA) transactivates chimeric receptors composed of the glucocorticoid receptor DNA binding domain and the ligand binding regions of PPARalpha, PPARbeta (NUC-1) and LXRbeta (NER) receptors. In the same assays, ligands for PPARs (oleic acid, WY-14643 and L-631,033) and LXRs (hydroxycholesterols) maintain their respective receptor selectivity. TOFA and hydroxycholesterols also stimulate transcription from a minimal fibrinogen promoter that is under the control of AP-1 or NF-kappaB transcription factor binding sites. In addition to their effects on transcription, these LXRbeta activators induce neuronal differentiation in rat pheochromocytoma cells. TOFA and the natural LXR agonist, 22 (R)-hydroxycholesterol, stimulate neurite outgrowth in 55 and 28% of cells, respectively. No neurite outgrowth was induced by the related 22(S)-hydroxycholesterol, which does not activate the LXR family. These results suggest that the hydroxycholesterol signaling pathway has a complex effect on transcription that mediates the activity of TOFA and hydroxycholesterol on neuronal differentiation in pheochromocytoma cells.

  5. Natural Cinnamic Acids, Synthetic Derivatives and Hybrids with Antimicrobial Activity

    Directory of Open Access Journals (Sweden)

    Juan David Guzman

    2014-11-01

    Full Text Available Antimicrobial natural preparations involving cinnamon, storax and propolis have been long used topically for treating infections. Cinnamic acids and related molecules are partly responsible for the therapeutic effects observed in these preparations. Most of the cinnamic acids, their esters, amides, aldehydes and alcohols, show significant growth inhibition against one or several bacterial and fungal species. Of particular interest is the potent antitubercular activity observed for some of these cinnamic derivatives, which may be amenable as future drugs for treating tuberculosis. This review intends to summarize the literature data on the antimicrobial activity of the natural cinnamic acids and related derivatives. In addition, selected hybrids between cinnamic acids and biologically active scaffolds with antimicrobial activity were also included. A comprehensive literature search was performed collating the minimum inhibitory concentration (MIC of each cinnamic acid or derivative against the reported microorganisms. The MIC data allows the relative comparison between series of molecules and the derivation of structure-activity relationships.

  6. Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) activates promyogenic signaling pathways, thereby promoting myoblast differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang-Jin; Go, Ga-Yeon; Yoo, Miran; Kim, Yong Kee [Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Seo, Dong-Wan [College of Pharmacy, Dankook University, Cheonan 330-714 (Korea, Republic of); Kang, Jong-Sun [Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon 440-746 (Korea, Republic of); Bae, Gyu-Un, E-mail: gbae@sookmyung.ac.kr [Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of)

    2016-01-29

    Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) regulates postnatal myogenesis by alleviating myostatin activity, but the molecular mechanisms by which it regulates myogenesis are not fully understood. In this study, we investigate molecular mechanisms of PPARβ/δ in myoblast differentiation. C2C12 myoblasts treated with a PPARβ/δ agonist, GW0742 exhibit enhanced myotube formation and muscle-specific gene expression. GW0742 treatment dramatically activates promyogenic kinases, p38MAPK and Akt, in a dose-dependent manner. GW0742-stimulated myoblast differentiation is mediated by p38MAPK and Akt, since it failed to restore myoblast differentiation repressed by inhibition of p38MAPK and Akt. In addition, GW0742 treatment enhances MyoD-reporter activities. Consistently, overexpression of PPARβ/δ enhances myoblast differentiation accompanied by elevated activation of p38MAPK and Akt. Collectively, these results suggest that PPARβ/δ enhances myoblast differentiation through activation of promyogenic signaling pathways. - Highlights: • A PPARβ/δ agonist, GW0742 promotes myoblast differentiation. • GW0742 activates both p38MAPK and Akt activation in myogenic differentiation. • GW0742 enhances MyoD activity for myogenic differentiation. • Overexpression of PPARβ/δ enhances myoblast differentiation via activating promyogenic signaling pathways. • This is the first finding for agonistic mechanism of PPARβ/δ in myogenesis.

  7. Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) activates promyogenic signaling pathways, thereby promoting myoblast differentiation

    International Nuclear Information System (INIS)

    Lee, Sang-Jin; Go, Ga-Yeon; Yoo, Miran; Kim, Yong Kee; Seo, Dong-Wan; Kang, Jong-Sun; Bae, Gyu-Un

    2016-01-01

    Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) regulates postnatal myogenesis by alleviating myostatin activity, but the molecular mechanisms by which it regulates myogenesis are not fully understood. In this study, we investigate molecular mechanisms of PPARβ/δ in myoblast differentiation. C2C12 myoblasts treated with a PPARβ/δ agonist, GW0742 exhibit enhanced myotube formation and muscle-specific gene expression. GW0742 treatment dramatically activates promyogenic kinases, p38MAPK and Akt, in a dose-dependent manner. GW0742-stimulated myoblast differentiation is mediated by p38MAPK and Akt, since it failed to restore myoblast differentiation repressed by inhibition of p38MAPK and Akt. In addition, GW0742 treatment enhances MyoD-reporter activities. Consistently, overexpression of PPARβ/δ enhances myoblast differentiation accompanied by elevated activation of p38MAPK and Akt. Collectively, these results suggest that PPARβ/δ enhances myoblast differentiation through activation of promyogenic signaling pathways. - Highlights: • A PPARβ/δ agonist, GW0742 promotes myoblast differentiation. • GW0742 activates both p38MAPK and Akt activation in myogenic differentiation. • GW0742 enhances MyoD activity for myogenic differentiation. • Overexpression of PPARβ/δ enhances myoblast differentiation via activating promyogenic signaling pathways. • This is the first finding for agonistic mechanism of PPARβ/δ in myogenesis.

  8. Erk1 positively regulates osteoclast differentiation and bone resorptive activity.

    Directory of Open Access Journals (Sweden)

    Yongzheng He

    Full Text Available The extracellular signal-regulated kinases (ERK1 and 2 are widely-expressed and they modulate proliferation, survival, differentiation, and protein synthesis in multiple cell lineages. Altered ERK1/2 signaling is found in several genetic diseases with skeletal phenotypes, including Noonan syndrome, Neurofibromatosis type 1, and Cardio-facio-cutaneous syndrome, suggesting that MEK-ERK signals regulate human skeletal development. Here, we examine the consequence of Erk1 and Erk2 disruption in multiple functions of osteoclasts, specialized macrophage/monocyte lineage-derived cells that resorb bone. We demonstrate that Erk1 positively regulates osteoclast development and bone resorptive activity, as genetic disruption of Erk1 reduced osteoclast progenitor cell numbers, compromised pit formation, and diminished M-CSF-mediated adhesion and migration. Moreover, WT mice reconstituted long-term with Erk1(-/- bone marrow mononuclear cells (BMMNCs demonstrated increased bone mineral density as compared to recipients transplanted with WT and Erk2(-/- BMMNCs, implicating marrow autonomous, Erk1-dependent osteoclast function. These data demonstrate Erk1 plays an important role in osteoclast functions while providing rationale for the development of Erk1-specific inhibitors for experimental investigation and/or therapeutic modulation of aberrant osteoclast function.

  9. Bioactive activities of natural products against herpesvirus infection.

    Science.gov (United States)

    Son, Myoungki; Lee, Minjung; Sung, Gi-Ho; Lee, Taeho; Shin, Yu Su; Cho, Hyosun; Lieberman, Paul M; Kang, Hyojeung

    2013-10-01

    More than 90% of adults have been infected with at least one human herpesvirus, which establish long-term latent infection for the life of the host. While anti-viral drugs exist that limit herpesvirus replication, many of these are ineffective against latent infection. Moreover, drug-resistant strains of herpesvirus emerge following chemotherapeutic treatment. For example, resistance to acyclovir and related nucleoside analogues can occur when mutations arise in either HSV thymidine kinase or DNA polymerases. Thus, there exists an unmet medical need to develop new anti-herpesvirus agents with different mechanisms of action. In this Review, we discuss the promise of anti-herpetic substances derived from natural products including extracts and pure compounds from potential herbal medicines. One example is Glycyrrhizic acid isolated from licorice that shows promising antiviral activity towards human gammaherpesviruses. Secondly, we discuss anti-herpetic mechanisms utilized by several natural products in molecular level. While nucleoside analogues inhibit replicating herpesviruses in lytic replication, some natural products can disrupt the herpesvirus latent infection in the host cell. In addition, natural products can stimulate immune responses against herpesviral infection. These findings suggest that natural products could be one of the best choices for development of new treatments for latent herpesvirus infection, and may provide synergistic anti-viral activity when supplemented with nucleoside analogues. Therefore, it is important to identify which natural products are more efficacious anti-herpetic agents, and to understand the molecular mechanism in detail for further advance in the anti-viral therapies.

  10. Peroxisome Proliferator-Activated Receptor Gamma Negatively Regulates the Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells Toward Myofibroblasts in Liver Fibrogenesis

    Directory of Open Access Journals (Sweden)

    Shuangshuang Jia

    2015-11-01

    Full Text Available Background/Aims: Bone marrow-derived mesenchymal stem cells (BMSCs have been confirmed to have capacity to differentiate toward hepatic myofibroblasts, which contribute to fibrogenesis in chronic liver diseases. Peroxisome proliferator-activated receptor gamma (PPARγ, a ligand-activated transcription factor, has gained a great deal of recent attention as it is involved in fibrosis and cell differentiation. However, whether it regulates the differentiation of BMSCs toward myofibroblasts remains to be defined. Methods: Carbon tetrachloride or bile duct ligation was used to induce mouse liver fibrosis. Expressions of PPARγ, α-smooth muscle actin, collagen α1 (I and collagen α1 (III were detected by real-time RT-PCR and Western blot or immunofluorescence assay. Results: PPARγ expression was decreased in mouse fibrotic liver. In addition, PPARγ was declined during the differentiation of BMSCs toward myofibroblasts induced by transforming growth factor β1. Activation of PPARγ stimulated by natural or synthetic ligands suppressed the differentiation of BMSCs. Additionally, knock down of PPARγ by siRNA contributed to BMSC differentiation toward myofibroblasts. Furthermore, PPARγ activation by natural ligand significantly inhibited the differentiation of BMSCs toward myofibroblasts in liver fibrogenesis and alleviated liver fibrosis. Conclusions: PPARγ negatively regulates the differentiation of BMSCs toward myofibroblasts, which highlights a further mechanism implicated in the BMSC differentiation.

  11. Microbial activities in soil near natural gas leaks

    Energy Technology Data Exchange (ETDEWEB)

    Adamse, A D; Hoeks, J; de Bont, J A.M.; van Kessel, J F

    1972-01-01

    From the present experiments it may be concluded that in the surroundings of natural gas leaks, methane, ethane and possibly some other components of the natural gas are oxidized by microbial activities as long as oxygen is available. This is demonstrated by an increased oxygen consumption and carbon dioxide production, as well as by increased numbers of different types of bacteria. The resulting deficiency of oxygen, the excess of carbon dioxide, and perhaps the formation of inhibitory amounts of ethylene, are considered to be mainly responsible for the death of trees near natural gas leaks. Also the long period of time needed by the soil to recover, may be due to prolonged microbial activities, as well as to the presence of e.g. ethylene. The present experiments suggest that especially methane-oxidizing bacteria of the Methylosinus trichosporium type were present in predominating numbers and consequently have mainly been responsible for the increased oxygen consumption. However, some fungi oxidizing components of natural gas, including methane and ethane may also have contributed to the increased microbial activities in the soil. The same will be true of a possible secondary microflora on products derived from microorganisms oxidizing natural gas components. 12 references, 9 figures, 7 tables.

  12. Natural gas storage with activated carbon from a bituminous coal

    Science.gov (United States)

    Sun, Jielun; Rood, M.J.; Rostam-Abadi, M.; Lizzio, A.A.

    1996-01-01

    Granular activated carbons ( -20 + 100 mesh; 0.149-0.84 mm) were produced by physical activation and chemical activation with KOH from an Illinois bituminous coal (IBC-106) for natural gas storage. The products were characterized by BET surface area, micropore volume, bulk density, and methane adsorption capacities. Volumetric methane adsorption capacities (Vm/Vs) of some of the granular carbons produced by physical activation are about 70 cm3/cm3 which is comparable to that of BPL, a commercial activated carbon. Vm/Vs values above 100 cm3/cm3 are obtainable by grinding the granular products to - 325 mesh (activated carbons, granular carbons produced by KOH activation have higher micropore volume and higher methane adsorption capacities (g/g). Their volumetric methane adsorption capacities are lower due to their lower bulk densities. Copyright ?? 1996 Elsevier Science Ltd.

  13. Catalytic Synthesis and Antifungal Activity of New Polychlorinated Natural Terpenes

    Directory of Open Access Journals (Sweden)

    Hana Ighachane

    2017-01-01

    Full Text Available Various unsaturated natural terpenes were selectively converted to the corresponding polychlorinated products in good yields using iron acetylacetonate in combination with nucleophilic cocatalyst. The synthesized compounds were evaluated for their in vitro antifungal activity. The antifungal bioassays showed that 2c and 2d possessed significant antifungal activity against Fusarium oxysporum f. sp. albedinis (Foa, Fusarium oxysporum f. sp. canariensis (Foc, and Verticillium dahliae (Vd.

  14. Do people differentiate between intrinsic and extrinsic goals for physical activity?

    Science.gov (United States)

    McLachlan, Sarah; Hagger, Martin S

    2011-04-01

    The distinction between intrinsic and extrinsic goals, and between goal pursuit for intrinsically and extrinsically motivated reasons, is a central premise of self-determination theory. Proponents of the theory have proposed that the pursuit of intrinsic goals and intrinsically motivated goal striving each predict adaptive psychological and behavioral outcomes relative to the pursuit of extrinsic goals and extrinsically motivated goal striving. Despite evidence to support these predictions, research has not explored whether individuals naturally differentiate between intrinsic and extrinsic goals. Two studies tested whether people make this differentiation when recalling goals for leisure-time physical activity. Using memory-recall methods, participants in Study 1 were asked to freely generate physical activity goals. A subsample (N = 43) was asked to code their freely generated goals as intrinsic or extrinsic. In Study 2, participants were asked to recall intrinsic and extrinsic goals after making a decision regarding their future physical activity. Results of these studies revealed that individuals' goal generation and recall exhibited significant clustering by goal type. Participants encountered some difficulties when explicitly coding goals. Findings support self-determination theory and indicate that individuals discriminate between intrinsic and extrinsic goals.

  15. Novel Differential Measurement of Natural and Added Phosphorus in Preserved versus Non-Enhanced Ham

    Science.gov (United States)

    Cupisti, Adamasco; Benini, Omar; Ferretti, Valerio; Gianfaldoni, Daniela; Kalantar-Zadeh, Kamyar

    2018-01-01

    Accurate assessment of the quantity and chemical type of phosphorus (P) content in processed meat products may have major clinical implications for management of kidney disease patients. We examined 40 lots of cooked ham including 20 without and 20 with P-containing preservatives. Novel spectro-photometrical methods were employed to measure total P and 3 different P subtypes, i.e., water-soluble (inorganic) P including added preservatives and natural P derived from phospholipids and phosphoproteins separately. Total Nitrogen and fat contents were assayed, as well. There was 66% more inorganic P in preserved vs. non-enhanced ham, i.e., 169±36 vs. 102±16 mg/100g (p0.05), indicating a small portion of unspecified P and/or undermeasurement Novel differential dietary P measurement detects added P-containing preservatives. Processed cooked ham has 66% more measurable inorganic P and 64% higher P-to-protein ratio than non-enhanced product. The contribution of processed food to global dietary phosphorus burden can negatively influence CKD outcome and counteract the efficacy of P-binder medications. PMID:22406120

  16. Spectral-Spatial Differentiation of Brain Activity During Mental Imagery of Improvisational Music Performance Using MEG

    Science.gov (United States)

    Boasen, Jared; Takeshita, Yuya; Kuriki, Shinya; Yokosawa, Koichi

    2018-01-01

    Group musical improvisation is thought to be akin to conversation, and therapeutically has been shown to be effective at improving communicativeness, sociability, creative expression, and overall psychological health. To understand these therapeutic effects, clarifying the nature of brain activity during improvisational cognition is important. Some insight regarding brain activity during improvisational music cognition has been gained via functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). However, we have found no reports based on magnetoencephalography (MEG). With the present study, we aimed to demonstrate the feasibility of improvisational music performance experimentation in MEG. We designed a novel MEG-compatible keyboard, and used it with experienced musicians (N = 13) in a music performance paradigm to spectral-spatially differentiate spontaneous brain activity during mental imagery of improvisational music performance. Analyses of source activity revealed that mental imagery of improvisational music performance induced greater theta (5–7 Hz) activity in left temporal areas associated with rhythm production and communication, greater alpha (8–12 Hz) activity in left premotor and parietal areas associated with sensorimotor integration, and less beta (15–29 Hz) activity in right frontal areas associated with inhibition control. These findings support the notion that musical improvisation is conversational, and suggest that creation of novel auditory content is facilitated by a more internally-directed, disinhibited cognitive state. PMID:29740300

  17. Spectral-Spatial Differentiation of Brain Activity During Mental Imagery of Improvisational Music Performance Using MEG.

    Science.gov (United States)

    Boasen, Jared; Takeshita, Yuya; Kuriki, Shinya; Yokosawa, Koichi

    2018-01-01

    Group musical improvisation is thought to be akin to conversation, and therapeutically has been shown to be effective at improving communicativeness, sociability, creative expression, and overall psychological health. To understand these therapeutic effects, clarifying the nature of brain activity during improvisational cognition is important. Some insight regarding brain activity during improvisational music cognition has been gained via functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). However, we have found no reports based on magnetoencephalography (MEG). With the present study, we aimed to demonstrate the feasibility of improvisational music performance experimentation in MEG. We designed a novel MEG-compatible keyboard, and used it with experienced musicians ( N = 13) in a music performance paradigm to spectral-spatially differentiate spontaneous brain activity during mental imagery of improvisational music performance. Analyses of source activity revealed that mental imagery of improvisational music performance induced greater theta (5-7 Hz) activity in left temporal areas associated with rhythm production and communication, greater alpha (8-12 Hz) activity in left premotor and parietal areas associated with sensorimotor integration, and less beta (15-29 Hz) activity in right frontal areas associated with inhibition control. These findings support the notion that musical improvisation is conversational, and suggest that creation of novel auditory content is facilitated by a more internally-directed, disinhibited cognitive state.

  18. Spectral-Spatial Differentiation of Brain Activity During Mental Imagery of Improvisational Music Performance Using MEG

    Directory of Open Access Journals (Sweden)

    Jared Boasen

    2018-04-01

    Full Text Available Group musical improvisation is thought to be akin to conversation, and therapeutically has been shown to be effective at improving communicativeness, sociability, creative expression, and overall psychological health. To understand these therapeutic effects, clarifying the nature of brain activity during improvisational cognition is important. Some insight regarding brain activity during improvisational music cognition has been gained via functional magnetic resonance imaging (fMRI and electroencephalography (EEG. However, we have found no reports based on magnetoencephalography (MEG. With the present study, we aimed to demonstrate the feasibility of improvisational music performance experimentation in MEG. We designed a novel MEG-compatible keyboard, and used it with experienced musicians (N = 13 in a music performance paradigm to spectral-spatially differentiate spontaneous brain activity during mental imagery of improvisational music performance. Analyses of source activity revealed that mental imagery of improvisational music performance induced greater theta (5–7 Hz activity in left temporal areas associated with rhythm production and communication, greater alpha (8–12 Hz activity in left premotor and parietal areas associated with sensorimotor integration, and less beta (15–29 Hz activity in right frontal areas associated with inhibition control. These findings support the notion that musical improvisation is conversational, and suggest that creation of novel auditory content is facilitated by a more internally-directed, disinhibited cognitive state.

  19. The nature of the active site in heterogeneous metal catalysis

    DEFF Research Database (Denmark)

    Nørskov, Jens Kehlet; Bligaard, Thomas; Larsen, Britt Hvolbæk

    2008-01-01

    This tutorial review, of relevance for the surface science and heterogeneous catalysis communities, provides a molecular-level discussion of the nature of the active sites in metal catalysis. Fundamental concepts such as "Bronsted-Evans-Polanyi relations'' and "volcano curves'' are introduced...

  20. Using Physical Activity for Emotional Recovery after a Natural Disaster

    Science.gov (United States)

    Wahl-Alexander, Zachary; Sinelnikov, Oleg A.

    2013-01-01

    After traumatic events, such as a natural disaster, children who are directly or indirectly affected by the event often have a number of intense emotional reactions. It is important for educators to understand common emotional and psychological responses to disastrous events and to try to help. This article describes a physical activity program…

  1. Active-constructive-interactive: a conceptual framework for differentiating learning activities.

    Science.gov (United States)

    Chi, Michelene T H

    2009-01-01

    Active, constructive, and interactive are terms that are commonly used in the cognitive and learning sciences. They describe activities that can be undertaken by learners. However, the literature is actually not explicit about how these terms can be defined; whether they are distinct; and whether they refer to overt manifestations, learning processes, or learning outcomes. Thus, a framework is provided here that offers a way to differentiate active, constructive, and interactive in terms of observable overt activities and underlying learning processes. The framework generates a testable hypothesis for learning: that interactive activities are most likely to be better than constructive activities, which in turn might be better than active activities, which are better than being passive. Studies from the literature are cited to provide evidence in support of this hypothesis. Moreover, postulating underlying learning processes allows us to interpret evidence in the literature more accurately. Specifying distinct overt activities for active, constructive, and interactive also offers suggestions for how learning activities can be coded and how each kind of activity might be elicited. Copyright © 2009 Cognitive Science Society, Inc.

  2. Active Sensing Air Pressure Using Differential Absorption Barometric Radar

    Science.gov (United States)

    Lin, B.

    2016-12-01

    Tropical storms and other severe weathers cause huge life losses and property damages and have major impacts on public safety and national security. Their observations and predictions need to be significantly improved. This effort tries to develop a feasible active microwave approach that measures surface air pressure, especially over open seas, from space using a Differential-absorption BArometric Radar (DiBAR) operating at 50-55 GHz O2 absorption band in order to constrain assimilated dynamic fields of numerical weather Prediction (NWP) models close to actual conditions. Air pressure is the most important variable that drives atmospheric dynamics, and currently can only be measured by limited in-situ observations over oceans. Even over land there is no uniform coverage of surface air pressure measurements. Analyses show that with the proposed space radar the errors in instantaneous (averaged) pressure estimates can be as low as 4mb ( 1mb) under all weather conditions. NASA Langley research team has made substantial progresses in advancing the DiBAR concept. The feasibility assessment clearly shows the potential of surface barometry using existing radar technologies. The team has also developed a DiBAR system design, fabricated a Prototype-DiBAR (P-DiBAR) for proof-of-concept, conducted laboratory, ground and airborne P-DiBAR tests. The flight test results are consistent with the instrumentation goals. The precision and accuracy of radar surface pressure measurements are within the range of the theoretical analysis of the DiBAR concept. Observational system simulation experiments for space DiBAR performance based on the existing DiBAR technology and capability show substantial improvements in tropical storm predictions, not only for the hurricane track and position but also for the hurricane intensity. DiBAR measurements will provide us an unprecedented level of the prediction and knowledge on global extreme weather and climate conditions.

  3. Bilobalide induces neuronal differentiation of P19 embryonic carcinoma cells via activating Wnt/β-catenin pathway.

    Science.gov (United States)

    Liu, Mei; Guo, Jingjing; Wang, Juan; Zhang, Luyong; Pang, Tao; Liao, Hong

    2014-08-01

    Bilobalide, a natural product extracted from Ginkgo biloba leaf, is known to exhibit a number of pharmacological activities. So far, whether it could affect embryonic stem cell differentiation is still unknown. The main aim of this study was to investigate the effect of bilobalide on P19 embryonic carcinoma cells differentiation and the underlying mechanisms. Our results showed that bilobalide induced P19 cells differentiation into neurons in a concentration- and time-dependent manner. We also found that bilobalide promoted neuronal differentiation through activation of Wnt/β-catenin signaling pathway. Exposure to bilobalide increased inactive GSK-3β phosphorylation, further induced the nuclear accumulation of β-catenin, and also up-regulated the expression of Wnt ligands Wnt1 and Wnt7a. Neuronal differentiation induced by bilobalide was totally abolished by XAV939, an inhibitor of Wnt/β-catenin pathway. These results revealed a novel role of bilobalide in neuronal differentiation from P19 embryonic cells acting through Wnt/β-catenin signaling pathway, which would provide a better insight into the beneficial effects of bilobalide in brain diseases.

  4. Determination of the binding mode for anti-inflammatory natural product xanthohumol with myeloid differentiation protein 2

    Directory of Open Access Journals (Sweden)

    Fu W

    2016-01-01

    Full Text Available Weitao Fu,1,* Lingfeng Chen,1,* Zhe Wang,1 Chengwei Zhao,1 Gaozhi Chen,1 Xing Liu,1 Yuanrong Dai,2 Yuepiao Cai,1 Chenglong Li,1,3 Jianmin Zhou,1 Guang Liang1 1Chemical Biology Research Center, School of Pharmaceutical Sciences, 2Department of Respiratory Medicine, the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Ohio State University, Columbus, OH, USA *These authors contributed equally to this work Abstract: It is recognized that myeloid differentiation protein 2 (MD-2, a coreceptor of toll-like receptor 4 (TLR4 for innate immunity, plays an essential role in activation of the lipopolysaccharide signaling pathway. MD-2 is known as a neoteric and suitable therapeutical target. Therefore, there is great interest in the development of a potent MD-2 inhibitor for anti-inflammatory therapeutics. Several studies have reported that xanthohumol (XN, an anti-inflammatory natural product from hops and beer, can block the TLR4 signaling by binding to MD-2 directly. However, the interaction between MD-2 and XN remains unknown. Herein, our work aims at characterizing interactions between MD-2 and XN. Using a combination of experimental and theoretical modeling analysis, we found that XN can embed into the hydrophobic pocket of MD-2 and form two stable hydrogen bonds with residues ARG-90 and TYR-102 of MD-2. Moreover, we confirmed that ARG-90 and TYR-102 were two necessary residues during the recognition process of XN binding to MD-2. Results from this study identified the atomic interactions between the MD-2 and XN, which will contribute to future structural design of novel MD-2-targeting molecules for the treatment of inflammatory diseases. Keywords: myeloid differentiation 2, xanthohumol, binding mode, inflammation, molecular dynamics simulation 

  5. An Update on Antitumor Activity of Naturally Occurring Chalcones

    Directory of Open Access Journals (Sweden)

    En-Hui Zhang

    2013-01-01

    Full Text Available Chalcones, which have characteristic 1,3-diaryl-2-propen-1-one skeleton, are mainly produced in roots, rhizomes, heartwood, leaves, and seeds of genera Angelica, Sophora, Glycyrrhiza, Humulus, Scutellaria, Parartocarpus, Ficus, Dorstenia, Morus, Artocarpus, and so forth. They have become of interest in the research and development of natural antitumor agents over the past decades due to their broad range of mechanisms including anti-initiation, induction of apoptosis, antiproliferation, antimetastasis, antiangiogenesis, and so forth. This review summarizes the studies on the antitumor activity of naturally occurring chalcones and their underlying mechanisms in detail during the past decades.

  6. Differential Effects of Naja naja atra Venom on Immune Activity

    Directory of Open Access Journals (Sweden)

    Jian-Qun Kou

    2014-01-01

    Full Text Available Previous studies reported that Naja naja atra venom (NNAV inhibited inflammation and adjuvant arthritis. Here we investigated the role of NNAV in regulation of immune responses in mice. Oral administration of NNAV to normal mice showed significant increase in natural killer cell activity, B lymphocyte proliferation stimulated by lipopolysaccharides, and antibody production in response to sheep red blood cells. Meanwhile, NNAV markedly decreased T lymphocyte proliferation stimulated by concanavalin A, arrested the cell cycle at G0/G1 phase, and suppressed CD4 and CD8 T cell divisions. Furthermore, NNAV inhibited the dinitrofluorobenzene-induced delayed-type hypersensitivity reaction. This modulation of immune responses may be partly attributed to the selective increase in Th1 and Th2 cytokines (IFN-γ, IL-4 secretion and inhibition of Th17 cytokine (IL-17 production. In dexamethasone-induced immunosuppressed mice, NNAV restored the concentration of serum IgG and IgM, while decreasing the percentage of CD4 and CD8 T-cell subsets. These results indicate that NNAV enhances the innate and humoral immune responses while inhibiting CD4 Th17 and CD8 T cell actions, suggesting that NNAV could be a potential therapeutic agent for autoimmune diseases.

  7. Patterns of population differentiation and natural selection on the celiac disease background risk network.

    Science.gov (United States)

    Sams, Aaron; Hawks, John

    2013-01-01

    Celiac disease is a common small intestinal inflammatory condition induced by wheat gluten and related proteins from rye and barley. Left untreated, the clinical presentation of CD can include failure to thrive, malnutrition, and distension in juveniles. The disease can additionally lead to vitamin deficiencies, anemia, and osteoporosis. Therefore, CD potentially negatively affected fitness in past populations utilizing wheat, barley, and rye. Previous analyses of CD risk variants have uncovered evidence for positive selection on some of these loci. These studies also suggest the possibility that risk for common autoimmune conditions such as CD may be the result of positive selection on immune related loci in the genome to fight infection. Under this evolutionary scenario, disease phenotypes may be a trade-off from positive selection on immunity. If this hypothesis is generally true, we can expect to find a signal of natural selection when we survey across the network of loci known to influence CD risk. This study examines the non-HLA autosomal network of gene loci associated with CD risk in Europe. We reject the null hypothesis of neutrality on this network of CD risk loci. Additionally, we can localize evidence of selection in time and space by adding information from the genome of the Tyrolean Iceman. While we can show significant differentiation between continental regions across the CD network, the pattern of evidence is not consistent with primarily recent (Holocene) selection across this network in Europe. Further localization of ancient selection on this network may illuminate the ecological pressures acting on the immune system during this critically interesting phase of our evolution.

  8. Patterns of population differentiation and natural selection on the celiac disease background risk network.

    Directory of Open Access Journals (Sweden)

    Aaron Sams

    Full Text Available Celiac disease is a common small intestinal inflammatory condition induced by wheat gluten and related proteins from rye and barley. Left untreated, the clinical presentation of CD can include failure to thrive, malnutrition, and distension in juveniles. The disease can additionally lead to vitamin deficiencies, anemia, and osteoporosis. Therefore, CD potentially negatively affected fitness in past populations utilizing wheat, barley, and rye. Previous analyses of CD risk variants have uncovered evidence for positive selection on some of these loci. These studies also suggest the possibility that risk for common autoimmune conditions such as CD may be the result of positive selection on immune related loci in the genome to fight infection. Under this evolutionary scenario, disease phenotypes may be a trade-off from positive selection on immunity. If this hypothesis is generally true, we can expect to find a signal of natural selection when we survey across the network of loci known to influence CD risk. This study examines the non-HLA autosomal network of gene loci associated with CD risk in Europe. We reject the null hypothesis of neutrality on this network of CD risk loci. Additionally, we can localize evidence of selection in time and space by adding information from the genome of the Tyrolean Iceman. While we can show significant differentiation between continental regions across the CD network, the pattern of evidence is not consistent with primarily recent (Holocene selection across this network in Europe. Further localization of ancient selection on this network may illuminate the ecological pressures acting on the immune system during this critically interesting phase of our evolution.

  9. Natural polysaccharides as active biomaterials in nanostructured films for sensing.

    Science.gov (United States)

    Eiras, Carla; Santos, Amanda C; Zampa, Maysa F; de Brito, Ana Cristina Facundo; Leopoldo Constantino, Carlos J; Zucolotto, Valtencir; dos Santos, José R

    2010-01-01

    The search for natural, biocompatible and degradable materials amenable to be used in biomedical/analytical applications has attracted attention, either from the environmental or medical point of view. Examples are the polysaccharides extracted from natural gums, which have found applications in the food and pharmaceutical industries as stabilizers or thickening agent. In a previous paper, however, it was shown that a Brazilian natural gum, chicha (Sterculia striata), is suitable for application as building block for nanostructured film fabrication in conjunction with phthalocyanines. The films displayed electroactivity and could be used in sensing. In the present paper, we introduce the use of two different natural gums, viz., angico (Anadenanthera colubrina) and caraia (Sterculia urens), as active biomaterials to be used to modification layers, in the form of nanostructured thin films, including the study of dopamine detection. The multilayer films were assembled in conjunction with nickel tetrasulfonated phthalocyanines (NiTsPC) and displayed good chemical and electrochemical stability, allowing their use as transducer elements in sensors for detection of specific neurotransmitters. It is suggested here that nanoscale manipulation of new biodegradable natural polymers opens up a variety of new opportunities for the use of these materials in advanced biomedical and analytical devices.

  10. Regulation of Th1 and Th17 cell differentiation and amelioration of experimental autoimmune encephalomyelitis by natural product compound berberine.

    Science.gov (United States)

    Qin, Xia; Guo, Bingshi T; Wan, Bing; Fang, Lei; Lu, Limin; Wu, Lili; Zang, Ying Qin; Zhang, Jingwu Z

    2010-08-01

    Berberine (BBR), an isoquinoline alkaloid derived from plants, is widely used as an anti-inflammatory remedy in traditional Chinese medicine. In this study, we showed that BBR was efficacious in the amelioration of experimental autoimmune encephalomyelitis (EAE) through novel regulatory mechanisms involving pathogenic Th1 and Th17 cells. BBR inhibited differentiation of Th17 cells and, to a lesser degree, Th1 cells through direct actions on the JAK/STAT pathway, whereas it had no effect on the relative number of CD4(+)Foxp3(+) regulatory T cells. In addition, BBR indirectly influenced Th17 and Th1 cell functions through its effect on the expression and function of costimulatory molecules and the production of IL-6, which was attributable to the inhibition of NF-kappaB activity in CD11b(+) APCs. BBR treatment completely abolished the encephalitogenicity of MOG(35-55)-reactive Th17 cells in an adoptive transfer EAE model, and the same treatment significantly inhibited the ability of MOG(35-55)-reactive Th1 cells to induce EAE. This study provides new evidence that natural compounds, such as BBR, are of great value in the search for novel anti-inflammatory agents and therapeutic targets for autoimmune diseases.

  11. Neutron-activation analysis of natural water applied to hydrogeology

    Energy Technology Data Exchange (ETDEWEB)

    Landstroem, O [AB Atomenergi, Stockholm (Sweden); Wenner, C G [Stockholm Univ. (Sweden). Dept. of Quaternary Research

    1965-12-15

    The natural content of elements in water has been utilized to characterize different groundwater supplies and reveal the presence of groundwater streams. A neutron-activation method including chemical group separation techniques has been used for the determination of trace elements. Analyzed water samples from three different places in northern Sweden illustrate the application to common and important hydrogeological problems, such as the quality and capacity of water supplies, the origin and existence of groundwater streams and groundwater exchange with rivers.

  12. Neutron-activation analysis of natural water applied to hydrogeology

    International Nuclear Information System (INIS)

    Landstroem, O.; Wenner, C.G.

    1965-12-01

    The natural content of elements in water has been utilized to characterize different groundwater supplies and reveal the presence of groundwater streams. A neutron-activation method including chemical group separation techniques has been used for the determination of trace elements. Analyzed water samples from three different places in northern Sweden illustrate the application to common and important hydrogeological problems, such as the quality and capacity of water supplies, the origin and existence of groundwater streams and groundwater exchange with rivers

  13. Electrochemical Behavior and Antioxidant and Prooxidant Activity of Natural Phenolics

    Directory of Open Access Journals (Sweden)

    Marija Todorović

    2007-10-01

    Full Text Available We have investigated the electrochemical oxidation of a number natural phenolics (salicylic acid, m-hydroxybenzoic acid, p-hydroxybenzoic acid, protocatechuic acid, o-coumaric acid, m-coumaric acid, p-coumaric acid, caffeic acid, quercetin and rutin using cyclic voltammetry. The antioxidant properties of these compounds were also studied. A structural analysis of the tested phenolics suggests that multiple OH substitution and conjugation are important determinants of the free radical scavenging activity and electrochemical behavior. Compounds with low oxidation potentials (Epa lower than 0.45 showed antioxidant activity, whereas compounds with high Epa values (>0.45 act as prooxidants.

  14. Activation of Natural Killer cells during microbial infections

    Directory of Open Access Journals (Sweden)

    Amir eHorowitz

    2012-01-01

    Full Text Available Natural killer (NK cells are large granular lymphocytes that express a diverse array of germline encoded inhibitory and activating receptors for MHC Class I and Class I-like molecules, classical co-stimulatory ligands and cytokines. The ability of NK cells to be very rapidly activated by inflammatory cytokines, to secrete effector cytokines and to kill infected or stressed host cells, suggests that they may be among the very early responders during infection. Recent studies have also identified a small number of pathogen-derived ligands that can bind to NK cell surface receptors and directly induce their activation. Here we review recent studies that have begun to elucidate the various pathways by which viral, bacterial and parasite pathogens activate NK cells. We also consider two emerging themes of NK cell-pathogen interactions, namely their contribution to adaptive immune responses and their potential to take on regulatory and immunomodulatory functions.

  15. Determination of antioxidant activity of spices and their active principles by differential pulse voltammetry.

    Science.gov (United States)

    Palma, Alberto; Ruiz Montoya, Mercedes; Arteaga, Jesús F; Rodríguez Mellado, Jose M

    2014-01-22

    The anodic oxidation of mercury in the presence of hydrogen peroxide in differential pulse voltammetry (DPV) was used to determine the antioxidant (AO) character of radical scavengers. Hydroperoxide radical is formed at the potentials of the oxidation peak on mercury electrodes, such radical reacting with the antioxidants in different extension. The parameter C10 (antioxidant concentration at which the peak area decreases by 10%) is used to measure the scavenging activity of the individual antioxidants. To establish the scavenging activity of antioxidant mixtures as a whole, the parameter, μ10 as the reverse of V10, V10 being the volume necessary to decrease the peak area in DPV by 10%, was selected. Higher μ10 values correspond to higher scavenging activity. The studies have been extended to aqueous extracts of some species. The results may be useful in explaining the effect of spices in vitro and in vivo studies.

  16. Behaviour of natural radionuclides on activated carbon filter

    International Nuclear Information System (INIS)

    Haberer, K.; Akkermann-Kubillus, A.; Dahlheimer, A.

    1998-01-01

    To investigate the behaviour of radon in adsorption/desorption processes at filter systems based on different activated carbon types, measurements were focused on adsorption capacity, adsorption velocity, retain capability, interaction with ions (poisoning of active centers) and adsorption of radon daughters. Various activated carbon types derived from hard coal, brown coal, peat and wood, were used in adsorption tests runs with activated carbons which are applied in water treatment facilities. In laboratory tests, water facility filter conditions were simulated using pilot plant columns filled with different carbon types. A small scale laboratory column was installed at a natural water source with elevated activity. Tests runs were conducted under varying flow rates and with different amounts of carbon. A full-scale waterworks filter system operated for 6 months was investigated for radon decay products adsorbed on the carbon. The main results observed were: 1. The amount of radioactivity adsorbed depends upon the type of carbon, its granular size and the contact time between the activated carbon and water. The decontamination capacity was between 19% and 94%. 2. The DOC-levels of water influences the adsorbable radioactivity due to the poisoning of the active centers of the carbon. The adsorption velocity decreased down to 15%. 3. The maximum decontamination rate of the water under waterworks conditions was 60%. (orig.) [de

  17. Biomass, energy and economic and natural resource differentiation in rural southern India

    International Nuclear Information System (INIS)

    Bhagavan, M.R.; Giriappa, S.

    1995-01-01

    The rural economy in India is as yet only partially monetized and continues to retain its semi-subsistence character, while at the same time undergoing the process of becoming more monetized and market-orientated. A large field study was conducted in rural Karnataka, a state in southern India, which uncovers the relations between the energy situations of the rural social classes and their access to labour, land, cash and physical assets. Of equal significance are regional variations in ecology, rainfall and irrigation. The study's principal focus is the rural household, but it also includes some analysis of the energy dimensions in agricultural activities and small-scale rural services. Eight villages were covered by the survey, one in each district, carefully selected to reflect the geographic, climatic, biomass-resource and socio-economic features of Karnataka. In each village an average of 55 households were studied in depth, making up a total of 450 households. Clear and marked differentiations are uncovered between the rural social classes in various aspects of energy production, purchase, sale and consumption, as well as in labour and cash inputs into the energy flows. It is found that traditional forms of biomass are still the dominant type of energy for all rural strata, and that only the rural middle class can be said to have begun the transition towards modern fuels, although its consumption of modern fuels is still negligibly small in absolute terms. The study reveals that the rural middle class faces no energy crisis, while the 'intermediate' class of the small peasantry is just about managing to make ends meet in energy terms. In contrast to this, the rural wage labour class continues to remain in a state of energy crisis. (author)

  18. Radical-scavenging Activity of Natural Methoxyphenols vs. Synthetic Ones using the Induction Period Method

    Directory of Open Access Journals (Sweden)

    Seiichiro Fujisawa

    2007-02-01

    Full Text Available The radical-scavenging activities of the synthetic antioxidants 2-allyl-4-X-phenol (X=NO2, Cl, Br, OCH3, COCH3, CH3, t-(CH33, C6H5 and 2,4-dimethoxyphenol, and the natural antioxidants eugenol and isoeugenol, were investigated using differential scanning calorimetry (DSC by measuring their anti-1,1-diphenyl-2-picrylhydrazyl (DPPH radical activity and the induction period for polymerization of methyl methacrylate (MMA initiated by thermal decomposition of 2,2'-azobisisobutyronitrile (AIBN and benzoyl peroxide (BPO. 2-Allyl-4-methoxyphenol and 2,4-dimethoxy-phenol scavenged not only oxygen-centered radicals (PhCOO. derived from BPO, but also carbon-centered radicals (R. derived from the AIBN and DPPH radical much more efficiently, in comparison with eugenol and isoeugenol. 2-Allyl-4-methoxyphenol may be useful for its lower prooxidative activity.

  19. Differential Recruitment to and Outcomes of Solidarity Activism

    DEFF Research Database (Denmark)

    Toubøl, Jonas

    This dissertation is the first major academic analysis of the Danish refugee solidarity movement that mobilized more than 100,000 citizens in the fall 2015 when the European refugee crisis reached Denmark. The dissertation makes four main contribution to the two questions of differential recruitm......This dissertation is the first major academic analysis of the Danish refugee solidarity movement that mobilized more than 100,000 citizens in the fall 2015 when the European refugee crisis reached Denmark. The dissertation makes four main contribution to the two questions of differential...... in a group culture that focuses on the political and contentious dimension of the matter. Fourth and finally, for activists engaged in the legal cases of refugees, experiencing an immigration-bureaucracy with little or no care for the human beings behind the dossiers combined with an experience of systematic...

  20. The impact of inflammation and immune activation on B cell differentiation during HIV-1 infection

    Directory of Open Access Journals (Sweden)

    Nicolas eRuffin

    2012-01-01

    Full Text Available HIV-1 infection is characterized by continuous antigenic stimulation, chronic immune activation and impaired survival of T and B cells. A decline of resting memory B cells has previously been reported to occur in both children and adults infected with HIV-1; these cells are responsible for mounting and maintaining an adequate serological response to antigens previously encountered in life through natural infection or vaccination. Further understanding of the mechanisms leading to impaired B cell differentiation and germinal center reaction might be essential to design new HIV vaccines and therapies that could improve humoral immune responses in HIV-1 infected individuals. In the present article we summarize the literature and present our view on critical mechanisms of B cell development which are impaired during HIV-1 infection. We also discuss the impact of microbial translocation, a driving force for persistent inflammation during HIV-1 infection, on survival of terminally differentiated B cells and how the altered expression of cytokines/chemokines pivotal for communication between T and B cells in lymphoid tissues may impair formation of memory B cells.

  1. Measurement of Antioxidant Activity Towards Superoxide in Natural Waters.

    Directory of Open Access Journals (Sweden)

    D. Whitney King

    2016-11-01

    Full Text Available Antioxidants are a class of molecules that provide a protective function against reactive oxygen species (ROS in biological systems by out competing physiologically important molecules for ROS oxidation. In natural waters, the reactivity of antioxidants gives an estimate of oxidative stress and may determine the reactivity and distribution of reactive oxidants. We present an analytical method to measure antioxidant activity in natural waters through the competition between ascorbic acid, an antioxidant, and MCLA, a chemiluminescent probe for superoxide. A numerical kinetic model of the analytical method has been developed to optimize analytical performance. Measurements of antioxidant concentrations in pure and seawater are possible with detection limits below 0.1 nM. Surface seawater samples collected at solar noon contained over 0.4 nM of antioxidants and exhibited first-order decay with a half-life of 3-7 minutes, consistent with a reactive species capable of scavenging photochemically produced superoxide.

  2. Antimicrobial and antioxidant activity of natural honeys of different origin

    Directory of Open Access Journals (Sweden)

    Miartina Fikselová

    2014-10-01

    Full Text Available To examine the antimicrobial and antioxidant activity of 15 natural honeys, honey samples were collected from different locations of Slovakia, Poland and Serbia. For antimicrobial activity determination honey solutions were prepared at three concentrations: 50, 25 and 12.5 % (by mass per volume. The potential antimicrobial activity of  selected samples against four species of bacteria (Escherichia coli CCM 3988, Pseudomonas aeroginosa CCM 1960, Staphylococcus epidermis CCM 4418, Bacillus cereus CCM 2010 and two species of yeasts (Saccharomyces cerevisiae CCM 8191, Candida albicans CCM 8216 was studied using the disc diffusion method. After incubation, the zones of inhibition of the growth of the microorganisms around the disks were measured. The strongest antimicrobial activity was shown at honey samples of 50 % concentration against Escherichia coli, Pseudomonas aeroginosa and Staphylococcus epidermis. Against Saccharomyces cerevisae and Candida albicans very low (at 50 %, 25 % concentration or zero antifugal (at 12.5 % concentration activity was determined. From the results obtained it was shown the variable ability of honey samples to scavenge stable free radical DPPH. TEACDPPH values ranged between 0.1-1.0 mmol.kg-1. As the antioxidative best source buckwheat honey was manifested and the lowest antioxidant activity was shown at acacia honey.

  3. Dispersion relations and sum rules for natural optical activity

    International Nuclear Information System (INIS)

    Thomaz, M.T.; Nussenzveig, H.M.

    1981-06-01

    Dispersion relations and sum rules are derived for the complex rotatory power of an arbitrary linear (nonmagnetic) isotropic medium showing natural optical activity. Both previously known dispersion relations and sum rules as well as new ones are obtained. It is shown that the Rosenfeld-Condon dispersion formula is inconsistent with the expected asymptotic behavior at high frequencies. A new dispersion formula based on quantum eletro-dynamics removes this inconsistency; however, it still requires modification in the low-frequency limit. (Author) [pt

  4. Mode of dendritic cell activation: the decisive hand in Th2/Th17 cell differentiation. Implications in asthma severity?

    Science.gov (United States)

    Vroman, Heleen; van den Blink, Bernt; Kool, Mirjam

    2015-02-01

    Asthma is a heterogeneous chronic inflammatory disease of the airways, with reversible airflow limitations and airway remodeling. The classification of asthma phenotypes was initially based on different combinations of clinical symptoms, but they are now unfolding to link biology to phenotype. As such, patients can suffer from a predominant eosinophilic, neutrophilic or even mixed eosinophilic/neutrophilic inflammatory response. In adult asthma patients, eosinophilic inflammation is usually seen in mild-to-moderate disease and neutrophilic inflammation in more severe disease. The underlying T cell response is predominated by T helper (Th) 2, Th17, or a mixed Th2/Th17 cell immune response. Dendritic cells (DCs) are "professional" antigen presenting cells (APCs), since their principal function is to present antigens and induce a primary immune response in resting naive T cells. DCs also drive the differentiation into distinctive Th subsets. The expression of co-stimulatory molecules and cytokines by DCs and surrounding cells determines the outcome of Th cell differentiation. The nature of DC activation will determine the expression of specific co-stimulatory molecules and cytokines, specifically needed for induction of the different Th cell programs. Thus DC activation is crucial for the subsequent effector Th immune responses. In this review, we will discuss underlying mechanisms that initiate DC activation in favor of Th2 differentiation versus Th1/Th17 and Th17 differentiation in the development of mild versus moderate to severe asthma. Copyright © 2014 Elsevier GmbH. All rights reserved.

  5. A Cbx8-containing polycomb complex facilitates the transition to gene activation during ES cell differentiation.

    Directory of Open Access Journals (Sweden)

    Catherine Creppe

    2014-12-01

    Full Text Available Polycomb proteins play an essential role in maintaining the repression of developmental genes in self-renewing embryonic stem cells. The exact mechanism allowing the derepression of polycomb target genes during cell differentiation remains unclear. Our project aimed to identify Cbx8 binding sites in differentiating mouse embryonic stem cells. Therefore, we used a genome-wide chromatin immunoprecipitation of endogenous Cbx8 coupled to direct massive parallel sequencing (ChIP-Seq. Our analysis identified 171 high confidence peaks. By crossing our data with previously published microarray analysis, we show that several differentiation genes transiently recruit Cbx8 during their early activation. Depletion of Cbx8 partially impairs the transcriptional activation of these genes. Both interaction analysis, as well as chromatin immunoprecipitation experiments support the idea that activating Cbx8 acts in the context of an intact PRC1 complex. Prolonged gene activation results in eviction of PRC1 despite persisting H3K27me3 and H2A ubiquitination. The composition of PRC1 is highly modular and changes when embryonic stem cells commit to differentiation. We further demonstrate that the exchange of Cbx7 for Cbx8 is required for the effective activation of differentiation genes. Taken together, our results establish a function for a Cbx8-containing complex in facilitating the transition from a Polycomb-repressed chromatin state to an active state. As this affects several key regulatory differentiation genes this mechanism is likely to contribute to the robust execution of differentiation programs.

  6. Development of QSAR model for immunomodulatory activity of natural coumarinolignoids

    Directory of Open Access Journals (Sweden)

    Dharmendra K Yadav

    2010-07-01

    Full Text Available Dharmendra K Yadav, Abha Meena, Ankit Srivastava, D Chanda, Feroz Khan, SK ChattopadhyayMetabolic and Structural Biology Department, Central Institute of Medicinal and Aromatic Plants, Council of Scientific and Industrial Research, PO-CIMAP, IndiaAbstract: Immunomodulation is the process of alteration in immune response due to foreign intrusion of molecules inside the body. Along with the available drugs, a large number of herbal drugs are promoted in traditional Indian treatments, for their immunomodulating activity. Natural coumarinolignoids isolated from the seeds of Cleome viscose have been recognized as having hepatoprotective action and have recently been tested preclinically for their immunomodulatory activity affecting both cell-mediated and humoral immune response. To explore the immunomodulatory compound from derivatives of coumarinolignoids, a quantitative structure activity relationship (QSAR and molecular docking studies were performed. Theoretical results are in accord with the in vivo experimental data studied on Swiss albino mice. Immunostimulatory activity was predicted through QSAR model, developed by forward feed multiple linear regression method with leave-one-out approach. Relationship correlating measure of QSAR model was 99% (R2 = 0.99 and predictive accuracy was 96% (RCV2 = 0.96. QSAR studies indicate that dipole moment, steric energy, amide group count, lambda max (UV-visible, and molar refractivity correlates well with biological activity, while decrease in dipole moment, steric energy, and molar refractivity has negative correlation. Docking studies also showed strong binding affinity to immunomodulatory receptors.Keywords: coumarinolignoids, immunomodulation, docking, QSAR, regression model

  7. Antimicrobial activity of new porphyrins of synthetic and natural origin

    Science.gov (United States)

    Gyulkhandanyan, Grigor V.; Ghazaryan, Robert K.; Paronyan, Marina H.; Ulikhanyan, Ghukas I.; Gyulkhandanyan, Aram G.; Sahakyan, Lida A.

    2012-03-01

    Antimicrobial photodynamic inactivation has been successfully used against Gram (+) microorganisms, but most of the photosensitizers (PSs) on Gram (-) bacteria acts weakly. PSs are the natural or synthetic origin dyes, mainly porphyrins. We have synthesized more than 100 new cationic porphyrins and metalloporphyrins with different functional groups (hydroxyethyl, butyl, allyl, methallyl) and metals (cobalt, iron, copper, zinc, silver and other); from the nettle have also been purified pheophytin (a+b) and pheophytin (a) and have synthesized their Ag-and Zn-metalloporphyrins. It was found that in the dark (cytotoxic) mode, the most highly efficiency against microorganisms showed Agmetalloporphyrins of both types of porphyrins (synthetic and natural). Metalloporphyrin of natural origin Ag-pheophytin (a + b) is a strong antibacterial agent and causes 100% death as the Gram (+) microorganisms (St. aureus and MRSA) and the Gram (-) microorganisms (E.coli and Salmonella). It is established that for the destruction of Gram (+) and Gram (-) microorganisms in photodynamic mode cationic water-soluble synthetic metalloporphyrins, especially Zn-TBut4PyP, many times more effective than pheophytins. In vivo conditions on mice established that the best therapeutic activity against various strains of the microorganism St. aureus has the synthetic metalloporphyrin Ag-TBut4PyP. It is significantly more efficient than known drug "Chlorophyllipt" (2.5-3 times) and leads the survival rate of animals up to 50-60%.

  8. Mechanisms of children's exposure to nature: Predicting adulthood environmental citizenship and commitment to nature-based activities

    Science.gov (United States)

    Stanley T. Asah; David N. Bengston; Lynne M. Westphal; Catherine H. Gowan

    2017-01-01

    Childhood-nature experiences have lifelong effects on environmental citizenship and commitment to nature-based activities. But, it is unclear whether, and to what extent, the different mechanisms through which children and youth experience nature are associated with these outcomes. To test these associations, an online questionnaire assessing mechanisms of childhood...

  9. Effect of radiotherapy on the natural killer (NK)-cell activity of cancer patients

    International Nuclear Information System (INIS)

    McGinnes, K.; Florence, J.; Penny, R.

    1987-01-01

    The aim of this study was to determine the effect of radiotherapy on peripheral blood natural killer (NK)-cell number and activity in 15 patients with cancer, prior to the commencement and at the completion of radiotherapy. The following observations were made. Prior to radiotherapy NK activity could not be correlated with the stage of malignancy. In all patients with advanced disease and with subnormal baseline NK activity, the outcome of radiotherapy was unfavorable. Following radiotherapy to sites including the mediastinum, patients had decreased NK activity compared with those receiving treatment to other sites. This decrease was not related to the dose of radiotherapy or stage of malignancy. The tumor response was favorable in most patients whose NK activity decreased as a result of radiotherapy. The decrease in NK activity may be associated with a decrease in the percentage of NK (N901) cells in the peripheral blood. The reduction in NK activity in those patients receiving mediastinal irradiation may be due to the large volume of blood which transits the field, so that the NK cells, or their more radiosensitive precursors, may be damaged and/or differentiation inhibited. Thus, these new observations show that radiotherapy does indeed affect the NK activity in cancer patients predominantly when the irradiation site includes the mediastinum

  10. Scaling down the size and increasing the throughput of glycosyltransferase assays: activity changes on stem cell differentiation.

    Science.gov (United States)

    Patil, Shilpa A; Chandrasekaran, E V; Matta, Khushi L; Parikh, Abhirath; Tzanakakis, Emmanuel S; Neelamegham, Sriram

    2012-06-15

    Glycosyltransferases (glycoTs) catalyze the transfer of monosaccharides from nucleotide-sugars to carbohydrate-, lipid-, and protein-based acceptors. We examined strategies to scale down and increase the throughput of glycoT enzymatic assays because traditional methods require large reaction volumes and complex chromatography. Approaches tested used (i) microarray pin printing, an appropriate method when glycoT activity was high; (ii) microwells and microcentrifuge tubes, a suitable method for studies with cell lysates when enzyme activity was moderate; and (iii) C(18) pipette tips and solvent extraction, a method that enriched reaction product when the extent of reaction was low. In all cases, reverse-phase thin layer chromatography (RP-TLC) coupled with phosphorimaging quantified the reaction rate. Studies with mouse embryonic stem cells (mESCs) demonstrated an increase in overall β(1,3)galactosyltransferase and α(2,3)sialyltransferase activity and a decrease in α(1,3)fucosyltransferases when these cells differentiate toward cardiomyocytes. Enzymatic and lectin binding data suggest a transition from Lewis(x)-type structures in mESCs to sialylated Galβ1,3GalNAc-type glycans on differentiation, with more prominent changes in enzyme activity occurring at later stages when embryoid bodies differentiated toward cardiomyocytes. Overall, simple, rapid, quantitative, and scalable glycoT activity analysis methods are presented. These use a range of natural and synthetic acceptors for the analysis of complex biological specimens that have limited availability. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Differentiation of IL-17-Producing Invariant Natural Killer T Cells Requires Expression of the Transcription Factor c-Maf

    Directory of Open Access Journals (Sweden)

    Jhang-Sian Yu

    2017-10-01

    Full Text Available c-Maf belongs to the large Maf family of transcription factors and plays a key role in the regulation of cytokine production and differentiation of TH2, TH17, TFH, and Tr1 cells. Invariant natural killer T (iNKT cells can rapidly produce large quantity of TH-related cytokines such as IFN-γ, IL-4, and IL-17A upon stimulation by glycolipid antigens, such as α-galactosylceramide (α-GalCer. However, the role of c-Maf in iNKT cells and iNKT cells-mediated diseases remains poorly understood. In this study, we demonstrate that α-GalCer-stimulated iNKT cells express c-Maf transcript and protein. By using c-Maf-deficient fetal liver cell-reconstituted mice, we further show that c-Maf-deficient iNKT cells produce less IL-17A than their wild-type counterparts after α-GalCer stimulation. While c-Maf deficiency does not affect the development and activation of iNKT cells, c-Maf is essential for the induction of IL-17-producing iNKT (iNKT17 cells by IL-6, TGF-β, and IL-1β, and the optimal expression of RORγt. Accordingly, c-Maf-deficient iNKT17 cells lose the ability to recruit neutrophils into the lungs. Taken together, c-Maf is a positive regulator for the expression of IL-17A and RORγt in iNKT17 cells. It is a potential therapeutic target in iNKT17 cell-mediated inflammatory disease.

  12. Naturally occurring variants of human Α9 nicotinic receptor differentially affect bronchial cell proliferation and transformation.

    Directory of Open Access Journals (Sweden)

    Anna Chikova

    Full Text Available Isolation of polyadenilated mRNA from human immortalized bronchial epithelial cell line BEP2D revealed the presence of multiple isoforms of RNA coded by the CHRNA9 gene for α9 nicotinic acetylcholine receptor (nAChR. BEP2D cells were homozygous for the rs10009228 polymorphism encoding for N442S amino acid substitution, and also contained mRNA coding for several truncated isoforms of α9 protein. To elucidate the biologic significance of the naturally occurring variants of α9 nAChR, we compared the biologic effects of overexpression of full-length α9 N442 and S442 proteins, and the truncated α9 variant occurring due to a loss of the exon 4 sequence that causes frame shift and early termination of the translation. These as well as control vector were overexpressed in the BEP2D cells that were used in the assays of proliferation rate, spontaneous vs. tobacco nitrosamine 4-(methylnitrosamino-1-(3-pyridyl-1-butanone (NNK-induced cellular transformation, and tumorigenicity in cell culture and mice. Overexpression of the S442 variant significantly increased cellular proliferation, and spontaneous and NNK-induced transformation. The N442 variant significantly decreased cellular transformation, without affecting proliferation rate. Overexpression of the truncated α9 significantly decreased proliferation and suppressed cellular transformation. These results suggested that α9 nAChR plays important roles in regulation of bronchial cell growth by endogenous acetylcholine and exogenous nicotine, and susceptibility to NNK-induced carcinogenic transformation. The biologic activities of α9 nAChR may be regulated at the splicing level, and genetic polymorphisms in CHRNA9 affecting protein levels, amino acid sequence and RNA splicing may influence the risk for lung cancer.

  13. Granivory of invasive, naturalized, and native plants in communities differentially susceptible to invasion

    Science.gov (United States)

    B. M. Connolly; D. E. Pearson; R. N. Mack

    2014-01-01

    Seed predation is an important biotic filter that can influence abundance and spatial distributions of native species through differential effects on recruitment. This filter may also influence the relative abundance of nonnative plants within habitats and the communities' susceptibility to invasion via differences in granivore identity, abundance, and food...

  14. Synaptic network activity induces neuronal differentiation of adult hippocampal precursor cells through BDNF signaling

    Directory of Open Access Journals (Sweden)

    Harish Babu

    2009-09-01

    Full Text Available Adult hippocampal neurogenesis is regulated by activity. But how do neural precursor cells in the hippocampus respond to surrounding network activity and translate increased neural activity into a developmental program? Here we show that long-term potential (LTP-like synaptic activity within a cellular network of mature hippocampal neurons promotes neuronal differentiation of newly generated cells. In co-cultures of precursor cells with primary hippocampal neurons, LTP-like synaptic plasticity induced by addition of glycine in Mg2+-free media for 5 min, produced synchronous network activity and subsequently increased synaptic strength between neurons. Furthermore, this synchronous network activity led to a significant increase in neuronal differentiation from the co-cultured neural precursor cells. When applied directly to precursor cells, glycine and Mg2+-free solution did not induce neuronal differentiation. Synaptic plasticity-induced neuronal differentiation of precursor cells was observed in the presence of GABAergic neurotransmission blockers but was dependent on NMDA-mediated Ca2+ influx. Most importantly, neuronal differentiation required the release of brain-derived neurotrophic factor (BDNF from the underlying substrate hippocampal neurons as well as TrkB receptor phosphorylation in precursor cells. This suggests that activity-dependent stem cell differentiation within the hippocampal network is mediated via synaptically evoked BDNF signaling.

  15. Explorative investigation of biomarkers of brain damage and coagulation system activation in clinical stroke differentiation

    DEFF Research Database (Denmark)

    Undén, Johan; Strandberg, Karin; Malm, Jan

    2009-01-01

    INTRODUCTION: A simple and accurate method of differentiating ischemic stroke and intracerebral hemorrhage (ICH) is potentially useful to facilitate acute therapeutic management. Blood measurements of biomarkers of brain damage and activation of the coagulation system may potentially serve as nov...

  16. Early endocrine disruptors exposure acts on 3T3-L1 differentiation and endocrine activity

    Directory of Open Access Journals (Sweden)

    Sofiane Boudalia

    2017-06-01

    Conclusion: This study confirms that EDs singularly or in mixtures, introduced during early stages of life, could affect the differentiation and the endocrine activity of adipocytes, and can act as potential factors for obesity.

  17. Differential effects of active and passive coping on secretory immunity

    NARCIS (Netherlands)

    Bosch, JA; de Geus, E.J.C.; Kelder, A.; Veerman, E.C.I.; Hoogstraten, J.; van Nieuw Amerongen, A.

    2001-01-01

    This study examined the acute immunological effects of two laboratory stressors, expected to evoke distinct patterns of cardiac autonomic activity; namely an "active coping" time-paced memory test, and a "passive coping" stressful video showing surgical operations. We measured salivary S-IgA,

  18. Activation of the Ca2+/calcineurin/NFAT2 pathway controls smooth muscle cell differentiation

    International Nuclear Information System (INIS)

    Larrieu, Daniel; Thiebaud, Pierre; Duplaa, Cecile; Sibon, Igor; Theze, Nadine; Lamaziere, Jean-Marie Daniel

    2005-01-01

    Cellular mechanisms controlling smooth muscle cells (SMCs) phenotypic modulation are largely unknown. Intracellular Ca 2+ movements are essential to ensure SMC functions; one of the roles of Ca 2+ is to regulate calcineurin, which in turn induces nuclear localization of the nuclear factor of activated T-cell (NFAT). In order to investigate, during phenotypic differentiation of SMCs, the effect of calcineurin inhibition on NFAT 2 nuclear translocation, we used a culture model of SMC differentiation in serum-free conditions. We show that the treatment of cultured SMC with the calcineurin inhibitor cyclosporine A induced their dedifferentiation while preventing their differentiation. These findings suggest that nuclear translocation of NFAT 2 is dependent of calcineurin activity during the in vitro SMC differentiation kinetic and that the nuclear presence of NFAT 2 is critical in the acquisition and maintenance of SMC differentiation

  19. Mitochondrial activity in the regulation of stem cell self-renewal and differentiation.

    Science.gov (United States)

    Khacho, Mireille; Slack, Ruth S

    2017-12-01

    Mitochondria are classically known as the essential energy producers in cells. As such, the activation of mitochondrial metabolism upon cellular differentiation was deemed a necessity to fuel the high metabolic needs of differentiated cells. However, recent studies have revealed a direct role for mitochondrial activity in the regulation of stem cell fate and differentiation. Several components of mitochondrial metabolism and respiration have now been shown to regulate different aspects of stem cell differentiation through signaling, transcriptional, proteomic and epigenetic modulations. In light of these findings mitochondrial metabolism is no longer considered a consequence of cellular differentiation, but rather a key regulatory mechanism of this process. This review will focus on recent progress that defines mitochondria as the epicenters for the regulation of stem cell fate decisions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. The transition from proliferation to differentiation in colorectal cancer is regulated by the calcium activated chloride channel A1.

    Directory of Open Access Journals (Sweden)

    Bo Yang

    Full Text Available Breaking the balance between proliferation and differentiation in animal cells can lead to cancer, but the mechanisms maintaining this balance remain largely undefined. The calcium activated chloride channel A1 (CLCA1 is a member of the calcium sensitive chloride conductance family of proteins and is expressed mainly in the colon, small intestine and appendix. We show that CLCA1 plays a functional role in differentiation and proliferation of Caco-2 cells and of intestinal tissue. Caco-2 cells spontaneously differentiate either in confluent culture or when treated with butyrate, a molecule present naturally in the diet. Here, we compared CLCA1 expressional levels between patients with and without colorectal cancer (CRC and determined the functional role of CLCA1 in differentiation and proliferation of Caco-2 cells. We showed that: 1 CLCA1 and CLCA4 expression were down-regulated significantly in CRC patients; 2 CLCA1 expression was up-regulated in Caco-2 cells induced to differentiate by confluent culture or by treatment with sodium butyrate (NaBT; 3 Knockdown of CLCA1 with siRNA significantly inhibited cell differentiation and promoted cell proliferation in Caco-2 confluent cultures, and 4 In Caco-2 3D culture, suppression of CLCA1 significantly increased cell proliferation and compromised NaBT-induced inhibition of proliferation. In conclusion, CLCA1 may contribute to promoting spontaneous differentiation and reducing proliferation of Caco-2 cells and may be a target of NaBT-induced inhibition of proliferation and therefore a potential diagnostic marker for CRC prognosis.

  1. Antibody complementarity-determining regions (CDRs can display differential antimicrobial, antiviral and antitumor activities.

    Directory of Open Access Journals (Sweden)

    Luciano Polonelli

    Full Text Available BACKGROUND: Complementarity-determining regions (CDRs are immunoglobulin (Ig hypervariable domains that determine specific antibody (Ab binding. We have shown that synthetic CDR-related peptides and many decapeptides spanning the variable region of a recombinant yeast killer toxin-like antiidiotypic Ab are candidacidal in vitro. An alanine-substituted decapeptide from the variable region of this Ab displayed increased cytotoxicity in vitro and/or therapeutic effects in vivo against various bacteria, fungi, protozoa and viruses. The possibility that isolated CDRs, represented by short synthetic peptides, may display antimicrobial, antiviral and antitumor activities irrespective of Ab specificity for a given antigen is addressed here. METHODOLOGY/PRINCIPAL FINDINGS: CDR-based synthetic peptides of murine and human monoclonal Abs directed to: a a protein epitope of Candida albicans cell wall stress mannoprotein; b a synthetic peptide containing well-characterized B-cell and T-cell epitopes; c a carbohydrate blood group A substance, showed differential inhibitory activities in vitro, ex vivo and/or in vivo against C. albicans, HIV-1 and B16F10-Nex2 melanoma cells, conceivably involving different mechanisms of action. Antitumor activities involved peptide-induced caspase-dependent apoptosis. Engineered peptides, obtained by alanine substitution of Ig CDR sequences, and used as surrogates of natural point mutations, showed further differential increased/unaltered/decreased antimicrobial, antiviral and/or antitumor activities. The inhibitory effects observed were largely independent of the specificity of the native Ab and involved chiefly germline encoded CDR1 and CDR2 of light and heavy chains. CONCLUSIONS/SIGNIFICANCE: The high frequency of bioactive peptides based on CDRs suggests that Ig molecules are sources of an unlimited number of sequences potentially active against infectious agents and tumor cells. The easy production and low cost of small

  2. CSK negatively regulates nerve growth factor induced neural differentiation and augments AKT kinase activity

    International Nuclear Information System (INIS)

    Dey, Nandini; Howell, Brian W.; De, Pradip K.; Durden, Donald L.

    2005-01-01

    Src family kinases are involved in transducing growth factor signals for cellular differentiation and proliferation in a variety of cell types. The activity of all Src family kinases (SFKs) is controlled by phosphorylation at their C-terminal 527-tyrosine residue by C-terminal SRC kinase, CSK. There is a paucity of information regarding the role of CSK and/or specific Src family kinases in neuronal differentiation. Pretreatment of PC12 cells with the Src family kinase inhibitor, PP1, blocked NGF-induced activation of SFKs and obliterated neurite outgrowth. To confirm a role for CSK and specific isoforms of SFKs in neuronal differentiation, we overexpressed active and catalytically dead CSK in the rat pheochromocytoma cell line, PC12. CSK overexpression caused a profound inhibition of NGF-induced activation of FYN, YES, RAS, and ERK and inhibited neurite outgrowth, NGF-stimulated integrin-directed migration and blocked the NGF-induced conversion of GDP-RAC to its GTP-bound active state. CSK overexpression markedly augmented the activation state of AKT following NGF stimulation. In contrast, kinase-dead CSK augmented the activation of FYN, RAS, and ERK and increased neurite outgrowth. These data suggest a distinct requirement for CSK in the regulation of NGF/TrkA activation of RAS, RAC, ERK, and AKT via the differential control of SFKs in the orchestration of neuronal differentiation

  3. On the differential nature of induced and incidental echolalia in autism.

    Science.gov (United States)

    Grossi, D; Marcone, R; Cinquegrana, T; Gallucci, M

    2013-10-01

    Echolalia is a verbal disorder, defined as 'a meaningless repetition of the words of others'. It is pathological, automatic and non-intentional behaviour, often observed in a variety of neurological and psychiatric disorders and above all in autism. We assume that echolalia is an imitative behaviour that is due to difficulties in inhibiting automatic repetition as seen in patients with frontal lobe damage. Our aim is to study the occurrence of echolalia under experimental conditions to investigate the nature of the phenomenon and its relationship with the severity of autism. Eighteen participants with autism from 17 to 36 years old were recruited; they were administrated the Vineland scale, the Observational Rating Scale of Basic Functions and the Echolalia Questionnaire. In the Echolalia Questionnaire, questions were directly addressed to the autistic subject (induced procedure) or to the subject's caregiver while the subject was free to do what he wanted (incidental procedure). The data were analysed by multivariate regressions and Pearson's correlations. The results showed that echolalia occurred in both experimental situations; the mean value was significantly higher in the induced procedure, but results did not support the correlation with Vineland's score in the incidental procedure. It is likely that the two situations activated different processes. In particular, echolalia was statistically higher in the induced procedure as compared with the incidental one only for subjects with low score on Vineland, but in the incidental procedure, the presence of echolalia appeared to be uninfluenced by the functional capacity of subjects. The two experimental conditions require different monitoring systems to control this verbal behaviour. The echolalic phenomenon is an expression of dependence on the environment and may occur in a situation in which the autistic person is participating in a communicative act and, lacking inhibitory control, repeats the other

  4. The assay of glucocerebrosidase activity using the natural substrate

    International Nuclear Information System (INIS)

    Strasberg, P.M.; Lowden, J.A.

    1982-01-01

    The authors have examined eight published methods for the assay of glucocerebrosidase using the natural substrate glucocerebroside and tabulated the variable components and conditions while comparing these methods to their own. In each case assays were performed using a 8000 fold, partially purified human placental enzyme, having a pH optimum of 5.4-5.6 and a Ksub(m) of approximately 0.60 mmol per liter. Results were obtained by following the release of radioactive ceramide or of unlabelled glucose. In many cases published results had been based on a one- or two-hour incubation time. Apparent specific activities varied over a 70-fold difference between the various procedures. When the authors measured activities from the linear (15-30 min) portion of rate curves the values increased by 1.4 to 3 times but still ranged from 6x10 3 -180x10 3 nmol. mg -1 protein h -1 . They obtained maximum velocity using 1.2 mmol glucocerebroside, 0.5% (w/v) crude taurocholate and 2 μg enzyme protein/ml. Specific activities reported from different laboratories are not directly comparable. Conditions for assay should be optimized for the enzyme preparation to be studied. (Auth.)

  5. RAPID-COMMUNICATION Genetic diversity and differentiation in natural populations of Arapaima gigas from lower Amazon revealed by microsatellites.

    Science.gov (United States)

    Fazzi-Gomes, P F; Melo, N; Palheta, G; Guerreiro, S; Amador, M; Ribeiro-Dos-Santos, A K; Santos, S; Hamoy, I

    2017-02-08

    Genetic variability is one of the important criteria for species conservation decisions. This study aimed to analyze the genetic diversity and the population differentiation of two natural populations of Arapaima gigas, a species with a long history of being commercially exploited. We collected 87 samples of A. gigas from Grande Curuai Lake and Paru Lake, located in the Lower Amazon region of Amazônia, Brazil, and genotyped these samples using a multiplex panel of microsatellite markers. Our results showed that the populations of A. gigas analyzed had high levels of genetic variability, which were similar to those described in previous studies. These two populations had a significant population differentiation supported by the estimates of F ST and R ST (0.06), by Bayesian analysis (K = 2), and by population assignment tests, which revealed a moderate genetic distance.

  6. Differential modulation of FXR activity by chlorophacinone and ivermectin analogs

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Chia-Wen [NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (United States); Hsieh, Jui-Hua [National Toxicology Program, National Institutes of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (United States); Huang, Ruili [NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (United States); Pijnenburg, Dirk [PamGene International B.V., Wolvenhoek 10, 5211 HH ' s-Hertogenbosch (Netherlands); Khuc, Thai [NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (United States); Hamm, Jon [Integrated Laboratory System, Inc., Morrisville, NC (United States); Zhao, Jinghua; Lynch, Caitlin [NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (United States); Beuningen, Rinie van [PamGene International B.V., Wolvenhoek 10, 5211 HH ' s-Hertogenbosch (Netherlands); Chang, Xiaoqing [Integrated Laboratory System, Inc., Morrisville, NC (United States); Houtman, René [PamGene International B.V., Wolvenhoek 10, 5211 HH ' s-Hertogenbosch (Netherlands); Xia, Menghang, E-mail: mxia@mail.nih.gov [NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (United States)

    2016-12-15

    Chemicals that alter normal function of farnesoid X receptor (FXR) have been shown to affect the homeostasis of bile acids, glucose, and lipids. Several structural classes of environmental chemicals and drugs that modulated FXR transactivation were previously identified by quantitative high-throughput screening (qHTS) of the Tox21 10 K chemical collection. In the present study, we validated the FXR antagonist activity of selected structural classes, including avermectin anthelmintics, dihydropyridine calcium channel blockers, 1,3-indandione rodenticides, and pyrethroid pesticides, using in vitro assay and quantitative structural-activity relationship (QSAR) analysis approaches. (Z)-Guggulsterone, chlorophacinone, ivermectin, and their analogs were profiled for their ability to alter CDCA-mediated FXR binding using a panel of 154 coregulator motifs and to induce or inhibit transactivation and coactivator recruitment activities of constitutive androstane receptor (CAR), liver X receptor alpha (LXRα), or pregnane X receptor (PXR). Our results showed that chlorophacinone and ivermectin had distinct modes of action (MOA) in modulating FXR-coregulator interactions and compound selectivity against the four aforementioned functionally-relevant nuclear receptors. These findings collectively provide mechanistic insights regarding compound activities against FXR and possible explanations for in vivo toxicological observations of chlorophacinone, ivermectin, and their analogs. - Highlights: • A subset of Tox21 chemicals was investigated for FXR antagonism. • In vitro and computational approaches were used to evaluate FXR antagonists. • Chlorophacinone and ivermectin had distinct patterns in modulating FXR activity.

  7. Uranium Biomineralization By Natural Microbial Phosphatase Activities in the Subsurface

    Energy Technology Data Exchange (ETDEWEB)

    Taillefert, Martial [Georgia Tech Research Corporation, Atlanta, GA (United States)

    2015-04-01

    This project investigated the geochemical and microbial processes associated with the biomineralization of radionuclides in subsurface soils. During this study, it was determined that microbial communities from the Oak Ridge Field Research subsurface are able to express phosphatase activities that hydrolyze exogenous organophosphate compounds and result in the non-reductive bioimmobilization of U(VI) phosphate minerals in both aerobic and anaerobic conditions. The changes of the microbial community structure associated with the biomineralization of U(VI) was determined to identify the main organisms involved in the biomineralization process, and the complete genome of two isolates was sequenced. In addition, it was determined that both phytate, the main source of natural organophosphate compounds in natural environments, and polyphosphate accumulated in cells could also be hydrolyzed by native microbial population to liberate enough orthophosphate and precipitate uranium phosphate minerals. Finally, the minerals produced during this process are stable in low pH conditions or environments where the production of dissolved inorganic carbon is moderate. These findings suggest that the biomineralization of U(VI) phosphate minerals is an attractive bioremediation strategy to uranium bioreduction in low pH uranium-contaminated environments. These efforts support the goals of the SBR long-term performance measure by providing key information on "biological processes influencing the form and mobility of DOE contaminants in the subsurface".

  8. Detecting Differential Transcription Factor Activity from ATAC-Seq Data

    Directory of Open Access Journals (Sweden)

    Ignacio J. Tripodi

    2018-05-01

    Full Text Available Transcription factors are managers of the cellular factory, and key components to many diseases. Many non-coding single nucleotide polymorphisms affect transcription factors, either by directly altering the protein or its functional activity at individual binding sites. Here we first briefly summarize high-throughput approaches to studying transcription factor activity. We then demonstrate, using published chromatin accessibility data (specifically ATAC-seq, that the genome-wide profile of TF recognition motifs relative to regions of open chromatin can determine the key transcription factor altered by a perturbation. Our method of determining which TFs are altered by a perturbation is simple, is quick to implement, and can be used when biological samples are limited. In the future, we envision that this method could be applied to determine which TFs show altered activity in response to a wide variety of drugs and diseases.

  9. Natural lecithin promotes neural network complexity and activity

    Science.gov (United States)

    Latifi, Shahrzad; Tamayol, Ali; Habibey, Rouhollah; Sabzevari, Reza; Kahn, Cyril; Geny, David; Eftekharpour, Eftekhar; Annabi, Nasim; Blau, Axel; Linder, Michel; Arab-Tehrany, Elmira

    2016-01-01

    Phospholipids in the brain cell membranes contain different polyunsaturated fatty acids (PUFAs), which are critical to nervous system function and structure. In particular, brain function critically depends on the uptake of the so-called “essential” fatty acids such as omega-3 (n-3) and omega-6 (n-6) PUFAs that cannot be readily synthesized by the human body. We extracted natural lecithin rich in various PUFAs from a marine source and transformed it into nanoliposomes. These nanoliposomes increased neurite outgrowth, network complexity and neural activity of cortical rat neurons in vitro. We also observed an upregulation of synapsin I (SYN1), which supports the positive role of lecithin in synaptogenesis, synaptic development and maturation. These findings suggest that lecithin nanoliposomes enhance neuronal development, which may have an impact on devising new lecithin delivery strategies for therapeutic applications. PMID:27228907

  10. Natural lecithin promotes neural network complexity and activity.

    Science.gov (United States)

    Latifi, Shahrzad; Tamayol, Ali; Habibey, Rouhollah; Sabzevari, Reza; Kahn, Cyril; Geny, David; Eftekharpour, Eftekhar; Annabi, Nasim; Blau, Axel; Linder, Michel; Arab-Tehrany, Elmira

    2016-05-27

    Phospholipids in the brain cell membranes contain different polyunsaturated fatty acids (PUFAs), which are critical to nervous system function and structure. In particular, brain function critically depends on the uptake of the so-called "essential" fatty acids such as omega-3 (n-3) and omega-6 (n-6) PUFAs that cannot be readily synthesized by the human body. We extracted natural lecithin rich in various PUFAs from a marine source and transformed it into nanoliposomes. These nanoliposomes increased neurite outgrowth, network complexity and neural activity of cortical rat neurons in vitro. We also observed an upregulation of synapsin I (SYN1), which supports the positive role of lecithin in synaptogenesis, synaptic development and maturation. These findings suggest that lecithin nanoliposomes enhance neuronal development, which may have an impact on devising new lecithin delivery strategies for therapeutic applications.

  11. Antimycobacterial and cytotoxicity activity of synthetic and natural compounds

    Directory of Open Access Journals (Sweden)

    Ana O. de Souza

    2007-01-01

    Full Text Available Antimycobacterial and cytotoxicity activity of synthetic and natural compounds. Secondary metabolites from Curvularia eragrostidis and Drechslera dematioidea, Clusia sp. floral resin, alkaloids from Pilocarpus alatus, salicylideneanilines, piperidine amides, the amine 1-cinnamylpiperazine and chiral pyridinium salts were assayed on Mycobacterium tuberculosis H37Rv. N-(salicylidene-2-hydroxyaniline was the most effective compound with a minimal inhibitory concentration (MIC of 8 µmol/L. Dihydrocurvularin was moderately effective with a MIC of 40 µmol/L. Clusia sp. floral resin and a gallocatechin-epigallocatechin mixture showed MIC of 0.02 g/L and 38 µmol/L, respectively. The cytotoxicity was evaluated for N-(salicylidene-2-hydroxyaniline, curvularin, dihydrocurvularin and Clusia sp. floral resin, and the selectivity indexes were > 125, 0.47, 0.75 and 5, respectively.

  12. Natural coagulation inhibitors and active protein c resistance in preeclampsia

    Directory of Open Access Journals (Sweden)

    Cengiz Demir

    2010-01-01

    Full Text Available INTRODUCTION: The etiology of preeclampsia is not fully established. A few studies have shown a relationship between natural coagulation inhibitors and preeclampsia. OBJECTIVES: The purpose of this study was to investigate the status of natural coagulation inhibitors and active protein C resistance (APC-R in preeclampsia. PATIENTS AND METHODS: We studied 70 women with preeclampsia recruited consecutively and 70 healthy pregnant and 70 nonpregnant women as controls. Plasma protein C (PC, free protein S (fPS, antithrombin III (ATIII and APC-R were evaluated. RESULTS: ATIII values were found to be significantly lower in preeclamptic patients than in the control groups (p< 0.001. Nevertheless, there was no significant difference between the healthy pregnant and nonpregnant women groups (p=0.141. The fPS values of the preeclamptic and healthy pregnant groups were lower than that of the nonpregnant group (p< 0.001, and the fPS value of the preeclamptic pregnant women was lower than that of healthy pregnant women (p<0.001. The PC value of the preeclamptic pregnant women was lower than that of the control groups (p< 0.001. The PC value of the healthy pregnant women was lower than that of the nonpregnant women (p< 0.001. The mean APC activity values were lower in the preeclamptic patients than that of the control groups (p< 0.001, p< 0.001. The APC-R positivity rates of the preeclamptic groups were higher than that of the control groups (p<0.001. CONCLUSIONS: This study demonstrated that ATIII, fPS, PC values and APC resistance were lower and APC-R positivity was higher in preeclamptic women than in normal pregnant and nonpregnant women.

  13. Smartphone Location-Independent Physical Activity Recognition Based on Transportation Natural Vibration Analysis

    Directory of Open Access Journals (Sweden)

    Taeho Hur

    2017-04-01

    Full Text Available Activity recognition through smartphones has been proposed for a variety of applications. The orientation of the smartphone has a significant effect on the recognition accuracy; thus, researchers generally propose using features invariant to orientation or displacement to achieve this goal. However, those features reduce the capability of the recognition system to differentiate among some specific commuting activities (e.g., bus and subway that normally involve similar postures. In this work, we recognize those activities by analyzing the vibrations of the vehicle in which the user is traveling. We extract natural vibration features of buses and subways to distinguish between them and address the confusion that can arise because the activities are both static in terms of user movement. We use the gyroscope to fix the accelerometer to the direction of gravity to achieve an orientation-free use of the sensor. We also propose a correction algorithm to increase the accuracy when used in free living conditions and a battery saving algorithm to consume less power without reducing performance. Our experimental results show that the proposed system can adequately recognize each activity, yielding better accuracy in the detection of bus and subway activities than existing methods.

  14. Smartphone Location-Independent Physical Activity Recognition Based on Transportation Natural Vibration Analysis.

    Science.gov (United States)

    Hur, Taeho; Bang, Jaehun; Kim, Dohyeong; Banos, Oresti; Lee, Sungyoung

    2017-04-23

    Activity recognition through smartphones has been proposed for a variety of applications. The orientation of the smartphone has a significant effect on the recognition accuracy; thus, researchers generally propose using features invariant to orientation or displacement to achieve this goal. However, those features reduce the capability of the recognition system to differentiate among some specific commuting activities (e.g., bus and subway) that normally involve similar postures. In this work, we recognize those activities by analyzing the vibrations of the vehicle in which the user is traveling. We extract natural vibration features of buses and subways to distinguish between them and address the confusion that can arise because the activities are both static in terms of user movement. We use the gyroscope to fix the accelerometer to the direction of gravity to achieve an orientation-free use of the sensor. We also propose a correction algorithm to increase the accuracy when used in free living conditions and a battery saving algorithm to consume less power without reducing performance. Our experimental results show that the proposed system can adequately recognize each activity, yielding better accuracy in the detection of bus and subway activities than existing methods.

  15. Differential accumulation and distribution of natural gas and its main controlling factors in the Sinian Dengying Fm, Sichuan Basin

    Directory of Open Access Journals (Sweden)

    Shugen Liu

    2015-01-01

    Full Text Available In order to disclose the genetic relationship between the hydrocarbon reservoirs and the transformation mechanism between ancient and modern gas reservoirs in the Sinian Dengying Fm in the Sichuan Basin, by using the drilling data, and geologic, geophysical and geochemical methods together, the differential accumulation and distribution of natural gas and its main controlling factors in this study area were identified following the idea of corroborating macroscopic, mesoscopic and microscopic results each other. The results demonstrate as follows. (1 The crude oil in the paleo-oil reservoirs of the Dengying Fm cracked into gas to form the early overpressure paleo-gas reservoirs 100 Ma. From 100 Ma to 20 Ma, the constant uplifting of the Sichuan Basin coupled with the shift of structural highs and the initial occurrence of Weiyuan anticline caused the adjustment of the early overpressure paleo-gas reservoirs into the late overpressure paleo-gas reservoirs. (2 With the increase of uplifting magnitude since 20 Ma, the formations overlying the Dengying Fm in Weiyuan structure experienced rapid erosion, resulting in decline of the caprock sealing ability and damage to the preservation conditions. Therefore, the natural gas in the Dengying Fm started to leak and dissipate from the eroded window of the Lower Triassic Jialingjiang Fm located on the top of the Weiyuan anticline, which is the beginning of the differential accumulation and dissipation of the natural gas in the Dengying Fm across the Sichuan Basin. During the process of the differential accumulation and dissipation, the gas below the spill point of the structural gas traps in Ziyang, Jinshi and Longnüsi–Moxi–Anpingdian–Gaoshiti areas migrated to the Weiyuan anticline along the unconformity of the Dengying Fm, and dissipated through the eroded window of the Jialingjiang Fm on the top of the Weiyuan anticline, resulting in a transformation of abnormal high pressure of gas reservoir

  16. Activity-based differentiation of pathologists' workload in surgical pathology.

    Science.gov (United States)

    Meijer, G A; Oudejans, J J; Koevoets, J J M; Meijer, C J L M

    2009-06-01

    Adequate budget control in pathology practice requires accurate allocation of resources. Any changes in types and numbers of specimens handled or protocols used will directly affect the pathologists' workload and consequently the allocation of resources. The aim of the present study was to develop a model for measuring the pathologists' workload that can take into account the changes mentioned above. The diagnostic process was analyzed and broken up into separate activities. The time needed to perform these activities was measured. Based on linear regression analysis, for each activity, the time needed was calculated as a function of the number of slides or blocks involved. The total pathologists' time required for a range of specimens was calculated based on standard protocols and validated by comparing to actually measured workload. Cutting up, microscopic procedures and dictating turned out to be highly correlated to number of blocks and/or slides per specimen. Calculated workload per type of specimen was significantly correlated to the actually measured workload. Modeling pathologists' workload based on formulas that calculate workload per type of specimen as a function of the number of blocks and slides provides a basis for a comprehensive, yet flexible, activity-based costing system for pathology.

  17. Nature of activities and natural, artificial, accidental exposures. Magnitude of these exposures

    International Nuclear Information System (INIS)

    Aurengo, A.

    2009-01-01

    The exposure to ionizing radiation (I.R.) is linked to radioelements of organism (9%), earth (12%), cosmic radiation (10%), radon (37%), atmospheric fallout ( nuclear tests 2.5% and industry 0.5%) and to medical procedures (29%). The natural exposure varies in France from 2.5 to 5 mSv by year. In some areas in the world it reaches several tens of mSv by year. The medical exposure is very heterogeneous and concerns particularly old people. For a same examination, the patients exposure varies in an important way ( sometimes from 1 to 10) according to the country, even in France. In France, 250 000 persons are occupationally exposed to ionizing radiation. Among these ones, the most of cases exceeded regulatory limits for exposure to IR concern the health sector. The accidental exposures are in relation with industrial activities (51%) research (20%) civil nuclear (13%) or military (5%) and medical activities (11%). The exposures and then the consequences are very variable, ranging from death to unapparent consequences. in the most of cases a human error is involved and these accidents could have been avoided through measures of prevention and training. (N.C.)

  18. Potent In Vitro Antifungal Activities of Naturally Occurring Acetylenic Acids▿

    Science.gov (United States)

    Li, Xing-Cong; Jacob, Melissa R.; Khan, Shabana I.; Ashfaq, M. Khalid; Babu, K. Suresh; Agarwal, Ameeta K.; ElSohly, Hala N.; Manly, Susan P.; Clark, Alice M.

    2008-01-01

    Our continuing effort in antifungal natural product discovery has led to the identification of five 6-acetylenic acids with chain lengths from C16 to C20: 6-hexadecynoic acid (compound 1), 6-heptadecynoic acid (compound 2), 6-octadecynoic acid (compound 3), 6-nonadecynoic acid (compound 4), and 6-icosynoic acid (compound 5) from the plant Sommera sabiceoides. Compounds 2 and 5 represent newly isolated fatty acids. The five acetylenic acids were evaluated for their in vitro antifungal activities against Candida albicans, Candida glabrata, Candida krusei, Candida tropicalis, Candida parapsilosis, Cryptococcus neoformans, Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Trichophyton mentagrophytes, and Trichophyton rubrum by comparison with the positive control drugs amphotericin B, fluconazole, ketoconazole, caspofungin, terbinafine, and undecylenic acid. The compounds showed various degrees of antifungal activity against the 21 tested strains. Compound 4 was the most active, in particular against the dermatophytes T. mentagrophytes and T. rubrum and the opportunistic pathogens C. albicans and A. fumigatus, with MICs comparable to several control drugs. Inclusion of two commercially available acetylenic acids, 9-octadecynoic acid (compound 6) and 5,8,11,14-eicosatetraynoic acid (compound 7), in the in vitro antifungal testing further demonstrated that the antifungal activities of the acetylenic acids were associated with their chain lengths and positional triple bonds. In vitro toxicity testing against mammalian cell lines indicated that compounds 1 to 5 were not toxic at concentrations up to 32 μM. Furthermore, compounds 3 and 4 did not produce obvious toxic effects in mice at a dose of 34 μmol/kg of body weight when administered intraperitoneally. Taking into account the low in vitro and in vivo toxicities and significant antifungal potencies, these 6-acetylenic acids may be excellent leads for further preclinical studies. PMID:18458131

  19. Potent in vitro antifungal activities of naturally occurring acetylenic acids.

    Science.gov (United States)

    Li, Xing-Cong; Jacob, Melissa R; Khan, Shabana I; Ashfaq, M Khalid; Babu, K Suresh; Agarwal, Ameeta K; Elsohly, Hala N; Manly, Susan P; Clark, Alice M

    2008-07-01

    Our continuing effort in antifungal natural product discovery has led to the identification of five 6-acetylenic acids with chain lengths from C(16) to C(20): 6-hexadecynoic acid (compound 1), 6-heptadecynoic acid (compound 2), 6-octadecynoic acid (compound 3), 6-nonadecynoic acid (compound 4), and 6-icosynoic acid (compound 5) from the plant Sommera sabiceoides. Compounds 2 and 5 represent newly isolated fatty acids. The five acetylenic acids were evaluated for their in vitro antifungal activities against Candida albicans, Candida glabrata, Candida krusei, Candida tropicalis, Candida parapsilosis, Cryptococcus neoformans, Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Trichophyton mentagrophytes, and Trichophyton rubrum by comparison with the positive control drugs amphotericin B, fluconazole, ketoconazole, caspofungin, terbinafine, and undecylenic acid. The compounds showed various degrees of antifungal activity against the 21 tested strains. Compound 4 was the most active, in particular against the dermatophytes T. mentagrophytes and T. rubrum and the opportunistic pathogens C. albicans and A. fumigatus, with MICs comparable to several control drugs. Inclusion of two commercially available acetylenic acids, 9-octadecynoic acid (compound 6) and 5,8,11,14-eicosatetraynoic acid (compound 7), in the in vitro antifungal testing further demonstrated that the antifungal activities of the acetylenic acids were associated with their chain lengths and positional triple bonds. In vitro toxicity testing against mammalian cell lines indicated that compounds 1 to 5 were not toxic at concentrations up to 32 muM. Furthermore, compounds 3 and 4 did not produce obvious toxic effects in mice at a dose of 34 mumol/kg of body weight when administered intraperitoneally. Taking into account the low in vitro and in vivo toxicities and significant antifungal potencies, these 6-acetylenic acids may be excellent leads for further preclinical studies.

  20. Study of antioxidant activity of natural food supplements

    Directory of Open Access Journals (Sweden)

    Tetyana Lozova

    2013-11-01

    Full Text Available 96 Normal 0 false false false CS JA X-NONE This article describes the results of a study of antioxidant activity of natural food supplements suggested for use in flour confectionery production. Oxidation rate of the model substance - cumene - was measured using a volumetric unit. Diagram of absorbed oxygen amount as a function of time (∆HO2 over t was built by measuring time in minutes and absorbed oxygen volume in cm3. This diagram was subsequently used to graphically determine the oxidation rate as the slope ratio of the line in specified coordinates. Afterwards, the oxidation rate was measured at a different initiation rate (different azobisisobutyronitrile solution volume, while all other parameters of the experiment remained unaltered. On the basis of the resulting data, diagrams of oxidation rate as a function of initiation rate were built for all investigated substances (both extracts and powders. The study revealed that apian products, including pollen and propolis, as well as kidney bean powder and phytosupplements (leaves of leather bergenia, lime blossom, heartsease, wild chamomile, pepper mint, bog rosemary, and elderflowers, possessed high antioxidant activity. According to the research data, the highest activity was detected in propolis  0.482·20 pollen 0.802 and powdered forms of pepper mint 1.066 leather bergenia leaves 0.937 heartsease 0.385 lime blossom 0.331 and kidney beans 0.323. Relatively lower antioxidant activity was found in powdered bog rosemary 0.242 elderflowers 0.238 and wild chamomile 0.212. (Introduction of the investigated supplements will allow inhibiting oxidation processes in the lipide fraction of foodstuffs, including flour confectionery, to ensure stability of their qualitative characteristics over a longer period.

  1. Differential Gambling Motivations and Recreational Activity Preferences Among Casino Gamblers.

    Science.gov (United States)

    Lee, Choong-Ki; Bernhard, Bo Jason; Kim, Jungsun; Fong, Timothy; Lee, Tae Kyung

    2015-12-01

    This study investigated three different types of gamblers (recreational, problem, and pathological gamblers) to determine differences in gambling motivations and recreational activity preferences among casino gamblers. We collected data from 600 gamblers recruited in an actual gambling environment inside a major casino in South Korea. Findings indicate that motivational factors of escape, sightseeing, and winning were significantly different among these three types of gamblers. When looking at motivations to visit the casino, pathological gamblers were more likely to be motivated by winning, whereas recreational gamblers were more likely to be motivated by scenery and culture in the surrounding casino area. Meanwhile, the problem gamblers fell between these two groups, indicating higher preferences for non-gambling activities than the pathological gamblers. As this study builds upon a foundational previous study by Lee et al. (Psychiatry Investig 6(3):141-149, 2009), the results of this new study were compared with those of the previous study to see if new developments within a resort-style casino contribute to changes in motivations and recreational activity preferences.

  2. Immunometabolic Activation of Invariant Natural Killer T Cells

    Directory of Open Access Journals (Sweden)

    Francesca A. Ververs

    2018-05-01

    Full Text Available Invariant natural killer T (iNKT cells are lipid-reactive T cells with profound immunomodulatory potential. They are unique in their restriction to lipid antigens presented in CD1d molecules, which underlies their role in lipid-driven disorders such as obesity and atherosclerosis. In this review, we discuss the contribution of iNKT cell activation to immunometabolic disease, metabolic programming of lipid antigen presentation, and immunometabolic activation of iNKT cells. First, we outline the role of iNKT cells in immunometabolic disease. Second, we discuss the effects of cellular metabolism on lipid antigen processing and presentation to iNKT cells. The synthesis and processing of glycolipids and other potential endogenous lipid antigens depends on metabolic demand and may steer iNKT cells toward adopting a Th1 or Th2 signature. Third, external signals such as toll-like receptor ligands, adipokines, and cytokines modulate antigen presentation and subsequent iNKT cell responses. Finally, we will discuss the relevance of metabolic programming of iNKT cells in human disease, focusing on their role in disorders such as obesity and atherosclerosis. The critical response to metabolic changes places iNKT cells at the helm of immunometabolic disease.

  3. Natural products as a resource for biologically active compounds

    International Nuclear Information System (INIS)

    Hanke, F.J.

    1986-01-01

    The goal of this study was to investigate various sources of biologically active natural products in an effort to identify the active pesticidal compounds involved. The study is divided into several parts. Chapter 1 contains a discussion of several new compounds from plant and animal sources. Chapter 2 introduces a new NMR technique. In section 2.1 a new technique for better utilizing the lanthanide relaxation agent Gd(fod) 3 is presented which allows the predictable removal of resonances without line broadening. Section 2.2 discusses a variation of this technique for use in an aqueous solvent by applying this technique towards identifying the binding sites of metals of biological interest. Section 2.3 presents an unambiguous 13 C NMR assignment of melibiose. Chapter 3 deals with work relating to the molting hormone of most arthropods, 20-hydroxyecdysone. Section 3.1 discusses the use of two-dimensional NMR (2D NMR) to assign the 1 H NMR spectrum of this biologically important compound. Section 3.2 presents a new application for Droplet countercurrent chromatography (DCCC). Chapter 4 presents a basic improvement to the commercial DCCC instrument that is currently being applied to future commercial instruments. Chapter 5 discusses a curious observation of the effects that two previously known compounds, nagilactone C and (-)-epicatechin, have on lettuce and rice and suggest a possible new role for the ubiquitous flavanol (-)-epicatechin in plants

  4. Tritium volume activity in natural waters of NPP Temelin region

    Energy Technology Data Exchange (ETDEWEB)

    Tomasek, M; Wilhelmova, L [Academy of Sciences of the Czech Rep., Prague (Czech Republic). Nuclear Physics Inst., Dept. of Radiation Dosimetry

    1996-12-31

    This paper presents the results of tritium measurement in selected rivers of NPP Temelin before its operation obtained during the period 1991-1994. Particular attention is paid to Vltava river into which liquid effluents will be discharged and which is also utilized as a drinking water supply for the capital Prague. Samples from the Vltava river were collected near the mouth of NPP waste canal (point Hladna)and in front of the intake into Prague water works (point Podoli). Tritium content was analysed also in surface waters of Paleckuv, Temelinsky and Strouha streams which can be affected by gaseous effluents due to atmospheric removal processes. Tritium activity was measured with Tric-Carb 1050 TR/LL liquid scintillation counter. The mean annual tritium activities of investigated river waters varied within 1.9-3.0 Bq/l during the period 1991-1994 and that their trend has been slowly decreasing. This fact, as well as seasonal variability, suggests, that tritium level in the surface waters of studied region is largely governed by this radionuclide global atmospheric fallout. The results of this work indicate the trend of background tritium in examined natural waters and make possible the evaluation of their potential future contamination. (J.K.) 1 tab., 2 figs., 4 refs.

  5. Varying Inundation Regimes Differentially Affect Natural and Sand-Amended Marsh Sediments.

    Directory of Open Access Journals (Sweden)

    C Wigand

    Full Text Available Climate change is altering sea level rise rates and precipitation patterns worldwide. Coastal wetlands are vulnerable to these changes. System responses to stressors are important for resource managers and environmental stewards to understand in order to best manage them. Thin layer sand or sediment application to drowning and eroding marshes is one approach to build elevation and resilience. The above- and below-ground structure, soil carbon dioxide emissions, and pore water constituents in vegetated natural marsh sediments and sand-amended sediments were examined at varying inundation regimes between mean sea level and mean high water (0.82 m NAVD88 to 1.49 m NAVD88 in a field experiment at Laws Point, part of the Plum Island Sound Estuary (MA. Significantly lower salinities, pH, sulfides, phosphates, and ammonium were measured in the sand-amended sediments than in the natural sediments. In natural sediments there was a pattern of increasing salinity with increasing elevation while in the sand-amended sediments the trend was reversed, showing decreasing salinity with increasing elevation. Sulfide concentrations generally increased from low to high inundation with highest concentrations at the highest inundation (i.e., at the lowest elevations. High pore water phosphate concentrations were measured at low elevations in the natural sediments, but the sand-amended treatments had mostly low concentrations of phosphate and no consistent pattern with elevation. At the end of the experiment the lowest elevations generally had the highest measures of pore water ammonium. Soil carbon dioxide emissions were greatest in the sand-amended mesocosms and at higher elevations. Differences in coarse root and rhizome abundances and volumes among the sediment treatments were detected with CT imaging, but by 20 weeks the natural and sand-amended treatments showed similar total belowground biomass at the intermediate and high elevations. Although differences in

  6. Tissue transglutaminase (TG2 activity regulates osteoblast differentiation and mineralization in the SAOS-2 cell line

    Directory of Open Access Journals (Sweden)

    Xiaoxue Yin

    2012-08-01

    Full Text Available Tissue transglutaminase (type II, TG2 has long been postulated to directly promote skeletal matrix calcification and play an important role in ossification. However, limited information is available on the expression, function and modulating mechanism of TG2 during osteoblast differentiation and mineralization. To address these issues, we cultured the well-established human osteosarcoma cell line SAOS-2 with osteo-inductive conditioned medium and set up three time points (culture days 4, 7, and 14 to represent different stages of SAOS-2 differentiation. Osteoblast markers, mineralization, as well as TG2 expression and activity, were then assayed in each stage. Furthermore, we inhibited TG activity with cystamine and then checked SAOS-2 differentiation and mineralization in each stage. The results showed that during the progression of osteoblast differentiation SAOS-2 cells presented significantly high levels of osteocalcin (OC mRNA, bone morphogenetic protein-2 (BMP-2 and collagen I, significantly high alkaline phosphatase (ALP activity, and the increased formation of calcified matrix. With the same tendency, TG2 expression and activity were up-regulated. Furthermore, inhibition of TG activity resulted in a significant decrease of OC, collagen I, and BMP-2 mRNA and of ALP activity and mineralization. This study demonstrated that TG2 is involved in osteoblast differentiation and may play a role in the initiation and regulation of the mineralization processes. Moreover, the modulating effects of TG2 on osteoblasts may be related to BMP-2.

  7. Emotional stability, anxiety, and natural killer activity under examination stress.

    Science.gov (United States)

    Borella, P; Bargellini, A; Rovesti, S; Pinelli, M; Vivoli, R; Solfrini, V; Vivoli, G

    1999-08-01

    This study was performed to evaluate the relation between a stable personality trait, a mood state and immune response to an examination stress. A self-reported measure of emotional stability (BFQ-ES scale) was obtained in a sample (n = 39) randomly selected from 277 cadets; this personality trait was also investigated by completing a neuroticism scale (Eysenck personality inventory) and a trait-anxiety scale (STAI). Natural killer (NK) cell activity was measured at baseline, long before the examination time and the examination day. The state-anxiety scale evaluated the response to the stressful stimulus. Taking subjects all together, the academic task did not result in significant modification over baseline in NK cell activity. Subjects were then divided into three groups based on emotional stability and state-anxiety scores: high emotional stability/low anxiety, medium, and low emotional stability/high anxiety. Examination stress induced significant increases in NK cell activity in the high emotional stability/low anxiety group, no effect in the medium group, and significant decreases in the low emotional stability/high anxiety group. The repeated-measure ANOVA revealed a significant interaction of group x period (baseline vs. examination) for both lytic units and percent cytolysis. The results did not change after introducing coffee and smoking habits as covariates. Our findings suggest that the state-anxiety acts in concert with a stable personality trait to modulate NK response in healthy subjects exposed to a psychological naturalistic stress. The relation between anxiety and poor immune control has been already described, whereas the ability of emotional stability to associate with an immunoenhancement has not yet reported. The peculiarity of our population, a very homogeneous and healthy group for life style and habits, can have highlighted the role of emotional stability, and may account for the difference with other studies.

  8. Integration and Differentiation as the Universal Scientific Categories and their Reflection in the Theory and Practice of Natural Science Education

    Directory of Open Access Journals (Sweden)

    V. A. Ignatova

    2013-01-01

    Full Text Available The post-industrial society gives way to the qualitatively new formation of education, integrated at its every level: integration with science and production; cooperation of different educational establishments; succession of educational levels; cross-disciplinary and inter-disciplinary expertise development; choice of methods, technologies and organizational forms of education and upbringing, etc. The integration and differentiation in their didactic unity reflect the complexity and contradiction of educational process, either of them dominating in certain socio-economic conditions of the given historic period. The retrospective analysis of the above correlation regarding the natural science disciplines demonstrates the lack of theoretical and methodological bases for integration, and its accidental unsystematic character in educational processes. The main conclusion of the study is the need for the complex competence model to combine the ideas of integration and differentiation providing both the wide outlook and professional training. For overcoming the predominance of differentiated education, the author suggests adapting the concepts of post-non-classical science, and selection and structuring of educational information with the reference to the semantic universals of systematic synergetic approach. The research findings can be used in pedagogic research methodology, educational process design and modeling, its content, technology and organization. 

  9. GR and ER co-activation alters the expression of differentiation genes and associates with improved ER+ breast cancer outcome

    Science.gov (United States)

    West, Diana C.; Pan, Deng; Tonsing-Carter, Eva Y.; Hernandez, Kyle M.; Pierce, Charles F.; Styke, Sarah C.; Bowie, Kathleen R.; Garcia, Tzintzuni I.; Kocherginsky, Masha; Conzen, Suzanne D.

    2016-01-01

    In estrogen receptor (ER)-negative breast cancer (BC), high tumor glucocorticoid receptor (GR) expression has been associated with a relatively poor outcome. In contrast, using a meta-analysis of several genomic datasets, here we find that tumor GR mRNA expression is associated with improved ER+ relapse-free survival (RFS) (independently of progesterone receptor (PR) expression). To understand the mechanism by which GR expression is associated with a better ER+ BC outcome, the global effect of GR-mediated transcriptional activation in ER+ BC cells was studied. Analysis of GR chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) in ER+/GR+ MCF-7 cells revealed that upon co-activation of GR and ER, GR chromatin association became enriched at proximal promoter regions. Furthermore, following ER activation, increased GR chromatin association was observed at ER, FOXO, and AP1 response elements. In addition, ER associated with GR response elements, suggesting that ER and GR interact in a complex. Co-activation of GR and ER resulted in increased expression (relative to ER activation alone) of transcripts that encode proteins promoting cellular differentiation (e.g. KDM4B, VDR) and inhibiting the Wnt-signaling pathway (IGFBP4). Finally, expression of these individual pro-differentiation genes was associated with significantly improved RFS in ER+ BC patients. Together, these data suggest that the co-expression and subsequent activity of tumor cell GR and ER contribute to the less aggressive natural history of early-stage BC by coordinating the altered expression of genes favoring differentiation. Implications The interaction between estrogen and glucocorticoid receptor activity highlights the importance of context-dependent nuclear receptor function in cancer. PMID:27141101

  10. Epigenetic Differentiation of Natural Populations of Lilium bosniacum Associated with Contrasting Habitat Conditions

    OpenAIRE

    Zoldoš, Vlatka; Biruš, Ivan; Muratović, Edina; Šatović, Zlatko; Vojta, Aleksandar; Robin, Odile; Pustahija, Fatima; Bogunić, Faruk; Vičić Bočkor, Vedrana; Siljak-Yakovlev, Sonja

    2018-01-01

    Abstract Epigenetic variation in natural populations with contrasting habitats might be an important element, in addition to the genetic variation, in plant adaptation to environmental stress. Here, we assessed genetic, epigenetic, and cytogenetic structure of the three Lilium bosniacum populations growing on distinct habitats. One population was growing under habitual ecological conditions for this species and the other two were growing under stress associated with high altitude and serpenti...

  11. A potent Brucella abortus 2308 Δery live vaccine allows for the differentiation between natural and vaccinated infection.

    Science.gov (United States)

    Zhang, Junbo; Yin, Shuanghong; Guo, Fei; Meng, Ren; Chen, Chuangfu; Zhang, Hui; Li, Zhiqiang; Fu, Qiang; Shi, Huijun; Hu, Shengwei; Ni, Wei; Li, Tiansen; Zhang, Ke

    2014-08-01

    Brucellosis is a globally distributed zoonotic disease that causes animal and human diseases. However, the current Brucella abortus vaccines (S19 and RB51) are deficient; they can cause abortion in pregnant animals. Moreover, when the vaccine S19 is used, tests cannot differentiate natural from vaccinated infection. Therefore, a safer and more potent vaccine is needed. A Brucella abortus 2308 ery promoter mutant (Δery) was constructed to overcome these drawbacks. The growth of the Δery mutant was significantly attenuated in macrophages and mice and induced high protective immunity in mice. Moreover, Δery induced an anti-Brucella-specific IgG (immunoglobulin G) response and stimulated the expression of interferon-gamma (INF-γ) and interleukin-4 (IL-4). Furthermore, the expression of EryA antigen allowed for the serological differentiation between natural and vaccinated infection in mice. These results indicate that the Δery mutant is a potential attenuated live vaccine candidate against virulent Brucella abortus 2308 (S2308) infection.

  12. Water soluble bioactives of nacre mediate antioxidant activity and osteoblast differentiation.

    Directory of Open Access Journals (Sweden)

    Ratna Chaturvedi

    Full Text Available The water soluble matrix of nacre is a proven osteoinductive material. In spite of the differences in the biomolecular compositions of nacre obtained from multiple species of oysters, the common biochemical properties of those principles substantiate their biological activity. However, the mechanism by which nacre stimulates bone differentiation remains largely unknown. Since the positive impact of antioxidants on bone metabolism is well acknowledged, in this study we investigated the antioxidant potential of a water soluble matrix (WSM obtained from the nacre of the marine oyster Pinctada fucata, which could regulate its osteoblast differentiation activity. Enhanced levels of ALP activity observed in pre-osteoblast cells upon treatment with WSM, suggested the induction of bone differentiation events. Furthermore, bone nodule formation and up-regulation of bone differentiation marker transcripts, i.e. collagen type-1 and osteocalcin by WSM confirmed its ability to induce differentiation of the pre-osteoblasts into mature osteoblasts. Remarkably, same WSM fraction upon pre-treatment lowered the H2O2 and UV-B induced oxidative damages in keratinocytes, thus indicating the antioxidant potential of WSM. This was further confirmed from the in vitro scavenging of ABTS and DPPH free radicals and inhibition of lipid peroxidation by WSM. Together, these results indicate that WSM poses both antioxidant potential and osteoblast differentiation property. Thus, bioactivities associated with nacre holds potential in the development of therapeutics for bone regeneration and against oxidative stress induced damages in cells.

  13. Activation of PPARγ is not involved in butyrate-induced epithelial cell differentiation

    International Nuclear Information System (INIS)

    Ulrich, S.; Waechtershaeuser, A.; Loitsch, S.; Knethen, A. von; Bruene, B.; Stein, J.

    2005-01-01

    Histone deacetylase-inhibitors affect growth and differentiation of intestinal epithelial cells by inducing expression of several transcription factors, e.g. Peroxisome proliferator-activated receptor γ (PPARγ) or vitamin D receptor (VDR). While activation of VDR by butyrate mainly seems to be responsible for cellular differentiation, the activation of PPARγ in intestinal cells remains to be elucidated. The aim of this study was to determine the role of PPARγ in butyrate-induced cell growth inhibition and differentiation induction in Caco-2 cells. Treatment with PPARγ ligands ciglitazone and BADGE (bisphenol A diglycidyl) enhanced butyrate-induced cell growth inhibition in a dose- and time-dependent manner, whereas cell differentiation was unaffected after treatment with PPARγ ligands rosiglitazone and MCC-555. Experiments were further performed in dominant-negative PPARγ mutant cells leading to an increase in cell growth whereas butyrate-induced cell differentiation was again unaffected. The present study clearly demonstrated that PPARγ is involved in butyrate-induced inhibition of cell growth, but seems not to play an essential role in butyrate-induced cell differentiation

  14. Tasting calories differentially affects brain activation during hunger and satiety.

    Science.gov (United States)

    van Rijn, Inge; de Graaf, Cees; Smeets, Paul A M

    2015-02-15

    An important function of eating is ingesting energy. Our objectives were to assess whether oral exposure to caloric and non-caloric stimuli elicits discriminable responses in the brain and to determine in how far these responses are modulated by hunger state and sweetness. Thirty women tasted three stimuli in two motivational states (hunger and satiety) while their brain responses were measured using functional magnetic resonance imaging in a randomized crossover design. Stimuli were solutions of sucralose (sweet, no energy), maltodextrin (non-sweet, energy) and sucralose+maltodextrin (sweet, energy). We found no main effect of energy content and no interaction between energy content and sweetness. However, there was an interaction between hunger state and energy content in the median cingulate (bilaterally), ventrolateral prefrontal cortex, anterior insula and thalamus. This indicates that the anterior insula and thalamus, areas in which hunger state and taste of a stimulus are integrated, also integrate hunger state with caloric content of a taste stimulus. Furthermore, in the median cingulate and ventrolateral prefrontal cortex, tasting energy resulted in more activation during satiety compared to hunger. This finding indicates that these areas, which are known to be involved in processes that require approach and avoidance, are also involved in guiding ingestive behavior. In conclusion, our results suggest that energy sensing is a hunger state dependent process, in which the median cingulate, ventrolateral prefrontal cortex, anterior insula and thalamus play a central role by integrating hunger state with stimulus relevance. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Differential activity of innate defense antimicrobial peptides against Nocardia species.

    Science.gov (United States)

    Rieg, Siegbert; Meier, Benjamin; Fähnrich, Eva; Huth, Anja; Wagner, Dirk; Kern, Winfried V; Kalbacher, Hubert

    2010-02-23

    Members of the genus Nocardia are ubiquitous environmental saprophytes capable to cause human pulmonary, disseminated and cutaneous nocardiosis or bovine mastitis. Innate immunity appears to play an important role in early defense against Nocardia species. To elucidate the contribution of antimicrobial peptides (AMPs) in innate defense against Nocardia, the activity of human alpha-defensins human neutrophil peptides (HNPs) 1-3, human beta-defensin (hBD)-3 and cathelicidin LL-37 as well as bovine beta-defensins lingual and tracheal antimicrobial peptides (LAP, TAP) and bovine neutrophil-derived indolicidin against four important Nocardia species was investigated. Whereas N. farcinica ATCC 3318 and N. nova ATCC 33726 were found to be susceptible to all investigated human and bovine AMPs, N. asteroides ATCC 19247 was killed exclusively by neutrophil-derived human alpha-defensins HNP 1-3 and bovine indolicidin. N. brasiliensis ATCC 19296 was found to exhibit complete resistance to investigated human AMPs and to be susceptible only to bovine indolicidin. Selected AMPs are capable to contribute to the first line of defense against Nocardia, yet, susceptibility appears to vary across different Nocardia species. Obtained results of neutrophil-derived AMPs to possess the broadest antinocardial spectrum are remarkable, since nocardiosis is characterized by a neutrophil-rich infiltrate in vivo.

  16. Differential activity of innate defense antimicrobial peptides against Nocardia species

    Directory of Open Access Journals (Sweden)

    Wagner Dirk

    2010-02-01

    Full Text Available Abstract Background Members of the genus Nocardia are ubiquitous environmental saprophytes capable to cause human pulmonary, disseminated and cutaneous nocardiosis or bovine mastitis. Innate immunity appears to play an important role in early defense against Nocardia species. To elucidate the contribution of antimicrobial peptides (AMPs in innate defense against Nocardia, the activity of human α-defensins human neutrophil peptides (HNPs 1-3, human β-defensin (hBD-3 and cathelicidin LL-37 as well as bovine β-defensins lingual and tracheal antimicrobial peptides (LAP, TAP and bovine neutrophil-derived indolicidin against four important Nocardia species was investigated. Results Whereas N. farcinica ATCC 3318 and N. nova ATCC 33726 were found to be susceptible to all investigated human and bovine AMPs, N. asteroides ATCC 19247 was killed exclusively by neutrophil-derived human α-defensins HNP 1-3 and bovine indolicidin. N. brasiliensis ATCC 19296 was found to exhibit complete resistance to investigated human AMPs and to be susceptible only to bovine indolicidin. Conclusion Selected AMPs are capable to contribute to the first line of defense against Nocardia, yet, susceptibility appears to vary across different Nocardia species. Obtained results of neutrophil-derived AMPs to possess the broadest antinocardial spectrum are remarkable, since nocardiosis is characterized by a neutrophil-rich infiltrate in vivo.

  17. Removal of Iron and Manganese from Natural Groundwater by Continuous Reactor Using Activated and Natural Mordenite Mineral Adsorption

    Science.gov (United States)

    Zevi, Y.; Dewita, S.; Aghasa, A.; Dwinandha, D.

    2018-01-01

    Mordenite minerals derived from Sukabumi natural green stone founded in Indonesia was tested in order to remove iron and manganese from natural groundwater. This research used two types of adsorbents which were consisted of physically activated and natural mordenite. Physical activation of the mordenite was carried out by heating at 400-600°C for two hours. Batch system experiments was also conducted as a preliminary experiment. Batch system proved that both activated and natural mordenite minerals were capable of reducing iron and manganese concentration from natural groundwater. Then, continuous experiment was conducted using down-flow system with 45 ml/minute of constant flow rate. The iron & manganese removal efficiency using continuous reactor for physically activated and natural mordenite were 1.38-1.99%/minute & 0.8-1.49%/minute and 2.26%/minute & 1.37-2.26%/minute respectively. In addition, the regeneration treatment using NH4Cl solution managed to improve the removal efficiency of iron & manganese to 1.98%/minute & 1.77-1.90%/minute and 2.25%/minute & 2.02-2.21%/minute on physically activated mordenite and natural mordenite respectively. Subsequently, the activation of the new mordenite was carried out by immersing mordenite in NH4Cl solution. This chemical activation showed 2.42-2.75%/minute & 0.96 - 2.67 %/minute and 2.66 - 2.78 %/minute & 1.34 - 2.32 %/minute of iron & manganese removal efficiency per detention time for chemically activated and natural mordenite respectively.

  18. THE NATURE OF OPTICALLY DULL ACTIVE GALACTIC NUCLEI IN COSMOS

    International Nuclear Information System (INIS)

    Trump, Jonathan R.; Impey, Chris D.; Gabor, Jared M.; Taniguchi, Yoshi; Nagao, Tohru; Shioya, Yasuhiro; Brusa, Marcella; Civano, Francesca; Elvis, Martin; Kelly, Brandon C.; Huchra, John P.; Jahnke, Knud; Koekemoer, Anton M.; Salvato, Mara; Capak, Peter; Scoville, Nick Z.; Kartaltepe, Jeyhan S.; Lanzuisi, Giorgio; McCarthy, Patrick J.; Maineri, Vincenzo

    2009-01-01

    We present infrared, optical, and X-ray data of 48 X-ray bright, optically dull active galactic nuclei (AGNs) in the COSMOS field. These objects exhibit the X-ray luminosity of an AGN but lack broad and narrow emission lines in their optical spectrum. We show that despite the lack of optical emission lines, most of these optically dull AGNs are not well described by a typical passive red galaxy spectrum: instead they exhibit weak but significant blue emission like an unobscured AGN. Photometric observations over several years additionally show significant variability in the blue emission of four optically dull AGNs. The nature of the blue and infrared emission suggest that the optically inactive appearance of these AGNs cannot be caused by obscuration intrinsic to the AGNs. Instead, up to ∼70% of optically dull AGNs are diluted by their hosts, with bright or simply edge-on hosts lying preferentially within the spectroscopic aperture. The remaining ∼30% of optically dull AGNs have anomalously high f X /f O ratios and are intrinsically weak, not obscured, in the optical. These optically dull AGNs are best described as a weakly accreting AGN with a truncated accretion disk from a radiatively inefficient accretion flow.

  19. Studying nature of oxide catalyst activity in olefine hydrogenetion

    International Nuclear Information System (INIS)

    Minachev, Kh.M.; Khodakov, Yu.S.; Makarov, P.A.

    1978-01-01

    La 2 O 3 activity nature in ethylene hydrogenation is discussed. The adsorbed forms of H 2 , ethylene, as well as CO, CO 2 , H 2 O, isolated at thermovacuum treatment, are studied. The conclusions on the mechanism of La 2 O 3 poizoning are made on the basis of investigation into interaction of C 2 H 4 and H 2 adsorbed forms with one another and with CO, CO 2 , H 2 O. It has been found that La 2 O 3 poisoning by water, CO and CO 2 at low-temperature ethylene hydrogenation is connected with the adsorptive hydrogen displacement. At adsorption temperatures of 20,-68,-78 deg, CO and CO 2 have been adsorbed in α-, β-, γ-forms; ethylene in α-and β-forms, and hydrogen only in the α-form. The adsorbed hydrogen at -68, -78 deg is irreversibly desorbed by CO and CO 2 . The adsorptive C 2 H 4 displacement by the above materials is observed only at 20 deg. According to the specific toxic effect of ethylene hydrogenation on La 2 O 3 poisons are placed in the following way: CO > CO 2 > H 2 O

  20. Active ingredients from natural botanicals in the treatment of obesity.

    Science.gov (United States)

    Zhang, W-L; Zhu, L; Jiang, J-G

    2014-12-01

    Obesity is considered as a chronic disease that can induce a series of comorbidities and complications. Chinese medicine has long clinical experiences in the treatment of obesity. This review summarizes the natural products from traditional Chinese medicine (TCM) that are reported to have anti-obesity effects in the past two decades. Botanic TCM comprises 90% of total Chinese crude drugs, and generally contains various active ingredients, in which the effective anti-obesity ingredients identified can be divided into saponins, polysaccharides, alkaloids, polyphenols and others. Astragaloside IV, glycyrrhizin, macrostemonoside A, berberine, betaine, capsaicin, matrine, methyl piperate, piperine, rutaecarpine, asimilobine, epigallocatechingallate, magnolol, resveratrol, soybean-isoflavone, α-linolenic acid, emodin, geniposide, phillyrin, salidroside and ursolic acid are specified in this review, and their sources, models, efficacy are described. It is concluded that the mechanisms of these components for the treatment of obesity include: (i) suppression of appetite, increase of satiety, reduction of energy intake; (ii) reduction in the digestion and absorption of exogenous lipid; (iii) attenuation of the synthesis of endogenous lipid; (iv) promotion of the oxidation and expenditure of lipid and (v) improvement of lipid metabolism disorder. Authors believe that the effective compounds from TCM will provide an alternative and hopeful way for the treatment of obesity. © 2014 World Obesity.

  1. Differential natural organic matter fouling of ceramic versus polymeric ultrafiltration membranes.

    Science.gov (United States)

    Lee, Seung-Jin; Kim, Jae-Hong

    2014-01-01

    Ceramic ultrafiltration membranes has drawn increasing attention in drinking water treatment sectors as an alternative to traditional polymeric counterparts, yet only limited information has been made available about the characteristics of ceramic membrane fouling by natural organic matter. The effects of solution chemistry including ionic strength, divalent ion concentration and pH on the flux behavior were comparatively evaluated for ceramic and polymeric ultrafiltration of synthetic water containing model natural organic matter. Filtration characteristics were further probed via resistance-in-series model analysis, fouling visualization using quantum dots, batch adsorption test, contact angle measurement, solute-membrane surface adhesion force measurement, and quantitative comparison of fouling characteristics between ceramic and polymeric membranes. The results collectively suggested that the effects of solution chemistry on fouling behavior of ceramic membranes were generally similar to polymeric counterparts in terms of trends, while the extent varied significantly depending on water quality parameters. Lower fouling tendency and enhanced cleaning efficiency were observed with the ceramic membrane, further promoting the potential for ceramic membrane application to surface water treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Differential impact of lipoxygenase 2 and jasmonates on natural and stress-induced senescence in Arabidopsis.

    Science.gov (United States)

    Seltmann, Martin A; Stingl, Nadja E; Lautenschlaeger, Jens K; Krischke, Markus; Mueller, Martin J; Berger, Susanne

    2010-04-01

    Jasmonic acid and related oxylipins are controversially discussed to be involved in regulating the initiation and progression of leaf senescence. To this end, we analyzed profiles of free and esterified oxylipins during natural senescence and upon induction of senescence-like phenotypes by dark treatment and flotation on sorbitol in Arabidopsis (Arabidopsis thaliana). Jasmonic acid and free 12-oxo-phytodienoic acid increased during all three processes, with the strongest increase of jasmonic acid after dark treatment. Arabidopside content only increased considerably in response to sorbitol treatment. Monogalactosyldiacylglycerols and digalactosyldiacylglycerols decreased during these treatments and aging. Lipoxygenase 2-RNA interference (RNAi) plants were generated, which constitutively produce jasmonic acid and 12-oxo-phytodienoic acid but do not exhibit accumulation during natural senescence or upon stress treatment. Chlorophyll loss during aging and upon dark incubation was not altered, suggesting that these oxylipins are not involved in these processes. In contrast, lipoxygenase 2-RNAi lines and the allene oxid synthase-deficient mutant dde2 were less sensitive to sorbitol than the wild type, indicating that oxylipins contribute to the response to sorbitol stress.

  3. Natural variation in Arabidopsis thaliana as a tool for highlighting differential drought responses.

    Directory of Open Access Journals (Sweden)

    Oumaya Bouchabke

    Full Text Available To test whether natural variation in Arabidopsis could be used to dissect out the genetic basis of responses to drought stress, we characterised a number of accessions. Most of the accessions belong to a core collection that was shown to maximise the genetic diversity captured for a given number of individual accessions in Arabidopsis thaliana. We measured total leaf area (TLA, Electrolyte Leakage (EL, Relative Water Content (RWC, and Cut Rosette Water Loss (CRWL in control and mild water deficit conditions. A Principal Component Analysis revealed which traits explain most of the variation and showed that some accessions behave differently compared to the others in drought conditions, these included Ita-0, Cvi-0 and Shahdara. This study relied on genetic variation found naturally within the species, in which populations are assumed to be adapted to their environment. Overall, Arabidopsis thaliana showed interesting phenotypic variations in response to mild water deficit that can be exploited to identify genes and alleles important for this complex trait.

  4. Impacts of ICT on the Spatial Differentiation of Social Vulnerability to Natural Hazards in Poland

    Directory of Open Access Journals (Sweden)

    Werner Piotr

    2015-12-01

    Full Text Available The development of information and communication technologies (ICTs has significant economic and social impacts at both the global and regional level. Some of these implications have been perceived as positive and unexpected. While both the positive and negative social and economic impacts have been highlighted in the literature, opinions on these impacts remain ambiguous. Those aspects considered to be advantageous include faster communication, ease of use, development in the range of services and revenues, and an increase in individuals’ free time allowance. ICT penetrates all branches of the economy as a set of general purpose technologies. New information and communication technologies ease everyday life, serve as tools to help people in extreme situations, e.g. accidents, illnesses or natural disasters, and are also the pillars of contemporary entertainment media. The usefulness of ICT has been stressed and loudly disseminated to a large extent by the media. On the other hand, these new technologies sensitize society in quite new ways to the well-known natural hazards that people have encountered in the past.

  5. Differentiation of naturally-occurring vs. artificial hydrocarbons in a landfill groundwater investigation

    International Nuclear Information System (INIS)

    Beaver, J.L.; Hartness, J.A.; Breeding, L.B.; Buchanan, D.M.

    1994-01-01

    Interpretation of groundwater sampling data at a large municipal/industrial landfill indicates contamination by both artificial and naturally-occurring hydrocarbons. Site hydrogeology consists of three different water bearing zones. The uppermost (shallow) aquifer is an unconfined unit consisting of silt, clay, and sand deposits. An intermediate depth semiconfined aquifer underlies the unconfined unit, and consists of a chert rubble zone and the upper portion of a fractured and solution-enhanced limestone formation. A regionally-extensive organic-rich shale underlies the semiconfined aquifer and separates it from the deep confined aquifer, which also consists of limestone. Groundwater investigations at the landfill have detected chlorinated and non-chlorinated hydrocarbons in the different aquifer intervals. Chlorinated hydrocarbons detected include tetrachloroethene, dichloroethene, and vinyl chloride and occur almost exclusively in the shallow aquifer. Aromatic hydrocarbons detected include benzene, toluene, ethylbenzene, and xylene (BTEX) and-occur in the intermediate and deep aquifers. The landfill was originally interpreted as the source of the contaminants. The observation of free-phase liquid hydrocarbons in the intermediate aquifer at the site, and high dissolved BTEX levels in the deep and intermediate aquifers upgradient of the landfill suggest that the aromatics were derived from a source other than the landfill. A potential source of BTEX contamination may be abandoned (pre-1930) natural gas wells located near the landfill. An additional BTEX source may be the organic-rich shale formation (a documented petroleum source rock)

  6. Differential responses to natural and recombinant allergens in a murine model of fish allergy.

    Science.gov (United States)

    van der Ventel, Michelle L; Nieuwenhuizen, Natalie E; Kirstein, Frank; Hikuam, Christoph; Jeebhay, Mohamed F; Swoboda, Ines; Brombacher, Frank; Lopata, Andreas L

    2011-01-01

    Aerosolized fish proteins are an important cause of allergic airway reactions in both the domestic and the occupational environment. The aim of this study was to investigate inhalant fish-induced allergy in a mouse model and compare immune responses generated by raw and heat-treated fish extracts as well as natural and recombinant forms of the major fish allergen parvalbumin. Mice were sensitized with raw or cooked pilchard extract and challenged intranasally with cooked pilchard extract, purified natural pilchard parvalbumin or recombinant carp parvalbumin (rCyp c1.01). Cooked pilchard extract predominantly sensitized mice to parvalbumin and induced specific IgG1 and IgE antibodies against both pilchard parvalbumin and rCyp c1.01, whereas additional allergens were recognized by mice sensitized with raw extract, including a 36 kDa allergen that was also recognized by fish processing workers and was identified as glyceraldehyde-3-phosphate dehydrogenase. Mice challenged with cooked extract and purified pilchard parvalbumin had increased Th2 cytokine production in mediastinal lymph node cells and splenocytes, whereas mice challenged with rCyp c1.01 did not. This study identifies a new IgE-binding protein that may be important in occupational allergy to fish and demonstrates the feasibility of testing recombinant allergens for immunotherapeutic potential in vivo. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Targeting activator protein 1 signaling pathway by bioactive natural agents: Possible therapeutic strategy for cancer prevention and intervention.

    Science.gov (United States)

    Tewari, Devesh; Nabavi, Seyed Fazel; Nabavi, Seyed Mohammad; Sureda, Antoni; Farooqi, Ammad Ahmad; Atanasov, Atanas G; Vacca, Rosa Anna; Sethi, Gautam; Bishayee, Anupam

    2018-02-01

    Activator protein 1 (AP-1) is a key transcription factor in the control of several cellular processes responsible for cell survival proliferation and differentiation. Dysfunctional AP-1 expression and activity are involved in several severe diseases, especially inflammatory disorders and cancer. Therefore, targeting AP-1 has recently emerged as an attractive therapeutic strategy for cancer prevention and therapy. This review summarizes our current understanding of AP-1 biology and function as well as explores and discusses several natural bioactive compounds modulating AP-1-associated signaling pathways for cancer prevention and intervention. Current limitations, challenges, and future directions of research are also critically discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Linguistic confusion in economics: utility, causality, product differentiation, and the supply of natural resources.

    Science.gov (United States)

    Simon, J L

    1982-01-01

    Lack of careful attention to the language used in the discussion of economic concepts has resulted in considerable confusion and error. 2 frequent sources of confusion include tautology and the absence of operational definitions of concepts. This paper outlines a more effective scientific practice through reference to 2 economic examples: 1) the concept of utility, where it is demonstrated that choice of an operational definition of the concept facilitates interpersonal comparisons; and 2) causality, where a multidimensional operational definition is needed to discriminate among the various meanings of the term in theoretical, empirical, and policy contexts. The paper further discusses the example of natural resource scarcity, where application of the term "finite" reveals that there is no empirical evidence of physical limits to growth in the use of resources. A more appropriate measure of scarcity is the economic concept of price.

  9. Was Queen Victoria depressed? 1. Natural history and differential diagnosis of presenting problem.

    Science.gov (United States)

    Powles, W E; Alexander, M G

    1987-02-01

    For some years we have speculated as to whether Queen Victoria suffered a definable psychiatric illness in her notorious and prolonged seclusion after the Prince Consort's death. We here summarize criteria for grief and depression from three authorities. Against these, we examine the natural history of the Queen's bereavement and restitution. We find that her suffering and her portrayal of the role of widow were related to her personal style and were culturally accepted. Her self-esteem, ego functions, and object relatedness were preserved. While some clinicians might favour a diagnosis of Dysthymic Disorder, we find the evidence strongly in favour of an intense, prolonged, normal human grief (Uncomplicated Bereavement of DSM III) coloured by a romantic and histrionic personal style. Intensity and duration do not, in this case, establish a diagnosis of depression.

  10. Differential CCR7 Targeting in Dendritic Cells by Three Naturally Occurring CC-Chemokines

    DEFF Research Database (Denmark)

    Hjorto, Gertrud M.; Larsen, Olav; Steen, Anne

    2016-01-01

    The CCR7 ligands CCL19 and CCL21 are increasingly recognized as functionally different (biased). Using mature human dendritic cells (DCs), we show that CCL19 is more potent than CCL21 in inducing 3D chemotaxis. Intriguingly, CCL21 induces prolonged and more efficient ERK1/2 activation compared...

  11. The euryhaline yeast Debaryomyces hansenii has two catalase genes encoding enzymes with differential activity profile.

    Science.gov (United States)

    Segal-Kischinevzky, Claudia; Rodarte-Murguía, Beatriz; Valdés-López, Victor; Mendoza-Hernández, Guillermo; González, Alicia; Alba-Lois, Luisa

    2011-03-01

    Debaryomyces hansenii is a spoilage yeast able to grow in a variety of ecological niches, from seawater to dairy products. Results presented in this article show that (i) D. hansenii has an inherent resistance to H2O2 which could be attributed to the fact that this yeast has a basal catalase activity which is several-fold higher than that observed in Saccharomyces cerevisiae under the same culture conditions, (ii) D. hansenii has two genes (DhCTA1 and DhCTT1) encoding two catalase isozymes with a differential enzymatic activity profile which is not strictly correlated with a differential expression profile of the encoding genes.

  12. Correlation Water Velocity and TSS with Natural Radionuclides Activity

    International Nuclear Information System (INIS)

    Tri Harningsih; Muzakky; Agus Taftazani

    2007-01-01

    Correlation water velocity and TSS with natural radionuclides activity has been studied. For that purpose, the study is to correlation water velocity and TSS with radionuclides on water and sediment samples in alongside river Code Yogyakarta. This research selected radionuclides, for examples Ra-226, Pb-212, Ac- 228, and K-40. Election of this radionuclides to spread over gamma gross composition alongside river of Code. Gamma gross influenced by water velocity and TSS, so that require to correct between water velocity and TSS to radionuclides. Sampling water and sediment conducted when dry season of August, 2006 at 11 locations, start from Boyong Bridge until Pacar Bridge. Result of analysis showed that water velocity range from 8-1070 L/dt and TSS range from 2.81 E-06 - 8.02 E-04 mg/L. The accumulation of radionuclides in water samples non correction water velocity for Ra-226: 0.302-2.861 Bq/L, Pb-212: 0.400-3.390 Bq/L, Ac- 228: 0.0029-0.0047 Bq/L and K-40: 0.780-9.178 Bq/L. The accumulation of radionuclide in water samples correction water velocity for Ra-226: 1.112-70.454 Bq/L, Pb-212: 0.850-77.113 Bq/L, Ac-228: 0.7187- 60.859 Bq/L and K-40: 2.420-208.8 Bq/L. While distribution of radionuclide in sediment for the Ra-226: 0.0012-0.0211 Bq/kg, Pb-212: 0.0017-0.0371 Bq/kg, Ac-228: 0.0021-0.0073 Bq/kg and K-40: 0.0006-0.0084 Bq/kg. (author)

  13. People participation in natural outdoors recreation activities and its ...

    African Journals Online (AJOL)

    ... of the visitors believe natural outdoor recreation in the south-west of the country ... These identified benefits of Natural Outdoors Recreational in the course of the ... promotion, employment, urban aesthetic, healthy livings and improve tourism ... outdoor recreation centres to augment medical service in improving life span ...

  14. Differentiating the Spatiotemporal Distribution of Natural and Anthropogenic Processes on River Water-Quality Variation Using a Self-Organizing Map With Factor Analysis.

    Science.gov (United States)

    Wang, Yeuh-Bin; Liu, Chen-Wuing; Lee, Jin-Jing

    2015-08-01

    To elucidate the historical improvement and advanced measure of river water quality in the Taipei metropolitan area, this study applied the self-organizing map (SOM) technique with factor analysis (FA) to differentiate the spatiotemporal distribution of natural and anthropogenic processes on river water-quality variation spanning two decades. The SOM clustered river water quality into five groups: very low pollution, low pollution, moderate pollution, high pollution, and very high pollution. FA was then used to extract four latent factors that dominated water quality from 1991 to 2011 including three anthropogenic process factors (organic, industrial, and copper pollution) and one natural process factor [suspended solids (SS) pollution]. The SOM revealed that the water quality improved substantially over time. However, the downstream river water quality was still classified as high pollution because of an increase in anthropogenic activity. FA showed the spatiotemporal pattern of each factor score decreasing over time, but the organic pollution factor downstream of the Tamsui River, as well as the SS factor scores in the upstream major tributary (the Dahan Stream), remained within the high pollution level. Therefore, we suggest that public sewage-treatment plants should be upgraded from their current secondary biological processing to advanced treatment processing. The conservation of water and soil must also be reinforced to decrease the SS loading of the Dahan Stream from natural erosion processes in the future.

  15. NMDA modulates oligodendrocyte differentiation of subventricular zone cells through PKC activation

    Directory of Open Access Journals (Sweden)

    Fabio eCavaliere

    2013-12-01

    Full Text Available Multipotent cells from the juvenile subventricular zone (SVZ possess the ability to differentiate into new neural cells. Depending on local signals, SVZ can generate new neurons, astrocytes or oligodendrocytes. We previously demonstrated that activation of NMDA receptors in SVZ progenitors increases the rate of oligodendrocyte differentiation. Here we investigated the mechanisms involved in NMDA receptor-dependent differentiation. Using functional studies performed with the reporter gene luciferase we found that activation of NMDA receptor stimulates PKC. In turn, stimulation of PKC precedes the activation of NADPH oxidase (NOX as demonstrated by translocation of the p67phox subunit to the cellular membrane. We propose that NOX2 is involved in the transduction of the signal from NMDA receptors through PKC activation as the inhibitor gp91 reduced their pro-differentiation effect. In addition, our data and that from other groups suggest that signaling through the NMDA receptor/PKC/NOX2 cascade generates ROS that activate the PI3/mTOR pathway and finally leads to the generation of new oligodendrocytes.

  16. CHD1 regulates cell fate determination by activation of differentiation-induced genes

    DEFF Research Database (Denmark)

    Baumgart, Simon J; Najafova, Zeynab; Hossan, Tareq

    2017-01-01

    The coordinated temporal and spatial activation of gene expression is essential for proper stem cell differentiation. The Chromodomain Helicase DNA-binding protein 1 (CHD1) is a chromatin remodeler closely associated with transcription and nucleosome turnover downstream of the transcriptional start...... site (TSS). In this study, we show that CHD1 is required for the induction of osteoblast-specific gene expression, extracellular-matrix mineralization and ectopic bone formation in vivo. Genome-wide occupancy analyses revealed increased CHD1 occupancy around the TSS of differentiation-activated genes....... Furthermore, we observed that CHD1-dependent genes are mainly induced during osteoblast differentiation and are characterized by higher levels of CHD1 occupancy around the TSS. Interestingly, CHD1 depletion resulted in increased pausing of RNA Polymerase II (RNAPII) and decreased H2A.Z occupancy close...

  17. The Transcription Factor AHR Prevents the Differentiation of a Stage 3 Innate Lymphoid Cell Subset to Natural Killer Cells

    Directory of Open Access Journals (Sweden)

    Tiffany Hughes

    2014-07-01

    Full Text Available Accumulating evidence indicates that human natural killer (NK cells develop in secondary lymphoid tissue (SLT through a so-called “stage 3” developmental intermediate minimally characterized by a CD34−CD117+CD94− immunophenotype that lacks mature NK cell function. This stage 3 population is heterogeneous, potentially composed of functionally distinct innate lymphoid cell (ILC types that include interleukin-1 receptor (IL-1R1-positive, IL-22-producing ILC3s. Whether human ILC3s are developmentally related to NK cells is a subject of ongoing investigation. Here, we show that antagonism of the aryl hydrocarbon receptor (AHR or silencing of AHR gene expression promotes the differentiation of tonsillar IL-22-producing IL-1R1hi human ILC3s to CD56brightCD94+ interferon (IFN-γ-producing cytolytic mature NK cells expressing eomesodermin (EOMES and T-Box Protein 21 (TBX21 or TBET. Hence, we demonstrate the lineage plasticity of human ILCs by identifying AHR as a transcription factor that prevents IL-1R1hi ILC3s from differentiating into NK cells.

  18. Natural abundant solid state NMR studies in designed tripeptides for differentiation of multiple conformers.

    Science.gov (United States)

    Jayanthi, S; Chatterjee, Bhaswati; Raghothama, S

    2009-10-01

    Solid state NMR (SSNMR) experiments on heteronuclei in natural abundance are described for three synthetically designed tripeptides Piv-(L)Pro-(L)Pro-(L)Phe-OMe (1), Piv-(D)Pro-(L)Pro-(L)Phe-OMe (2), and Piv-(D)Pro-(L)Pro-(L)Phe-NHMe (3). These peptides exist in different conformation as shown by solution state NMR and single crystal X-ray analysis (Chatterjee et al., Chem Eur J 2008, 14, 6192). In this study, SSNMR has been used to probe the conformations of these peptides in their powder form. The (13)C spectrum of peptide (1) showed doubling of resonances corresponding to cis/cis form, unlike in solution where the similar doubling is attributed to cis/trans form. This has been confirmed by the chemical shift differences of C(beta) and C(gamma) carbon of Proline in peptide (1) both in solution and SSNMR. Peptide (2) and (3) provided single set of resonances which represented all trans form across the di-Proline segment. The results are in agreement with the X-ray analysis. Solid state (15)N resonances, especially from Proline residues provided additional information, which is normally not observable in solution state NMR. (1)H chemical shifts are also obtained from a two-dimensional heteronuclear correlation experiment between (1)H--(13)C. The results confirm the utility of NMR as a useful tool for identifying different conformers in peptides in the solid state. (c) 2009 Wiley Periodicals, Inc. Biopolymers 91: 851-860, 2009.

  19. Genetic, epigenetic, and HPLC fingerprint differentiation between natural and ex situ populations of Rhodiola sachalinensis from Changbai Mountain, China.

    Directory of Open Access Journals (Sweden)

    Wei Zhao

    Full Text Available Rhodiola sachalinensis is an endangered species with important medicinal value. We used inter-simple sequence repeat (ISSR and methylation-sensitive amplified polymorphism (MSAP markers to analyze genetic and epigenetic differentiation in different populations of R. sachalinensis, including three natural populations and an ex situ population. Chromatographic fingerprint was used to reveal HPLC fingerprint differentiation. According to our results, the ex situ population of R. sachalinensis has higher level genetic diversity and greater HPLC fingerprint variation than natural populations, but shows lower epigenetic diversity. Most genetic variation (54.88% was found to be distributed within populations, and epigenetic variation was primarily distributed among populations (63.87%. UPGMA cluster analysis of ISSR and MSAP data showed identical results, with individuals from each given population grouping together. The results of UPGMA cluster analysis of HPLC fingerprint patterns was significantly different from results obtained from ISSR and MSAP data. Correlation analysis revealed close relationships among altitude, genetic structure, epigenetic structure, and HPLC fingerprint patterns (R2 = 0.98 for genetic and epigenetic distance; R2 = 0.90 for DNA methylation level and altitude; R2 = -0.95 for HPLC fingerprint and altitude. Taken together, our results indicate that ex situ population of R. sachalinensis show significantly different genetic and epigenetic population structures and HPLC fingerprint patterns. Along with other potential explanations, these findings suggest that the ex situ environmental factors caused by different altitude play an important role in keeping hereditary characteristic of R. sachalinensis.

  20. Differentially expressed genes linked to natural variation in long-term memory formation in Cotesia parasitic wasps

    Directory of Open Access Journals (Sweden)

    Joke J. F. A. Van Vugt

    2015-09-01

    Full Text Available Even though learning and memory are universal traits in the Animal Kingdom, closely related species reveal substantial variation in learning rate and memory dynamics. To determine the genetic background of this natural variation, we studied two congeneric parasitic wasp species, Cotesia glomerata and C. rubecula, which lay their eggs in caterpillars of the large and small cabbage white butterfly. A successful egg laying event serves as an unconditioned stimulus in a classical conditioning paradigm, where plant odors become associated to the encounter of a suitable host caterpillar. Depending on the host species, the number of conditioning trials and the parasitic wasp species, three different types of transcription-dependent long-term memory (LTM and one type of transcription-independent, anesthesia-resistant memory (ARM can be distinguished. To identify transcripts underlying these differences in memory formation, we isolated mRNA from parasitic wasp heads at three different time points between induction and consolidation of each of the four memory types, and for each sample three biological replicates, where after strand-specific paired-end 100 bp deep sequencing. Transcriptomes were assembled de novo and differential expression was determined for each memory type and time point after conditioning, compared to unconditioned wasps. Most differentially expressed (DE genes and antisense transcripts were only DE in one of the LTM types. Among the DE genes that were DE in two or more LTM types, were many protein kinases and phosphatases, small GTPases, receptors and ion channels. Some genes were DE in opposing directions between any of the LTM memory types and ARM, suggesting that ARM in Cotesia requires the transcription of genes inhibiting LTM or vice versa. We discuss our findings in the context of neuronal functioning, including RNA splicing and transport, epigenetic regulation, neurotransmitter/peptide synthesis and antisense transcription. In

  1. Genetic, epigenetic, and HPLC fingerprint differentiation between natural and ex situ populations of Rhodiola sachalinensis from Changbai Mountain, China.

    Science.gov (United States)

    Zhao, Wei; Shi, Xiaozheng; Li, Jiangnan; Guo, Wei; Liu, Chengbai; Chen, Xia

    2014-01-01

    Rhodiola sachalinensis is an endangered species with important medicinal value. We used inter-simple sequence repeat (ISSR) and methylation-sensitive amplified polymorphism (MSAP) markers to analyze genetic and epigenetic differentiation in different populations of R. sachalinensis, including three natural populations and an ex situ population. Chromatographic fingerprint was used to reveal HPLC fingerprint differentiation. According to our results, the ex situ population of R. sachalinensis has higher level genetic diversity and greater HPLC fingerprint variation than natural populations, but shows lower epigenetic diversity. Most genetic variation (54.88%) was found to be distributed within populations, and epigenetic variation was primarily distributed among populations (63.87%). UPGMA cluster analysis of ISSR and MSAP data showed identical results, with individuals from each given population grouping together. The results of UPGMA cluster analysis of HPLC fingerprint patterns was significantly different from results obtained from ISSR and MSAP data. Correlation analysis revealed close relationships among altitude, genetic structure, epigenetic structure, and HPLC fingerprint patterns (R2 = 0.98 for genetic and epigenetic distance; R2 = 0.90 for DNA methylation level and altitude; R2 = -0.95 for HPLC fingerprint and altitude). Taken together, our results indicate that ex situ population of R. sachalinensis show significantly different genetic and epigenetic population structures and HPLC fingerprint patterns. Along with other potential explanations, these findings suggest that the ex situ environmental factors caused by different altitude play an important role in keeping hereditary characteristic of R. sachalinensis.

  2. Organotins Are Potent Activators of PPARγ and Adipocyte Differentiation in Bone Marrow Multipotent Mesenchymal Stromal Cells

    Science.gov (United States)

    Yanik, Susan C.; Baker, Amelia H.; Mann, Koren K.; Schlezinger, Jennifer J.

    2011-01-01

    Adipocyte differentiation in bone marrow is potentially deleterious to both bone integrity and lymphopoiesis. Here, we examine the hypothesis that organotins, common environmental contaminants that are dual ligands for peroxisome proliferator–activated receptor (PPAR) γ and its heterodimerization partner retinoid X receptor (RXR), are potent activators of bone marrow adipogenesis. A C57Bl/6-derived bone marrow multipotent mesenchymal stromal cell (MSC) line, BMS2, was treated with rosiglitazone, a PPARγ agonist, bexarotene, an RXR agonist, or a series of organotins. Rosiglitazone and bexarotene potently activated adipocyte differentiation; however, bexarotene had a maximal efficacy of only 20% of that induced by rosiglitazone. Organotins (tributyltin [TBT], triphenyltin, and dibutyltin) also stimulated adipocyte differentiation (EC50 of 10–20nM) but with submaximal, structure-dependent efficacy. In coexposures, both bexarotene and TBT enhanced rosiglitazone-induced adipogenesis. To investigate the contribution of PPARγ to TBT-induced adipogenesis, we examined expression of PPARγ2, as well as its transcriptional target FABP4. TBT-induced PPARγ2 and FABP4 protein expression with an efficacy intermediate between rosiglitazone and bexarotene, similar to lipid accumulation. A PPARγ antagonist and PPARγ-specific small hairpin RNA suppressed TBT-induced differentiation, although to a lesser extent than rosiglitazone-induced differentiation, suggesting that TBT may engage alternate pathways. TBT and bexarotene, but not rosiglitazone, also induced the expression of TGM2 (an RXR target) and ABCA1 (a liver X receptor target). The results show that an environmental contaminant, acting with the same potency as a therapeutic drug, induces PPARγ-dependent adipocyte differentiation in bone marrow MSCs. Activation of multiple nuclear receptor pathways by organotins may have significant implications for bone physiology. PMID:21622945

  3. Human Activity Differentially Redistributes Large Mammals in the Canadian Rockies National Parks

    Directory of Open Access Journals (Sweden)

    James Kimo. Rogala

    2011-09-01

    Full Text Available National parks are important for conservation of species such as wolves (Canis lupus and elk (Cervus canadensis. However, topography, vegetation conditions, and anthropogenic infrastructure within parks may limit available habitat. Human activity on trails and roads may lead to indirect habitat loss, further limiting available habitat. Predators and prey may respond differentially to human activity, potentially disrupting ecological processes. However, research on such impacts to wildlife is incomplete, especially at fine spatial and temporal scales. Our research investigated the relationship between wolf and elk distribution and human activity using fine-scale Global Positioning System (GPS wildlife telemetry locations and hourly human activity measures on trails and roads in Banff, Kootenay, and Yoho National Parks, Canada. We observed a complex interaction between the distance animals were located from trails and human activity level resulting in species adopting both mutual avoidance and differential response behaviors. In areas < 50 m from trails human activity led to a mutual avoidance response by both wolves and elk. In areas 50 - 400 m from trails low levels of human activity led to differential responses; wolves avoided these areas, whereas elk appeared to use these areas as a predation refugia. These differential impacts on elk and wolves may have important implications for trophic dynamics. As human activity increased above two people/hour, areas 50 - 400 m from trails were mutually avoided by both species, resulting in the indirect loss of important montane habitat. If park managers are concerned with human impacts on wolves and elk, or on these species' trophic interactions with other species, they can monitor locations near trails and roads and consider hourly changes of human activity levels in areas important to wildlife.

  4. Natural differentiation in the teaching of mathematics to children starting school

    Directory of Open Access Journals (Sweden)

    Petra Scherer

    2013-06-01

    Full Text Available This article presents a number of carefully selected activities for the mathematics classroom in the early grades. The motivation for their selection is the development of concepts rather than the learning of the procedural skills of arithmetic. As the teacher is faced with a great heterogeneity of children starting school, the concrete learning environment should fulfil several requirements. On the one hand, the environment has to represent core mathematical principles, and, on the other hand, they have to be suitable for all learners in an inclusive classroom. The concrete formats themselves serve a specific conceptual purpose, while, at the same time, addressing, in an integrated way, the needs of a variety of learners with different levels of competence.

  5. Diosgenin promotes oligodendrocyte progenitor cell differentiation through estrogen receptor-mediated ERK1/2 activation to accelerate remyelination.

    Science.gov (United States)

    Xiao, Lin; Guo, Dazhi; Hu, Chun; Shen, Weiran; Shan, Lei; Li, Cui; Liu, Xiuyun; Yang, Wenjing; Zhang, Weidong; He, Cheng

    2012-07-01

    Differentiation of oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes is a prerequisite for remyelination after demyelination, and impairment of this process is suggested to be a major reason for remyelination failure. Diosgenin, a plant-derived steroid, has been implicated for therapeutic use in many diseases, but little is known about its effect on the central nervous system. In this study, using a purified rat OPC culture model, we show that diosgenin significantly and specifically promotes OPC differentiation without affecting the viability, proliferation, or migration of OPC. Interestingly, the effect of diosgenin can be blocked by estrogen receptor (ER) antagonist ICI 182780 but not by glucocorticoid and progesterone receptor antagonist RU38486, nor by mineralocorticoid receptor antagonist spirolactone. Moreover, it is revealed that both ER-alpha and ER-beta are expressed in OPC, and diosgenin can activate the extracellular signal-regulated kinase 1/2 (ERK1/2) in OPC via ER. The pro-differentiation effect of diosgenin can also be obstructed by the ERK inhibitor PD98059. Furthermore, in the cuprizone-induced demyelination model, it is demonstrated that diosgenin administration significantly accelerates/enhances remyelination as detected by Luxol fast blue stain, MBP immunohistochemistry and real time RT-PCR. Diosgenin also increases the number of mature oligodendrocytes in the corpus callosum while it does not affect the number of OPCs. Taking together, our results suggest that diosgenin promotes the differentiation of OPC into mature oligodendrocyte through an ER-mediated ERK1/2 activation pathway to accelerate remyelination, which implicates a novel therapeutic usage of this steroidal natural product in demyelinating diseases such as multiple sclerosis (MS). Copyright © 2012 Wiley Periodicals, Inc.

  6. Black ginseng activates Akt signaling, thereby enhancing myoblast differentiation and myotube growth

    Directory of Open Access Journals (Sweden)

    Soo-Yeon Lee

    2018-01-01

    Conclusion: BG enhances myoblast differentiation and myotube hypertrophy by activating Akt/mTOR/p70S6k axis. Thus, our study demonstrates that BG has promising potential to treat or prevent muscle loss related to aging or other pathological conditions, such as diabetes.

  7. Task Rotation: Strategies for Differentiating Activities and Assessments by Learning Style. A Strategic Teacher PLC Guide

    Science.gov (United States)

    Silver, Harvey; Moirao, Daniel; Jackson, Joyce

    2011-01-01

    One of the hardest jobs in teaching is to differentiate learning activities and assessments to your students' learning styles. But you and your colleagues can learn how to do this together when each of you has this guide to the Task Rotation strategy from our ultimate guide to teaching strategies, "The Strategic Teacher". Use the guide in your…

  8. Improved of Natural Gas Storage with Adsorbed Natural Gas (ANG) Technology Using Activated Carbon from Plastic Waste Polyethylene Terepthalate

    Science.gov (United States)

    Yuliusman; Nasruddin; Sanal, A.; Bernama, A.; Haris, F.; Hardhi, M.

    2017-07-01

    Indonesia imports high amount of Fuel Oil. Although Indonesia has abundant amount of natural gas reserve, the obstacle lies within the process of natural gas storage itself. In order to create a safe repository, the ANG (Adsorbed Natural Gas) technology is planned. ANG technology in itself has been researched much to manufacture PET-based activated carbon for natural gas storage, but ANG still has several drawbacks. This study begins with making preparations for the equipment and materials that will be used, by characterizing the natural gas, measuring the empty volume, and degassing. The next step will be to examine the adsorption process. The maximum storage capacity obtained in this study for a temperature of 27°C and pressure of 35 bar is 0.0586 kg/kg, while for the desorption process, a maximum value for desorption efficiency was obtained on 35°C temperature with a value of 73.39%.

  9. Differentiation of human lymphocytes into nuclear vlimata by meiosis. The cytotoxic effect of calcium-activated neutral proteinase inhibitor

    OpenAIRE

    Logothetou-Rella, H.

    1994-01-01

    Phytohaemagglutinin (PHA)-activated lymphocytes differentiated into nuclear vlimata (NVs) in vitro. Lymphocyte attachment was followed by formation and extrusion of cytoplasmic vesicles. nuclear elongation and fragmentation into NVs. NVs and cytoplasmic vesicles were detached and organized into large cell nodules in suspension. Immunocytochemistry showed that T-lymphocytes differentiated mainly to NVs while B-lymphocytes to buds. During differentiation ther...

  10. Intracellular glutathione status regulates mouse bone marrow monocyte-derived macrophage differentiation and phagocytic activity

    International Nuclear Information System (INIS)

    Kim, Jin-Man; Kim, Hyunsoo; Kwon, Soon Bok; Lee, Soo Young; Chung, Sung-Chang; Jeong, Dae-Won; Min, Byung-Moo

    2004-01-01

    Although a redox shift can regulate the development of cells, including proliferation, differentiation, and survival, the role of the glutathione (GSH) redox status in macrophage differentiation remains unclear. In order to elucidate the role of a redox shift, macrophage-like cells were differentiated from the bone marrow-derived monocytes that were treated with a macrophage colony stimulating factor (M-CSF or CSF-1) for 3 days. The macrophagic cells were characterized by a time-dependent increase in three major symptoms: the number of phagocytic cells, the number of adherent cells, and the mRNA expression of c-fms, a M-CSF receptor that is one of the macrophage-specific markers and mediates development signals. Upon M-CSF-driven macrophage differentiation, the GSH/GSSG ratio was significantly lower on day 1 than that observed on day 0 but was constant on days 1-3. To assess the effect of the GSH-depleted and -repleted status on the differentiation and phagocytosis of the macrophages, GSH depletion by BSO, a specific inhibitor of the de novo GSH synthesis, inhibited the formation of the adherent macrophagic cells by the down-regulation of c-fms, but did not affect the phagocytic activity of the macrophages. To the contrary, GSH repletion by the addition of NAC, which is a GSH precursor, or reduced GSH in media had no effect on macrophage differentiation, and led to a decrease in the phagocytic activity. Furthermore, we observed that there is checkpoint that is capable of releasing from the inhibition of the formation of the adherent macrophagic cells according to GSH depletion by BSO. Summarizing, these results indicate that the intracellular GSH status plays an important role in the differentiation and phagocytosis of macrophages

  11. Alcohol Inhibits Odontogenic Differentiation of Human Dental Pulp Cells by Activating mTOR Signaling

    Directory of Open Access Journals (Sweden)

    Wei Qin

    2017-01-01

    Full Text Available Long-term heavy alcohol consumption could result in a range of health, social, and behavioral problems. People who abuse alcohol are at high risks of seriously having osteopenia, periodontal disease, and compromised oral health. However, the role of ethanol (EtOH in the biological functions of human dental pulp cells (DPCs is unknown. Whether EtOH affects the odontoblastic differentiation of DPCs through the mechanistic target of rapamycin (mTOR remains unexplored. The objective of this study was to investigate the effects of EtOH on DPC differentiation and mineralization. DPCs were isolated and purified from human dental pulps. The proliferation and odontoblastic differentiation of DPCs treated with EtOH were subsequently investigated. Different doses of EtOH were shown to be cytocompatible with DPCs. EtOH significantly activated the mTOR pathway in a dose-dependent manner. In addition, EtOH downregulated the alkaline phosphatase activity, attenuated the mineralized nodule formation, and suppressed the expression of odontoblastic markers including ALP, DSPP, DMP-1, Runx2, and OCN. Moreover, the pretreatment with rapamycin, a specific mTOR inhibitor, markedly reversed the EtOH-induced odontoblastic differentiation and cell mineralization. Our findings show for the first time that EtOH can suppress DPC differentiation and mineralization in a mTOR-dependent manner, indicating that EtOH may be involved in negatively regulating the dental pulp repair.

  12. TET2 Regulates Mast Cell Differentiation and Proliferation through Catalytic and Non-catalytic Activities

    Directory of Open Access Journals (Sweden)

    Sara Montagner

    2016-05-01

    Full Text Available Summary: Dioxygenases of the TET family impact genome functions by converting 5-methylcytosine (5mC in DNA to 5-hydroxymethylcytosine (5hmC. Here, we identified TET2 as a crucial regulator of mast cell differentiation and proliferation. In the absence of TET2, mast cells showed disrupted gene expression and altered genome-wide 5hmC deposition, especially at enhancers and in the proximity of downregulated genes. Impaired differentiation of Tet2-ablated cells could be relieved or further exacerbated by modulating the activity of other TET family members, and mechanistically it could be linked to the dysregulated expression of C/EBP family transcription factors. Conversely, the marked increase in proliferation induced by the loss of TET2 could be rescued exclusively by re-expression of wild-type or catalytically inactive TET2. Our data indicate that, in the absence of TET2, mast cell differentiation is under the control of compensatory mechanisms mediated by other TET family members, while proliferation is strictly dependent on TET2 expression. : The impact of TET enzymes on gene expression and cell function is incompletely understood. Montagner et al. investigate the TET-mediated regulation of mast cell differentiation and function, uncover transcriptional pathways regulated by TET2, and identify both enzymatic activity-dependent and -independent functions of TET2. Keywords: differentiation, DNA hydroxymethylation, epigenetics, mast cells, proliferation, TET

  13. Alcohol Inhibits Odontogenic Differentiation of Human Dental Pulp Cells by Activating mTOR Signaling.

    Science.gov (United States)

    Qin, Wei; Huang, Qi-Ting; Weir, Michael D; Song, Zhi; Fouad, Ashraf F; Lin, Zheng-Mei; Zhao, Liang; Xu, Hockin H K

    2017-01-01

    Long-term heavy alcohol consumption could result in a range of health, social, and behavioral problems. People who abuse alcohol are at high risks of seriously having osteopenia, periodontal disease, and compromised oral health. However, the role of ethanol (EtOH) in the biological functions of human dental pulp cells (DPCs) is unknown. Whether EtOH affects the odontoblastic differentiation of DPCs through the mechanistic target of rapamycin (mTOR) remains unexplored. The objective of this study was to investigate the effects of EtOH on DPC differentiation and mineralization. DPCs were isolated and purified from human dental pulps. The proliferation and odontoblastic differentiation of DPCs treated with EtOH were subsequently investigated. Different doses of EtOH were shown to be cytocompatible with DPCs. EtOH significantly activated the mTOR pathway in a dose-dependent manner. In addition, EtOH downregulated the alkaline phosphatase activity, attenuated the mineralized nodule formation, and suppressed the expression of odontoblastic markers including ALP, DSPP, DMP-1, Runx2, and OCN. Moreover, the pretreatment with rapamycin, a specific mTOR inhibitor, markedly reversed the EtOH-induced odontoblastic differentiation and cell mineralization. Our findings show for the first time that EtOH can suppress DPC differentiation and mineralization in a mTOR-dependent manner, indicating that EtOH may be involved in negatively regulating the dental pulp repair.

  14. Furosin, an ellagitannin, suppresses RANKL-induced osteoclast differentiation and function through inhibition of MAP kinase activation and actin ring formation

    International Nuclear Information System (INIS)

    Park, Eui Kyun; Kim, Myung Sunny; Lee, Seung Ho; Kim, Kyung Hee; Park, Ju-Young; Kim, Tae-Ho; Lee, In-Seon; Woo, Je-Tae; Jung, Jae-Chang; Shin, Hong-In; Choi, Je-Yong; Kim, Shin-Yoon

    2004-01-01

    Phenolic compounds including tannins and flavonoids have been implicated in suppression of osteoclast differentiation/function and prevention of bone diseases. However, the effects of hydrolysable tannins on bone metabolism remain to be elucidated. In this study, we found that furosin, a hydrolysable tannin, markedly decreased the differentiation of both murine bone marrow mononuclear cells and Raw264.7 cells into osteoclasts, as revealed by the reduced number of tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells and decreased TRAP activity. Furosin appears to target at the early stage of osteoclastic differentiation while having no cytotoxic effect on osteoclast precursors. Analysis of the inhibitory mechanisms of furosin revealed that it inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced activation of p38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK)/activating protein-1 (AP-1). Furthermore, furosin reduced resorption pit formation in osteoclasts, which was accompanied by disruption of the actin rings. Taken together, these results demonstrate that naturally occurring furosin has an inhibitory activity on both osteoclast differentiation and function through mechanisms involving inhibition of the RANKL-induced p38MAPK and JNK/AP-1 activation as well as actin ring formation

  15. Purity-activity relationships of natural products: the case of anti-TB active ursolic acid.

    Science.gov (United States)

    Jaki, Birgit U; Franzblau, Scott G; Chadwick, Lucas R; Lankin, David C; Zhang, Fangqiu; Wang, Yuehong; Pauli, Guido F

    2008-10-01

    The present study explores the variability of biological responses from the perspective of sample purity and introduces the concept of purity-activity relationships (PARs) in natural product research. The abundant plant triterpene ursolic acid (1) was selected as an exemplary natural product due to the overwhelming number yet inconsistent nature of its approximate 120 reported biological activities, which include anti-TB potential. Nine different samples of ursolic acid with purity certifications were obtained, and their purity was independently assessed by means of quantitative 1H NMR (qHNMR). Biological evaluation consisted of determining MICs against two strains of virulent Mycobacterium tuberculosis and IC50 values in Vero cells. Ab initio structure elucidation provided unequivocal structural confirmation and included an extensive 1H NMR spin system analysis, determination of nearly all J couplings and the complete NOE pattern, and led to the revision of earlier reports. As a net result, a sigmoid PAR profile of 1 was obtained, demonstrating the inverse correlation of purity and anti-TB bioactivity. The results imply that synergistic effects of 1 and its varying impurities are the likely cause of previously reported antimycobacterial potential. Generating PARs is a powerful extension of the routinely performed quantitative correlation of structure and activity ([Q]SAR). Advanced by the use of primary analytical methods such as qHNMR, PARs enable the elucidation of cases like 1 when increasing purity voids biological activity. This underlines the potential of PARs as a tool in drug discovery and synergy research and accentuates the need to routinely combine biological testing with purity assessment.

  16. Sphingosine 1-phosphate receptor activation enhances BMP-2-induced osteoblast differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Chieri [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Iwasaki, Tsuyoshi, E-mail: tsuyo-i@huhs.ac.jp [Division of Pharmacotherapy, Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe 650-8530 (Japan); Kitano, Sachie; Tsunemi, Sachi; Sano, Hajime [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan)

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer We investigated the role of S1P signaling for osteoblast differentiation. Black-Right-Pointing-Pointer Both S1P and FTY enhanced BMP-2-stimulated osteoblast differentiation by C2C12 cells. Black-Right-Pointing-Pointer S1P signaling enhanced BMP-2-stimulated Smad and ERK phosphorylation by C2C12 cells. Black-Right-Pointing-Pointer MEK/ERK signaling is a pathway underlying S1P signaling for osteoblast differentiation. -- Abstract: We previously demonstrated that sphingosine 1-phosphate (S1P) receptor-mediated signaling induced proliferation and prostaglandin productions by synovial cells from rheumatoid arthritis (RA) patients. In the present study we investigated the role of S1P receptor-mediated signaling for osteoblast differentiation. We investigated osteoblast differentiation using C2C12 myoblasts, a cell line derived from murine satellite cells. Osteoblast differentiation was induced by the treatment of bone morphogenic protein (BMP)-2 in the presence or absence of either S1P or FTY720 (FTY), a high-affinity agonist of S1P receptors. Osteoblast differentiation was determined by osteoblast-specific transcription factor, Runx2 mRNA expression, alkaline phosphatase (ALP) activity and osteocalcin production by the cells. Smad1/5/8 and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation was examined by Western blotting. Osteocalcin production by C2C12 cells were determined by ELISA. Runx2 expression and ALP activity by BMP-2-stimulated C2C12 cells were enhanced by addition of either S1P or FTY. Both S1P and FTY enhanced BMP-2-induced ERK1/2 and Smad1/5/8 phosphorylation. The effect of FTY was stronger than that of S1P. S1P receptor-mediated signaling on osteoblast differentiation was inhibited by addition of mitogen-activated protein kinase/ERK kinase (MEK) 1/2 inhibitor, indicating that the S1P receptor-mediated MEK1/2-ERK1/2 signaling pathway enhanced BMP-2-Smad signaling. These results indicate that S1P

  17. Sphingosine 1-phosphate receptor activation enhances BMP-2-induced osteoblast differentiation

    International Nuclear Information System (INIS)

    Sato, Chieri; Iwasaki, Tsuyoshi; Kitano, Sachie; Tsunemi, Sachi; Sano, Hajime

    2012-01-01

    Highlights: ► We investigated the role of S1P signaling for osteoblast differentiation. ► Both S1P and FTY enhanced BMP-2-stimulated osteoblast differentiation by C2C12 cells. ► S1P signaling enhanced BMP-2-stimulated Smad and ERK phosphorylation by C2C12 cells. ► MEK/ERK signaling is a pathway underlying S1P signaling for osteoblast differentiation. -- Abstract: We previously demonstrated that sphingosine 1-phosphate (S1P) receptor-mediated signaling induced proliferation and prostaglandin productions by synovial cells from rheumatoid arthritis (RA) patients. In the present study we investigated the role of S1P receptor-mediated signaling for osteoblast differentiation. We investigated osteoblast differentiation using C2C12 myoblasts, a cell line derived from murine satellite cells. Osteoblast differentiation was induced by the treatment of bone morphogenic protein (BMP)-2 in the presence or absence of either S1P or FTY720 (FTY), a high-affinity agonist of S1P receptors. Osteoblast differentiation was determined by osteoblast-specific transcription factor, Runx2 mRNA expression, alkaline phosphatase (ALP) activity and osteocalcin production by the cells. Smad1/5/8 and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation was examined by Western blotting. Osteocalcin production by C2C12 cells were determined by ELISA. Runx2 expression and ALP activity by BMP-2-stimulated C2C12 cells were enhanced by addition of either S1P or FTY. Both S1P and FTY enhanced BMP-2-induced ERK1/2 and Smad1/5/8 phosphorylation. The effect of FTY was stronger than that of S1P. S1P receptor-mediated signaling on osteoblast differentiation was inhibited by addition of mitogen-activated protein kinase/ERK kinase (MEK) 1/2 inhibitor, indicating that the S1P receptor-mediated MEK1/2-ERK1/2 signaling pathway enhanced BMP-2-Smad signaling. These results indicate that S1P receptor-mediated signaling plays a crucial role for osteoblast differentiation.

  18. Identification of PPARgamma partial agonists of natural origin (II: in silico prediction in natural extracts with known antidiabetic activity.

    Directory of Open Access Journals (Sweden)

    Laura Guasch

    Full Text Available BACKGROUND: Natural extracts have played an important role in the prevention and treatment of diseases and are important sources for drug discovery. However, to be effectively used in these processes, natural extracts must be characterized through the identification of their active compounds and their modes of action. METHODOLOGY/PRINCIPAL FINDINGS: From an initial set of 29,779 natural products that are annotated with their natural source and using a previously developed virtual screening procedure (carefully validated experimentally, we have predicted as potential peroxisome proliferators-activated receptor gamma (PPARγ partial agonists 12 molecules from 11 extracts known to have antidiabetic activity. Six of these molecules are similar to molecules with described antidiabetic activity but whose mechanism of action is unknown. Therefore, it is plausible that these 12 molecules could be the bioactive molecules responsible, at least in part, for the antidiabetic activity of the extracts containing them. In addition, we have also identified as potential PPARγ partial agonists 10 molecules from 16 plants with undescribed antidiabetic activity but that are related (i.e., they are from the same genus to plants with known antidiabetic properties. None of the 22 molecules that we predict as PPARγ partial agonists show chemical similarity with a group of 211 known PPARγ partial agonists obtained from the literature. CONCLUSIONS/SIGNIFICANCE: Our results provide a new hypothesis about the active molecules of natural extracts with antidiabetic properties and their mode of action. We also suggest plants with undescribed antidiabetic activity that may contain PPARγ partial agonists. These plants represent a new source of potential antidiabetic extracts. Consequently, our work opens the door to the discovery of new antidiabetic extracts and molecules that can be of use, for instance, in the design of new antidiabetic drugs or functional foods focused

  19. Low pressure storage of natural gas on activated carbon

    Science.gov (United States)

    Wegrzyn, J.; Wiesmann, H.; Lee, T.

    The introduction of natural gas to the transportation energy sector offers the possibility of displacing imported oil with an indigenous fuel. The barrier to the acceptance of natural gas vehicles (NGV) is the limited driving range due to the technical difficulties of on-board storage of a gaseous fuel. In spite of this barrier, compressed natural gas (CNG) vehicles are today being successfully introduced into the market place. The purpose of this work is to demonstrate an adsorbent natural gas (ANG) storage system as a viable alternative to CNG storage. It can be argued that low pressure ANG has reached near parity with CNG, since the storage capacity of CNG (2400 psi) is rated at 190 V/V, while low pressure ANG (500 psi) has reached storage capacities of 180 V/V in the laboratory. A program, which extends laboratory results to a full-scale vehicle test, is necessary before ANG technology will receive widespread acceptance. The objective of this program is to field test a 150 V/V ANG vehicle in FY 1994. As a start towards this goal, carbon adsorbents have been screened by Brookhaven for their potential use in a natural gas storage system. This paper reports on one such carbon, trade name Maxsorb, manufactured by Kansai Coke under an Amoco license.

  20. Regulation of AMP-activated protein kinase by natural and synthetic activators

    Directory of Open Access Journals (Sweden)

    David Grahame Hardie

    2016-01-01

    Full Text Available The AMP-activated protein kinase (AMPK is a sensor of cellular energy status that is almost universally expressed in eukaryotic cells. While it appears to have evolved in single-celled eukaryotes to regulate energy balance in a cell-autonomous manner, during the evolution of multicellular animals its role has become adapted so that it also regulates energy balance at the whole body level, by responding to hormones that act primarily on the hypothalamus. AMPK monitors energy balance at the cellular level by sensing the ratios of AMP/ATP and ADP/ATP, and recent structural analyses of the AMPK heterotrimer that have provided insight into the complex mechanisms for these effects will be discussed. Given the central importance of energy balance in diseases that are major causes of morbidity or death in humans, such as type 2 diabetes, cancer and inflammatory disorders, there has been a major drive to develop pharmacological activators of AMPK. Many such activators have been described, and the various mechanisms by which these activate AMPK will be discussed. A particularly large class of AMPK activators are natural products of plants derived from traditional herbal medicines. While the mechanism by which most of these activate AMPK has not yet been addressed, I will argue that many of them may be defensive compounds produced by plants to deter infection by pathogens or grazing by insects or herbivores, and that many of them will turn out to be inhibitors of mitochondrial function.

  1. PDK1 Is a Regulator of Epidermal Differentiation that Activates and Organizes Asymmetric Cell Division

    Directory of Open Access Journals (Sweden)

    Teruki Dainichi

    2016-05-01

    Full Text Available Asymmetric cell division (ACD in a perpendicular orientation promotes cell differentiation and organizes the stratified epithelium. However, the upstream cues regulating ACD have not been identified. Here, we report that phosphoinositide-dependent kinase 1 (PDK1 plays a critical role in establishing ACD in the epithelium. Production of phosphatidyl inositol triphosphate (PIP3 is localized to the apical side of basal cells. Asymmetric recruitment of atypical protein kinase C (aPKC and partitioning defective (PAR 3 is impaired in PDK1 conditional knockout (CKO epidermis. PDK1CKO keratinocytes do not undergo calcium-induced activation of aPKC or IGF1-induced activation of AKT and fail to differentiate. PDK1CKO epidermis shows decreased expression of Notch, a downstream effector of ACD, and restoration of Notch rescues defective expression of differentiation-induced Notch targets in vitro. We therefore propose that PDK1 signaling regulates the basal-to-suprabasal switch in developing epidermis by acting as both an activator and organizer of ACD and the Notch-dependent differentiation program.

  2. Intercellular signaling pathways active during intervertebral disc growth, differentiation, and aging.

    Science.gov (United States)

    Dahia, Chitra Lekha; Mahoney, Eric J; Durrani, Atiq A; Wylie, Christopher

    2009-03-01

    Intervertebral discs at different postnatal ages were assessed for active intercellular signaling pathways. To generate a spatial and temporal map of the signaling pathways active in the postnatal intervertebral disc (IVD). The postnatal IVD is a complex structure, consisting of 3 histologically distinct components, the nucleus pulposus, fibrous anulus fibrosus, and endplate. These differentiate and grow during the first 9 weeks of age in the mouse. Identification of the major signaling pathways active during and after the growth and differentiation period will allow functional analysis using mouse genetics and identify targets for therapy for individual components of the disc. Antibodies specific for individual cell signaling pathways were used on cryostat sections of IVD at different postnatal ages to identify which components of the IVD were responding to major classes of intercellular signal, including sonic hedgehog, Wnt, TGFbeta, FGF, and BMPs. We present a spatial/temporal map of these signaling pathways during growth, differentiation, and aging of the disc. During growth and differentiation of the disc, its different components respond at different times to different intercellular signaling ligands. Most of these are dramatically downregulated at the end of disc growth.

  3. A Cultural Historical Activity Theory Approach in Natural Sciences Education Laboratory Lessons towards Reforming Teachers Training

    Science.gov (United States)

    Kolokouri, Eleni; Theodoraki, Xarikleia; Plakitsi, Katerina

    2012-01-01

    This paper focuses on connecting natural sciences education with Cultural Historical Activity Theory (CHAT). In this sense, natural sciences education is considered as a lifelong learning procedure, not seen as an individual but as a collective activity. Moreover, learning becomes a human activity in which theory and praxis are strongly connected…

  4. Active geothermal systems as natural analogs of HLW repositories

    International Nuclear Information System (INIS)

    Elders, W.A.; Williams, A.E.; Cohen, L.H.

    1988-01-01

    Geologic analogs of long-lived processes in high-level waste (HLW) repositories have been much studied in recent years. However, most of these occurrences either involve natural processes going on today at 25 degree C, or, if they are concerned with behavior at temperatures similar to the peak temperatures anticipated near HLW canisters, have long since ended. This paper points out the usefulness of studying modern geothermal systems as natural analogs, and to illustrate the concept with a dramatic example, the Salton Sea geothermal system (SSGS)

  5. Differential sensitivity of coral larvae to natural levels of ultraviolet radiation during the onset of larval competence.

    KAUST Repository

    Aranda, Manuel

    2011-07-01

    Scleractinian corals are the major builders of the complex structural framework of coral reefs. They live in tropical waters around the globe where they are frequently exposed to potentially harmful ultraviolet radiation (UVR). The eggs and early embryonic stages of some coral species are highly buoyant and remain near the sea surface for prolonged periods of time and may therefore be the most sensitive life stages with respect to UVR. Here, we analysed gene expression changes in five developmental stages of the Caribbean coral Montastraea faveolata to natural levels of UVR using high-density cDNA microarrays (10 930 clones). We found that larvae exhibit low sensitivity to natural levels of UVR during early development as reflected by comparatively few transcriptomic changes in response to UVR. However, we identified a time window of high UVR sensitivity that coincides with the motile planula stage and the onset of larval competence. These processes have been shown to be affected by UVR exposure, and the transcriptional changes we identified explain these observations well. Our analysis of differentially expressed genes indicates that UVR alters the expression of genes associated with stress response, the endoplasmic reticulum, Ca(2+) homoeostasis, development and apoptosis during the motile planula stage and affects the expression of neurogenesis-related genes that are linked to swimming and settlement behaviour at later stages. Taken together, our study provides further data on the impact of natural levels of UVR on coral larvae. Furthermore, our results might allow a better prediction of settlement and recruitment rates after coral spawning events if UVR climate data are taken into account.

  6. Anticancer and reversing multidrug resistance activities of natural isoquinoline alkaloids and their structure-activity relationship.

    Science.gov (United States)

    Qing, Zhi-Xing; Huang, Jia-Lu; Yang, Xue-Yi; Liu, Jing-Hong; Cao, Hua-Liang; Xiang, Feng; Cheng, Pi; Zeng, Jian-Guo

    2017-09-20

    The severe anticancer situation as well as the emergence of multidrug-resistant (MDR) cancer cells has created an urgent need for the development of novel anticancer drugs with different mechanisms of action. A large number of natural alkaloids, such as paclitaxel, vinblastine and camptothecin have already been successfully developed into chemotherapy agents. Following the success of these natural products, in this review, twenty-six types of isoquinoline alkaloid (a total of 379 alkaloids), including benzyltetrahydroisoquinoline, aporphine, oxoaporphine, isooxoaporphine, dimeric aporphine, bisbenzylisoquinoline, tetrahydroprotoberberine, protoberberine, protopine, dihydrobenzophenanthridine, benzophenanthridine, benzophenanthridine dimer, ipecac, simple isoquinoline, pavine, montanine, erythrina, chelidonine, tropoloisoquinoline, azafluoranthene, phthalideisoquinoline, naphthylisoquinoline, lycorine, crinane, narciclasine, and phenanthridone, were summarized based on their cytotoxic and MDR reversing activities against various cancer cells. Additionally, the structure-activity relationships of different types of isoquinoline alkaloid were also discussed. Interestingly, some aporphine, oxoaporphine, isooxoaporphine, bisbenzylisoquinoline, and protoberberine alkaloids display more potent anticancer activities or anti-MDR effects than positive control against the tested cancer cells and are regarded as attractive targets for discovery new anticancer drugs or lead compounds. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Reduced Expression of Siglec-7, NKG2A, and CD57 on Terminally Differentiated CD56-CD16+ Natural Killer Cell Subset Is Associated with Natural Killer Cell Dysfunction in Chronic HIV-1 Clade C Infection.

    Science.gov (United States)

    Zulu, Michael Z; Naidoo, Kewreshini K; Mncube, Zenele; Jaggernath, Manjeetha; Goulder, Philip J R; Ndung'u, Thumbi; Altfeld, Marcus; Thobakgale, Christina F

    2017-12-01

    HIV-1 viremia has been shown to induce several phenotypic and functional abnormalities in natural killer (NK) cells. To assess immune defects associated with HIV viremia, we examined NK cell function, differentiation status, and phenotypic alterations based on expression of inhibitory and activating receptors on NK cells in HIV-1 subtype C chronically infected participants from Durban, South Africa. NK cell phenotypic profiles were characterized by assessing sialic acid-binding immunoglobulin-like lectin-7 (Siglec-7), NKG2A, and NKG2C markers on frozen peripheral blood mononuclear cells from viremic, antiretroviral therapy (ART)-naive HIV-1 chronically infected participants (n = 23), HIV-1 chronically infected participants who had been on combination antiretroviral therapy (cART) for at least 12 months (n = 23) compared with healthy donors (n = 23). NK cell differentiation was assessed by measurement of killer immunoglobulin receptor (KIR) and NKG2A expression; CD57 and CD107a measurements were carried out in HIV viremic and healthy donors. All phenotypic and functional assessments were analyzed by using multicolor flow cytometry. HIV-1-infected participants displayed greater frequencies of the CD56 - CD16 + (CD56negative) NK cell subset compared with healthy donors (p < .0001). Downregulation of Siglec-7 and NKG2A and upregulation of NKG2C were more pronounced in the CD56negative NK cell subset of viremic participants. The CD56negative subset demonstrated a differentiated (KIR + NKG2A - ) phenotype with reduced CD57 expression and lower degranulation capacity in HIV-1-infected participants compared with healthy donors. HIV-1 infection induces the expansion of the CD56negative NK cell subset marked by altered receptor expression profiles that are indicative of impaired function and may explain the overall NK cell dysfunction observed in chronic HIV-1 infection.

  8. Gradual Increase of FcγRIIIa/CD16a Expression and Shift toward IFN-γ Secretion during Differentiation of CD56dim Natural Killer Cells

    Directory of Open Access Journals (Sweden)

    Laurie Lajoie

    2017-11-01

    Full Text Available Natural killer (NK cell effector functions include cytotoxicity and secretion of cytokines such as interferon-γ (IFN-γ. The immature CD56bright subset of human NK cells lacks expression of FcγRIIIa/CD16a, one of the low-affinity immunoglobulin G receptors, or exhibits low-density expression (CD56brightCD16−/dim and produces IFN-γ in response to cytokine stimulation, whereas the mature CD56dimCD16+ subset is the most cytotoxic one. A further differentiation/maturation of the latter subset according to the gradual loss of NKG2A and/or gain of KIR2DL (CD158a and CD158b has been demonstrated and the ability to produce IFN-γ in response to activating receptor (AR co-engagement is gradually acquired during terminal differentiation. In the course of flow cytometry analysis of CD56dim NK cells, we noted a substantial intraindividual heterogeneity of expression of FcγRIIIa. FcγRIIIa is unique among ARs: it does not require the co-engagement of other ARs to induce substantial cytotoxicity or cytokine synthesis in CD56dim cells. We, therefore, investigated whether individual differentiation/maturation of polyclonal CD56dim NK cells defined by expression of NKG2A/KIR2DL is related to FcγRIIIa expression and to the heterogeneity of NK cell responses upon FcγRIIIa engagement. When we analyzed unstimulated CD56dim cells by increasing level of FcγRIIIa expression, we found that the proportion of the more differentiated CD158a,h+ and/or CD158b,j+ cells and that of the less differentiated NKG2A+ cells gradually increased and decreased, respectively. FcγRIIIa engagement by using plate-bound murine anti-CD16 monoclonal antibody (mAb or rituximab or trastuzumab (two therapeutic mAbs, resulted in donor-dependent partial segregation of IFN-γ-producing and/or degranulating CD56dim cells. Importantly, the proportion of CD158a,h/b,j+ cells and that of NKG2A+ cells was increased and decreased, respectively, IFN-γ-producing cells, whereas these proportions

  9. Data publication activities in the Natural Environment Research Council

    Science.gov (United States)

    Leadbetter, A.; Callaghan, S.; Lowry, R.; Moncoiffé, G.; Donnegan, S.; Pepler, S.; Cunningham, N.; Kirsch, P.; Ault, L.; Bell, P.; Bowie, R.; Harrison, K.; Smith-Haddon, B.; Wetherby, A.; Wright, D.; Thorley, M.

    2012-04-01

    The Natural Environment Research Council (NERC) is implementing its Science Information Strategy in order to provide a world class service to deliver integrated data for earth system science. One project within this strategy is Data Citation and Publication, which aims to put the promotion and recognition stages of the data lifecycle into place alongside the traditional data management activities of NERC's Environmental Data Centres (EDCs). The NERC EDCs have made a distinction between the serving of data and its publication. Data serving is defined in this case as the day-to-day data management tasks of: • acquiring data and metadata from the originating scientists; • metadata and format harmonisation prior to database ingestion; • ensuring the metadata is adequate and accurate and that the data are available in appropriate file formats; • and making the data available for interested parties. Whereas publication: • requires the assignment of a digital object identifier to a dataset which guarantees that an EDC has assessed the quality of the metadata and the file format and will maintain an unchanged version of the data for the foreseeable future • requires the peer-review of the scientific quality of the data by a scientist with knowledge of the scientific domain in which the data were collected, using a framework for peer-review of datasets such as that developed by the CLADDIER project. • requires collaboration with journal publishers who have access to a well established peer-review system The first of these requirements can be managed in-house by the EDCs, while the remainder require collaboration with the wider scientific and publishing communities. It is anticipated that a scientist may achieve a lower level of academic credit for a dataset which is assigned a DOI but does not follow through to the scientific peer-review stage, similar to publication in a report or other non-peer reviewed publication normally described as grey literature, or

  10. Multiple Active Contours Guided by Differential Evolution for Medical Image Segmentation

    Science.gov (United States)

    Cruz-Aceves, I.; Avina-Cervantes, J. G.; Lopez-Hernandez, J. M.; Rostro-Gonzalez, H.; Garcia-Capulin, C. H.; Torres-Cisneros, M.; Guzman-Cabrera, R.

    2013-01-01

    This paper presents a new image segmentation method based on multiple active contours guided by differential evolution, called MACDE. The segmentation method uses differential evolution over a polar coordinate system to increase the exploration and exploitation capabilities regarding the classical active contour model. To evaluate the performance of the proposed method, a set of synthetic images with complex objects, Gaussian noise, and deep concavities is introduced. Subsequently, MACDE is applied on datasets of sequential computed tomography and magnetic resonance images which contain the human heart and the human left ventricle, respectively. Finally, to obtain a quantitative and qualitative evaluation of the medical image segmentations compared to regions outlined by experts, a set of distance and similarity metrics has been adopted. According to the experimental results, MACDE outperforms the classical active contour model and the interactive Tseng method in terms of efficiency and robustness for obtaining the optimal control points and attains a high accuracy segmentation. PMID:23983809

  11. Multiple Active Contours Guided by Differential Evolution for Medical Image Segmentation

    Directory of Open Access Journals (Sweden)

    I. Cruz-Aceves

    2013-01-01

    Full Text Available This paper presents a new image segmentation method based on multiple active contours guided by differential evolution, called MACDE. The segmentation method uses differential evolution over a polar coordinate system to increase the exploration and exploitation capabilities regarding the classical active contour model. To evaluate the performance of the proposed method, a set of synthetic images with complex objects, Gaussian noise, and deep concavities is introduced. Subsequently, MACDE is applied on datasets of sequential computed tomography and magnetic resonance images which contain the human heart and the human left ventricle, respectively. Finally, to obtain a quantitative and qualitative evaluation of the medical image segmentations compared to regions outlined by experts, a set of distance and similarity metrics has been adopted. According to the experimental results, MACDE outperforms the classical active contour model and the interactive Tseng method in terms of efficiency and robustness for obtaining the optimal control points and attains a high accuracy segmentation.

  12. Differentially activated macrophages orchestrate myogenic precursor cell fate during human skeletal muscle regeneration

    DEFF Research Database (Denmark)

    Saclier, Marielle; Yacoub-Youssef, Houda; Mackey, Abigail

    2013-01-01

    , we explored both in vitro and in vivo, in human, the interactions of differentially activated MPs with myogenic precursor cells (MPCs) during adult myogenesis and skeletal muscle regeneration. We showed in vitro that through the differential secretion of cytokines and growth factors, proinflammatory...... anti-inflammatory markers. These data demonstrate for the first time in human that MPs sequentially orchestrate adult myogenesis during regeneration of damaged skeletal muscle. These results support the emerging concept that inflammation, through MP activation, controls stem cell fate and coordinates......Macrophages (MPs) exert either beneficial or deleterious effects on tissue repair, depending on their activation/polarization state. They are crucial for adult skeletal muscle repair, notably by acting on myogenic precursor cells. However, these interactions have not been fully characterized. Here...

  13. Anti-inflammatory activity of natural stilbenoids: A review

    Czech Academy of Sciences Publication Activity Database

    Dvořáková, Marcela; Landa, Přemysl

    2017-01-01

    Roč. 124, OCT (2017), s. 126-145 ISSN 1043-6618 R&D Projects: GA ČR(CZ) GA16-07193S Institutional support: RVO:61389030 Keywords : Bioavailability * Encapsulation * Inflammation * Metabolites * Multi-targeted therapy * Natural stilbenes Subject RIV: GM - Food Processing OBOR OECD: Biochemistry and molecular biology Impact factor: 4.480, year: 2016

  14. GCN5 Regulates FGF Signaling and Activates Selective MYC Target Genes during Early Embryoid Body Differentiation

    Directory of Open Access Journals (Sweden)

    Li Wang

    2018-01-01

    Full Text Available Precise control of gene expression during development is orchestrated by transcription factors and co-regulators including chromatin modifiers. How particular chromatin-modifying enzymes affect specific developmental processes is not well defined. Here, we report that GCN5, a histone acetyltransferase essential for embryonic development, is required for proper expression of multiple genes encoding components of the fibroblast growth factor (FGF signaling pathway in early embryoid bodies (EBs. Gcn5−/− EBs display deficient activation of ERK and p38, mislocalization of cytoskeletal components, and compromised capacity to differentiate toward mesodermal lineage. Genomic analyses identified seven genes as putative direct targets of GCN5 during early differentiation, four of which are cMYC targets. These findings established a link between GCN5 and the FGF signaling pathway and highlighted specific GCN5-MYC partnerships in gene regulation during early differentiation.

  15. Transcription factor activating protein 2 beta (TFAP2B) mediates noradrenergic neuronal differentiation in neuroblastoma.

    Science.gov (United States)

    Ikram, Fakhera; Ackermann, Sandra; Kahlert, Yvonne; Volland, Ruth; Roels, Frederik; Engesser, Anne; Hertwig, Falk; Kocak, Hayriye; Hero, Barbara; Dreidax, Daniel; Henrich, Kai-Oliver; Berthold, Frank; Nürnberg, Peter; Westermann, Frank; Fischer, Matthias

    2016-02-01

    Neuroblastoma is an embryonal pediatric tumor that originates from the developing sympathetic nervous system and shows a broad range of clinical behavior, ranging from fatal progression to differentiation into benign ganglioneuroma. In experimental neuroblastoma systems, retinoic acid (RA) effectively induces neuronal differentiation, and RA treatment has been therefore integrated in current therapies. However, the molecular mechanisms underlying differentiation are still poorly understood. We here investigated the role of transcription factor activating protein 2 beta (TFAP2B), a key factor in sympathetic nervous system development, in neuroblastoma pathogenesis and differentiation. Microarray analyses of primary neuroblastomas (n = 649) demonstrated that low TFAP2B expression was significantly associated with unfavorable prognostic markers as well as adverse patient outcome. We also found that low TFAP2B expression was strongly associated with CpG methylation of the TFAP2B locus in primary neuroblastomas (n = 105) and demethylation with 5-aza-2'-deoxycytidine resulted in induction of TFAP2B expression in vitro, suggesting that TFAP2B is silenced by genomic methylation. Tetracycline inducible re-expression of TFAP2B in IMR-32 and SH-EP neuroblastoma cells significantly impaired proliferation and cell cycle progression. In IMR-32 cells, TFAP2B induced neuronal differentiation, which was accompanied by up-regulation of the catecholamine biosynthesizing enzyme genes DBH and TH, and down-regulation of MYCN and REST, a master repressor of neuronal genes. By contrast, knockdown of TFAP2B by lentiviral transduction of shRNAs abrogated RA-induced neuronal differentiation of SH-SY5Y and SK-N-BE(2)c neuroblastoma cells almost completely. Taken together, our results suggest that TFAP2B is playing a vital role in retaining RA responsiveness and mediating noradrenergic neuronal differentiation in neuroblastoma. Copyright © 2015 Federation of European Biochemical Societies

  16. Weekday and weekend sedentary time and physical activity in differentially active children.

    Science.gov (United States)

    Fairclough, Stuart J; Boddy, Lynne M; Mackintosh, Kelly A; Valencia-Peris, Alexandra; Ramirez-Rico, Elena

    2015-07-01

    To investigate whether weekday-weekend differences in sedentary time and specific intensities of physical activity exist among children categorised by physical activity levels. Cross-sectional observational study. Seven-day accelerometer data were obtained from 810 English children (n=420 girls) aged 10-11 years. Daily average minday(-1) spent in moderate to vigorous physical activity were calculated for each child. Sex-specific moderate to vigorous physical activity quartile cut-off values categorised boys and girls separately into four graded groups representing the least (Q1) through to the most active (Q4) children. Sex- and activity quartile-specific multilevel linear regression analyses analysed differences in sedentary time, light physical activity, moderate physical activity, vigorous physical activity, and moderate to vigorous physical activity between weekdays and weekends. On weekdays Q2 boys spent longer in light physical activity (pboys (pphysical activity, and Q1-Q3 boys accumulated significantly more vigorous physical activity and moderate to vigorous physical activity than at weekends. There were no significant differences in weekday and weekend sedentary time or physical activity for Q4 boys. On weekdays Q2 and Q3 girls accumulated more sedentary time (pgirls did significantly more moderate physical activity (pgirls engaged in more vigorous physical activity (pphysical activity (pgirls' sedentary time and physical activity varied little between weekdays and weekends. The most active children maintained their sedentary time and physical activity levels at weekends, while among less active peers weekend sedentary time and physical activity at all intensities was lower. Low active children may benefit most from weekend intervention strategies. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  17. Host markers in Quantiferon supernatants differentiate active TB from latent TB infection: preliminary report

    Directory of Open Access Journals (Sweden)

    Walzl Gerhard

    2009-05-01

    Full Text Available Abstract Background Interferon gamma release assays, including the QuantiFERON® TB Gold In Tube (QFT have been shown to be accurate in diagnosing Mycobacterium tuberculosis infection. These assays however, do not discriminate between latent TB infection (LTBI and active TB disease. Methods We recruited twenty-three pulmonary TB patients and 34 household contacts from Cape Town, South Africa and performed the QFT test. To investigate the ability of new host markers to differentiate between LTBI and active TB, levels of 29 biomarkers in QFT supernatants were evaluated using a Luminex multiplex cytokine assay. Results Eight out of 29 biomarkers distinguished active TB from LTBI in a pilot study. Baseline levels of epidermal growth factor (EGF soluble CD40 ligand (sCD40L, antigen stimulated levels of EGF, and the background corrected antigen stimulated levels of EGF and macrophage inflammatory protein (MIP-1β were the most informative single markers for differentiation between TB disease and LTBI, with AUCs of 0.88, 0.84, 0.87, 0.90 and 0.79 respectively. The combination of EGF and MIP-1β predicted 96% of active TB cases and 92% of LTBIs. Combinations between EGF, sCD40L, VEGF, TGF-α and IL-1α also showed potential to differentiate between TB infection states. EGF, VEGF, TGF-α and sCD40L levels were higher in TB patients. Conclusion These preliminary data suggest that active TB may be accurately differentiated from LTBI utilizing adaptations of the commercial QFT test that includes measurement of EGF, sCD40L, MIP-1β, VEGF, TGF-α or IL-1α in supernatants from QFT assays. This approach holds promise for development as a rapid diagnostic test for active TB.

  18. Influence of terbutaline on natural killer cell activity

    International Nuclear Information System (INIS)

    Stenius-Aarniala, B.; Vesterinen, E.; Kiviranta, K.; Timonen, T.

    1988-01-01

    Studies on the effect of cAMO-inducing agents on NK activity have been contradictory. The aim of this study was to investigate the acute effects of beta-agonists on NK activity in vivo in 15 asthmatics and 3 healthy volunteers. Blood samples of NK activity were taken at regular intervals after placebo and after subcutaneous injection of 7 μg/kg of terbutaline. NK activity was measured by the standard 4-h Chromium 51 release assay against the leukemic line K 562 at a 50:1 effector/target cell ratio. Compared with placebo, terbutaline induced within 30-60 min a significant increase in NK activity which lasted less than 2 h. Further studies are necessary to investigate the effect of long-term beta-agonist treatment on NK activity. (author)

  19. Association between Natural Resources for OutdoorActivities and Physical Inactivity

    Data.gov (United States)

    U.S. Environmental Protection Agency — it includes available natural resources for outdoor activities, Physical inactivity and households income. This dataset is associated with the following publication:...

  20. Acid activation of natural clays aiming their application in adsorption

    International Nuclear Information System (INIS)

    Silva, M.M. da; Sousa, A.K.F. de; Lima, W.S.; Vasconcelos, P.N.M. de; Rodrigues, M. G.F.

    2012-01-01

    Clays of smectite type have wide application in industrial, mainly due to their adsorption properties. However, it is necessary to subject them to chemical treatments to optimize their potential. This study aimed to analyze the effects of acid activation on the clay Brasgel fresh. In the acid activation was used concentrated hydrochloric acid at different concentrations (3M, 4.5 M and 6 M) at a temperature of 70 ° C for 30 minutes. The samples fresh and activated technique were characterized by X-ray Diffraction (XRD). The results show that the properties of clay after activation are improved, it could be used as adsorbents in the treatment of wastewater. (author)

  1. Antifungal activity of natural and synthetic amides from Piper species

    Energy Technology Data Exchange (ETDEWEB)

    Marques, Joaquim V.; Oliveira, Alberto de; Kato, Massuo J., E-mail: majokato@iq.usp.b [Universidade de Sao Paulo (IQ/USP), SP (Brazil). Inst. de Quimica; Raggi, Ludmila; Young, Maria C. [Instituto de Botanica, Sao Paulo, SP (Brazil). Secao de Fisiologia e Bioquimica de Plantas

    2010-07-01

    The antifungal leaves extract from Piper scutifolium was submitted to bioactivity-guided chromatographic separation against Cladosporium cladosporioides and C. sphaerospermum yielding piperine, piperlonguminine and corcovadine as the active principles which displayed a detection limit of 1 {mu}g. Structure-activity relationships were investigated with the preparation of twelve analogs having differences in the number of unsaturations, aromatic ring substituents and in the amide moiety. Analogs having a single double-bond and no substituent in the aromatic ring displayed higher activity, while N,N,-diethyl analogs displayed higher dose-dependent activity. (author)

  2. The physical nature and manufacture of activated carbon

    Energy Technology Data Exchange (ETDEWEB)

    McDougall, G.J. (NCP, Bedfordview (South Africa))

    1991-04-01

    After defining activated carbon, the author describes its structure and outlines the physical characteristics distinguishing one type of activated carbon from another. The adsorptive properties of these carbons, the raw materials used, and the manufacturing processes - chemical activation, and physical or thermal activation - are eoutlined. The high-temperature thermal route (which is the most important for the products employed in gold recovery) using coconut shells or coals as the raw material is then discussed in some detail. 20 refs., 11 figs., 2 tabs.

  3. Natural compounds' activity against cancer stem-like or fast-cycling melanoma cells.

    Directory of Open Access Journals (Sweden)

    Malgorzata Sztiller-Sikorska

    Full Text Available BACKGROUND: Accumulating evidence supports the concept that melanoma is highly heterogeneous and sustained by a small subpopulation of melanoma stem-like cells. Those cells are considered as responsible for tumor resistance to therapies. Moreover, melanoma cells are characterized by their high phenotypic plasticity. Consequently, both melanoma stem-like cells and their more differentiated progeny must be eradicated to achieve durable cure. By reevaluating compounds in heterogeneous melanoma populations, it might be possible to select compounds with activity not only against fast-cycling cells but also against cancer stem-like cells. Natural compounds were the focus of the present study. METHODS: We analyzed 120 compounds from The Natural Products Set II to identify compounds active against melanoma populations grown in an anchorage-independent manner and enriched with cells exerting self-renewing capacity. Cell viability, cell cycle arrest, apoptosis, gene expression, clonogenic survival and label-retention were analyzed. FINDINGS: Several compounds efficiently eradicated cells with clonogenic capacity and nanaomycin A, streptonigrin and toyocamycin were effective at 0.1 µM. Other anti-clonogenic but not highly cytotoxic compounds such as bryostatin 1, siomycin A, illudin M, michellamine B and pentoxifylline markedly reduced the frequency of ABCB5 (ATP-binding cassette, sub-family B, member 5-positive cells. On the contrary, treatment with maytansine and colchicine selected for cells expressing this transporter. Maytansine, streptonigrin, toyocamycin and colchicine, even if highly cytotoxic, left a small subpopulation of slow-dividing cells unaffected. Compounds selected in the present study differentially altered the expression of melanocyte/melanoma specific microphthalmia-associated transcription factor (MITF and proto-oncogene c-MYC. CONCLUSION: Selected anti-clonogenic compounds might be further investigated as potential adjuvants

  4. Nature on the doorstep : the relationship between protected natural areas and residential activity in the European countryside

    NARCIS (Netherlands)

    Elbersen, Berien Sjamkea

    2002-01-01

    The main objective of this study is to gain insight into the ability of protected natural areas to attract new residential activity and in the role they play in the enhancement of the quality of life of local rural residents. To understand these processes information was collected on the

  5. Metformin induces differentiation in acute promyelocytic leukemia by activating the MEK/ERK signaling pathway

    International Nuclear Information System (INIS)

    Huai, Lei; Wang, Cuicui; Zhang, Cuiping; Li, Qihui; Chen, Yirui; Jia, Yujiao; Li, Yan; Xing, Haiyan; Tian, Zheng; Rao, Qing; Wang, Min; Wang, Jianxiang

    2012-01-01

    Highlights: ► Metformin induces differentiation in NB4 and primary APL cells. ► Metformin induces activation of the MEK/ERK signaling pathway in APL cells. ► Metformin synergizes with ATRA to trigger maturation of NB4 and primary APL cells. ► Metformin induces the relocalization and degradation of the PML-RARα fusion protein. ► The study may be applicable for new differentiation therapy in cancer treatment. -- Abstract: Recent studies have shown that metformin, a widely used antidiabetic agent, may reduce the risk of cancer development. In this study, we investigated the antitumoral effect of metformin on both acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL) cells. Metformin induced apoptosis with partial differentiation in an APL cell line, NB4, but only displayed a proapoptotic effect on several non-M3 AML cell lines. Further analysis revealed that a strong synergistic effect existed between metformin and all-trans retinoic acid (ATRA) during APL cell maturation and that metformin induced the hyperphosphorylation of extracellular signal-regulated kinase (ERK) in APL cells. U0126, a specific MEK/ERK activation inhibitor, abrogated metformin-induced differentiation. Finally, we found that metformin induced the degradation of the oncoproteins PML-RARα and c-Myc and activated caspase-3. In conclusion, these results suggest that metformin treatment may contribute to the enhancement of ATRA-induced differentiation in APL, which may deepen the understanding of APL maturation and thus provide insight for new therapy strategies.

  6. Metformin induces differentiation in acute promyelocytic leukemia by activating the MEK/ERK signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Huai, Lei; Wang, Cuicui; Zhang, Cuiping; Li, Qihui; Chen, Yirui; Jia, Yujiao; Li, Yan; Xing, Haiyan; Tian, Zheng; Rao, Qing; Wang, Min [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020 (China); Wang, Jianxiang, E-mail: wangjx@ihcams.ac.cn [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020 (China)

    2012-06-08

    Highlights: Black-Right-Pointing-Pointer Metformin induces differentiation in NB4 and primary APL cells. Black-Right-Pointing-Pointer Metformin induces activation of the MEK/ERK signaling pathway in APL cells. Black-Right-Pointing-Pointer Metformin synergizes with ATRA to trigger maturation of NB4 and primary APL cells. Black-Right-Pointing-Pointer Metformin induces the relocalization and degradation of the PML-RAR{alpha} fusion protein. Black-Right-Pointing-Pointer The study may be applicable for new differentiation therapy in cancer treatment. -- Abstract: Recent studies have shown that metformin, a widely used antidiabetic agent, may reduce the risk of cancer development. In this study, we investigated the antitumoral effect of metformin on both acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL) cells. Metformin induced apoptosis with partial differentiation in an APL cell line, NB4, but only displayed a proapoptotic effect on several non-M3 AML cell lines. Further analysis revealed that a strong synergistic effect existed between metformin and all-trans retinoic acid (ATRA) during APL cell maturation and that metformin induced the hyperphosphorylation of extracellular signal-regulated kinase (ERK) in APL cells. U0126, a specific MEK/ERK activation inhibitor, abrogated metformin-induced differentiation. Finally, we found that metformin induced the degradation of the oncoproteins PML-RAR{alpha} and c-Myc and activated caspase-3. In conclusion, these results suggest that metformin treatment may contribute to the enhancement of ATRA-induced differentiation in APL, which may deepen the understanding of APL maturation and thus provide insight for new therapy strategies.

  7. p62 modulates Akt activity via association with PKCζ in neuronal survival and differentiation

    International Nuclear Information System (INIS)

    Joung, Insil; Kim, Hak Jae; Kwon, Yunhee Kim

    2005-01-01

    p62 is a ubiquitously expressed phosphoprotein that interacts with a number of signaling molecules and a major component of neurofibrillary tangles in the brain of Alzheimer's disease patients. It has been implicated in important cellular functions such as cell proliferation and anti-apoptotic pathways. In this study, we have addressed the potential role of p62 during neuronal differentiation and survival using HiB5, a rat neuronal progenitor cell. We generated a recombinant adenovirus encoding T7-epitope tagged p62 to reliably transfer p62 cDNA into the neuronal cells. The results show that an overexpression of p62 led not only to neuronal differentiation, but also to decreased cell death induced by serum withdrawal in HiB5 cells. In this process p62-dependent Akt phosphorylation occurred via the release of Akt from PKCζ by association of p62 and PKCζ, which is known as a negative regulator of Akt activation. These findings indicate that p62 facilitates cell survival through novel signaling cascades that result in Akt activation. Furthermore, we found that p62 expression was induced during neuronal differentiation. Taken together, the data suggest p62 is a regulator of neuronal cell survival and differentiation

  8. CHD1 regulates cell fate determination by activation of differentiation-induced genes.

    Science.gov (United States)

    Baumgart, Simon J; Najafova, Zeynab; Hossan, Tareq; Xie, Wanhua; Nagarajan, Sankari; Kari, Vijayalakshmi; Ditzel, Nicholas; Kassem, Moustapha; Johnsen, Steven A

    2017-07-27

    The coordinated temporal and spatial activation of gene expression is essential for proper stem cell differentiation. The Chromodomain Helicase DNA-binding protein 1 (CHD1) is a chromatin remodeler closely associated with transcription and nucleosome turnover downstream of the transcriptional start site (TSS). In this study, we show that CHD1 is required for the induction of osteoblast-specific gene expression, extracellular-matrix mineralization and ectopic bone formation in vivo. Genome-wide occupancy analyses revealed increased CHD1 occupancy around the TSS of differentiation-activated genes. Furthermore, we observed that CHD1-dependent genes are mainly induced during osteoblast differentiation and are characterized by higher levels of CHD1 occupancy around the TSS. Interestingly, CHD1 depletion resulted in increased pausing of RNA Polymerase II (RNAPII) and decreased H2A.Z occupancy close to the TSS, but not at enhancer regions. These findings reveal a novel role for CHD1 during osteoblast differentiation and provide further insights into the intricacies of epigenetic regulatory mechanisms controlling cell fate determination. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Microbial activities in soil near natural gas leaks

    Energy Technology Data Exchange (ETDEWEB)

    Adamse, A D; Hoeks, J; de Bont, J A.M.

    1971-01-01

    Gas leaks cause the death of more than half the trees that perish in the streets since natural gas has been distributed in the Netherlands. Measurements performed in pot experiments, in which a sandy soil was supplied with a constant stream of a mixture of natural gas and air, proved that gas components, such as methane (81.6%), ethane (2.7%), propane (0.37%), were oxidized. Consumption of methane and oxygen, and production of carbon dioxide could be clearly demonstrated. Oxidation of methane started after an extended lag phase during which propane and ethane were found to be consumed. Methane oxidation was demonstrated by a sharp rise of the oxygen-consumption curve, followed by a fall until it became rather constant. After the gas supply had been stopped, a long recovery period was found to be needed for restoring the normal oxygen consumption of the soil. The rate of oxidation was subject to seasonal differences in temperature. Counts of bacteria in soil were carried out using Oxiod membrane filters on Whatman paper discs soaked with a basic salts solutions according to Leadbetter and Foster (1958) or on soil-extract agar plates. Incubation temperature was 30C. The presence of natural gas in soil resulted in an adaptation of the aerobic microflora to this substrate. Moreover, it stimulated the total aerobic microflora as counted on soil-extract agar plates.

  10. Statins activate GATA-6 and induce differentiated vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Wada, Hiromichi; Abe, Mitsuru; Ono, Koh; Morimoto, Tatsuya; Kawamura, Teruhisa; Takaya, Tomohide; Satoh, Noriko; Fujita, Masatoshi; Kita, Toru; Shimatsu, Akira; Hasegawa, Koji

    2008-01-01

    The beneficial effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) beyond cholesterol lowering involve their direct actions on vascular smooth muscle cells (VSMCs). However, the effects of statins on phenotypic modulation of VSMCs are unknown. We herein show that simvastatin (Sm) and atorvastatin (At) inhibited DNA synthesis in human aortic VSMCs dose-dependently, while cell toxicity was not observed below the concentration of 1 μM of Sm or 100 nM of At. Stimulating proliferative VSMCs with Sm or At induced the expression of SM-α-actin and SM-MHC, highly specific markers of differentiated phenotype. Sm up-regulated the binding activity of GATA-6 to SM-MHC GATA site and activated the transfected SM-MHC promoter in proliferative VSMCs, while mutating the GATA-6 binding site abolished this activation. Geranylgeranylpyrophosphate (10 μM), an inhibitor of Rho family proteins, abolished the statin-mediated induction of the differentiated phenotype in VSMCs. These findings suggest that statins activate GATA-6 and induce differentiated VSMCs

  11. Statins activate GATA-6 and induce differentiated vascular smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Wada, Hiromichi [Division of Translational Research, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555 (Japan); Abe, Mitsuru; Ono, Koh [Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Morimoto, Tatsuya; Kawamura, Teruhisa; Takaya, Tomohide [Division of Translational Research, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555 (Japan); Satoh, Noriko [Division of Metabolic Research, National Hospital Organization Kyoto Medical Center, Kyoto (Japan); Fujita, Masatoshi [Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Kita, Toru [Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Shimatsu, Akira [Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto (Japan); Hasegawa, Koji [Division of Translational Research, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555 (Japan)

    2008-10-03

    The beneficial effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) beyond cholesterol lowering involve their direct actions on vascular smooth muscle cells (VSMCs). However, the effects of statins on phenotypic modulation of VSMCs are unknown. We herein show that simvastatin (Sm) and atorvastatin (At) inhibited DNA synthesis in human aortic VSMCs dose-dependently, while cell toxicity was not observed below the concentration of 1 {mu}M of Sm or 100 nM of At. Stimulating proliferative VSMCs with Sm or At induced the expression of SM-{alpha}-actin and SM-MHC, highly specific markers of differentiated phenotype. Sm up-regulated the binding activity of GATA-6 to SM-MHC GATA site and activated the transfected SM-MHC promoter in proliferative VSMCs, while mutating the GATA-6 binding site abolished this activation. Geranylgeranylpyrophosphate (10 {mu}M), an inhibitor of Rho family proteins, abolished the statin-mediated induction of the differentiated phenotype in VSMCs. These findings suggest that statins activate GATA-6 and induce differentiated VSMCs.

  12. Intercellular signaling pathways active during and after growth and differentiation of the lumbar vertebral growth plate.

    Science.gov (United States)

    Dahia, Chitra Lekha; Mahoney, Eric J; Durrani, Atiq A; Wylie, Christopher

    2011-06-15

    Vertebral growth plates at different postnatal ages were assessed for active intercellular signaling pathways. To generate a spatial and temporal map of the major signaling pathways active in the postnatal mouse lumbar vertebral growth plate. The growth of all long bones is known to occur by cartilaginous growth plates. The growth plate is composed of layers of chondrocyets that actively proliferate, differentiate, die and, are replaced by bone. The role of major cell signaling pathways has been suggested for regulation of the fetal long bones. But not much is known about the molecular or cellular signals that control the postnatal vertebral growth plate and hence postnatal vertebral bone growth. Understanding such molecular mechanisms will help design therapeutic treatments for vertebral growth disorders such as scoliosis. Antibodies against activated downstream intermediates were used to identify cells in the growth plate responding to BMP, TGFβ, and FGF in cryosections of lumbar vertebrae from different postnatal age mice to identify the zones that were responding to these signals. Reporter mice were used to identify the chondrocytes responding to hedgehog (Ihh), and Wnt signaling. We present a spatial/temporal map of these signaling pathways during growth, and differentiation of the mouse lumbar vertebral growth plate. During growth and differentiation of the vertebral growth plate, its different components respond at different times to different intercellular signaling ligands. Response to most of these signals is dramatically downregulated at the end of vertebral growth.

  13. Induction of osteoblast differentiation by selective activation of kinase-mediated actions of the estrogen receptor.

    Science.gov (United States)

    Kousteni, Stavroula; Almeida, Maria; Han, Li; Bellido, Teresita; Jilka, Robert L; Manolagas, Stavros C

    2007-02-01

    Estrogens control gene transcription by cis or trans interactions of the estrogen receptor (ER) with target DNA or via the activation of cytoplasmic kinases. We report that selective activation of kinase-mediated actions of the ER with 4-estren-3alpha,17beta-diol (estren) or an estradiol-dendrimer conjugate, each a synthetic compound that stimulates kinase-mediated ER actions 1,000 to 10,000 times more potently than direct DNA interactions, induced osteoblastic differentiation in established cell lines of uncommitted osteoblast precursors and primary cultures of osteoblast progenitors by stimulating Wnt and BMP-2 signaling in a kinase-dependent manner. In sharp contrast, 17beta-estradiol (E(2)) suppressed BMP-2-induced osteoblast progenitor commitment and differentiation. Consistent with the in vitro findings, estren, but not E(2), stimulated Wnt/beta-catenin-mediated transcription in T-cell factor-lacZ transgenic mice. Moreover, E(2) stimulated BMP signaling in mice in which ERalpha lacks DNA binding activity and classical estrogen response element-mediated transcription (ERalpha(NERKI/-)) but not in wild-type controls. This evidence reveals for the first time the existence of a large signalosome in which inputs from the ER, kinases, bone morphogenetic proteins, and Wnt signaling converge to induce differentiation of osteoblast precursors. ER can either induce it or repress it, depending on whether the activating ligand (and presumably the resulting conformation of the receptor protein) precludes or accommodates ERE-mediated transcription.

  14. The role of signal transducer and activator of transcription 5 in the inhibitory effects of GH on adipocyte differentiation

    DEFF Research Database (Denmark)

    Richter, H E; Albrektsen, T; Billestrup, Nils

    2003-01-01

    GH inhibits primary rat preadipocyte differentiation and expression of late genes required for terminal differentiation. Here we show that GH-mediated inhibition of fatty acid-binding protein aP2 gene expression correlates with the activation of the Janus kinase-2/signal transducer and activator ...

  15. Using the Activity Model of Inquiry to Enhance General Chemistry Students' Understanding of Nature of Science

    Science.gov (United States)

    Marchlewicz, Sara C.; Wink, Donald J.

    2011-01-01

    Nature of science refers to the processes of scientific activity and the social and cultural premises involved in the creation of scientific knowledge. Having an informed view of nature of science is important in the development of scientifically literate citizens. However, students often come to the classroom with misconceptions about nature of…

  16. Natural occurrence, biological activities and synthesis of eight-, nine-, and eleven-membered ring lactones

    Directory of Open Access Journals (Sweden)

    Helena M. C. Ferraz

    2008-01-01

    Full Text Available The natural occurrence, biological activities and synthetic approaches to natural eight-, nine-, and eleven-membered lactones is reviewed. These medium ring lactones are grouped according to ring size, and their syntheses are discussed. The structures of some natural products early identified as medium-ring lactones were revised after total synthesis.

  17. HL-60 differentiating activity and flavonoid content of the readily extractable fraction prepared from citrus juices.

    Science.gov (United States)

    Kawaii, S; Tomono, Y; Katase, E; Ogawa, K; Yano, M

    1999-01-01

    Citrus plants are rich sources of various bioactive flavonoids. To eliminate masking effects caused by hesperidin, naringin, and neoeriocitrin, the abundant flavonoid glycosides which make up 90% of the conventionally prepared sample, the readily extractable fraction from Citrus juice was prepared by adsorbing on HP-20 resin and eluting with EtOH and acetone from the resin and was subjected to HL-60 differentiation assay and quantitative analysis of major flavonoids. Screening of 34 Citrus juices indicated that King (C. nobilis) had a potent activity for inducing differentiation of HL-60, and the active principles were isolated and identified as four polymethoxylated flavonoids, namely, nobiletin, 3,3',4',5,6,7, 8-heptamethoxyflavone, natsudaidain, and tangeretin. HPLC analysis of the readily extractable fraction also indicated that King contained high amounts of these polymethoxylated flavonoids among the Citrus juices examined. Principal component and cluster analyses of the readily extractable flavonoids indicated peculiarities of King and Bergamot.

  18. Natural Environments and Childhood Experiences Promoting Physical Activity, Examining the Mediational Effects of Feelings about Nature and Social Networks.

    Science.gov (United States)

    Calogiuri, Giovanna

    2016-04-21

    The importance of natural environments (NEs) for physical activity (PA) has been studied extensively. However, there is scant evidence to explain the motivational processes underlying the NE-PA relation. The aim of this study was to investigate the NE-PA relation using an ecological framework, focusing on perception of NEs, childhood experiences and possible intra- and inter-individual mediators. Data were retrieved from a cross-sectional survey among 2168 adults from all over Norway. In addition, the coverage of NEs by municipalities was retrieved from national registers. Logistic regression showed that, unlike the self-reported proximity to NEs, higher ratings of perceived supportiveness of NEs for PA predicted participation in NE-based PA for at least 60 min/week or 150 min/week, before and after controlling for socio-demographic characteristics. Reporting frequent experiences in nature during childhood was also an important predictor of higher levels of NE-based PA. Furthermore, a mediational analysis showed that the effect of both predictors was mediated by "feelings about nature" and "social networks". These findings indicate that to encourage the use of local NE for PA, not only should environmental perceptions be taken into account, positive feelings towards nature alongside opportunities to share activity in nature with others should also be promoted.

  19. Methyl jasmonate differentially affects tocopherol content and tyrosine amino transferase activity in cultured cells of Amaranthus caudatus and Chenopodium quinoa.

    Science.gov (United States)

    Antognoni, F; Faudale, M; Poli, F; Biondi, S

    2009-03-01

    Tocopherols are lipid-soluble compounds synthesised exclusively by photosynthetic organisms. In this study, in vitro callus cultures were established from two plants that are naturally rich in tocopherols, Amaranthus caudatus and Chenopodium quinoa, in order to examine whether callus cultures were able to produce these compounds at levels comparable to those observed in planta. In both species, cotyledon explants produced the best callus induction and, once established, callus cultures were grown under two different hormonal treatments to check for effects of growth and to induce chloroplast differentiation in the cells. A rapid differentiation of chloroplasts occurred only in C. quinoa cell aggregates grown in the presence of benzyladenine, leading to the production of a homogeneous green callus. In both species, only alpha-tocopherol was produced by callus cultures, although levels were much lower than in planta, and the production was not influenced by the hormonal conditions. Interestingly, cell cultures of the two species responded in different ways to methyl jasmonate (MJ). In A. caudatus cultures, treatment with 100 mum MJ increased the production of alpha-tocopherol up to fivefold, and the inductive effect was influenced by the hormonal composition of the medium. This increase in alpha-tocopherol was associated with a proportional increase in tyrosine aminotransferase (TAT) activity, one of the key enzymes involved in tocopherol biosynthesis. By contrast, in C. quinoa cultures, elicitation with MJ did not have any effect, neither on tocopherol production, nor on TAT activity. These results are discussed in relation to chloroplast differentiation and the interplay between jasmonates and phytohormones.

  20. Pena Blanca Natural Analogue Project: Summary of activities

    Energy Technology Data Exchange (ETDEWEB)

    Levy, S.; Goldstein, S.; Dobson, P.F.; Goodell, P.; Ku, T.-L.; Abdel-Fattah, A.; Saulnier, G.; Fayek, M.; de la Garza, R.

    2011-02-01

    The inactive Nopal I uranium mine in silicic tuff north of Chihuahua City, Chihuahua, Mexico, was studied as a natural analogue for an underground nuclear-waste repository in the unsaturated zone. Site stratigraphy was confirmed from new drill cores. Data from site studies include chemical and isotopic compositions of saturated- and unsaturated-zone waters. A partial geochronology of uranium enrichment and mineralization was established. Evidence pertinent to uranium-series transport in the soil zone and changing redox conditions was collected. The investigations contributed to preliminary, scoping-level performance assessment modeling.

  1. Pena blanca natural analogue project: summary of activities

    International Nuclear Information System (INIS)

    Levy, Schon S.; Goldstein, Steven J.; Abdel-Fattah, Amr I.

    2010-01-01

    The inactive Nopal I uranium mine in silicic tuff north of Chihuahua City, Chihuahua, Mexico, was studied as a natural analogue for an underground nuclear-waste repository in the unsaturated zone. Site stratigraphy was confirmed from new drill core. Datafrom site studies include chemical and isotopic compositions of saturated- and unsaturated-zone waters. A partial geochronology of uranium enrichment and mineralization was established. Evidence pertinent to uranium-series transport in the soil zone and changing redox conditions was collected. The investigations contributed to preliminary, scoping-level performance assessment modeling.

  2. Pena blanca natural analogue project: summary of activities

    Energy Technology Data Exchange (ETDEWEB)

    Levy, Schon S [Los Alamos National Laboratory; Goldstein, Steven J [Los Alamos National Laboratory; Abdel - Fattah, Amr I [Los Alamos National Laboratory

    2010-12-08

    The inactive Nopal I uranium mine in silicic tuff north of Chihuahua City, Chihuahua, Mexico, was studied as a natural analogue for an underground nuclear-waste repository in the unsaturated zone. Site stratigraphy was confirmed from new drill core. Datafrom site studies include chemical and isotopic compositions of saturated- and unsaturated-zone waters. A partial geochronology of uranium enrichment and mineralization was established. Evidence pertinent to uranium-series transport in the soil zone and changing redox conditions was collected. The investigations contributed to preliminary, scoping-level performance assessment modeling.

  3. Pena Blanca Natural Analogue Project: Summary of activities

    International Nuclear Information System (INIS)

    Levy, S.; Goldstein, S.; Dobson, P.F.; Goodell, P.; Ku, T.-L.; Abdel-Fattah, A.; Saulnier, G.; Fayek, M.; de la Garza, R.

    2011-01-01

    The inactive Nopal I uranium mine in silicic tuff north of Chihuahua City, Chihuahua, Mexico, was studied as a natural analogue for an underground nuclear-waste repository in the unsaturated zone. Site stratigraphy was confirmed from new drill cores. Data from site studies include chemical and isotopic compositions of saturated- and unsaturated-zone waters. A partial geochronology of uranium enrichment and mineralization was established. Evidence pertinent to uranium-series transport in the soil zone and changing redox conditions was collected. The investigations contributed to preliminary, scoping-level performance assessment modeling.

  4. Natural gas adsorption on biomass derived activated carbons: A mini review

    Directory of Open Access Journals (Sweden)

    Hamza Usman D.

    2016-01-01

    Full Text Available Activated carbon materials are good candidates for natural gas storage due excellent textural properties that are easy to enhance and modify. Natural gas is much cleaner fuel than coal and other petroleum derivatives. Storage of natural gas on porous sorbents at lower pressure is safer and cheaper compared to compressed and liquefied natural gas. This article reviews some works conducted on natural gas storage on biomass based activated carbon materials. Methane storage capacities and deliveries of the various sorbents were given. The effect of factors such as surface area, pore characteristic, heat of adsorption, packing density on the natural gas storage capacity on the activated carbons are discussed. Challenges, improvements and future directions of natural gas storage on porous carbonaceous materials are highlighted.

  5. Active form Notch4 promotes the proliferation and differentiation of 3T3-L1 preadipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Peng-Yeh [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China); Tsai, Chong-Bin [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China); Department of Ophthalmology, Chiayi Christian Hospital, Chiayi 600, Taiwan, ROC (China); Tseng, Min-Jen, E-mail: biomjt@ccu.edu.tw [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China)

    2013-01-18

    Highlights: ► Notch4IC modulates the ERK pathway and cell cycle to promote 3T3-L1 proliferation. ► Notch4IC facilitates 3T3-L1 differentiation by up-regulating proadipogenic genes. ► Notch4IC promotes proliferation during the early stage of 3T3-L1 adipogenesis. ► Notch4IC enhances differentiation during subsequent stages of 3T3-L1 adipogenesis. -- Abstract: Adipose tissue is composed of adipocytes, which differentiate from precursor cells in a process called adipogenesis. Many signal molecules are involved in the transcriptional control of adipogenesis, including the Notch pathway. Previous adipogenic studies of Notch have focused on Notch1 and HES1; however, the role of other Notch receptors in adipogenesis remains unclear. Q-RT-PCR analyses showed that the augmentation of Notch4 expression during the differentiation of 3T3-L1 preadipocytes was comparable to that of Notch1. To elucidate the role of Notch4 in adipogenesis, the human active form Notch4 (N4IC) was transiently transfected into 3T3-L1 cells. The expression of HES1, Hey1, C/EBPδ and PPARγ was up-regulated, and the expression of Pref-1, an adipogenic inhibitor, was down-regulated. To further characterize the effect of N4IC in adipogenesis, stable cells expressing human N4IC were established. The expression of N4IC promoted proliferation and enhanced differentiation of 3T3-L1 cells compared with those of control cells. These data suggest that N4IC promoted proliferation through modulating the ERK pathway and the cell cycle during the early stage of 3T3-L1 adipogenesis and facilitated differentiation through up-regulating adipogenic genes such as C/EBPα, PPARγ, aP2, LPL and HSL during the middle and late stages of 3T3-L1 adipogenesis.

  6. Activated Fps/Fes tyrosine kinase regulates erythroid differentiation and survival.

    Science.gov (United States)

    Sangrar, Waheed; Gao, Yan; Bates, Barbara; Zirngibl, Ralph; Greer, Peter A

    2004-10-01

    A substantial body of evidence implicates the cytoplasmic protein tyrosine kinase Fps/Fes in regulation of myeloid differentiation and survival. In this study we wished to determine if Fps/Fes also plays a role in the regulation of erythropoiesis. Mice tissue-specifically expressing a "gain-of-function" mutant fps/fes transgene (fps(MF)) encoding an activated variant of Fps/Fes (MFps), were used to explore the in vivo biological role of Fps/Fes. Erythropoiesis in these mice was assessed by hematological analysis, lineage marker analysis, bone-marrow colony assays, and biochemical approaches. fps(MF) mice displayed reductions in peripheral red cell counts. However, there was an accumulation of immature erythroid precursors, which displayed increased survival. Fps/Fes and the related Fer kinase were both detected in early erythroid progenitors/blasts and in mature red cells. Fps/Fes was also activated in response to erythropoietin (EPO) and stem cell factor (SCF), two critical factors in erythroid development. In addition, increased Stat5A/B activation and reduced Erk1/2 phosphorylation was observed in fps(MF) primary erythroid cells in response to EPO or SCF, respectively. These data support a role for Fps/Fes in regulating the survival and differentiation of erythroid cells through modulation of Stat5A/B and Erk kinase pathways induced by EPO and SCF. The increased numbers and survival of erythroid progenitors from fps(MF) mice, and their differential responsiveness to SCF and EPO, implicates Fps/Fes in the commitment of multilineage progenitors to the erythroid lineage. The anemic phenotype in fps(MF) mice suggests that downregulation of Fps/Fes activity might be required for terminal erythroid differentiation.

  7. Linear variable differential transformer sensor using glass-covered amorphous wires as active core

    International Nuclear Information System (INIS)

    Chiriac, H.; Hristoforou, E.; Neagu, Maria; Pieptanariu, M.

    2000-01-01

    Results concerning linear variable differential transformer (LVDT) displacement sensor using as movable core glass-covered amorphous wires are presented. The LVDT response is linear for a displacement of the movable core up to about 14 mm, with an accuracy of 1 μm. LVDT using glass-covered amorphous wire as an active core presents a high sensitivity and good mechanical and corrosion resistance

  8. DNA supercoiling: changes during cellular differentiation and activation of chromatin transcription

    International Nuclear Information System (INIS)

    Luchnik, A.N.; Bakayev, V.V.; Glaser, V.M.; Moscow State Univ., USSR)

    1983-01-01

    In this paper it is reported that elastic DNA torsional tension has been observed in a fraction of isolated SV40 minichromosomes, which are shown to be transcriptionally active, and that the number of DNA topological (titratable superhelical) turns in closed superhelical loops of nuclear DNA decreases during cellular differentiation, which, we propose, may be responsible for the coordinate switch in transcription of genes controlling cellular proliferation. 37 references, 6 figures, 2 tables

  9. Differential contributions to the transcriptome of duplicated genes in response to abiotic stresses in natural and synthetic polyploids.

    Science.gov (United States)

    Dong, Shaowei; Adams, Keith L

    2011-06-01

    Polyploidy has occurred throughout plant evolution and can result in considerable changes to gene expression when it takes place and over evolutionary time. Little is known about the effects of abiotic stress conditions on duplicate gene expression patterns in polyploid plants. We examined the expression patterns of 60 duplicated genes in leaves, roots and cotyledons of allotetraploid Gossypium hirsutum in response to five abiotic stress treatments (heat, cold, drought, high salt and water submersion) using single-strand conformation polymorphism assays, and 20 genes in a synthetic allotetraploid. Over 70% of the genes showed stress-induced changes in the relative expression levels of the duplicates under one or more stress treatments with frequent variability among treatments. Twelve pairs showed opposite changes in expression levels in response to different abiotic stress treatments. Stress-induced expression changes occurred in the synthetic allopolyploid, but there was little correspondence in patterns between the natural and synthetic polyploids. Our results indicate that abiotic stress conditions can have considerable effects on duplicate gene expression in a polyploid, with the effects varying by gene, stress and organ type. Differential expression in response to environmental stresses may be a factor in the preservation of some duplicated genes in polyploids. © 2011 The Authors. New Phytologist © 2011 New Phytologist Trust.

  10. Vanadium Dioxide as a Natural Disordered Metamaterial: Perfect Thermal Emission and Large Broadband Negative Differential Thermal Emittance

    Directory of Open Access Journals (Sweden)

    Mikhail A. Kats

    2013-10-01

    Full Text Available We experimentally demonstrate that a thin (approximately 150-nm film of vanadium dioxide (VO_{2} deposited on sapphire has an anomalous thermal emittance profile when heated, which arises because of the optical interaction between the film and the substrate when the VO_{2} is at an intermediate state of its insulator-metal transition (IMT. Within the IMT region, the VO_{2} film comprises nanoscale islands of the metal and dielectric phases and can thus be viewed as a natural, disordered metamaterial. This structure displays “perfect” blackbodylike thermal emissivity over a narrow wavelength range (approximately 40  cm^{-1}, surpassing the emissivity of our black-soot reference. We observe large broadband negative differential thermal emittance over a >10 °C range: Upon heating, the VO_{2}-sapphire structure emits less thermal radiation and appears colder on an infrared camera. Our experimental approach allows for a direct measurement and extraction of wavelength- and temperature-dependent thermal emittance. We anticipate that emissivity engineering with thin-film geometries comprising VO_{2} and other thermochromic materials will find applications in infrared camouflage, thermal regulation, and infrared tagging and labeling.

  11. Detection and quantification of natural contaminants of wine by gas chromatography-differential ion mobility spectrometry (GC-DMS).

    Science.gov (United States)

    Camara, Malick; Gharbi, Nasser; Lenouvel, Audrey; Behr, Marc; Guignard, Cédric; Orlewski, Pierre; Evers, Danièle

    2013-02-06

    Rapid and direct, in situ headspace screening for odoriferous volatile organic compounds (VOCs) present in fresh grapes and in wines is a very promising method for quality control because the economic value of a wine is closely related to its aroma. Long used for the detection of VOCs in complex mixtures, miniature differential ion mobility spectrometry (DMS) seems therefore adequate for in situ trace detection of many kinds of VOCs of concern appearing in the headspace of selected foodstuffs. This work aims at a rapid detection, identification, and quantification of some natural and volatile contaminants of wine such as geosmin, 2-methylisoborneol (2-MIB), 1-octen-3-ol, 1-octen-3-one, and pyrazines (2-isopropyl-3-methoxypyrazine, IPMP, and 3-isobutyl-2-methoxypyrazine, IBMP). In the present study, these compounds were spiked at a known concentration in wine and analyzed with a hyphenated trap-GC-DMS device. The detection of all target compounds at concentrations below the human olfactory threshold was demonstrated.

  12. Natural convection in square enclosures differentially heated at sides using alumina-water nanofluids with temperature-dependent physical properties

    Directory of Open Access Journals (Sweden)

    Cianfrini Marta

    2015-01-01

    Full Text Available Laminar natural convection of Al2O3 + H2O nanofluids inside square cavities differentially heated at sides is studied numerically. A computational code based on the SIMPLE-C algorithm is used for the solution of the system of the mass, momentum and energy transfer governing equations. Assuming that the nanofluid behaves like a single-phase fluid, these equations are the same as those valid for a pure fluid, provided that the thermophysical properties appearing in them are the nanofluid effective properties. The thermal conductivity and dynamic viscosity of the nanofluid are calculated by means of a couple of empirical equations based on a wide variety of experimental data reported in the literature. The other effective properties are evaluated by the conventional mixing theory. Simulations are performed for different values of the nanoparticle volume fraction in the range 0-0.06, the diameter of the suspended nanoparticles in the range 25-100 nm, the temperature of the cooled sidewall in the range 293-313 K, the temperature of the heated sidewall in the range 298-343 K, and the Rayleigh number of the base fluid in the range 103-107. All computations are executed in the hypothesis of temperature-dependent effective properties. The main result obtained is the existence of an optimal particle loading for maximum heat transfer, that is found to increase as the size of the suspended nanoparticles is decreased, and the nanofluid average temperature is increased.

  13. Postlearning stress differentially affects memory for emotional gist and detail in naturally cycling women and women on hormonal contraceptives.

    Science.gov (United States)

    Nielsen, Shawn E; Ahmed, Imran; Cahill, Larry

    2014-08-01

    Sex differences in emotional memory have received increasing interest over the past decade. However, to date, no work has explored how a postlearning stressor might modulate the influence of sex hormone status on memory for gist and peripheral detail in an emotional versus neutral context. Here, we tested 3 predictions. First, compared with naturally cycling (NC) women in the luteal phase, women on hormonal contraception (HC) would have significantly blunted hypothalamic-pituitary-adrenal reactivity to physical stress. Second, postlearning stress would enhance detail and gist memory from an emotional story in NC women, and finally, postlearning stress would not affect emotional memory for details or gist in HC women. Healthy NC and HC women viewed a brief, narrated story containing neutral or emotionally arousing elements. Immediately after, cold pressor stress (CPS) or a control procedure was administered. One week later, participants received a surprise free recall test for story elements. NC women exhibited significantly greater cortisol increases to CPS compared with HC women. NC women who viewed the emotional story and were administered CPS recalled the most peripheral details overall and more gist from the emotional compared with the neutral story. In HC women, however, the postlearning cortisol release did not affect memory for gist or peripheral details from the emotional or neutral story in any way. Additionally, NC and HC women performed similarly on measures of attention and arousal. These findings suggest that in women, postlearning stress differentially affects memory for emotional information depending on their hormonal contraceptive status.

  14. Antiviral Activity of Natural Products Extracted from Marine Organisms

    Directory of Open Access Journals (Sweden)

    Sobia Tabassum

    2011-11-01

    Full Text Available Many epidemics have broken out over the centuries. Hundreds and thousands of humans have died over a disease. Available treatments for infectious diseases have always been limited. Some infections are more deadly than the others, especially viral pathogens. These pathogens have continuously resisted all kinds of medical treatment, due to a need for new treatments to be developed. Drugs are present in nature and are also synthesized in vitro and they help in combating diseases and restoring health. Synthesizing drugs is a hard and time consuming task, which requires a lot of man power and financial aid. However, the natural compounds are just lying around on the earth, may it be land or water. Over a thousand novel compounds isolated from marine organisms are used as antiviral agents. Others are being pharmacologically tested. Today, over forty antiviral compounds are present in the pharmacological market. Some of these compounds are undergoing clinical and pre-clinical stages. Marine compounds are paving the way for a new trend in modern medicine.

  15. Mechanical regulation of stem-cell differentiation by the stretch-activated Piezo channel.

    Science.gov (United States)

    He, Li; Si, Guangwei; Huang, Jiuhong; Samuel, Aravinthan D T; Perrimon, Norbert

    2018-03-01

    Somatic stem cells constantly adjust their self-renewal and lineage commitment by integrating various environmental cues to maintain tissue homeostasis. Although numerous chemical and biological signals have been identified that regulate stem-cell behaviour, whether stem cells can directly sense mechanical signals in vivo remains unclear. Here we show that mechanical stress regulates stem-cell differentiation in the adult Drosophila midgut through the stretch-activated ion channel Piezo. We find that Piezo is specifically expressed in previously unidentified enteroendocrine precursor cells, which have reduced proliferation ability and are destined to become enteroendocrine cells. Loss of Piezo activity reduces the generation of enteroendocrine cells in the adult midgut. In addition, ectopic expression of Piezo in all stem cells triggers both cell proliferation and enteroendocrine cell differentiation. Both the Piezo mutant and overexpression phenotypes can be rescued by manipulation of cytosolic Ca 2+ levels, and increases in cytosolic Ca 2+ resemble the Piezo overexpression phenotype, suggesting that Piezo functions through Ca 2+ signalling. Further studies suggest that Ca 2+ signalling promotes stem-cell proliferation and differentiation through separate pathways. Finally, Piezo is required for both mechanical activation of stem cells in a gut expansion assay and the increase of cytosolic Ca 2+ in response to direct mechanical stimulus in a gut compression assay. Thus, our study demonstrates the existence of a specific group of stem cells in the fly midgut that can directly sense mechanical signals through Piezo.

  16. Generalized query-based active learning to identify differentially methylated regions in DNA.

    Science.gov (United States)

    Haque, Md Muksitul; Holder, Lawrence B; Skinner, Michael K; Cook, Diane J

    2013-01-01

    Active learning is a supervised learning technique that reduces the number of examples required for building a successful classifier, because it can choose the data it learns from. This technique holds promise for many biological domains in which classified examples are expensive and time-consuming to obtain. Most traditional active learning methods ask very specific queries to the Oracle (e.g., a human expert) to label an unlabeled example. The example may consist of numerous features, many of which are irrelevant. Removing such features will create a shorter query with only relevant features, and it will be easier for the Oracle to answer. We propose a generalized query-based active learning (GQAL) approach that constructs generalized queries based on multiple instances. By constructing appropriately generalized queries, we can achieve higher accuracy compared to traditional active learning methods. We apply our active learning method to find differentially DNA methylated regions (DMRs). DMRs are DNA locations in the genome that are known to be involved in tissue differentiation, epigenetic regulation, and disease. We also apply our method on 13 other data sets and show that our method is better than another popular active learning technique.

  17. Muscle activation described with a differential equation model for large ensembles of locally coupled molecular motors.

    Science.gov (United States)

    Walcott, Sam

    2014-10-01

    Molecular motors, by turning chemical energy into mechanical work, are responsible for active cellular processes. Often groups of these motors work together to perform their biological role. Motors in an ensemble are coupled and exhibit complex emergent behavior. Although large motor ensembles can be modeled with partial differential equations (PDEs) by assuming that molecules function independently of their neighbors, this assumption is violated when motors are coupled locally. It is therefore unclear how to describe the ensemble behavior of the locally coupled motors responsible for biological processes such as calcium-dependent skeletal muscle activation. Here we develop a theory to describe locally coupled motor ensembles and apply the theory to skeletal muscle activation. The central idea is that a muscle filament can be divided into two phases: an active and an inactive phase. Dynamic changes in the relative size of these phases are described by a set of linear ordinary differential equations (ODEs). As the dynamics of the active phase are described by PDEs, muscle activation is governed by a set of coupled ODEs and PDEs, building on previous PDE models. With comparison to Monte Carlo simulations, we demonstrate that the theory captures the behavior of locally coupled ensembles. The theory also plausibly describes and predicts muscle experiments from molecular to whole muscle scales, suggesting that a micro- to macroscale muscle model is within reach.

  18. Assessment of the potential activity of major dietary compounds as selective estrogen receptor modulators in two distinct cell models for proliferation and differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Lecomte, Sylvain; Lelong, Marie; Bourgine, Gaëlle [Institut de Recherche en Santé-Environnement-Travail (IRSET), Inserm UMR 1085, Team Transcription, Environment and Cancer, University of Rennes 1, 9 Avenue du Pr Léon Bernard, 35000 Rennes (France); Efstathiou, Theo [Laboratoire Nutrinov, Technopole Atalante Champeaux, 8 rue Jules Maillard de la Gournerie, 35012 Rennes Cedex (France); Saligaut, Christian [Institut de Recherche en Santé-Environnement-Travail (IRSET), Inserm UMR 1085, Team Transcription, Environment and Cancer, University of Rennes 1, 9 Avenue du Pr Léon Bernard, 35000 Rennes (France); Pakdel, Farzad, E-mail: farzad.pakdel@univ-rennes1.fr [Institut de Recherche en Santé-Environnement-Travail (IRSET), Inserm UMR 1085, Team Transcription, Environment and Cancer, University of Rennes 1, 9 Avenue du Pr Léon Bernard, 35000 Rennes (France)

    2017-06-15

    Estrogen receptors (ERs) α and β are distributed in most tissues of women and men. ERs are bound by estradiol (E2), a natural hormone, and mediate the pleiotropic and tissue-specific effects of E2, such as proliferation of breast epithelial cells or protection and differentiation of neuronal cells. Numerous environmental molecules, called endocrine disrupting compounds, also interact with ERs. Phytoestrogens belong to this large family and are considered potent therapeutic molecules that act through their selective estrogen receptor modulator (SERM) activity. Using breast cancer cell lines as a model of estrogen-dependent proliferation and a stably ER-expressing PC12 cell line as a model of neuronal differentiating cells, we studied the SERM activity of major dietary compounds, such as apigenin, liquiritigenin, daidzein, genistein, coumestrol, resveratrol and zearalenone. The ability of these compounds to induce ER-transactivation and breast cancer cell proliferation and enhance Nerve Growth Factor (NGF) -induced neuritogenesis was assessed. Surprisingly, although all compounds were able to activate the ER through an estrogen responsive element reporter gene, they showed differential activity toward proliferation or differentiation. Apigenin and resveratrol showed a partial or no proliferative effect on breast cancer cells but fully contributed to the neuritogenesis effect of NGF. However, daidzein and zearalenone showed full effects on cellular proliferation but did not induce cellular differentiation. In summary, our results suggest that the therapeutic potential of phytoestrogens can diverge depending on the molecule and the phenotype considered. Hence, apigenin and resveratrol might be used in the development of therapeutics for breast cancer and brain diseases. - Highlights: • SERM activity of dietary compounds on proliferation and differentiation is studied. • All the dietary compounds tested transactivate estrogen receptors. • Apigenin and

  19. Activity during natural hibernation in three species of Vespertilionid bats

    NARCIS (Netherlands)

    Daan, Serge

    1973-01-01

    1. Patterns of winter-activity in three species of bats (Myotis mystacinus, M. daubentoni, M. dasycneme) were studied in three hibernation quarters in The Netherlands. The methods of investigation involved: individual marking, automatic recording of intracave and extracave flights and assessment of

  20. Termite activity in relation to natural grassland soil attributes

    NARCIS (Netherlands)

    Kaschuk, G.; Pires Santos, J.C.; Almeida, J.A.; Sinhorati, D.S.; Berton-Junior, J.F.

    2006-01-01

    Soil-feeding termites transport soil for mound building, and this process can affect soil characteristics. To verify the influence of soil termite activity on soil characteristics, samples were collected from top, bottom and center of termite mounds, and of the adjacent area, to assess chemical and

  1. Inhibition of Ape1 Redox Activity Promotes Odonto/osteogenic Differentiation of Dental Papilla Cells.

    Science.gov (United States)

    Chen, Tian; Liu, Zhi; Sun, Wenhua; Li, Jingyu; Liang, Yan; Yang, Xianrui; Xu, Yang; Yu, Mei; Tian, Weidong; Chen, Guoqing; Bai, Ding

    2015-12-07

    Dentinogenesis is the formation of dentin, a substance that forms the majority of teeth, and this process is performed by odontoblasts. Dental papilla cells (DPCs), as the progenitor cells of odontoblasts, undergo the odontogenic differentiation regulated by multiple cytokines and paracrine signal molecules. Ape1 is a perfect paradigm of the function complexity of a biological macromolecule with two major functional regions for DNA repair and redox regulation, respectively. To date, it remains unclear whether Ape1 can regulate the dentinogenesis in DPCs. In the present study, we firstly examed the spatio-temporal expression of Ape1 during tooth germ developmental process, and found the Ape1 expression was initially high and then gradually reduced along with the tooth development. Secondly, the osteo/odontogenic differentiation capacity of DPCs was up-regulated when treated with either Ape1-shRNA or E3330 (a specific inhibitor of the Ape1 redox function), respectively. Moreover, we found that the canonical Wnt signaling pathway was activated in this process, and E3330 reinforced-osteo/odontogenic differentiation capacity was suppressed by Dickkopf1 (DKK1), a potent antagonist of canonical Wnt signaling pathway. Taken together, we for the first time showed that inhibition of Ape1 redox regulation could promote the osteo/odontogenic differentiation capacity of DPCs via canonical Wnt signaling pathway.

  2. pPKCδ activates SC35 splicing factor during H9c2 myoblastic differentiation.

    Science.gov (United States)

    Zara, Susi; Falconi, Mirella; Rapino, Monica; Zago, Michela; Orsini, Giovanna; Mazzotti, Giovanni; Cataldi, Amelia; Teti, Gabriella

    2011-01-01

    Although Protein Kinase C (PKC) isoforms' role in the neonatal and adult cardiac tissue development and ageing has been widely described "in vivo", the interaction of such enzymes with specific nuclear substrates needs to be investigated. The aim of our research has been the study of the expression, localization and interaction with the splicing factor SC35 of PKC isoforms (α, δ, ε, ζ) and their potential role in modulating the transcription machinery. H9c2 cells induced to myoblast differentiation in the presence of 1% Horse Serum (HS) have represented our experimental model. The expression of PKC isoforms, their distribution and interaction with SC35 have been evaluated by western blotting, co-immunoprecipitation and double gold immunolabeling for transmission and scanning electron microscopy. Our results show PKCδ as the most expressed isoform in differentiated cells. Surprisingly, the distribution of PKCδ and SC35 does not show any significant modification between 10%FBS and 1%HS treated samples and no co-localization is observed. Moreover the interaction between the phosphorylated form of PKCδ (pPKCδ) and SC35 increases, is distributed and co-localizes within the nucleus of differentiated H9c2. These data represent reasonable evidence of pPKCδ mediated SC35 splicing factor activation, suggesting its direct effect on transcription via interaction with the transcription machinery. Furthermore, this co-localization represents a crucial event resulting in downstream changes in transcription of components which determine the morphological modifications related to cardiomyoblast differentiated phenotype.

  3. Romidepsin Promotes Osteogenic and Adipocytic Differentiation of Human Mesenchymal Stem Cells through Inhibition of Histondeacetylase Activity

    Directory of Open Access Journals (Sweden)

    Dalia Ali

    2018-01-01

    Full Text Available Bone marrow mesenchymal stem cells (BMSCs are adult multipotent stem cells that can differentiate into mesodermal lineage cells, including adipocytes and osteoblasts. However, the epigenetic mechanisms governing the lineage-specific commitment of BMSCs into adipocytes or osteoblasts are under investigation. Herein, we investigated the epigenetic effect of romidepsin, a small molecule dual inhibitor targeting HDAC1 and HDAC2 identified through an epigenetic library functional screen. BMSCs exposed to romidepsin (5 nM exhibited enhanced adipocytic and osteoblastic differentiation. Global gene expression and signaling pathway analyses of differentially expressed genes revealed a strong enrichment of genes involved in adipogenesis and osteogenesis in romidepsin-treated BMSCs during induction into adipocytes or osteoblasts, respectively. Pharmacological inhibition of FAK signaling during adipogenesis or inhibition of FAK or TGFβ signaling during osteogenesis diminished the biological effects of romidepsin on BMSCs. The results of chromatin immunoprecipitation combined with quantitative polymerase chain reaction indicated a significant increase in H3K9Ac epigenetic markers in the promoter regions of peroxisome proliferator-activated receptor gamma (PPARγ and KLF15 (related to adipogenesis or SP7 (Osterix and alkaline phosphatase (ALP (related to osteogenesis in romidepsin-treated BMSCs. Our data indicated that romidepsin is a novel in vitro modulator of adipocytic and osteoblastic differentiation of BMSCs.

  4. Attempting to be active: Self-efficacy and barrier limitation differentiate activity levels of working mothers.

    Science.gov (United States)

    Gierc, Madelaine; Locke, Sean; Jung, Mary; Brawley, Lawrence

    2016-07-01

    Working mothers are less physically active than working women without children and mothers who do not work. The purpose of this study was to examine concurrent self-regulatory efficacy and barriers to physical activity in a sample of working mothers. Women completed a mixed-methods survey which included measures of physical activity, concurrent self-regulatory efficacy, and barriers. Sufficiently active women experienced significantly greater concurrent self-regulatory efficacy and significantly less barrier limitation and frequency. No significant group differences were found for age, domestic duties performed, and children's extracurricular activities. Thematic analysis of barriers revealed six themes of common and unique factors, including limited time and family activities. © The Author(s) 2014.

  5. The Rac Activator DOCK2 Mediates Plasma Cell Differentiation and IgG Antibody Production

    Directory of Open Access Journals (Sweden)

    Miho Ushijima

    2018-02-01

    Full Text Available A hallmark of humoral immune responses is the production of antibodies. This process involves a complex cascade of molecular and cellular interactions, including recognition of specific antigen by the B cell receptor (BCR, which triggers activation of B cells and differentiation into plasma cells (PCs. Although activation of the small GTPase Rac has been implicated in BCR-mediated antigen recognition, its precise role in humoral immunity and the upstream regulator remain elusive. DOCK2 is a Rac-specific guanine nucleotide exchange factor predominantly expressed in hematopoietic cells. We found that BCR-mediated Rac activation was almost completely lost in DOCK2-deficient B cells, resulting in defects in B cell spreading over the target cell-membrane and sustained growth of BCR microclusters at the interface. When wild-type B cells were stimulated in vitro with anti-IgM F(ab′2 antibody in the presence of IL-4 and IL-5, they differentiated efficiently into PCs. However, BCR-mediated PC differentiation was severely impaired in the case of DOCK2-deficient B cells. Similar results were obtained in vivo when DOCK2-deficient B cells expressing a defined BCR specificity were adoptively transferred into mice and challenged with the cognate antigen. In addition, by generating the conditional knockout mice, we found that DOCK2 expression in B-cell lineage is required to mount antigen-specific IgG antibody. These results highlight important role of the DOCK2–Rac axis in PC differentiation and IgG antibody responses.

  6. The Rac Activator DOCK2 Mediates Plasma Cell Differentiation and IgG Antibody Production.

    Science.gov (United States)

    Ushijima, Miho; Uruno, Takehito; Nishikimi, Akihiko; Sanematsu, Fumiyuki; Kamikaseda, Yasuhisa; Kunimura, Kazufumi; Sakata, Daiji; Okada, Takaharu; Fukui, Yoshinori

    2018-01-01

    A hallmark of humoral immune responses is the production of antibodies. This process involves a complex cascade of molecular and cellular interactions, including recognition of specific antigen by the B cell receptor (BCR), which triggers activation of B cells and differentiation into plasma cells (PCs). Although activation of the small GTPase Rac has been implicated in BCR-mediated antigen recognition, its precise role in humoral immunity and the upstream regulator remain elusive. DOCK2 is a Rac-specific guanine nucleotide exchange factor predominantly expressed in hematopoietic cells. We found that BCR-mediated Rac activation was almost completely lost in DOCK2-deficient B cells, resulting in defects in B cell spreading over the target cell-membrane and sustained growth of BCR microclusters at the interface. When wild-type B cells were stimulated in vitro with anti-IgM F(ab') 2 antibody in the presence of IL-4 and IL-5, they differentiated efficiently into PCs. However, BCR-mediated PC differentiation was severely impaired in the case of DOCK2-deficient B cells. Similar results were obtained in vivo when DOCK2-deficient B cells expressing a defined BCR specificity were adoptively transferred into mice and challenged with the cognate antigen. In addition, by generating the conditional knockout mice, we found that DOCK2 expression in B-cell lineage is required to mount antigen-specific IgG antibody. These results highlight important role of the DOCK2-Rac axis in PC differentiation and IgG antibody responses.

  7. Place of residence as a factor differentiating physical activity in the life style of Ukrainian students.

    Science.gov (United States)

    Bergier, Józef; Bergier, Barbara; Tsos, Anatolii

    2016-12-23

    Determining the state of physical activity of societies as an important component of a health promoting life style is a very up-to-date problem. Studies of physical activity among students, the future elites in their environments, become of increasing importance. An important problem is the recognition of factors differentiating this activity on the example of place of residence. For this purpose, the study covered 2,125 students (60.8% females and 39.2% males) from the National Institute in Lutsk, Ukraine, aged 17-22 (mean age: 20.4). The method of a diagnostic survey was applied which included the International Physical Activity Questionnaire (IPAQ). The following measures of physical activity according to the place of residence (rural area, small town with a population up to 100,000; medium-size town - 100,000-200,000 inhabitants; large city - over 200,000) were taken into consideration: level of physical activity, self-reported physical fitness, sports disciplines practiced by the respondents, and those which they would like to practice, and the BMI, and leisure time possessed. The study showed that the place of residence positively differentiated physical activity among students from medium-size towns and rural areas, compared to their contemporaries from small towns and large cities. Significant differences were also found with respect to the BMI, which was significantly less favourable among respondents from the rural environment. However, no differences were observed between the place of residence for leisure time, self-reported physical activity, and forms of physical activity practiced, and those which the respondents would like to practice.

  8. Physical activity interventions differentially affect exercise task and barrier self-efficacy: A meta-analysis

    Science.gov (United States)

    Higgins, Torrance J.; Middleton, Kathryn R.; Winner, Larry; Janelle, Christopher M.; Middleton, Kathryn R.

    2014-01-01

    Objective Researchers have yet to establish how interventions to increase physical activity influence specific self-efficacy beliefs. The current study sought to quantify the effect of interventions to increase physical activity among healthy adults on exercise task (EXSE) and barrier self-efficacy (BSE) via meta-analysis. Intervention characteristics associated with self-efficacy and physical activity changes were also identified. Methods A systematic database search and manual searches through reference lists of related publications were conducted for articles on randomized, controlled physical activity interventions. Published intervention studies reporting changes in physical activity behavior and either EXSE or BSE in healthy adults were eligible for inclusion. Results Of the 1,080 studies identified, 20 were included in the meta-analyses. Interventions had a significant effect of g = 0.208, 95% confidence interval (CI) [0.027, 0.388], p physical activity. Moderator analyses indicated shorter interventions that did not include structured exercise sessions effectively increased EXSE and physical activity, whereas long interventions improved BSE. Interventions that did not provide support increased BSE and physical activity levels. Further, interventions that did not require the use of daily exercise logs improved EXSE and physical activity behavior. Conclusion Interventions designed to increase physical activity differentially influenced EXSE and BSE. EXSE appeared to play a more significant role during exercise adoption, whereas BSE was involved in the maintenance of exercise behavior. Recommendations are offered for the design of future interventions. PMID:23957904

  9. Natural Translating Locomotion Modulates Cortical Activity at Action Observation

    Directory of Open Access Journals (Sweden)

    Thierry Pozzo

    2017-11-01

    Full Text Available The present study verified if the translational component of locomotion modulated cortical activity recorded at action observation. Previous studies focusing on visual processing of biological motion mainly presented point light walker that were fixed on a spot, thus removing the net translation toward a goal that yet remains a critical feature of locomotor behavior. We hypothesized that if biological motion recognition relies on the transformation of seeing in doing and its expected sensory consequences, a significant effect of translation compared to centered displays on sensorimotor cortical activity is expected. To this aim, we explored whether EEG activity in the theta (4–8 Hz, alpha (8–12 Hz, beta 1 (14–20 Hz and beta 2 (20–32 Hz frequency bands exhibited selectivity as participants viewed four types of stimuli: a centered walker, a centered scrambled, a translating walker and a translating scrambled. We found higher theta synchronizations for observed stimulus with familiar shape. Higher power decreases in the beta 1 and beta 2 bands, indicating a stronger motor resonance was elicited by translating compared to centered stimuli. Finally, beta bands modulation in Superior Parietal areas showed that the translational component of locomotion induced greater motor resonance than human shape. Using a Multinomial Logistic Regression classifier we found that Dorsal-Parietal and Inferior-Frontal regions of interest (ROIs, constituting the core of action-observation system, were the only areas capable to discriminate all the four conditions, as reflected by beta activities. Our findings suggest that the embodiment elicited by an observed scenario is strongly mediated by horizontal body displacement.

  10. Uranium Biomineralization by Natural Microbial Phosphatase Activities in the Subsurface

    Energy Technology Data Exchange (ETDEWEB)

    Sobecky, Patricia A. [Univ. of Alabama, Tuscaloosa, AL (United States)

    2015-04-06

    In this project, inter-disciplinary research activities were conducted in collaboration among investigators at The University of Alabama (UA), Georgia Institute of Technology (GT), Lawrence Berkeley National Laboratory (LBNL), Brookhaven National Laboratory (BNL), the DOE Joint Genome Institute (JGI), and the Stanford Synchrotron Radiation Light source (SSRL) to: (i) confirm that phosphatase activities of subsurface bacteria in Area 2 and 3 from the Oak Ridge Field Research Center result in solid U-phosphate precipitation in aerobic and anaerobic conditions; (ii) investigate the eventual competition between uranium biomineralization via U-phosphate precipitation and uranium bioreduction; (iii) determine subsurface microbial community structure changes of Area 2 soils following organophosphate amendments; (iv) obtain the complete genome sequences of the Rahnella sp. Y9-602 and the type-strain Rahnella aquatilis ATCC 33071 isolated from these soils; (v) determine if polyphosphate accumulation and phytate hydrolysis can be used to promote U(VI) biomineralization in subsurface sediments; (vi) characterize the effect of uranium on phytate hydrolysis by a new microorganism isolated from uranium-contaminated sediments; (vii) utilize positron-emission tomography to label and track metabolically-active bacteria in soil columns, and (viii) study the stability of the uranium phosphate mineral product. Microarray analyses and mineral precipitation characterizations were conducted in collaboration with DOE SBR-funded investigators at LBNL. Thus, microbial phosphorus metabolism has been shown to have a contributing role to uranium immobilization in the subsurface.

  11. Uranium Biomineralization by Natural Microbial Phosphatase Activities in the Subsurface

    International Nuclear Information System (INIS)

    Sobecky, Patricia A.

    2015-01-01

    In this project, inter-disciplinary research activities were conducted in collaboration among investigators at The University of Alabama (UA), Georgia Institute of Technology (GT), Lawrence Berkeley National Laboratory (LBNL), Brookhaven National Laboratory (BNL), the DOE Joint Genome Institute (JGI), and the Stanford Synchrotron Radiation Light source (SSRL) to: (i) confirm that phosphatase activities of subsurface bacteria in Area 2 and 3 from the Oak Ridge Field Research Center result in solid U-phosphate precipitation in aerobic and anaerobic conditions; (ii) investigate the eventual competition between uranium biomineralization via U-phosphate precipitation and uranium bioreduction; (iii) determine subsurface microbial community structure changes of Area 2 soils following organophosphate amendments; (iv) obtain the complete genome sequences of the Rahnella sp. Y9-602 and the type-strain Rahnella aquatilis ATCC 33071 isolated from these soils; (v) determine if polyphosphate accumulation and phytate hydrolysis can be used to promote U(VI) biomineralization in subsurface sediments; (vi) characterize the effect of uranium on phytate hydrolysis by a new microorganism isolated from uranium-contaminated sediments; (vii) utilize positron-emission tomography to label and track metabolically-active bacteria in soil columns, and (viii) study the stability of the uranium phosphate mineral product. Microarray analyses and mineral precipitation characterizations were conducted in collaboration with DOE SBR-funded investigators at LBNL. Thus, microbial phosphorus metabolism has been shown to have a contributing role to uranium immobilization in the subsurface.

  12. An upstream activation element exerting differential transcriptional activation on an archaeal promoter

    DEFF Research Database (Denmark)

    Peng, Nan; Xia, Qiu; Chen, Zhengjun

    2009-01-01

    S gene encoding an arabinose binding protein was characterized using an Sulfolobus islandicus reporter gene system. The minimal active araS promoter (P(araS)) was found to be 59 nucleotides long and harboured four promoter elements: an ara-box, an upstream transcription factor B-responsive element (BRE......), a TATA-box and a proximal promoter element, each of which contained important nucleotides that either greatly decreased or completely abolished promoter activity upon mutagenesis. The basal araS promoter was virtually inactive due to intrinsically weak BRE element, and the upstream activating sequence...... (UAS) ara-box activated the basal promoter by recruiting transcription factor B to its BRE. While this UAS ensured a general expression from an inactive or weak basal promoter in the presence of other tested carbon resources, it exhibited a strong arabinose-responsive transcriptional activation. To our...

  13. Natural Environments and Childhood Experiences Promoting Physical Activity, Examining the Mediational Effects of Feelings about Nature and Social Networks

    Directory of Open Access Journals (Sweden)

    Giovanna Calogiuri

    2016-04-01

    Full Text Available The importance of natural environments (NEs for physical activity (PA has been studied extensively. However, there is scant evidence to explain the motivational processes underlying the NE-PA relation. The aim of this study was to investigate the NE-PA relation using an ecological framework, focusing on perception of NEs, childhood experiences and possible intra- and inter-individual mediators. Data were retrieved from a cross-sectional survey among 2168 adults from all over Norway. In addition, the coverage of NEs by municipalities was retrieved from national registers. Logistic regression showed that, unlike the self-reported proximity to NEs, higher ratings of perceived supportiveness of NEs for PA predicted participation in NE-based PA for at least 60 min/week or 150 min/week, before and after controlling for socio-demographic characteristics. Reporting frequent experiences in nature during childhood was also an important predictor of higher levels of NE-based PA. Furthermore, a mediational analysis showed that the effect of both predictors was mediated by “feelings about nature” and “social networks”. These findings indicate that to encourage the use of local NE for PA, not only should environmental perceptions be taken into account, positive feelings towards nature alongside opportunities to share activity in nature with others should also be promoted.

  14. Effects of low dose radiation on differentiation, activation and apoptosis of thymocytes in mice

    International Nuclear Information System (INIS)

    Su Xu; Zhang Yingchun; Wan Hong; Liu Shuzheng

    1997-01-01

    Objective: To elucidate the possible mechanism of immunoenhancement after low dose radiation (LDR), the differentiation, activation and apoptosis of thymocytes following low dose irradiation were studied. Method: Kunming mice were whole-body irradiated (WBI) with low dose X-rays. The expressions of CD4, CD8, TCR, CD3, IL-2R, (Ca 2+ ) i , Bcl-2 Bax and apoptosis of thymocytes were analyzed by flow cytometry. Results: It was found that the ratio of T H /T S showed no significant changes after LDR. Thymocyte apoptosis was not increased after LDR. The increase of Bcl-2/Bax ratio after LDR might be one of its mechanisms. LDR could expedites the process of differentiation of, and facilitate the signal transduction in, thymocytes. Conclusion: The results indicate that the mechanism of immunoenhancement might be related to the expedition of the maturation, differentiation and activation of thymocytes, thus up-regulating the capability of supplying more mature T lymphocytes to the periphery by the thymus after LDR

  15. LIX1 regulates YAP1 activity and controls the proliferation and differentiation of stomach mesenchymal progenitors.

    Science.gov (United States)

    McKey, Jennifer; Martire, Delphine; de Santa Barbara, Pascal; Faure, Sandrine

    2016-04-28

    Smooth muscle cell (SMC) plasticity maintains the balance between differentiated SMCs and proliferative mesenchymal progenitors, crucial for muscular tissue homeostasis. Studies on the development of mesenchymal progenitors into SMCs have proven useful in identifying molecular mechanisms involved in digestive musculature plasticity in physiological and pathological conditions. Here, we show that Limb Expression 1 (LIX1) molecularly defines the population of mesenchymal progenitors in the developing stomach. Using in vivo functional approaches in the chick embryo, we demonstrate that LIX1 is a key regulator of stomach SMC development. We show that LIX1 is required for stomach SMC determination to regulate the expression of the pro-proliferative gene YAP1 and mesenchymal cell proliferation. However, as stomach development proceeds, sustained LIX1 expression has a negative impact on further SMC differentiation and this is associated with a decrease in YAP1 activity. We demonstrate that expression of LIX1 must be tightly regulated to allow fine-tuning of the transcript levels and state of activation of the pro-proliferative transcriptional coactivator YAP1 to regulate proliferation rates of stomach mesenchymal progenitors and their differentiation. Our data highlight dual roles for LIX1 and YAP1 and provide new insights into the regulation of cell density-dependent proliferation, which is essential for the development and homeostasis of organs.

  16. Activation of GLP-1 Receptor Promotes Bone Marrow Stromal Cell Osteogenic Differentiation through β-Catenin

    Directory of Open Access Journals (Sweden)

    Jingru Meng

    2016-04-01

    Full Text Available Glucagon-like peptide 1 (GLP-1 plays an important role in regulating bone remodeling, and GLP-1 receptor agonist shows a positive relationship with osteoblast activity. However, GLP-1 receptor is not found in osteoblast, and the mechanism of GLP-1 receptor agonist on regulating bone remodeling is unclear. Here, we show that the GLP-1 receptor agonist exendin-4 (Ex-4 promoted bone formation and increased bone mass and quality in a rat unloading-induced bone loss model. These functions were accompanied by an increase in osteoblast number and serum bone formation markers, while the adipocyte number was decreased. Furthermore, GLP-1 receptor was detected in bone marrow stromal cells (BMSCs, but not in osteoblast. Activation of GLP-1 receptor by Ex-4 promoted the osteogenic differentiation and inhibited BMSC adipogenic differentiation through regulating PKA/β-catenin and PKA/PI3K/AKT/GSK3β signaling. These findings reveal that GLP-1 receptor regulates BMSC osteogenic differentiation and provide a molecular basis for therapeutic potential of GLP-1 against osteoporosis.

  17. Differential active site loop conformations mediate promiscuous activities in the lactonase SsoPox.

    Directory of Open Access Journals (Sweden)

    Julien Hiblot

    Full Text Available Enzymes are proficient catalysts that enable fast rates of Michaelis-complex formation, the chemical step and products release. These different steps may require different conformational states of the active site that have distinct binding properties. Moreover, the conformational flexibility of the active site mediates alternative, promiscuous functions. Here we focused on the lactonase SsoPox from Sulfolobus solfataricus. SsoPox is a native lactonase endowed with promiscuous phosphotriesterase activity. We identified a position in the active site loop (W263 that governs its flexibility, and thereby affects the substrate specificity of the enzyme. We isolated two different sets of substitutions at position 263 that induce two distinct conformational sampling of the active loop and characterized the structural and kinetic effects of these substitutions. These sets of mutations selectively and distinctly mediate the improvement of the promiscuous phosphotriesterase and oxo-lactonase activities of SsoPox by increasing active-site loop flexibility. These observations corroborate the idea that conformational diversity governs enzymatic promiscuity and is a key feature of protein evolvability.

  18. Mercury determination in natural waters using neutron activation analysis

    International Nuclear Information System (INIS)

    Cagnone, M.; Marques, R.O.

    1994-01-01

    Available as short communication only. An analytical method for quantitative determination of Mercury traces in river and sea water is proposed. The neutron activation method and radiochemical separation of Mercury by developing of C L 4 Hg -2 complex, and their chromatographic separation using anionic exchange resin Dowex 1 X 8 of 400 mesh is used. The quantitative determination is done by gamma spectrometric analysis. The selection limits reached with this method showed that this is an amenable procedure in routine mercury determination in the ppb level, specially useful in the environmental contamination analysis. (author). 3 refs, 2 figs, 1 tab

  19. LUSI LAB: a multidisciplinary project in a natural active laboratory

    Science.gov (United States)

    Mazzini, Adriano; Lusi Lab Team

    2016-04-01

    The 29th of May 2006 several gas and mud eruption sites suddenly appeared along a strike-slip fault (Watukosek fault system) in the NE of Java, Indonesia. The eruption occurred almost two days after a 6.3 M earthquake striking the island of Java. Within weeks several villages were submerged by boiling mud. The most prominent eruption site was named Lusi. To date Lusi is still active. This disaster has forced 50.000 people to be evacuated and an area of ~7 km2 is covered by mud. The social impact of the eruption and its spectacular dimensions still attract the attention of international media reporting on the "largest mud eruption site on Earth". LUSI LAB (ERC grant n° 308126) focuses on five main aspects in order to complete a comprehensive regional investigation of this impressive event: 1) sampling and monitoring the active Lusi eruption site; 2) monitoring and sampling the neighbouring volcanic arc; 3) monitoring the local micro-seismicity and its relationship with regional seismicity; 4) monitoring the fault system originating from the volcanic arc, crossing Lusi and extending to the NE of Java island; 5) numerical modelling of Lusi activity and the strike-slip/magmatic complex system. We completed several field expeditions. Our studies investigated the mechanisms of reactivation of the Watukosek fault system that crosses Lusi locality and continues to the NE of Java. Results show that after the 27-05-2009 earthquake it was activated the lateral movement of this strike-slip system resulting in these several aligned eruptions sites including Lusi. Further, our geochemical studies of the erupted fluids reveal a mantle signature and point to a connection with the neighboring Arjuno-Welirang volcanic complex indicating that Lusi is a sedimentary hosted geothermal system. We have designed, developed and constructed the Lusi drone. This is a remote controlled hexacopter developed and assembled in order to complete multidisciplinary studies in extreme and

  20. Saprophytic Activity and Sporulation of Cryphonectria parasitica on Dead Chestnut Wood in Forests with Naturally Established Hypovirulence.

    Science.gov (United States)

    Prospero, S; Conedera, M; Heiniger, U; Rigling, D

    2006-12-01

    ABSTRACT Sustainable biological control of the chestnut blight fungus Crypho-nectria parasitica with hypovirulence depends on the production and dissemination of hypovirus-infected propagules of the pathogen. We investigated the ability of C. parasitica to sporulate and produce hypo-virus-infected spores on recently dead chestnut wood in coppice stands in southern Switzerland where hypovirulence has been naturally established. The number and type (active, inactive, or none) of cankers was assessed on experimentally cut and stacked stems, firewood stacks, and natural dead wood. Hypovirus-free and hypovirus-infected strains readily survived for more than 1 year in the chestnut blight cankers of the stacked stems. Sporulation of C. parasitica was observed on the surface of preexisting inactive and active cankers, as well as on newly colonized bark areas and was significantly more abundant than on comparable cankers on living stems. On all types of dead wood, we observed more stromata with perithecia than with pycnidia; however, a large proportion of the stromata was not differentiated. All perithecia examined yielded only hypovirus-free ascospores. The incidence of pycnidia that produced hypovirus-infected conidia ranged from 5% on natural dead wood to 41% on the experimental stacks. The mean virus transmission rate into conidia was 69%. Our study demonstrates a considerable saprophytic activity of C. parasitica on recently dead chestnut wood and supports the hypothesis of a role of this saprophytic phase in the epidemiology of hypovirulence.

  1. Reactive oxygen species activate differentiation gene transcription of acute myeloid leukemia cells via the JNK/c-JUN signaling pathway.

    Science.gov (United States)

    Lam, Chung Fan; Yeung, Hoi Ting; Lam, Yuk Man; Ng, Ray Kit

    2018-05-01

    Reactive oxygen species (ROS) and altered cellular redox status are associated with many malignancies. Acute myeloid leukemia (AML) cells are maintained at immature state by differentiation blockade, which involves deregulation of transcription factors in myeloid differentiation. AML cells can be induced to differentiate by phorbol-12-myristate-13-acetate (PMA), which possesses pro-oxidative activity. However, the signaling events mediated by ROS in the activation of transcriptional program during AML differentiation has not been fully elucidated. Here, we investigated AML cell differentiation by treatment with PMA and ROS scavenger N-acetyl-l-cysteine (NAC). We observed elevation of intracellular ROS level in the PMA-treated AML cells, which correlated with differentiated cell morphology and increased CD11b + mature cell population. The effect of PMA can be abolished by NAC co-treatment, supporting the involvement of ROS in the process. Moreover, we demonstrated that short ROS elevation mediated cell cycle arrest, but failed to activate myeloid gene transcription; whereas prolonged ROS elevation activated JNK/c-JUN signaling pathway. Inhibition of JNK suppressed the expression of key myeloid transcriptional regulators c-JUN, SPI-1 and MAFB, and prevented AML cells from undergoing terminal differentiation. These findings provide new insights into the crucial role of JNK/c-Jun signaling pathway in the activation of transcriptional program during ROS-mediated AML differentiation. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Inhibition of Protein Farnesylation Arrests Adipogenesis and Affects PPARγ Expression and Activation in Differentiating Mesenchymal Stem Cells

    Science.gov (United States)

    Rivas, Daniel; Akter, Rahima; Duque, Gustavo

    2007-01-01

    Protein farnesylation is required for the activation of multiple proteins involved in cell differentiation and function. In white adipose tissue protein, farnesylation has shown to be essential for the successful differentiation of preadipocytes into adipocytes. We hypothesize that protein farnesylation is required for PPARγ2 expression and activation, and therefore for the differentiation of human mesenchymal stem cells (MSCs) into adipocytes. MSCs were plated and induced to differentiate into adipocytes for three weeks. Differentiating cells were treated with either an inhibitor of farnesylation (FTI-277) or vehicle alone. The effect of inhibition of farnesylation in differentiating adipocytes was determined by oil red O staining. Cell survival was quantified using MTS Formazan. Additionally, nuclear extracts were obtained and prelamin A, chaperon protein HDJ-2, PPARγ, and SREBP-1 were determined by western blot. Finally, DNA binding PPARγ activity was determined using an ELISA-based PPARγ activation quantification method. Treatment with an inhibitor of farnesylation (FTI-277) arrests adipogenesis without affecting cell survival. This effect was concomitant with lower levels of PPARγ expression and activity. Finally, accumulation of prelamin A induced an increased proportion of mature SREBP-1 which is known to affect PPARγ activity. In summary, inhibition of protein farnesylation arrests the adipogenic differentiation of MSCs and affects PPARγ expression and activity. PMID:18274630

  3. Physical activity interventions differentially affect exercise task and barrier self-efficacy: a meta-analysis.

    Science.gov (United States)

    Higgins, Torrance J; Middleton, Kathryn R; Winner, Larry; Janelle, Christopher M

    2014-08-01

    Researchers have yet to establish how interventions to increase physical activity influence specific self-efficacy beliefs. The current study sought to quantify the effect of interventions to increase physical activity among healthy adults on exercise task (EXSE) and barrier self-efficacy (BSE) via meta-analysis. Intervention characteristics associated with self-efficacy and physical activity changes were also identified. A systematic database search and manual searches through reference lists of related publications were conducted for articles on randomized, controlled physical activity interventions. Published intervention studies reporting changes in physical activity behavior and either EXSE or BSE in healthy adults were eligible for inclusion. Of the 1,080 studies identified, 20 were included in the meta-analyses. Interventions had a significant effect of g = 0.208, 95% confidence interval (CI) [0.027, 0.388], p exercise sessions effectively increased EXSE and physical activity, whereas long interventions improved BSE. Interventions that did not provide support increased BSE and physical activity levels. Further, interventions that did not require the use of daily exercise logs improved EXSE and physical activity behavior. Interventions designed to increase physical activity differentially influenced EXSE and BSE. EXSE appeared to play a more significant role during exercise adoption, whereas BSE was involved in the maintenance of exercise behavior. Recommendations are offered for the design of future interventions.

  4. Efficient solution of ordinary differential equations modeling electrical activity in cardiac cells.

    Science.gov (United States)

    Sundnes, J; Lines, G T; Tveito, A

    2001-08-01

    The contraction of the heart is preceded and caused by a cellular electro-chemical reaction, causing an electrical field to be generated. Performing realistic computer simulations of this process involves solving a set of partial differential equations, as well as a large number of ordinary differential equations (ODEs) characterizing the reactive behavior of the cardiac tissue. Experiments have shown that the solution of the ODEs contribute significantly to the total work of a simulation, and there is thus a strong need to utilize efficient solution methods for this part of the problem. This paper presents how an efficient implicit Runge-Kutta method may be adapted to solve a complicated cardiac cell model consisting of 31 ODEs, and how this solver may be coupled to a set of PDE solvers to provide complete simulations of the electrical activity.

  5. [Biologically active fragment of the differentiation factor from HL-60 cell line. Identification and properties].

    Science.gov (United States)

    Kostanian, I A; Astapova, M V; Navolotskaia, E V; Lepikhova, T N; Dranitsyna, S M; Telegin, G B; Rodionov, I L; Baĭdakova, L K; Zolotarev, Iu A; Molotkovskaia, I M; Lipkin, V M

    2000-07-01

    Six-membered peptide fragment TGENHR (HLDF-6) was identified in the HL-60 cell culture of human promyelocyte leukemia treated with retinoic acid when studying the differentiation factor HLDF of this cell line. HLDF-6 retains the ability of the full-size factor to induce the differentiation and arrest the proliferation of the starting HL-60 cells. It was shown that the synthetic peptide HLDF-6 has no specific receptors on the surface of the HL-60 cells but can affect the binding of interleukin IL-1 beta, a cytokine involved in proliferation, to the cell surface. It was found on a model of transplantable NSO myeloma that HLDF-6 has an antitumor activity.

  6. The flavonoid fisetin promotes osteoblasts differentiation through Runx2 transcriptional activity.

    Science.gov (United States)

    Léotoing, Laurent; Davicco, Marie-Jeanne; Lebecque, Patrice; Wittrant, Yohann; Coxam, Véronique

    2014-06-01

    Flavonoids represent a group of polyphenolic compounds commonly found in daily nutrition with proven health benefits. Among this group, the flavonol fisetin has been previously shown to protect bone by repressing osteoclast differentiation. In the present study, we investigated the role of fisetin in regulating osteoblasts physiology. In vivo mice treated with LPSs exhibited osteoporosis features associated with a dramatic repression of osteoblast marker expression. In this model, inhibition of osteocalcin and type I collagen alpha 1 transcription was partially countered by a daily consumption of fisetin. Interestingly, in vitro, fisetin promoted both osteoblast alkaline phosphatase activity and mineralization process. To decipher how fisetin may exert its positive effect on osteoblastogenesis, we analyzed its ability to control the runt-related transcription factor 2 (Runx2), a key organizer in developing and maturing osteoblasts. While fisetin did not impact Runx2 mRNA and protein levels, it upregulated its transcriptional activity. Actually, fisetin stimulated the luciferase activity of a reporter plasmid driven by the osteocalcin gene promoter that contains Runx2 binding sites and promoted the mRNA expression of osteocalcin and type I collagen alpha 1 targets. Bone sparing properties of fisetin also rely on its positive influence on osteoblast differentiation and activity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Differential paths to activism: a study of social movement organizations in Three Mile Island communities

    International Nuclear Information System (INIS)

    Cable, S.M.

    1985-01-01

    This project compares political activists from four community protest organizations in Three Mile Island (TMI) communities that were formed as a response of the March 1979 accident at the TMI nuclear power plant. These organizations constituted four separate groups of activists concerned with the same set of grievances. The purpose of the study was to compare the activists across groups to assess differential paths to activism. The data were gathered over a three-year period from March 1979 to March 1982 and included monthly newsletters published by the organizations, newspaper accounts of relevant events; and a systematic survey of 149 of the most active participants. The thesis of differential paths to activism was supported by the data; two relatively distinct paths were found to dominate the TMI communities. In the path that dominated in communities within five miles of the plant, activists tended to be older, more conservative, and less ideologically inclined to protest prior to the accident. In the path to activism that dominated in communities further from the plant site, activists tended to be younger, more liberal, and more experienced in protests

  8. natural

    Directory of Open Access Journals (Sweden)

    Elías Gómez Macías

    2006-01-01

    Full Text Available Partiendo de óxido de magnesio comercial se preparó una suspensión acuosa, la cual se secó y calcinó para conferirle estabilidad térmica. El material, tanto fresco como usado, se caracterizó mediante DRX, área superficial BET y SEM-EPMA. El catalizador mostró una matriz de MgO tipo periclasa con CaO en la superficie. Las pruebas de actividad catalítica se efectuaron en lecho fijo empacado con partículas obtenidas mediante prensado, trituración y clasificación del material. El flujo de reactivos consistió en mezclas gas natural-aire por debajo del límite inferior de inflamabilidad. Para diferentes flujos y temperaturas de entrada de la mezcla reactiva, se midieron las concentraciones de CH4, CO2 y CO en los gases de combustión con un analizador de gases tipo infrarrojo no dispersivo (NDIR. Para alcanzar conversión total de metano se requirió aumentar la temperatura de entrada al lecho a medida que se incrementó el flujo de gases reaccionantes. Los resultados obtenidos permiten desarrollar un sistema de combustión catalítica de bajo costo con un material térmicamente estable, que promueva la alta eficiencia en la combustión de gas natural y elimine los problemas de estabilidad, seguridad y de impacto ambiental negativo inherentes a los procesos de combustión térmica convencional.

  9. Spermicidal Activity of the Safe Natural Antimicrobial Peptide Subtilosin

    Directory of Open Access Journals (Sweden)

    Michael L. Chikindas

    2008-10-01

    Full Text Available Bacterial vaginosis (BV, a condition affecting millions of women each year, is primarily caused by the gram-variable organism Gardnerella vaginalis. A number of organisms associated with BV cases have been reported to develop multidrug resistance, leading to the need for alternative therapies. Previously, we reported the antimicrobial peptide subtilosin has proven antimicrobial activity against G. vaginalis, but not against the tested healthy vaginal microbiota of lactobacilli. After conducting tissue sensitivity assays using an ectocervical tissue model, we determined that human cells remained viable after prolonged exposures to partially-purified subtilosin, indicating the compound is safe for human use. Subtilosin was shown to eliminate the motility and forward progression of human spermatozoa in a dose-dependent manner, and can therefore be considered a general spermicidal agent. These results suggest subtilosin would be a valuable component in topical personal care products aimed at contraception and BV prophylaxis and treatment.

  10. Petroleum production: the nature of the development activity

    Energy Technology Data Exchange (ETDEWEB)

    1977-09-01

    The French Petroleum Institute has studied not only the technological aspects of petroleum exploration and development, but also the economic and managerial aspects. The development strategy for a given company is determined by these economic and political factors: cooperation with other companies, exchange of information concerning the market, study of the economic situation in other countries, and current analysis of the available technical information. Also important are the availability of raw materials and of competent technical personnel. Beside the general field in which the company is active, the decision to undertake a given project will depend on the chances of commercialization and on the particular talents and expertise of the technical personnel. The latter can be enhanced by a development program of human resources. It should be mentioned that practically all such work requires teamwork.

  11. Mechanisms of Earth activity forsed by external celestial bodies:energy budjet and nature of cyclicity

    Science.gov (United States)

    Barkin, Yu. V.; Ferrandiz, J. M.

    2003-04-01

    In given report we discuss tidal and non-tidal mechanisms of forced tectonic (endogenous) activity of the Earth caused by gravitational attraction of the Moon, Sun and the planets. On the base of the classical solution of the problem of elasticity for model of the Earth with concentric mass distribution the evaluations of the tidal energy and power of Earth lunar-solar deformations, including their joint effect, were obtained. Important role of the joint energetic effect of rotational deformation of the Earth with lunar and solar tides was illustrated. Gravitational interaction of the Moon and Sun with non-spherical, non-homogeneous shells of the Earth generates big additional mechanical forces and moments of the interaction of the neighboring shells (rigid core, liquid core, mantle, lithosphere and separate plates). Acting of these forces and moments in the different time scales on the corresponding sells generates cyclic perturbations of the tensional state of the shells, their deformations, small relative translational displacements and small relative rotational oscillations of the shells. In geological period of time it leads to a fundamental tectonic reconstruction of the Earth. These additional forces and moments of the cyclic celestial-mechanical nature produce cyclic deformations of the all layers of the body and organize and control practically all natural processes. The additional force between mantle and core is cyclic and characterized by the wide basis of frequencies typical for orbital motions (of the Sun, Moon and planets), for rotational motion of the Earth, Moon and Sun and for many from observed natural processes. The problem about small relative translatory-rotary motion of the two shells separated by the thin viscous-elastic layer is studied. The differential equations of motion were obtained and have been studied in particular cases (plane motion of system; case of two axisymmetrical interacting shells and oth.) by approximate methods of small

  12. Can Building Design Impact Physical Activity? A Natural Experiment.

    Science.gov (United States)

    Eyler, Amy A; Hipp, Aaron; Valko, Cheryl Ann; Ramadas, Ramya; Zwald, Marissa

    2018-05-01

    Workplace design can impact workday physical activity (PA) and sedentary time. The purpose of this study was to evaluate PA behavior among university employees before and after moving into a new building. A pre-post, experimental versus control group study design was used. PA data were collected using surveys and accelerometers from university faculty and staff. Accelerometry was used to compare those moving into the new building (MOVERS) and those remaining in existing buildings (NONMOVERS) and from a control group (CONTROLS). Survey results showed increased self-reported PA for MOVERS and NONMOVERS. All 3 groups significantly increased in objectively collected daily energy expenditure and steps per day. The greatest steps per day increase was in CONTROLS (29.8%) compared with MOVERS (27.5%) and NONMOVERS (15.9%), but there were no significant differences between groups at pretest or posttest. Self-reported and objectively measured PA increased from pretest to posttest in all groups; thus, the increase cannot be attributed to the new building. Confounding factors may include contamination bias due to proximity of control site to experimental site and introduction of a university PA tracking contest during postdata collection. Methodology and results can inform future studies on best design practices for increasing PA.

  13. Use of green fluorescent fusion protein to track activation of the transcription factor osterix during early osteoblast differentiation

    International Nuclear Information System (INIS)

    Tai Guangping; Christodoulou, Ioannis; Bishop, Anne E.; Polak, Julia M.

    2005-01-01

    Osterix (Osx) is a transcription factor required for the differentiation of preosteoblasts into fully functioning osteoblasts. However, the pattern of Osx activation during preosteoblast differentiation and maturation has not been clearly defined. Our aim was to study Osx activation during these processes in osteoblasts differentiating from murine and human embryonic stem cells (ESC). To do this, we constructed an Osx-GFP fusion protein reporter system to track Osx translocation within the cells. The distribution of Osx-GFP at representative stages of differentiation was also investigated by screening primary osteoblasts, mesenchymal stem cells, synoviocytes, and pre-adipocytes. Our experiments revealed that Osx-GFP protein was detectable in the cytoplasm of cultured, differentiated ESC 4 days after plating of enzymatically dispersed embryoid bodies. Osterix-GFP protein became translocated into the nucleus on day 7 following transfer of differentiated ESC to osteogenic medium. After 14 days of differentiation, cells showing nuclear translocation of Osx-GFP formed rudimentary bone nodules that continued to increase in number over the following weeks (through day 21). We also found that Osx translocated into the nuclei of mesenchymal stem cells (C3H10T1/2) and pre-osteoblasts (MC3T3-E1) and showed partial activation in pre-adipocytes (MC3T3-L1). These data suggest that Osx activation occurs at a very early point in the differentiation of the mesenchymal-osteoblastic lineage

  14. Differential activation of G-proteins by μ-opioid receptor agonists

    Science.gov (United States)

    Saidak, Zuzana; Blake-Palmer, Katherine; Hay, Debbie L; Northup, John K; Glass, Michelle

    2006-01-01

    We investigated the ability of the activated μ-opioid receptor (MOR) to differentiate between myristoylated Gαi1 and GαoA type Gα proteins, and the maximal activity of a range of synthetic and endogenous agonists to activate each Gα protein. Membranes from HEK293 cells stably expressing transfected MOR were chaotrope extracted to denature endogenous G-proteins and reconstituted with specific purified G-proteins. The Gα subunits were generated in bacteria and were demonstrated to be recognised equivalently to bovine brain purified Gα protein by CB1 cannabinoid receptors. The ability of agonists to catalyse the MOR-dependent GDP/[35S]GTPγS exchange was then compared for Gαi1 and GαoA. Activation of MOR by DAMGO produced a high-affinity saturable interaction for GαoA (Km=20±1 nM) but a low-affinity interaction with Gαi1 (Km=116±12 nM). DAMGO, met-enkephalin and leucine-enkephalin displayed maximal Gα activation among the agonists evaluated. Endomorphins 1 and 2, methadone and β-endorphin activated both Gα to more than 75% of the maximal response, whereas fentanyl partially activated both G-proteins. Buprenorphine and morphine demonstrated a statistically significant difference between the maximal activities between Gαi1 and GαoA. Interestingly, DAMGO, morphine, endomorphins 1 and 2, displayed significant differences in the potencies for the activation of the two Gα. Differences in maximal activity and potency, for Gαi1 versus GαoA, are both indicative of agonist selective activation of G-proteins in response to MOR activation. These findings may provide a starting point for the design of drugs that demonstrate greater selectivity between these two G-proteins and therefore produce a more limited range of effects. PMID:16415903

  15. Preparation of activated carbon from waste plastics polyethylene terephthalate as adsorbent in natural gas storage

    Science.gov (United States)

    Yuliusman; Nasruddin; Sanal, A.; Bernama, A.; Haris, F.; Ramadhan, I. T.

    2017-02-01

    The main problem is the process of natural gas storage and distribution, because in normal conditions of natural gas in the gas phase causes the storage capacity be small and efficient to use. The technology is commonly used Compressed Natural Gas (CNG) and Liquefied Natural Gas (LNG). The weakness of this technology safety level is low because the requirement for high-pressure CNG (250 bar) and LNG requires a low temperature (-161°C). It takes innovation in the storage of natural gas using the technology ANG (Adsorbed Natural Gas) with activated carbon as an adsorbent, causing natural gas can be stored in a low pressure of about 34.5. In this research, preparation of activated carbon using waste plastic polyethylene terephthalate (PET). PET plastic waste is a good raw material for making activated carbon because of its availability and the price is a lot cheaper. Besides plastic PET has the appropriate characteristics as activated carbon raw material required for the storage of natural gas because the material is hard and has a high carbon content of about 62.5% wt. The process of making activated carbon done is carbonized at a temperature of 400 ° C and physical activation using CO2 gas at a temperature of 975 ° C. The parameters varied in the activation process is the flow rate of carbon dioxide and activation time. The results obtained in the carbonization process yield of 21.47%, while the yield on the activation process by 62%. At the optimum process conditions, the CO2 flow rate of 200 ml/min and the activation time of 240 minutes, the value % burn off amounted to 86.69% and a surface area of 1591.72 m2/g.

  16. Differential Regulation of Telomerase Reverse Transcriptase Promoter Activation and Protein Degradation by Histone Deacetylase Inhibition.

    Science.gov (United States)

    Qing, Hua; Aono, Jun; Findeisen, Hannes M; Jones, Karrie L; Heywood, Elizabeth B; Bruemmer, Dennis

    2016-06-01

    Telomerase reverse transcriptase (TERT) maintains telomeres and is rate limiting for replicative life span. While most somatic tissues silence TERT transcription resulting in telomere shortening, cells derived from cancer or cardiovascular diseases express TERT and activate telomerase. In the present study, we demonstrate that histone deacetylase (HDAC) inhibition induces TERT transcription and promoter activation. At the protein level in contrast, HDAC inhibition decreases TERT protein abundance through enhanced degradation, which decreases telomerase activity and induces senescence. Finally, we demonstrate that HDAC inhibition decreases TERT expression during vascular remodeling in vivo. These data illustrate a differential regulation of TERT transcription and protein stability by HDAC inhibition and suggest that TERT may constitute an important target for the anti-proliferative efficacy of HDAC inhibitors. © 2015 Wiley Periodicals, Inc.

  17. Insects: an underrepresented resource for the discovery of biologically active natural products

    Directory of Open Access Journals (Sweden)

    Lauren Seabrooks

    2017-07-01

    Full Text Available Nature has been the source of life-changing and -saving medications for centuries. Aspirin, penicillin and morphine are prime examples of Nature׳s gifts to medicine. These discoveries catalyzed the field of natural product drug discovery which has mostly focused on plants. However, insects have more than twice the number of species and entomotherapy has been in practice for as long as and often in conjunction with medicinal plants and is an important alternative to modern medicine in many parts of the world. Herein, an overview of current traditional medicinal applications of insects and characterization of isolated biologically active molecules starting from approximately 2010 is presented. Insect natural products reviewed were isolated from ants, bees, wasps, beetles, cockroaches, termites, flies, true bugs, moths and more. Biological activities of these natural products from insects include antimicrobial, antifungal, antiviral, anticancer, antioxidant, anti-inflammatory and immunomodulatory effects.

  18. Opposing actions of endocannabinoids on cholangiocarcinoma growth is via the differential activation of Notch signaling

    Energy Technology Data Exchange (ETDEWEB)

    Frampton, Gabriel; Coufal, Monique [Department of Internal Medicine, Texas A and M Health Science Center College of Medicine, Temple, TX (United States); Li, Huang [Department of Internal Medicine, Texas A and M Health Science Center College of Medicine, Temple, TX (United States); Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Ramirez, Jonathan [Digestive Disease Research Center, Scott and White Hospital, Temple, TX (United States); DeMorrow, Sharon, E-mail: demorrow@medicine.tamhsc.edu [Department of Internal Medicine, Texas A and M Health Science Center College of Medicine, Temple, TX (United States); Digestive Disease Research Center, Scott and White Hospital, Temple, TX (United States)

    2010-05-15

    The endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2-AG) have opposing effects on cholangiocarcinoma growth. Implicated in cancer, Notch signaling requires the {gamma}-secretase complex for activation. The aims of this study were to determine if the opposing effects of endocannabinoids depend on the differential activation of the Notch receptors and to demonstrate that the differential activation of these receptors are due to presenilin 1 containing- and presenilin 2 containing-{gamma}-secretase complexes. Mz-ChA-1 cells were treated with AEA or 2-AG. Notch receptor expression, activation, and nuclear translocation were determined. Specific roles for Notch 1 and 2 on cannabinoid-induced effects were determined by transient transfection of Notch 1 or 2 shRNA vectors before stimulation with AEA or 2-AG. Expression of presenilin 1 and 2 was determined after AEA or 2-AG treatment, and the involvement of presenilin 1 and 2 in the cannabinoid-induced effects was demonstrated in cell lines with low presenilin 1 or 2 expression. Antiproliferative effects of AEA required increased Notch 1 mRNA, activation, and nuclear translocation, whereas the growth-promoting effects induced by 2-AG required increased Notch 2 mRNA expression, activation, and nuclear translocation. AEA increased presenilin 1 expression and recruitment into the {gamma}-secretase complex, whereas 2-AG increased expression and recruitment of presenilin 2. The development of novel therapeutic strategies aimed at modulating the endocannabinoid system or mimicking the mode of action of AEA on Notch signaling pathways would prove beneficial for cholangiocarcinoma management.

  19. Hedgehog signal activation coordinates proliferation and differentiation of fetal liver progenitor cells

    International Nuclear Information System (INIS)

    Hirose, Yoshikazu; Itoh, Tohru; Miyajima, Atsushi

    2009-01-01

    Hedgehog (Hh) signaling plays crucial roles in development and homeostasis of various organs. In the adult liver, it regulates proliferation and/or viability of several types of cells, particularly under injured conditions, and is also implicated in stem/progenitor cell maintenance. However, the role of this signaling pathway during the normal developmental process of the liver remains elusive. Although Sonic hedgehog (Shh) is expressed in the ventral foregut endoderm from which the liver derives, the expression disappears at the onset of the liver bud formation, and its possible recurrence at the later stages has not been investigated. Here we analyzed the activation and functional relevance of Hh signaling during the mouse fetal liver development. At E11.5, Shh and an activation marker gene for Hh signaling, Gli1, were expressed in Dlk + hepatoblasts, the fetal liver progenitor cells, and the expression was rapidly decreased thereafter as the development proceeded. In the culture of Dlk + hepatoblasts isolated from the E11.5 liver, activation of Hh signaling stimulated their proliferation and this effect was cancelled by a chemical Hh signaling inhibitor, cyclopamine. In contrast, hepatocyte differentiation of Dlk + hepatoblasts in vitro as manifested by the marker gene expression and acquisition of ammonia clearance activity was significantly inhibited by forced activation of Hh signaling. Taken together, these results demonstrate the temporally restricted manner of Hh signal activation and its role in promoting the hepatoblast proliferation, and further suggest that the pathway needs to be shut off for the subsequent hepatic differentiation of hepatoblasts to proceed normally.

  20. Opposing actions of endocannabinoids on cholangiocarcinoma growth is via the differential activation of Notch signaling

    International Nuclear Information System (INIS)

    Frampton, Gabriel; Coufal, Monique; Li, Huang; Ramirez, Jonathan; DeMorrow, Sharon

    2010-01-01

    The endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2-AG) have opposing effects on cholangiocarcinoma growth. Implicated in cancer, Notch signaling requires the γ-secretase complex for activation. The aims of this study were to determine if the opposing effects of endocannabinoids depend on the differential activation of the Notch receptors and to demonstrate that the differential activation of these receptors are due to presenilin 1 containing- and presenilin 2 containing-γ-secretase complexes. Mz-ChA-1 cells were treated with AEA or 2-AG. Notch receptor expression, activation, and nuclear translocation were determined. Specific roles for Notch 1 and 2 on cannabinoid-induced effects were determined by transient transfection of Notch 1 or 2 shRNA vectors before stimulation with AEA or 2-AG. Expression of presenilin 1 and 2 was determined after AEA or 2-AG treatment, and the involvement of presenilin 1 and 2 in the cannabinoid-induced effects was demonstrated in cell lines with low presenilin 1 or 2 expression. Antiproliferative effects of AEA required increased Notch 1 mRNA, activation, and nuclear translocation, whereas the growth-promoting effects induced by 2-AG required increased Notch 2 mRNA expression, activation, and nuclear translocation. AEA increased presenilin 1 expression and recruitment into the γ-secretase complex, whereas 2-AG increased expression and recruitment of presenilin 2. The development of novel therapeutic strategies aimed at modulating the endocannabinoid system or mimicking the mode of action of AEA on Notch signaling pathways would prove beneficial for cholangiocarcinoma management.

  1. Young Scientists Explore Nature. Book 10--Intermediate Level. A Good Apple Activity Book.

    Science.gov (United States)

    DeBruin, Jerry

    Designed to develop creativity in young learners, this book contains interdisciplinary activities which focus on the theme of nature. Activity pages are provided that can serve as front and back covers of a student booklet and the suggested activities can be duplicated for insertion between the covers resulting in a booklet for each student. A…

  2. Recurrent exposure to nicotine differentiates human bronchial epithelial cells via epidermal growth factor receptor activation

    International Nuclear Information System (INIS)

    Martinez-Garcia, Eva; Irigoyen, Marta; Anso, Elena; Martinez-Irujo, Juan Jose; Rouzaut, Ana

    2008-01-01

    Cigarette smoking is the major preventable cause of lung cancer in developed countries. Nicotine (3-(1-methyl-2-pyrrolidinyl)-pyridine) is one of the major alkaloids present in tobacco. Besides its addictive properties, its effects have been described in panoply of cell types. In fact, recent studies have shown that nicotine behaves as a tumor promoter in transformed epithelial cells. This research focuses on the effects of acute repetitive nicotine exposure on normal human bronchial epithelial cells (NHBE cells). Here we show that treatment of NHBE cells with recurrent doses of nicotine up to 500 μM triggered cell differentiation towards a neuronal-like phenotype: cells emitted filopodia and expressed neuronal markers such as neuronal cell adhesion molecule, neurofilament-M and the transcription factors neuronal N and Pax-3. We also demonstrate that nicotine treatment induced NF-kB translocation to the nucleus, phosphorylation of the epidermal growth factor receptor (EGFR), and accumulation of heparin binding-EGF in the extracellular medium. Moreover, addition of AG1478, an inhibitor of EGFR tyrosine phosphorylation, or cetuximab, a monoclonal antibody that precludes ligand binding to the same receptor, prevented cell differentiation by nicotine. Lastly, we show that differentiated cells increased their adhesion to the extracellular matrix and their protease activity. Given that several lung pathologies are strongly related to tobacco consumption, these results may help to better understand the damaging consequences of nicotine exposure

  3. Adipogenic Differentiation of Muscle Derived Cells is Repressed by Inhibition of GSK-3 Activity

    Directory of Open Access Journals (Sweden)

    Zoe Redshaw

    2018-06-01

    Full Text Available Intramuscular fat is important in large animal livestock species in regard to meat quality and in humans is of clinical significance in particular in relation to insulin resistance. The canonical Wnt signalling pathway has been implicated at a whole body level in regulating relative levels of adiposity versus lean body mass. Previously we have shown that pig muscle cells can undergo adipogenic differentiation to a degree that is dependent upon the specific muscle source. In this work we examine the role of the canonical Wnt pathway which acts through inactivation of glycogen synthase kinase-3 (GSK-3 in the regulation of adipogenic differentiation in muscle cells derived from the pig semimembranosus muscle.The application of lithium chloride to muscle derived cells significantly increased the phosphorylation of GSK-3β and thus inhibited its activity thus mimicking Wnt signaling. This was associated with a significant decrease in the expression of the adipogenic transcription factor PPARγ and an almost complete inhibition of adipogenesis in the cells. The data also suggest that GSK-3α plays, at most, a small role in this process.Studies in vivo have suggested that the Wnt pathway is a major regulator of whole body adiposity. In this study we have shown that the ability of cells derived from porcine skeletal muscle to differentiate along an adipogenic lineage, in vitro, is severely impaired by mimicking the action of this pathway. This was done by inactivation of GSK-3β by the use of Lithium Chloride.

  4. Activity measurement and effective dose modelling of natural radionuclides in building material

    International Nuclear Information System (INIS)

    Maringer, F.J.; Baumgartner, A.; Rechberger, F.; Seidel, C.; Stietka, M.

    2013-01-01

    In this paper the assessment of natural radionuclides' activity concentration in building materials, calibration requirements and related indoor exposure dose models is presented. Particular attention is turned to specific improvements in low-level gamma-ray spectrometry to determine the activity concentration of necessary natural radionuclides in building materials with adequate measurement uncertainties. Different approaches for the modelling of the effective dose indoor due to external radiation resulted from natural radionuclides in building material and results of actual building material assessments are shown. - Highlights: • Dose models for indoor radiation exposure due to natural radionuclides in building materials. • Strategies and methods in radionuclide metrology, activity measurement and dose modelling. • Selection of appropriate parameters in radiation protection standards for building materials. • Scientific-based limitations of indoor exposure due to natural radionuclides in building materials

  5. Induction of polyclonal B cell activation and differentiation by the AIDS retrovirus (HTLV-III/LAV)

    International Nuclear Information System (INIS)

    Higgins, S.E.; Schnittman, S.M.; Lane, H.C.; Folks, T.; Koenig, S.; Fauci, A.S.

    1986-01-01

    The immune systems of individuals infected with HTLV-III/LAV are characterized by a profound defect in cellular immunity together with paradoxical polyclonal B cell activation. The present study examined the direct effects of HTLV-III/LAV on B lymphocytes. Peripheral blood B cells from healthy donors were incubated with a variety of HTLV-III/LAV isolates for 1 h and 3 H-thymidine incorporation was measured at multiple time points. Responses ranged from 9000-28,000 cpm and peaked on day 4. This B cell activation was not enhanced by the addition of interleukin-2 to culture, was not synergistic with Staphylococcus aureus Cowan I, was not modulated by the addition of T lymphocytes to culture, and was not associated with B cell transformation. Supernatant Ig could first be detected in virus-activated cultures at day 4, plateaued by day 8, and yielded a mean of 12,500 ng IgG+IgM/ml/50,000 B cells. Thus, HTLV-III/LAV is a potent T cell independent B cell mitogen capable of inducing B cell activation, proliferation, and differentiation comparable in magnitude to that of the most potent B cell activators. This biological property of HTLV-III/LAV may help explain the profound polyclonal B cell activation observed in patients with AIDS and may provide investigators with another probe for investigating the mechanisms of B cell activation

  6. Differential binding activity of the transcription factor LIL-Stat in immature and differentiated normal and leukemic myeloid cells

    NARCIS (Netherlands)

    Tuyt, LML; Bregman, K; Lummen, C; Dokter, WHA; Vellenga, E

    1998-01-01

    Cytokines and growth factors induce activation of the family of signal transducers and activators of transcription (Stats) that directly activate gene expression. Recently, constitutively activated Stat1, Stat3, and Stat5 were identified in nuclear extracts of acute myeloid leukemia (AML) patients,

  7. Retinoblastoma pathway defects show differential ability to activate the constitutive DNA damage response in human tumorigenesis

    DEFF Research Database (Denmark)

    Tort, F.; Bartkova, J.; Sehested, M.

    2006-01-01

    culture models with differential defects of retinoblastoma pathway components, as overexpression of cyclin D1 or lack of p16(Ink4a), either alone or combined, did not elicit detectable DDR. In contrast, inactivation of pRb, the key component of the pathway, activated the DDR in cultured human or mouse...... with their hierarchical positions along the retinoblastoma pathway. Our data provide new insights into oncogene-evoked DDR in human tumorigenesis, with potential implications for individualized management of tumors with elevated cyclin D1 versus cyclin E, due to their distinct clinical variables and biological behavior....

  8. An important natural genetic resource of Oreochromis niloticus (Linnaeus, 1758) threatened by aquaculture activities in Loboi drainage, Kenya.

    Science.gov (United States)

    Ndiwa, Titus Chemandwa; Nyingi, Dorothy Wanja; Agnese, Jean-François

    2014-01-01

    The need to improve food security in Africa through culture of tilapias has led to transfer of different species from their natural ranges causing negative impacts on wild fish genetic resources. Loboi swamp in Kenya is fed by three hot springs: Lake Bogoria Hotel, Chelaba and Turtle Springs, hosting natural populations of Oreochromis niloticus. The present study aimed at better genetic characterization of these threatened populations. Partial mtDNA sequences of the D-loop region and variations at 16 microsatellite loci were assessed in the three hot spring populations and compared with three other natural populations of O. niloticus in the region. Results obtained indicated that the hot spring populations had mitochondrial and nuclear genetic variability similar to or higher than the large closely related populations. This may be attributed to the perennial nature of the hot springs, which do not depend on rainfall but rather receive permanent water supply from deep aquifers. The study also revealed that gene flow between the three different hot spring populations was sufficiently low thus allowing their differentiation. This differentiation was unexpected considering the very close proximity of the springs to each other. It is possible that the swamp creates a barrier to free movement of fish from one spring to the other thereby diminishing gene flow. Finally, the most surprising and worrying results were that the three hot spring populations are introgressed by mtDNA genes of O. leucostictus, while microsatellite analysis suggested that some nuclear genes may also have crossed the species barrier. It is very likely that the recent intensification of aquaculture activities in the Loboi drainage may be responsible for these introgressions. Taking into account the importance of these new genetic resources, protection and management actions of the Loboi swamp should be accorded top priority to prevent the loss of these spring populations.

  9. An important natural genetic resource of Oreochromis niloticus (Linnaeus, 1758 threatened by aquaculture activities in Loboi drainage, Kenya.

    Directory of Open Access Journals (Sweden)

    Titus Chemandwa Ndiwa

    Full Text Available The need to improve food security in Africa through culture of tilapias has led to transfer of different species from their natural ranges causing negative impacts on wild fish genetic resources. Loboi swamp in Kenya is fed by three hot springs: Lake Bogoria Hotel, Chelaba and Turtle Springs, hosting natural populations of Oreochromis niloticus. The present study aimed at better genetic characterization of these threatened populations. Partial mtDNA sequences of the D-loop region and variations at 16 microsatellite loci were assessed in the three hot spring populations and compared with three other natural populations of O. niloticus in the region. Results obtained indicated that the hot spring populations had mitochondrial and nuclear genetic variability similar to or higher than the large closely related populations. This may be attributed to the perennial nature of the hot springs, which do not depend on rainfall but rather receive permanent water supply from deep aquifers. The study also revealed that gene flow between the three different hot spring populations was sufficiently low thus allowing their differentiation. This differentiation was unexpected considering the very close proximity of the springs to each other. It is possible that the swamp creates a barrier to free movement of fish from one spring to the other thereby diminishing gene flow. Finally, the most surprising and worrying results were that the three hot spring populations are introgressed by mtDNA genes of O. leucostictus, while microsatellite analysis suggested that some nuclear genes may also have crossed the species barrier. It is very likely that the recent intensification of aquaculture activities in the Loboi drainage may be responsible for these introgressions. Taking into account the importance of these new genetic resources, protection and management actions of the Loboi swamp should be accorded top priority to prevent the loss of these spring populations.

  10. Hippocalcin Is Required for Astrocytic Differentiation through Activation of Stat3 in Hippocampal Neural Precursor Cells.

    Directory of Open Access Journals (Sweden)

    Min-Jeong Kang

    2016-10-01

    Full Text Available Hippocalcin (Hpca is a neuronal calcium sensor protein expressed in the mammalian brain. However, its function in neural stem/precursor cells has not yet been studied. Here, we clarify the function of Hpca in astrocytic differentiation in hippocampal neural precursor cells (HNPCs. When we overexpressed Hpca in HNPCs in the presence or absence of bFGF, expression levels of nerve-growth factors such as neurotrophin-3 (NT-3, neurotrophin-4/5 (NT-4/5 and brain-derived neurotrophic factor (BDNF, together with the proneural basic helix loop helix (bHLH transcription factors neuroD and neurogenin 1 (ngn1, increased significantly. In addition, there was an increase in the number of cells expressing glial fibrillary acidic protein (GFAP, an astrocyte marker, and in dendrite outgrowth, indicating astrocytic differentiation of the HNPCs. Downregulation of Hpca by transfection with Hpca siRNA reduced expression of NT-3, NT-4/5, BDNF, neuroD and ngn1 as well as levels of GFAP protein. Furthermore, overexpression of Hpca increased the phosphorylation of STAT3 (Ser727, and this effect was abolished by treatment with a STAT3 inhibitor (S3I-201, suggesting that STAT3 (Ser727 activation is involved in Hpca-mediated astrocytic differentiation. As expected, treatment with Stat3 siRNA or STAT3 inhibitor caused a complete inhibition of astrogliogenesis induced by Hpca overexpression. Taken together, this is the first report to show that Hpca, acting through Stat3, has an important role in the expression of neurotrophins and proneural bHLH transcription factors, and that it is an essential regulator of astrocytic differentiation and dendrite outgrowth in HNPCs.

  11. Differential activation of catalase expression and activity by PPAR agonists: Implications for astrocyte protection in anti-glioma therapy☆

    Science.gov (United States)

    Khoo, Nicholas K.H.; Hebbar, Sachin; Zhao, Weiling; Moore, Steven A.; Domann, Frederick E.; Robbins, Mike E.

    2013-01-01

    Glioma survival is dismal, in part, due to an imbalance in antioxidant expression and activity. Peroxisome proliferator-activated receptor (PPAR) agonists have antineoplastic properties which present new redox-dependent targets for glioma anticancer therapies. Herein, we demonstrate that treatment of primary cultures of normal rat astrocytes with PPAR agonists increased the expression of catalase mRNA protein, and enzymatic activity. In contrast, these same agonists had no effect on catalase expression and activity in malignant rat glioma cells. The increase in steady-state catalase mRNA observed in normal rat astrocytes was due, in part, to de novo mRNA synthesis as opposed to increased catalase mRNA stability. Moreover, pioglitazone-mediated induction of catalase activity in normal rat astrocytes was completely blocked by transfection with a PPARγ-dominant negative plasmid. These data suggest that defects in PPAR-mediated signaling and gene expression may represent a block to normal catalase expression and induction in malignant glioma. The ability of PPAR agonists to differentially increase catalase expression and activity in normal astrocytes but not glioma cells suggests that these compounds might represent novel adjuvant therapeutic agents for the treatment of gliomas. PMID:24024139

  12. Activation of the Extracellular Signal-Regulated Kinase Signaling Is Critical for Human Umbilical Cord Mesenchymal Stem Cell Osteogenic Differentiation

    Directory of Open Access Journals (Sweden)

    Chen-Shuang Li

    2016-01-01

    Full Text Available Human umbilical cord mesenchymal stem cells (hUCMSCs are recognized as candidate progenitor cells for bone regeneration. However, the mechanism of hUCMSC osteogenesis remains unclear. In this study, we revealed that mitogen-activated protein kinases (MAPKs signaling is involved in hUCMSC osteogenic differentiation in vitro. Particularly, the activation of c-Jun N-terminal kinases (JNK and p38 signaling pathways maintained a consistent level in hUCMSCs through the entire 21-day osteogenic differentiation period. At the same time, the activation of extracellular signal-regulated kinases (ERK signaling significantly increased from day 5, peaked at day 9, and declined thereafter. Moreover, gene profiling of osteogenic markers, alkaline phosphatase (ALP activity measurement, and alizarin red staining demonstrated that the application of U0126, a specific inhibitor for ERK activation, completely prohibited hUCMSC osteogenic differentiation. However, when U0126 was removed from the culture at day 9, ERK activation and osteogenic differentiation of hUCMSCs were partially recovered. Together, these findings demonstrate that the activation of ERK signaling is essential for hUCMSC osteogenic differentiation, which points out the significance of ERK signaling pathway to regulate the osteogenic differentiation of hUCMSCs as an alternative cell source for bone tissue engineering.

  13. Differential proteolytic activation of factor VIII-von Willebrand factor complex by thrombin

    International Nuclear Information System (INIS)

    Hill-Eubanks, D.C.; Parker, C.G.; Lollar, P.

    1989-01-01

    Blood coagulation factor VIII (fVIII) is a plasma protein that is decreased or absent in hemophilia A. It is isolated as a mixture of heterodimers that contain a variably sized heavy chain and a common light chain. Thrombin catalyzes the activation of fVIII in a reaction that is associated with cleavages in both types of chain. The authors isolated a serine protease from Bothrops jararacussu snake venom that catalyzes thrombin-like heavy-chain cleavage but not light-chain cleavage in porcine fVIII as judged by NaDodSO 4 /PAGE and N-terminal sequence analysis. Using a plasma-free assay of the ability of activated 125 I-fVIII to function as a cofactor in the activation of factor X by factor IXa, they found that fVIII is activated by the venom enzyme. The venom enzyme-activated fVIII was isolated in stable form by cation-exchange HPLC. von Willebrand factor inhibited venom enzyme-activated fVIII but not thrombin-activated fVIII. These results suggest that the binding of fVIII to von Willebrand factor depends on the presence of an intact light chain and that activated fVIII must dissociate from von Willebrand factor to exert its cofactor effect. Thus, proteolytic activation of fVIII-von Willebrand factor complex appears to be differentially regulated by light-chain cleavage to dissociate the complex and heavy-chain cleavage to activate the cofactor function

  14. High versus low radioiodine activity in patients with differentiated thyroid cancer - A meta-analysis

    International Nuclear Information System (INIS)

    Valachis, Antonis; Nearchou, Andreas

    2013-01-01

    Background: The purpose of the meta-analysis was to estimate the effectiveness and toxicity of low activity radioiodine ablation versus high activity in patients with differentiated thyroid cancer (DTC). Design: A systematic review and meta-analysis was performed by including all randomized trials of low activity versus high activity radioiodine ablation after thyroidectomy. Standard meta-analytic procedures were used to analyze the study outcomes. Results: Ten trials were considered eligible and were further analyzed. The pooled risk ratio (RR) of having a successful ablation for an activity of 1100 MBq versus 3700 MBq (seven trials, 1772 patients) was 0.94 (95% CI 0.85 - 1.04, p-value 0.21). The RR for successful ablation when only thyroid hormone withdrawal was used (five trials, 1116 patients) was 0.87 (95% CI 0.72 - 1.06, p-value 0.17) and it was comparable to RR when only recombinant-human TSH (rec-hTSH) (two trials, 812 patients) was used (1.00, 95% CI 0.93 - 1.07, p-value 0.92). Salivary dysfunction, nausea, and neck pain were significantly more frequent among patients with higher dose for ablation. Conclusion: Our meta-analysis provides some evidence from randomized trials that a lower activity of radioiodine ablation is as effective as higher dose after surgery in patients with DTC with lower toxicity

  15. High versus low radioiodine activity in patients with differentiated thyroid cancer - A meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Valachis, Antonis [Dept. of Oncology, Maelarsjukhuset., Eskilstuna (Sweden); Univ. of Uppsala,, (Sweden)], e-mail: Valachis@hotmail.com, Antonis.Valachis@akademiska.uu.se; Nearchou, Andreas [Dept, of Oncology, Maelarsjukhuset., Eskilstuna (Sweden); Univ. of Uppsala., Uppsala (Sweden)

    2013-08-15

    Background: The purpose of the meta-analysis was to estimate the effectiveness and toxicity of low activity radioiodine ablation versus high activity in patients with differentiated thyroid cancer (DTC). Design: A systematic review and meta-analysis was performed by including all randomized trials of low activity versus high activity radioiodine ablation after thyroidectomy. Standard meta-analytic procedures were used to analyze the study outcomes. Results: Ten trials were considered eligible and were further analyzed. The pooled risk ratio (RR) of having a successful ablation for an activity of 1100 MBq versus 3700 MBq (seven trials, 1772 patients) was 0.94 (95% CI 0.85 - 1.04, p-value 0.21). The RR for successful ablation when only thyroid hormone withdrawal was used (five trials, 1116 patients) was 0.87 (95% CI 0.72 - 1.06, p-value 0.17) and it was comparable to RR when only recombinant-human TSH (rec-hTSH) (two trials, 812 patients) was used (1.00, 95% CI 0.93 - 1.07, p-value 0.92). Salivary dysfunction, nausea, and neck pain were significantly more frequent among patients with higher dose for ablation. Conclusion: Our meta-analysis provides some evidence from randomized trials that a lower activity of radioiodine ablation is as effective as higher dose after surgery in patients with DTC with lower toxicity.

  16. Impaired IFN-α-mediated signal in dendritic cells differentiates active from latent tuberculosis.

    Directory of Open Access Journals (Sweden)

    Stefania Parlato

    Full Text Available Individuals exposed to Mycobacterium tuberculosis (Mtb may be infected and remain for the entire life in this condition defined as latent tuberculosis infection (LTBI or develop active tuberculosis (TB. Among the multiple factors governing the outcome of the infection, dendritic cells (DCs play a major role in dictating antibacterial immunity. However, current knowledge on the role of the diverse components of human DCs in shaping specific T-cell response during Mtb infection is limited. In this study, we performed a comparative evaluation of peripheral blood circulating DC subsets as well as of monocyte-derived Interferon-α DCs (IFN-DCs from patients with active TB, subjects with LTBI and healthy donors (HD. The proportion of circulating myeloid BDCA3+ DCs (mDC2 and plasmacytoid CD123+ DCs (pDCs declined significantly in active TB patients compared to HD, whereas the same subsets displayed a remarkable activation in LTBI subjects. Simultaneously, the differentiation of IFN-DCs from active TB patients resulted profoundly impaired compared to those from LTBI and HD individuals. Importantly, the altered developmental trait of IFN-DCs from active TB patients was associated with down-modulation of IFN-linked genes, marked changes in molecular signaling conveying antigen (Ag presentation and full inability to induce Ag-specific T cell response. Thus, these data reveal an important role of IFN-α in determining the induction of Mtb-specific immunity.

  17. Differential activation of Fyn kinase distinguishes saturated and unsaturated fats in mouse macrophages.

    Science.gov (United States)

    Tarabra, Elena; An Lee, Ting-Wen; Zammit, Victor A; Vatish, Manu; Yamada, Eijiro; Pessin, Jeffrey E; Bastie, Claire C

    2017-10-17

    Diet-induced obesity is associated with increased adipose tissue activated macrophages. Yet, how macrophages integrate fatty acid (FA) signals remains unclear. We previously demonstrated that Fyn deficiency ( fynKO ) protects against high fat diet-induced adipose tissue macrophage accumulation. Herein, we show that inflammatory markers and reactive oxygen species are not induced in fynKO bone marrow-derived macrophages exposed to the saturated FA palmitate, suggesting that Fyn regulates macrophage function in response to FA signals. Palmitate activates Fyn and re-localizes Fyn into the nucleus of RAW264.7, J774 and wild-type bone marrow-derived macrophages. Similarly, Fyn activity is increased in cells of adipose tissue stromal vascular fraction of high fat-fed control mice, with Fyn protein being located in the nucleus of these cells. We demonstrate that Fyn modulates palmitate-dependent oxidative stress in macrophages. Moreover, Fyn catalytic activity is necessary for its nuclear re-localization and downstream effects, as Fyn pharmacological inhibition abolishes palmitate-induced Fyn nuclear redistribution and palmitate-dependent increase of oxidative stress markers. Importantly, mono-or polyunsaturated FAs do not activate Fyn, and fail to re-localize Fyn to the nucleus. Together these data demonstrate that macrophages integrate nutritional FA signals via a differential activation of Fyn that distinguishes, at least partly, the effects of saturated versus unsaturated fats.

  18. The Limited Utility of Multiunit Data in Differentiating Neuronal Population Activity.

    Directory of Open Access Journals (Sweden)

    Corey J Keller

    Full Text Available To date, single neuron recordings remain the gold standard for monitoring the activity of neuronal populations. Since obtaining single neuron recordings is not always possible, high frequency or 'multiunit activity' (MUA is often used as a surrogate. Although MUA recordings allow one to monitor the activity of a large number of neurons, they do not allow identification of specific neuronal subtypes, the knowledge of which is often critical for understanding electrophysiological processes. Here, we explored whether prior knowledge of the single unit waveform of specific neuron types is sufficient to permit the use of MUA to monitor and distinguish differential activity of individual neuron types. We used an experimental and modeling approach to determine if components of the MUA can monitor medium spiny neurons (MSNs and fast-spiking interneurons (FSIs in the mouse dorsal striatum. We demonstrate that when well-isolated spikes are recorded, the MUA at frequencies greater than 100Hz is correlated with single unit spiking, highly dependent on the waveform of each neuron type, and accurately reflects the timing and spectral signature of each neuron. However, in the absence of well-isolated spikes (the norm in most MUA recordings, the MUA did not typically contain sufficient information to permit accurate prediction of the respective population activity of MSNs and FSIs. Thus, even under ideal conditions for the MUA to reliably predict the moment-to-moment activity of specific local neuronal ensembles, knowledge of the spike waveform of the underlying neuronal populations is necessary, but not sufficient.

  19. The Role of Biologically Active Ingredients from Natural Drug Treatments for Arrhythmias in Different Mechanisms

    OpenAIRE

    Li, Jie; Hu, Dan; Song, Xiaoli; Han, Tao; Gao, Yonghong; Xing, Yanwei

    2017-01-01

    Arrhythmia is a disease that is caused by abnormal electrical activity in the heart rate or rhythm. It is the major cause of cardiovascular morbidity and mortality. Although several antiarrhythmic drugs have been used in clinic for decades, their application is often limited by their adverse effects. As a result, natural drugs, which have fewer side effects, are now being used to treat arrhythmias. We searched for all articles on the role of biologically active ingredients from natural drug t...

  20. Ecological restoration success is higher for natural regeneration than for active restoration in tropical forests

    OpenAIRE

    Crouzeilles, Renato; Ferreira, Mariana S.; Chazdon, Robin L.; Lindenmayer, David B.; Sansevero, Jerônimo B. B.; Monteiro, Lara; Iribarrem, Alvaro; Latawiec, Agnieszka E.; Strassburg, Bernardo B. N.

    2017-01-01

    Is active restoration the best approach to achieve ecological restoration success (the return to a reference condition, that is, old-growth forest) when compared to natural regeneration in tropical forests? Our meta-analysis of 133 studies demonstrated that natural regeneration surpasses active restoration in achieving tropical forest restoration success for all three biodiversity groups (plants, birds, and invertebrates) and five measures of vegetation structure (cover, density, litter, biom...

  1. Natural vegetation cover in the landscape and edge effects: differential responses of insect orders in a fragmented forest.

    Science.gov (United States)

    González, Ezequiel; Salvo, Adriana; Valladares, Graciela

    2017-10-01

    Human activities have led to global simplification of ecosystems, among which Neotropical dry forests are some of the most threatened. Habitat loss as well as edge effects may affect insect communities. Here, we analyzed insects sampled with pan traps in 9 landscapes (at 5 scales, in 100-500 m diameter circles) comprising cultivated fields and Chaco Serrano forests, at overall community and taxonomic order level. In total 7043 specimens and 456 species of hexapods were captured, with abundance and richness being directly related to forest cover at 500 m and higher at edges in comparison with forest interior. Community composition also varied with forest cover and edge/interior location. Different responses were detected among the 8 dominant orders. Collembola, Hemiptera, and Orthoptera richness and/or abundance were positively related to forest cover at the larger scale, while Thysanoptera abundance increased with forest cover only at the edge. Hymenoptera abundance and richness were negatively related to forest cover at 100 m. Coleoptera, Diptera, and Hymenoptera were more diverse and abundant at the forest edge. The generally negative influence of forest loss on insect communities could have functional consequences for both natural and cultivated systems, and highlights the relevance of forest conservation. Higher diversity at the edges could result from the simultaneous presence of forest and matrix species, although "resource mapping" might be involved for orders that were richer and more abundant at edges. Adjacent crops could benefit from forest proximity since natural enemies and pollinators are well represented in the orders showing positive edge effects. © 2016 Institute of Zoology, Chinese Academy of Sciences.

  2. Leptin differentially regulate STAT3 activation in ob/ob mouse adipose mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Zhou Zhou

    2012-12-01

    Full Text Available Abstract Background Leptin-deficient ob/ob mice exhibit adipocyte hypertrophy and hyperplasia as well as elevated adipose tissue and systemic inflammation. Multipotent stem cells isolated from adult adipose tissue can differentiate into adipocytes ex vivo and thereby contribute toward increased adipocyte cell numbers, obesity, and inflamm ation. Currently, information is lacking regarding regulation of adipose stem cell numbers as well as leptin-induced inflammation and its signaling pathway in ob/ob mice. Methods Using leptin deficient ob/ob mice, we investigated whether leptin injection into ob/ob mice increases adipose stem cell numbers and adipose tissue inflammatory marker MCP-1 mRNA and secretion levels. We also determined leptin mediated signaling pathways in the adipose stem cells. Results We report here that adipose stem cell number is significantly increased following leptin injection in ob/ob mice and with treatment of isolated stem cells with leptin in vitro. Leptin also up-regulated MCP-1 secretion in a dose- and time-dependent manner. We further showed that increased MCP-1 mRNA levels were due to increased phosphorylation of Signal Transducer and Activator of Transcription 3 (STAT3 Ser727 but not STAT3 Tyr705 phosphorylation, suggesting differential regulation of MCP-1 gene expression under basal and leptin-stimulated conditions in adipose stem cells. Conclusions Taken together, these studies demonstrate that leptin increases adipose stem cell number and differentially activates STAT3 protein resulting in up-regulation of MCP-1 gene expression. Further studies of mechanisms mediating adipose stem cell hyperplasia and leptin signaling in obesity are warranted and may help identify novel anti-obesity target strategies.

  3. Khellin and visnagin differentially modulate AHR signaling and downstream CYP1A activity in human liver cells.

    Directory of Open Access Journals (Sweden)

    Radim Vrzal

    Full Text Available Khellin and visnagin are two furanochromones that can be frequently found in ethnomedical formulations in Asia and the Middle East. Both compounds possess anti-inflammatory and analgesic properties, therefore modern medicine uses these compounds or structurally related derivatives for treatment of vitiligo, bronchial asthma and renal colics. Despite their frequent usage, the potential toxic properties of visnagin and khellin are not well characterized up-to-now. Many natural compounds modulate the expression and activity of cytochrome P450 1A1 (CYP1A1, which is well-known to bioactivate pro-carcinogens. The expression of this enzyme is controlled by the aryl hydrocarbon receptor (AHR, a ligand-activated transcription factor and regulator of drug metabolism. Here, we investigated the influence of both furanochromones on AHR signaling in human HepG2 hepatocarcinoma cells and primary human hepatocytes. Both compounds transactivated xenobiotic response element (XRE-driven reporter gene activity in a dose-dependent manner and induced CYP1A1 transcription in HepG2 cells and primary hepatocytes. The latter was abolished in presence of a specific AHR antagonist. CYP1A enzyme activity assays done in HepG2 cells and primary hepatocytes revealed an inhibition of enzyme activity by both furanochromones, which may become relevant regarding the metabolism of xenobiotics and co-administered therapeutic drugs. The observed induction of several other members of the AHR gene battery, whose gene products are involved in regulation of cell growth, differentiation and migration, indicates that a further toxicological characterization of visnagin and khelllin is urgently required in order to minimize potential drug-drug interactions and other toxic side-effects that may occur during therapeutic usage of these furanochromones.

  4. Ecological restoration success is higher for natural regeneration than for active restoration in tropical forests.

    Science.gov (United States)

    Crouzeilles, Renato; Ferreira, Mariana S; Chazdon, Robin L; Lindenmayer, David B; Sansevero, Jerônimo B B; Monteiro, Lara; Iribarrem, Alvaro; Latawiec, Agnieszka E; Strassburg, Bernardo B N

    2017-11-01

    Is active restoration the best approach to achieve ecological restoration success (the return to a reference condition, that is, old-growth forest) when compared to natural regeneration in tropical forests? Our meta-analysis of 133 studies demonstrated that natural regeneration surpasses active restoration in achieving tropical forest restoration success for all three biodiversity groups (plants, birds, and invertebrates) and five measures of vegetation structure (cover, density, litter, biomass, and height) tested. Restoration success for biodiversity and vegetation structure was 34 to 56% and 19 to 56% higher in natural regeneration than in active restoration systems, respectively, after controlling for key biotic and abiotic factors (forest cover, precipitation, time elapsed since restoration started, and past disturbance). Biodiversity responses were based primarily on ecological metrics of abundance and species richness (74%), both of which take far less time to achieve restoration success than similarity and composition. This finding challenges the widely held notion that natural forest regeneration has limited conservation value and that active restoration should be the default ecological restoration strategy. The proposition that active restoration achieves greater restoration success than natural regeneration may have arisen because previous comparisons lacked controls for biotic and abiotic factors; we also did not find any difference between active restoration and natural regeneration outcomes for vegetation structure when we did not control for these factors. Future policy priorities should align the identified patterns of biophysical and ecological conditions where each or both restoration approaches are more successful, cost-effective, and compatible with socioeconomic incentives for tropical forest restoration.

  5. TRAF6 promotes myogenic differentiation via the TAK1/p38 mitogen-activated protein kinase and Akt pathways.

    Directory of Open Access Journals (Sweden)

    Fang Xiao

    Full Text Available p38 mitogen-activated protein kinase (MAPK is an essential kinase involved in myogenic differentiation. Although many substrates of p38 MAPK have been identified, little is known about its upstream activators during myogenic differentiation. TRAF6 is known to function in cytokine signaling during inflammatory responses. However, not much is known about its role in myogenic differentiation and muscle regeneration. We showed here that TRAF6 and its intrinsic ubiquitin E3 ligase activity are required for myogenic differentiation. In mouse myoblasts, knockdown of TRAF6 compromised the p38 MAPK and Akt pathways, while deliberate activation of either pathway rescued the differentiation defect caused by TRAF6 knockdown. TAK1 acted as a key signal transducer downstream of TRAF6 in myogenic differentiation. In vivo, knockdown of TRAF6 in mouse muscles compromised the injury-induced muscle regeneration without impairing macrophage infiltration and myoblast proliferation. Collectively, we demonstrated that TRAF6 promotes myogenic differentiation and muscle regeneration via the TAK1/p38 MAPK and Akt pathways.

  6. T cell activation and differentiation is modulated by a CD6 domain 1 antibody Itolizumab.

    Directory of Open Access Journals (Sweden)

    Usha Bughani

    Full Text Available CD6 is associated with T-cell modulation and is implicated in several autoimmune diseases. We previously demonstrated that Itolizumab, a CD6 domain 1 (CD6D1 specific humanized monoclonal antibody, inhibited the proliferation and cytokine production by T lymphocytes stimulated with anti-CD3 antibody or when co-stimulated with ALCAM. Aberrant IL-17 producing CD4+ helper T-cells (Th17 have been identified as pivotal for the pathogenesis of certain inflammatory autoimmune disorders, including psoriasis. Itolizumab has demonstrated efficacy in human diseases known to have an IL-17 driven pathogenesis. Here, in in vitro experiments we show that by day 3 of human PBMC activation using anti-CD3 and anti-CD28 co-stimulation in a Th17 polarizing milieu, 15-35% of CD4+ T-cells overexpress CD6 and there is an establishment of differentiated Th17 cells. Addition of Itolizumab reduces the activation and differentiation of T cells to Th17 cells and decreases production of IL-17. These effects are associated with the reduction of key transcription factors pSTAT3 and RORγT. Further, transcription analysis studies in these conditions indicate that Itolizumab suppressed T cell activation by primarily reducing cell cycle, DNA transcription and translation associated genes. To understand the mechanism of this inhibition, we evaluated the effect of this anti-human CD6D1 mAb on ALCAM-CD6 as well as TCR-mediated T cell activation. We show that Itolizumab but not its F(ab'2 fragment directly inhibits CD6 receptor hyper-phosphorylation and leads to subsequent decrease in associated ZAP70 kinase and docking protein SLP76. Since Itolizumab binds to CD6 expressed only on human and chimpanzee, we developed an antibody binding specifically to mouse CD6D1. This antibody successfully ameliorated the incidence of experimental autoimmune encephalitis in the mice model. These results position CD6 as a key molecule in sustaining the activation and differentiation of T cells and an

  7. Differences in muscle activity between natural forefoot and rearfoot strikers during running.

    Science.gov (United States)

    Yong, Jennifer R; Silder, Amy; Delp, Scott L

    2014-11-28

    Running research has focused on reducing injuries by changing running technique. One proposed method is to change from rearfoot striking (RFS) to forefoot striking (FFS) because FFS is thought to be a more natural running pattern that may reduce loading and injury risk. Muscle activity affects loading and influences running patterns; however, the differences in muscle activity between natural FFS runners and natural RFS runners are unknown. The purpose of this study was to measure muscle activity in natural FFS runners and natural RFS runners. We tested the hypotheses that tibialis anterior activity would be significantly lower while activity of the plantarflexors would be significantly greater in FFS runners, compared to RFS runners, during late swing phase and early stance phase. Gait kinematics, ground reaction forces and electromyographic patterns of ten muscles were collected from twelve natural RFS runners and ten natural FFS runners. The root mean square (RMS) of each muscle׳s activity was calculated during terminal swing phase and early stance phase. We found significantly lower RMS activity in the tibialis anterior in FFS runners during terminal swing phase, compared to RFS runners. In contrast, the medial and lateral gastrocnemius showed significantly greater RMS activity in terminal swing phase in FFS runners. No significant differences were found during early stance phase for the tibialis anterior or the plantarflexors. Recognizing the differences in muscle activity between FFS and RFS runners is an important step toward understanding how foot strike patterns may contribute to different types of injury. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Differential MR/GR Activation in Mice Results in Emotional States Beneficial or Impairing for Cognition

    Directory of Open Access Journals (Sweden)

    Vera Brinks

    2007-01-01

    Full Text Available Corticosteroids regulate stress response and influence emotion, learning, and memory via two receptors in the brain, the high‐affinity mineralocorticoid (MR and low‐affinity glucocorticoid receptor (GR. We test the hypothesis that MR- and GR-mediated effects interact in emotion and cognition when a novel situation is encountered that is relevant for a learning process. By adrenalectomy and additional constant corticosterone supplement we obtained four groups of male C57BL/6J mice with differential chronic MR and GR activations. Using a hole board task, we found that mice with continuous predominant MR and moderate GR activations were fast learners that displayed low anxiety and arousal together with high directed explorative behavior. Progressive corticosterone concentrations with predominant action via GR induced strong emotional arousal at the expense of cognitive performance. These findings underline the importance of a balanced MR/GR system for emotional and cognitive functioning that is critical for mental health.

  9. Telomerase activity promotes osteoblast differentiation by modulating IGF-signaling pathway

    DEFF Research Database (Denmark)

    Saeed, Hamid; Qiu, Weimin; Li, Chen

    2015-01-01

    -regulation of several components of insulin-like growth factor (IGF) signaling. Specifically, a significant increase in IGF-induced AKT phosphorylation and alkaline phosphatase (ALP) activity were observed in hMSC-TERT. Enhanced ALP activity was reduced in presence of IGF1 receptor inhibitor: picropodophyllin....... In addition, telomerase deficiency caused significant reduction in IGF signaling proteins in osteoblastic cells cultured from telomerase deficient mice (Terc (-/-)). The low bone mass exhibited by Terc (-/-) mice was associated with significant reduction in serum levels of IGF1 and IGFBP3 as well as reduced...... skeletal mRNA expression of Igf1, Igf2, Igf2r, Igfbp5 and Igfbp6. IGF1-induced osteoblast differentiation was also impaired in Terc (-/-) MSC. In conclusion, our data demonstrate that impaired IGF/AKT signaling contributes to the observed decreased bone mass and bone formation exhibited by telomerase...

  10. Activity measurement and effective dose modelling of natural radionuclides in building material.

    Science.gov (United States)

    Maringer, F J; Baumgartner, A; Rechberger, F; Seidel, C; Stietka, M

    2013-11-01

    In this paper the assessment of natural radionuclides' activity concentration in building materials, calibration requirements and related indoor exposure dose models is presented. Particular attention is turned to specific improvements in low-level gamma-ray spectrometry to determine the activity concentration of necessary natural radionuclides in building materials with adequate measurement uncertainties. Different approaches for the modelling of the effective dose indoor due to external radiation resulted from natural radionuclides in building material and results of actual building material assessments are shown. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Differentiation and fiber type-specific activity of a muscle creatine kinase intronic enhancer

    Directory of Open Access Journals (Sweden)

    Tai Phillip WL

    2011-07-01

    Full Text Available Abstract Background Hundreds of genes, including muscle creatine kinase (MCK, are differentially expressed in fast- and slow-twitch muscle fibers, but the fiber type-specific regulatory mechanisms are not well understood. Results Modulatory region 1 (MR1 is a 1-kb regulatory region within MCK intron 1 that is highly active in terminally differentiating skeletal myocytes in vitro. A MCK small intronic enhancer (MCK-SIE containing a paired E-box/myocyte enhancer factor 2 (MEF2 regulatory motif resides within MR1. The SIE's transcriptional activity equals that of the extensively characterized 206-bp MCK 5'-enhancer, but the MCK-SIE is flanked by regions that can repress its activity via the individual and combined effects of about 15 different but highly conserved 9- to 24-bp sequences. ChIP and ChIP-Seq analyses indicate that the SIE and the MCK 5'-enhancer are occupied by MyoD, myogenin and MEF2. Many other E-boxes located within or immediately adjacent to intron 1 are not occupied by MyoD or myogenin. Transgenic analysis of a 6.5-kb MCK genomic fragment containing the 5'-enhancer and proximal promoter plus the 3.2-kb intron 1, with and without MR1, indicates that MR1 is critical for MCK expression in slow- and intermediate-twitch muscle fibers (types I and IIa, respectively, but is not required for expression in fast-twitch muscle fibers (types IIb and IId. Conclusions In this study, we discovered that MR1 is critical for MCK expression in slow- and intermediate-twitch muscle fibers and that MR1's positive transcriptional activity depends on a paired E-box MEF2 site motif within a SIE. This is the first study to delineate the DNA controls for MCK expression in different skeletal muscle fiber types.

  12. Active Dendrites and Differential Distribution of Calcium Channels Enable Functional Compartmentalization of Golgi Cells.

    Science.gov (United States)

    Rudolph, Stephanie; Hull, Court; Regehr, Wade G

    2015-11-25

    Interneurons are essential to controlling excitability, timing, and synaptic integration in neuronal networks. Golgi cells (GoCs) serve these roles at the input layer of the cerebellar cortex by releasing GABA to inhibit granule cells (grcs). GoCs are excited by mossy fibers (MFs) and grcs and provide feedforward and feedback inhibition to grcs. Here we investigate two important aspects of GoC physiology: the properties of GoC dendrites and the role of calcium signaling in regulating GoC spontaneous activity. Although GoC dendrites are extensive, previous studies concluded they are devoid of voltage-gated ion channels. Hence, the current view holds that somatic voltage signals decay passively within GoC dendrites, and grc synapses onto distal dendrites are not amplified and are therefore ineffective at firing GoCs because of strong passive attenuation. Using whole-cell recording and calcium imaging in rat slices, we find that dendritic voltage-gated sodium channels allow somatic action potentials to activate voltage-gated calcium channels (VGCCs) along the entire dendritic length, with R-type and T-type VGCCs preferentially located distally. We show that R- and T-type VGCCs located in the dendrites can boost distal synaptic inputs and promote burst firing. Active dendrites are thus critical to the regulation of GoC activity, and consequently, to the processing of input to the cerebellar cortex. In contrast, we find that N-type channels are preferentially located near the soma, and control the frequency and pattern of spontaneous firing through their close association with calcium-activated potassium (KCa) channels. Thus, VGCC types are differentially distributed and serve specialized functions within GoCs. Interneurons are essential to neural processing because they modulate excitability, timing, and synaptic integration within circuits. At the input layer of the cerebellar cortex, a single type of interneuron, the Golgi cell (GoC), carries these functions. The

  13. Adventurous activities, embodiment and nature: spiritual, sensual and sustainable? Embodying environmental justice

    Directory of Open Access Journals (Sweden)

    Barbara Humberstone

    2013-09-01

    Full Text Available This paper examines research on adventurous physical activities in nature from the perspective of the sentient body. Drawing upon ethnographic and autoethnographic research, I examine what has been termed 'peak' happenings or 'flow' which many who practise adventurous activities claim to experience through their whole body when in the 'zone'. I consider the concept of 'edgework', voluntary risk-taking, and insightful mobile and social understanding of the relationships between body, emotions and the elements, where the adventurous activity is experienced and interpreted as oneness with nature or expressed as 'spiritual' not only in high but also low risk nature-based sport. I then consider if and in what ways these knowledges may bring about greater understanding and action in relation to social and environmental justice. I argue that adventurous activities/nature-based sport may provide processes and practices that are alternative or complementary to traditional sporting 'body techniques' or 'body pedagogics'. I suggest that modern embodied adventurous practices in nature challenge dominant narratives of body/mind separation and potentially provide a pedagogic process fostering kinetic empathy. Finally I draw attention to the paradox of (re-presenting sensorial experiences of sport in nature and ask for consideration on how we interconnect with the environment when we participate in adventureous nature-based sports.

  14. Autophagic flux is highly active in early mitosis and differentially regulated throughout the cell cycle.

    Science.gov (United States)

    Li, Zhiyuan; Ji, Xinmiao; Wang, Dongmei; Liu, Juanjuan; Zhang, Xin

    2016-06-28

    Mitosis is a fast process that involves dramatic cellular remodeling and has a high energy demand. Whether autophagy is active or inactive during the early stages of mitosis in a naturally dividing cell is still debated. Here we aimed to use multiple assays to resolve this apparent discrepancy. Although the LC3 puncta number was reduced in mitosis, the four different cell lines we tested all have active autophagic flux in both interphase and mitosis. In addition, the autophagic flux was highly active in nocodazole-induced, double-thymidine synchronization released as well as naturally occurring mitosis in HeLa cells. Multiple autophagy proteins are upregulated in mitosis and the increased Beclin-1 level likely contributes to the active autophagic flux in early mitosis. It is interesting that although the autophagic flux is active throughout the cell cycle, early mitosis and S phase have relatively higher autophagic flux than G1 and late G2 phases, which might be helpful to degrade the damaged organelles and provide energy during S phase and mitosis.

  15. Electromyographic Pattern during Gait Initiation Differentiates Yoga Practitioners among Physically Active Older Subjects

    Directory of Open Access Journals (Sweden)

    Thierry Lelard

    2017-06-01

    Full Text Available During gait initiation, postural adjustments are needed to deal with balance and movement. With aging, gait initiation changes and reflects functional degradation of frailty individuals. However, physical activities have demonstrated beneficial effects of daily motor tasks. The aim of our study was to compare center of pressure (COP displacement and ankle muscle co-activation during gait initiation in two physically active groups: a group of walkers (n = 12; mean age ± SD 72.6 ± 3.2 years and a yoga group (n = 11; 71.5 ± 3.8 years. COP trajectory and electromyography of leg muscles were recorded simultaneously during five successive trials of gait initiation. Our main finding was that yoga practitioners had slower COP displacements (p < 0.01 and lower leg muscles % of coactivation (p < 0.01 in comparison with walkers. These parameters which characterized gait initiation control were correlated (r = 0.76; p < 0.01. Our results emphasize that lengthy ankle muscle co-activation and COP path in gait initiation differentiate yoga practitioners among physically active subjects.

  16. Differential impacts of participation in organized activities and maltreatment types on adolescent academic and socioemotional development.

    Science.gov (United States)

    Kwak, Yoonyoung; Mihalec-Adkins, Brittany; Mishra, Aura A; Christ, Sharon L

    2018-04-01

    Participation in organized activities has been largely regarded as beneficial for academic and socioemotional development for adolescents, but the impacts of various types of organized activities for adolescents at risk for maltreatment have been rarely tested. In this study, we investigated the differential impacts of five types of maltreatment exposure (physical maltreatment, sexual maltreatment, neglect, other type, and multiple types) on the associations between four types of organized activities (mentored groups, art and music clubs, sport clubs, and academic clubs) and academic and socioemotional development (school engagement, delinquency, depressive symptoms, and trauma symptoms) of adolescents who were investigated by Child Protective Services (CPS) for maltreatment exposure. Data came from a national, longitudinal sample of 790 adolescents in contact with CPS in the U.S. After controlling for demographic characteristics of participants and prior levels of each outcome, multiple linear regression models were fitted to the data with interactions between the organized activities and the maltreatment types. The main findings of this study included: 1) adolescents who participated in mentored groups, sport clubs, and academic clubs reported higher levels of school engagement; 2) adolescents who participated in academic clubs reported fewer depressive symptoms; 3) adolescents who participated in art and music clubs reported more trauma symptoms compared to non-participants; and 4) the effects of participation in mentored groups on delinquency and trauma symptoms differed by maltreatment type. These results indicate both possible benefits and risks of organized activity participation for adolescents with certain maltreatment exposures. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Change of the natural radiation exposure due to agriculture and industrial activities in a high natural radioactivity area from Brazil

    International Nuclear Information System (INIS)

    Silva Amaral, E.C. da.

    1992-01-01

    The Pocos de Caldas Plateau, Minas Gerais State one of the biggest alkaline intrusions in the world. This study has shown the expected value for the mean annual radiation exposure due to the agricultural activities ranges from 6 up to 14 mSv/a depending on the age and living habits of the population group. The inhalation exposure of radon, thoron and their progenies represents the largest radiological health hazard (70-90%); this is followed by the external gamma irradiation from soil (10-25%). Ingestion of natural radionuclides with local food is only of minor radiological consequence. It was found that the lethal cancer risk might increase by 4% for a person born at the plateau, living and working there for the rest of her life. For the remote population the consumption the consumption of food products exported from the plateau leads to an expected value for the collective dose of 19 man Sv/a. This corresponding nominally to the small calculated number of 1 additional case of cancer per year. Therefore the main radiation impact of the agricultural activities are not the increased concentrations of natural radionuclides in food products but the fact that they are produced there with human labor and thus increasing the radiation exposure to a large number of farm workers and their families that move for occupational reasons to that region. The radiation exposure due to the mining and milling activities is, in spite of the significant increase of radionuclide activity concentrations in river waters, only of the order of 0.3 mSv/a. However as a recognized industrial source the ICRP dose limitation system has to be applied. Under this aspect the exposure calculated here, 0.3 mSv/a, should be considered as acceptable. (author). 93 refs, 16 figs, 58 tabs

  18. Differential activation of an identified motor neuron and neuromodulation provide Aplysia's retractor muscle an additional function.

    Science.gov (United States)

    McManus, Jeffrey M; Lu, Hui; Cullins, Miranda J; Chiel, Hillel J

    2014-08-15

    To survive, animals must use the same peripheral structures to perform a variety of tasks. How does a nervous system employ one muscle to perform multiple functions? We addressed this question through work on the I3 jaw muscle of the marine mollusk Aplysia californica's feeding system. This muscle mediates retraction of Aplysia's food grasper in multiple feeding responses and is innervated by a pool of identified neurons that activate different muscle regions. One I3 motor neuron, B38, is active in the protraction phase, rather than the retraction phase, suggesting the muscle has an additional function. We used intracellular, extracellular, and muscle force recordings in several in vitro preparations as well as recordings of nerve and muscle activity from intact, behaving animals to characterize B38's activation of the muscle and its activity in different behavior types. We show that B38 specifically activates the anterior region of I3 and is specifically recruited during one behavior, swallowing. The function of this protraction-phase jaw muscle contraction is to hold food; thus the I3 muscle has an additional function beyond mediating retraction. We additionally show that B38's typical activity during in vivo swallowing is insufficient to generate force in an unmodulated muscle and that intrinsic and extrinsic modulation shift the force-frequency relationship to allow contraction. Using methods that traverse levels from individual neuron to muscle to intact animal, we show how regional muscle activation, differential motor neuron recruitment, and neuromodulation are key components in Aplysia's generation of multifunctionality. Copyright © 2014 the American Physiological Society.

  19. Differential TOR activation and cell proliferation in Arabidopsis root and shoot apexes.

    Science.gov (United States)

    Li, Xiaojuan; Cai, Wenguo; Liu, Yanlin; Li, Hui; Fu, Liwen; Liu, Zengyu; Xu, Lin; Liu, Hongtao; Xu, Tongda; Xiong, Yan

    2017-03-07

    The developmental plasticity of plants relies on the remarkable ability of the meristems to integrate nutrient and energy availability with environmental signals. Meristems in root and shoot apexes share highly similar molecular players but are spatially separated by soil. Whether and how these two meristematic tissues have differential activation requirements for local nutrient, hormone, and environmental cues (e.g., light) remain enigmatic in photosynthetic plants. Here, we report that the activation of root and shoot apexes relies on distinct glucose and light signals. Glucose energy signaling is sufficient to activate target of rapamycin (TOR) kinase in root apexes. In contrast, both the glucose and light signals are required for TOR activation in shoot apexes. Strikingly, exogenously applied auxin is able to replace light to activate TOR in shoot apexes and promote true leaf development. A relatively low concentration of auxin in the shoot and high concentration of auxin in the root might be responsible for this distinctive light requirement in root and shoot apexes, because light is required to promote auxin biosynthesis in the shoot. Furthermore, we reveal that the small GTPase Rho-related protein 2 (ROP2) transduces light-auxin signal to activate TOR by direct interaction, which, in turn, promotes transcription factors E2Fa,b for activating cell cycle genes in shoot apexes. Consistently, constitutively activated ROP2 plants stimulate TOR in the shoot apex and cause true leaf development even without light. Together, our findings establish a pivotal hub role of TOR signaling in integrating different environmental signals to regulate distinct developmental transition and growth in the shoot and root.

  20. Differentiation-promoting activity of pomegranate (Punica granatum) fruit extracts in HL-60 human promyelocytic leukemia cells.

    Science.gov (United States)

    Kawaii, Satoru; Lansky, Ephraim P

    2004-01-01

    Differentiation refers to the ability of cancer cells to revert to their normal counterparts, and its induction represents an important noncytotoxic therapy for leukemia, and also breast, prostate, and other solid malignancies. Flavonoids are a group of differentiation-inducing chemicals with a potentially lower toxicology profile than retinoids. Flavonoid-rich polyphenol fractions from the pomegranate (Punica granatum) fruit exert anti-proliferative, anti-invasive, anti-eicosanoid, and pro-apoptotic actions in breast and prostate cancer cells and anti-angiogenic activities in vitro and in vivo. Here we tested flavonoid-rich fractions from fresh (J) and fermented (W) pomegranate juice and from an aqueous extraction of pomegranate pericarps (P) as potential differentiation-promoting agents of human HL-60 promyelocytic leukemia cells. Four assays were used to assess differentiation: nitro blue tetrazolium reducing activity, nonspecific esterase activity, specific esterase activity, and phagocytic activity. In addition, the effect of these extracts on HL-60 proliferation was evaluated. Extracts W and P were strong promoters of differentiation in all settings, with extract J showing only a relatively mild differentiation-promoting effect. The extracts had proportional inhibitory effects on HL-60 cell proliferation. The results highlight an important, previously unknown, mechanism of the cancer preventive and suppressive potential of pomegranate fermented juice and pericarp extracts.

  1. Activation of PKA/CREB Signaling is Involved in BMP9-Induced Osteogenic Differentiation of Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Hongyu Zhang

    2015-09-01

    Full Text Available Background/Aims: BMP9 is highly capable of promoting osteogenic differentiation of mesenchymal stem cells (MSCs although the molecular mechanism involved is largely unknown. Here, we explored the detail role of PKA/CREB signaling in BMP9-induced osteogenic differentiation. Methods: Activation status of PKA/CREB signaling is assessed by nonradioactive assay and Western blot. Using PKA inhibitors and a dominant negative protein of CREB (A-CREB, we investigated the effect of PKA/CREB signaling on BMP9-induced osteogenic differentiation. Results: We found that BMP9 promotes PKA activity and enhances CREB phosphorylation in MSCs. BMP9 is shown to down-regulate protein kinase A inhibitor γ (PKIγ expression. We demonstrated that PKA inhibitors suppress BMP9-induced early osteogenic marker alkaline phosphatase (ALP activity in MSCs as well as late osteogenic markers osteopontin (OPN, osteocalcin (OCN and matrix mineralization. We found that PKA inhibitor reduces BMP9-induced Runx2 activation and p38 phosphorylation in MSCs. Lastly, interference of CREB function by A-CREB decreased BMP9-induced osteogenic differentiation as well. Conclusion: Our results revealed that BMP9 may activate PKA/CREB signaling in MSCs through suppression of PKIγ expression. It is noteworthy that inhibition of PKA/CREB signaling may impair BMP9-induced osteogenic differentiation of MSCs, implying that activation of PKA/CREB signaling is required for BMP9 osteoinductive activity.

  2. Lipopolysaccharide induces proliferation and osteogenic differentiation of adipose-derived mesenchymal stromal cells in vitro via TLR4 activation

    Energy Technology Data Exchange (ETDEWEB)

    Herzmann, Nicole; Salamon, Achim [Department of Cell Biology, University Medicine Rostock, Schillingallee 69, D-18057 Rostock (Germany); Fiedler, Tomas [Institute for Medical Microbiology, Virology and Hygiene, University Medicine Rostock, Schillingallee 70, D-18057 Rostock (Germany); Peters, Kirsten, E-mail: kirsten.peters@med.uni-rostock.de [Department of Cell Biology, University Medicine Rostock, Schillingallee 69, D-18057 Rostock (Germany)

    2017-01-01

    Multipotent mesenchymal stromal cells (MSC) are capable of multi-lineage differentiation and support regenerative processes. In bacterial infections, resident MSC can come intocontact with and need to react to bacterial components. Lipopolysaccharide (LPS), a typical structure of Gram-negative bacteria, increases the proliferation and osteogenic differentiation of MSC. LPS is usually recognized by the toll-like receptor (TLR) 4 and induces pro-inflammatory reactions in numerous cell types. In this study, we quantified the protein expression of TLR4 and CD14 on adipose-derived MSC (adMSC) in osteogenic differentiation and investigated the effect of TLR4 activation by LPS on NF-κB activation, proliferation and osteogenic differentiation of adMSC. We found that TLR4 is expressed on adMSC whereas CD14 is not, and that osteogenic differentiation induced an increase of the amount of TLR4 protein whereas LPS stimulation did not. Moreover, we could show that NF-κB activation via TLR4 occurs upon LPS treatment. Furthermore, we were able to show that competitive inhibition of TLR4 completely abolished the stimulatory effect of LPS on the proliferation and osteogenic differentiation of adMSC. In addition, the inhibition of TLR4 leads to the complete absence of osteogenic differentiation of adMSC, even when osteogenically stimulated. Thus, we conclude that LPS induces proliferation and osteogenic differentiation of adMSC in vitro through the activation of TLR4 and that the TLR4 receptor seems to play a role during osteogenic differentiation of adMSC.

  3. Differential Impact of Passive versus Active Irrigation on Urban Forests in Semiarid Regions

    Science.gov (United States)

    Luketich, A. M.; Papuga, S. A.; Crimmins, M.

    2017-12-01

    The network of trees within a city provides a variety of ecosystem services such as flood mitigation and reduced heat island effects. To maintain these `urban forests' in semiarid cities, the use of scarce water resources for irrigation is often necessary. Rainwater harvesting has been widely adopted in Tucson, AZ as a sustainable water source for trees, but the effects of passive water harvesting versus active irrigation on tree canopy productivity and microclimate is largely unquantified. We hypothesize that regardless of whether trees are passively or actively irrigated, deep soil moisture will be elevated compared to natural conditions; however, we expect that increased deep soil moisture conditions will be more frequent using active irrigation. Additionally, we hypothesize that similar to natural settings, urban trees will need access deep soil moisture for transpiration. Therefore, we expect that actively irrigated trees will have more periods of transpiration than passively irrigated trees and that this will result in elevated and sustained phenological activity. We also expect that this difference will translate to more ecosystem services for a longer portion of the year in actively irrigated urban forests. Here, we compare key ecohydrological indicators of passive and active irrigation systems at two sites in Tucson, AZ. Our measurements include soil moisture, transpiration, air temperature, soil temperature, below- and within- canopy temperatures, and canopy phenology. Our first year of results suggest there are differences in transpiration, canopy greening and microclimate between the two irrigation techniques and that the magnitude of these differences are highly seasonal. This research can help to improve understanding of the practices and function of green infrastructure in semiarid cities and inform models that attempt to aggregate the influence of these urban forests for understanding watershed management strategies.

  4. Natural mediotrusive contact: does it affect the masticatory and neck EMG activity during tooth grinding?

    Science.gov (United States)

    Fuentes, Aler D; Martin, Conchita; Bull, Ricardo; Santander, Hugo; Gutiérrez, Mario F; Miralles, Rodolfo

    2016-07-01

    There is scarce knowledge regarding the influence of a natural mediotrusive contact on mandibular and cervical muscular activity. The purpose of this study was to analyze the EMG activity of the anterior temporalis (AT) and sternocleidomastoid (SCM) muscles during awake grinding in healthy subjects with or without a natural mediotrusive occlusal contact. Fifteen subjects with natural mediotrusive occlusal contact (Group 1) and 15 subjects without natural mediotrusive occlusal contact (Group 2) participated. Bilateral surface EMG activity of AT and SCM muscles was recorded during unilateral eccentric or concentric tooth grinding tasks. EMG activity was normalized against the activity recorded during maximal voluntary clenching in intercuspal position (IP) for AT muscles and during maximal intentional isometric head-neck rotation to each side, for SCM muscles. EMG activity of AT and SCM muscles showed no statistical difference between groups. EMG activity of AT muscle was higher in the working side (WS) than in the non-WS (NWS) in Group 1 during concentric grinding (0.492 vs 0.331, p = 0.047), whereas no difference was observed in Group 2. EMG activity of SCM was similar between working and NWSs in both groups and tasks. Asymmetry indexes (AIs) were not significantly different between groups. These findings in healthy subjects support the assumption that during awake tooth grinding, central nerve control predominates over peripheral inputs, and reinforce the idea of a functional link between the motor-neuron pools that control jaw and neck muscles.

  5. Immune functions in beluga whales (Delphinapterus leucas): Evaluation of natural killer cell activity.

    NARCIS (Netherlands)

    S. De Guise (Sylvain); P.S. Ross (Peter); A.D.M.E. Osterhaus (Albert); D. Martineau (Daniel); P. Beland; M. Fournier (Michel)

    1997-01-01

    textabstractNatural killer (NK) activity, an important non-specific defense mechanism against viral infections and tumors, was demonstrated in beluga whales using two different methods: 51Cr release and flow cytometry. Using the 51Cr release assay, NK activity in belugas was shown to be higher

  6. Embryogenic competence acquisition in sugarcane callus is associated with differential H+ pump abundance and activity.

    Science.gov (United States)

    Passamani, Lucas Z; Bertolazi, Amanda A; Ramos, Alessandro C; Santa-Catarina, Claudete; Thelen, Jay J; Silveira, Vanildo

    2018-06-22

    Somatic embryogenesis is an important biological process in several plant species, including sugarcane. Proteomics approaches have shown that H + pumps are differentially regulated during somatic embryogenesis; however, the relationship between H + flux and embryogenic competence is still unclear. This work aimed to elucidate the association between extracellular H + flux and somatic embryo maturation in sugarcane. We performed a microsomal proteomics analysis and analyzed changes in extracellular H + flux and H + pump (P-H + -ATPase, V-H + -ATPase and H + -PPase) activity in embryogenic and non-embryogenic callus. A total of 657 proteins were identified, 16 of which were H + pumps. We observed that P-H + -ATPase and H + -PPase were more abundant in embryogenic callus. Compared with non-embryogenic callus, embryogenic callus showed higher H + influx, especially on maturation day 14, as well as higher H+ pump activity (mainly P-H+-ATPase and H+-PPase activity). H+-PPase appears to be the major H + pump in embryogenic callus during somatic embryo formation, functioning in both vacuole acidification and PPi homeostasis. These results provide evidence for an association between higher H + pump protein abundance and, consequently, higher H + flux and embryogenic competence acquisition in the callus of sugarcane, allowing for optimization of the somatic embryo conversion process by modulating the activities of these H + pumps.

  7. Differential in vivo zymography: a method for observing matrix metalloproteinase activity in the zebrafish embryo.

    Science.gov (United States)

    Keow, Jonathan Y; Herrmann, Kurt M; Crawford, Bryan D

    2011-04-01

    Investigations into the molecular mechanisms of, and cellular signaling pathways modulating ECM remodeling are especially challenging due to the complex post-translational regulation of the primary effectors of ECM catabolism - the matrix metalloproteinases (MMPs). Recently a variety of approaches to the detection of MMP activity have been developed, and the prospect of visualizing ECM remodeling activity in living tissues is now opening exciting avenues of research for matrix biologists. In particular the use of FRET-quenched MMP substrates, which generate a fluorescent signal upon hydrolysis, is becoming increasingly popular, especially because linkers with defined and/or restricted proteolytic sensitivity can be used to bind fluorophore-quencher pairs, making these probes useful in characterizing the activity of specific proteases. We have taken advantage of the transparency and amenability to reverse genetics of the zebrafish embryo, in combination with these fluorogenic MMP substrates, to develop a multiplex in vivo assay for MMP activity that we dub "differential in vivo zymography." Copyright © 2011 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  8. Transcriptionally active LTR retrotransposons in Eucalyptus genus are differentially expressed and insertionally polymorphic.

    Science.gov (United States)

    Marcon, Helena Sanches; Domingues, Douglas Silva; Silva, Juliana Costa; Borges, Rafael Junqueira; Matioli, Fábio Filippi; Fontes, Marcos Roberto de Mattos; Marino, Celso Luis

    2015-08-14

    In Eucalyptus genus, studies on genome composition and transposable elements (TEs) are particularly scarce. Nearly half of the recently released Eucalyptus grandis genome is composed by retrotransposons and this data provides an important opportunity to understand TE dynamics in Eucalyptus genome and transcriptome. We characterized nine families of transcriptionally active LTR retrotransposons from Copia and Gypsy superfamilies in Eucalyptus grandis genome and we depicted genomic distribution and copy number in two Eucalyptus species. We also evaluated genomic polymorphism and transcriptional profile in three organs of five Eucalyptus species. We observed contrasting genomic and transcriptional behavior in the same family among different species. RLC_egMax_1 was the most prevalent family and RLC_egAngela_1 was the family with the lowest copy number. Most families of both superfamilies have their insertions occurring Eucalyptus species. Using EST analysis and qRT-PCRs, we observed transcriptional activity in several tissues and in all evaluated species. In some families, osmotic stress increases transcript values. Our strategy was successful in isolating transcriptionally active retrotransposons in Eucalyptus, and each family has a particular genomic and transcriptional pattern. Overall, our results show that retrotransposon activity have differentially affected genome and transcriptome among Eucalyptus species.

  9. Investigating the Structure-Activity Relationship of the Insecticidal Natural Product Rocaglamide.

    Science.gov (United States)

    Hall, Roger G; Bruce, Ian; Cooke, Nigel G; Diorazio, Louis J; Cederbaum, Fredrik; Dobler, Markus R; Irving, Ed

    2017-12-01

    The natural product Rocaglamide (1), isolated from the tree Aglaia elliptifolia, is a compelling but also challenging lead structure for crop protection. In laboratory assays, the natural product shows highly interesting insecticidal activity against chewing pests and beetles, but also phytotoxicity on some crop plants. Multi-step syntheses with control of stereochemistry were required to probe the structure-activity relationship (SAR), and seek simplified analogues. After a significant research effort, just two areas of the molecule were identified which allow modification whilst maintaining activity, as will be highlighted in this paper.

  10. Dimensional analysis yields the general second-order differential equation underlying many natural phenomena: the mathematical properties of a phenomenon's data plot then specify a unique differential equation for it.

    Science.gov (United States)

    Kepner, Gordon R

    2014-08-27

    This study uses dimensional analysis to derive the general second-order differential equation that underlies numerous physical and natural phenomena described by common mathematical functions. It eschews assumptions about empirical constants and mechanisms. It relies only on the data plot's mathematical properties to provide the conditions and constraints needed to specify a second-order differential equation that is free of empirical constants for each phenomenon. A practical example of each function is analyzed using the general form of the underlying differential equation and the observable unique mathematical properties of each data plot, including boundary conditions. This yields a differential equation that describes the relationship among the physical variables governing the phenomenon's behavior. Complex phenomena such as the Standard Normal Distribution, the Logistic Growth Function, and Hill Ligand binding, which are characterized by data plots of distinctly different sigmoidal character, are readily analyzed by this approach. It provides an alternative, simple, unifying basis for analyzing each of these varied phenomena from a common perspective that ties them together and offers new insights into the appropriate empirical constants for describing each phenomenon.

  11. Fasting enhances TRAIL-mediated liver natural killer cell activity via HSP70 upregulation.

    Directory of Open Access Journals (Sweden)

    Vu T A Dang

    Full Text Available Acute starvation, which is frequently observed in clinical practice, sometimes augments the cytolytic activity of natural killer cells against neoplastic cells. In this study, we investigated the molecular mechanisms underlying the enhancement of natural killer cell function by fasting in mice. The total number of liver resident natural killer cells in a unit weight of liver tissue obtained from C57BL/6J mice did not change after a 3-day fast, while the proportions of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL+ and CD69+ natural killer cells were significantly elevated (n = 7, p <0.01, as determined by flow cytometric analysis. Furthermore, we found that TRAIL- natural killer cells that were adoptively transferred into Rag-2-/- γ chain-/- mice could convert into TRAIL+ natural killer cells in fasted mice at a higher proportion than in fed mice. Liver natural killer cells also showed high TRAIL-mediated antitumor function in response to 3-day fasting. Since these fasted mice highly expressed heat shock protein 70 (n = 7, p <0.05 in liver tissues, as determined by western blot, the role of this protein in natural killer cell activation was investigated. Treatment of liver lymphocytes with 50 µg/mL of recombinant heat shock protein 70 led to the upregulation of both TRAIL and CD69 in liver natural killer cells (n = 6, p <0.05. In addition, HSP70 neutralization by intraperitoneally injecting an anti- heat shock protein 70 monoclonal antibody into mice prior to fasting led to the downregulation of TRAIL expression (n = 6, p <0.05. These findings indicate that acute fasting enhances TRAIL-mediated liver natural killer cell activity against neoplastic cells through upregulation of heat shock protein 70.

  12. Differentiation of the guinea pig eye: nuclear ultrastructure, template activity and DNA content

    International Nuclear Information System (INIS)

    Schmalenberger, B.

    1980-01-01

    Nuclei of various cell types in the eye of embryonal and adult Guinea pigs were studied by means of electron microscopy, cytophotometry and autoradiography. Striking differences in condensation and arrangement of chromatin were found between the different tissues and cells. Several nuclear types were analyzed quantitatively with regard to their content of condensed and decondensed chromatin by means of electron microscopic morphometry. Structural differences in chromatin organization coincided with different nuclear DNA contents in various cell types of the retina, such as bipolar cells, Mueller cells, rods and cones, and the pigmented epithelium. The differences between DNA-Feulgen means obtained by cytophotometric analysis were highly significant. Template activity as shown by 3 H-uridine incorporation made evident than the rate of RNA synthesis is positively correlated with the quantity of decondensed chromatin. It is speculated that differentiation of the Guinea pig eye involves differential DNA synthesis, and that the extra-DNA could have some ''trigger'' function for the pattern of chromatin condensation and thus the pattern of gene expression. (author)

  13. Cholesterol negatively regulates IL-9-producing CD8+ T cell differentiation and antitumor activity.

    Science.gov (United States)

    Ma, Xingzhe; Bi, Enguang; Huang, Chunjian; Lu, Yong; Xue, Gang; Guo, Xing; Wang, Aibo; Yang, Maojie; Qian, Jianfei; Dong, Chen; Yi, Qing

    2018-05-09

    CD8 + T cells can be polarized into IL-9-secreting (Tc9) cells. We previously showed that adoptive therapy using tumor-specific Tc9 cells generated stronger antitumor responses in mouse melanoma than classical Tc1 cells. To understand why Tc9 cells exert stronger antitumor responses, we used gene profiling to compare Tc9 and Tc1 cells. Tc9 cells expressed different levels of cholesterol synthesis and efflux genes and possessed significantly lower cholesterol content than Tc1 cells. Unique to Tc9, but not other CD8 + or CD4 + T cell subsets, manipulating cholesterol content in polarizing Tc9 cells significantly affected IL-9 expression and Tc9 differentiation and antitumor response in vivo. Mechanistic studies showed that IL-9 was indispensable for Tc9 cell persistence and antitumor effects, and cholesterol or its derivatives inhibited IL-9 expression by activating liver X receptors (LXRs), leading to LXR Sumoylation and reduced p65 binding to Il9 promoter. Our study identifies cholesterol as a critical regulator of Tc9 cell differentiation and function. © 2018 Ma et al.

  14. Trends in the use of natural antioxidants in active food packaging: a review.

    Science.gov (United States)

    Sanches-Silva, Ana; Costa, Denise; Albuquerque, Tânia G; Buonocore, Giovanna Giuliana; Ramos, Fernando; Castilho, Maria Conceição; Machado, Ana Vera; Costa, Helena S

    2014-01-01

    The demand for natural antioxidant active packaging is increasing due to its unquestionable advantages compared with the addition of antioxidants directly to the food. Therefore, the search for antioxidants perceived as natural, namely those that naturally occur in herbs and spices, is a field attracting great interest. In line with this, in the last few years, natural antioxidants such as α-tocopherol, caffeic acid, catechin, quercetin, carvacrol and plant extracts (e.g. rosemary extract) have been incorporated into food packaging. On the other hand, consumers and the food industry are also interested in active biodegradable/compostable packaging and edible films to reduce environmental impact, minimise food loss and minimise contaminants from industrial production and reutilisation by-products. The present review focuses on the natural antioxidants already applied in active food packaging, and it reviews the methods used to determine the oxidation protection effect of antioxidant active films and the methods used to quantify natural antioxidants in food matrices or food simulants. Lastly consumers' demands and industry trends are also addressed.

  15. Reduced pyrazinamidase activity and the natural resistance of Mycobacterium kansasii to the antituberculosis drug pyrazinamide.

    Science.gov (United States)

    Sun, Z; Zhang, Y

    1999-03-01

    Pyrazinamide (PZA), an analog of nicotinamide, is a prodrug that requires conversion to the bactericidal compound pyrazinoic acid (POA) by the bacterial pyrazinamidase (PZase) activity of nicotinamidase to show activity against Mycobacterium tuberculosis. Mutations leading to a loss of PZase activity cause PZA resistance in M. tuberculosis. M. kansasii is naturally resistant to PZA and has reduced PZase activity along with an apparently detectable nicotinamidase activity. The role of the reduction in PZase activity in the natural PZA resistance of M. kansasii is unknown. The MICs of PZA and POA for M. kansasii were determined to be 500 and 125 micrograms/ml, respectively. Using [14C]PZA and [14C]nicotinamide, we found that M. kansasii had about 5-fold-less PZase activity and about 25-fold-less nicotinamidase activity than M. tuberculosis. The M. kansasii pncA gene was cloned on a 1.8-kb BamHI DNA fragment, using M. avium pncA probe. Sequence analysis showed that the M. kansasii pncA gene encoded a protein with homology to its counterparts from M. tuberculosis (69.9%), M. avium (65.6%), and Escherichia coli (28.5%). Transformation of naturally PZA-resistant M. bovis BCG with M. kansasii pncA conferred partial PZA susceptibility. Transformation of M. kansasii with M. avium pncA caused functional expression of PZase and high-level susceptibility to PZA, indicating that the natural PZA resistance in M. kansasii results from a reduced PZase activity. Like M. tuberculosis, M. kansasii accumulated POA in the cells at an acidic pH; however, due to its highly active POA efflux pump, the naturally PZA-resistant species M. smegmatis did not. These findings suggest the existence of a weak POA efflux mechanism in M. kansasii.

  16. To the question of peculiarities of thermal activation of natural siliceous raw material

    Directory of Open Access Journals (Sweden)

    Chumachenko Natalya

    2017-01-01

    Full Text Available The results of research of activity enhancement of natural siliceous raw material are given in the article. Fossil meal of Khotynetsky deposit, diatomite of Sharlovsky deposit, silica clay of Balasheika deposit were used as natural active mineral admixtures. The influence of heat-treating temperature and dispersion on activity of different types of siliceous raw material is studied. The increase of activity of fixation of Ca(OH2 in several times is traced after heat-treating at a certain temperature in the range from 100 to 800°C. The type of activity change is discovered. Explanation is given connected with the change of silica structure in the surface layer. Parameters of the highest activity are defined for every type of siliceous raw material.

  17. Constitutive β-catenin activation in osteoblasts impairs terminal osteoblast differentiation and bone quality

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Quanwei; Chen, Sixu; Qin, Hao [State Key Laboratory of Trauma, Burn and Combined injury, Department of Trauma Surgery, Daping Hospital, Third Military Medical University, ChongQing 400042 (China); Feng, Jianquan [Department of Biomedical Sciences, Baylor College of Dentistry, Texas A& M Health Science Center, Dallas, TX 75246 (United States); Liu, Huayu; Liu, Daocheng; Li, Ang; Shen, Yue; Zhong, Xiaozheng; Li, Junfeng [State Key Laboratory of Trauma, Burn and Combined injury, Department of Trauma Surgery, Daping Hospital, Third Military Medical University, ChongQing 400042 (China); Zong, Zhaowen, E-mail: zongzhaowen@sina.cn [State Key Laboratory of Trauma, Burn and Combined injury, Department of Trauma Surgery, Daping Hospital, Third Military Medical University, ChongQing 400042 (China)

    2017-01-01

    Accumulating evidence suggests that Wnt/β-catenin signaling plays a central role in controlling bone mass. We previously reported that constitutive activation of β-catenin (CA-β-catenin) in osteoblasts potentially has side effects on the bone growth and bone remodeling process, although it could increase bone mass. The present study aimed to observe the effects of osteoblastic CA-β-catenin on bone quality and to investigate possible mechanisms of these effects. It was found that CA-β-catenin mice exhibited lower mineralization levels and disorganized collagen in long bones as confirmed by von Kossa staining and sirius red staining, respectively. Also, bone strength decreased significantly in CA-β-catenin mice. Then the effect of CA-β-catenin on biological functions of osteoblasts were investigated and it was found that the expression levels of osteocalcin, a marker for the late differentiation of osteoblasts, decreased in CA-β-catenin mice, while the expression levels of osterix and alkaline phosphatase, two markers for the early differentiation of osteoblasts, increased in CA-β-catenin mice. Furthermore, higher proliferation rate were revealed in osteoblasts that were isolated from CA-β-catenin mice. The Real-time PCR and western blot examination found that the expression level of c-myc and cyclin D1, two G1 progression-related molecules, increased in osteoblasts that were isolated from the CA-β-catenin mice, and the expression levels of CDK14 and cyclin Y, two mitotic-related molecules that can accelerate cells entering into S and G2/M phases, increased in osteoblasts that were isolated from the CA-β-catenin mice. In summary, osteoblastic CA-β-catenin kept osteoblasts in high proliferative state and impaired the terminal osteoblast differentiation, and this led to changed bone structure and decreased bone strength. - Highlights: • Wnt/β-catenin signaling plays a central role in controlling bone mass. • CA-β-catenin has side effects on the bone

  18. The discriminating nature of dopamine transporter image in parkinsonism: the competency of dopaminergic transporter imaging in differential diagnosis of parkinsonism 123I-FP-CIT SPECT study

    International Nuclear Information System (INIS)

    Kim, Bom Sahn; Jang, Sung June; Eo, Jae Seon; Park, Eun Kyung; Kim, Yu Kyeong; Kim, Jong Min; Lee, Won Woo; Kim, Sang Eun

    2007-01-01

    The aim of this study was to evaluate the discriminating nature of 123 I-FP-CIT SPECT in patients with parkinsonism. 123 I-FP-CIT SPECT images acquired from the 18 normal controls; NC (60.4 ± 10.0 yr) and 237 patients with parkinsonism (65.9 ± 9.2 yr) were analyzed. From spatially normalized images, regional counts of the caudate, putamen, and occipital lobe were obtained using region of interest method. Binding potential (BP) was calculated with the ratio of specific to nonspecific binding activity at equilibrium. Additionally, the BP ratio of putamen to caudate (PCR) and asymmetric index (ASI) were measured. BPs of NC (3.37 ± 0.57, 3.10± 0.41, 3.23 ± 0.48 for caudate, putamen, whole striatum, respectively) had no significant difference with those of essential tremor; ET (3.31 ± 0.64, 3.06 ± 0.61, 3.14 ± 0.63) and Alzheimer's disease; AD (3.33 ± 0.60, 3.29 ± 0.79, 3.31 ± 0.70), but were higher than those of Parkinson's disease; PD (1.92 ± 0.74, 1.39 ±0.68, 1.64 ± 0.68), multiple system atrophy; MSA (2.36 ± 1.07, 2.16 ± 0.91, 2.26 ± 0.96), and dementia with Lewy body; DLB (1.95± 0.72, 1.64 ± 0.65, 1.79 ± 0.66)(ρ 123 I-FP-CIT SPECT was a good value in differential diagnosis of parkinsonism

  19. Natural loss-of-function mutation of myeloid differentiation protein 88 disrupts its ability to form Myddosomes

    NARCIS (Netherlands)

    Nagpal, K.; Plantinga, T.S.; Sirois, C.M.; Monks, B.G.; Latz, E.; Netea, M.G.; Golenbock, D.T.

    2011-01-01

    Myeloid differentiation protein 88 (MyD88) is a key signaling adapter in Toll-like receptor (TLR) signaling. MyD88 is also one of the most polymorphic adapter proteins. We screened the reported nonsynonymous coding mutations in MyD88 to identify variants with altered function. In reporter assays, a

  20. Substitution between leisure activities: a quasi-natural experiment using sports viewing and cinema attendance

    OpenAIRE

    Izquierdo Sanchez, Sofia; Elliott, Caroline; Simmons, Rob

    2016-01-01

    The allocation of time between leisure activities and work has been extensively analysed in academic literature. However, leisure time is limited and there may not be sufficient time to enjoy all the leisure activities desired. Hence, this article considers the allocation of time between substitute leisure activities. International football tournaments provide an opportunity to consider consumers’ preferences for watching football and films in a quasi-natural experimental setting. A trade-off...

  1. Language experience differentiates prefrontal and subcortical activation of the cognitive control network in novel word learning.

    Science.gov (United States)

    Bradley, Kailyn A L; King, Kelly E; Hernandez, Arturo E

    2013-02-15

    The purpose of this study was to examine the cognitive control mechanisms in adult English speaking monolinguals compared to early sequential Spanish-English bilinguals during the initial stages of novel word learning. Functional magnetic resonance imaging during a lexico-semantic task after only 2h of exposure to novel German vocabulary flashcards showed that monolinguals activated a broader set of cortical control regions associated with higher-level cognitive processes, including the supplementary motor area (SMA), anterior cingulate (ACC), and dorsolateral prefrontal cortex (DLPFC), as well as the caudate, implicated in cognitive control of language. However, bilinguals recruited a more localized subcortical network that included the putamen, associated more with motor control of language. These results suggest that experience managing multiple languages may differentiate the learning strategy and subsequent neural mechanisms of cognitive control used by bilinguals compared to monolinguals in the early stages of novel word learning. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Fibronectin and laminin promote differentiation of human mesenchymal stem cells into insulin producing cells through activating Akt and ERK

    Directory of Open Access Journals (Sweden)

    Chiou Shih-Hwa

    2010-07-01

    Full Text Available Abstract Background Islet transplantation provides a promising cure for Type 1 diabetes; however it is limited by a shortage of pancreas donors. Bone marrow-derived multipotent mesenchymal stem cells (MSCs offer renewable cells for generating insulin-producing cells (IPCs. Methods We used a four-stage differentiation protocol, containing neuronal differentiation and IPC-conversion stages, and combined with pellet suspension culture to induce IPC differentiation. Results Here, we report adding extracellular matrix proteins (ECM such as fibronectin (FN or laminin (LAM enhances pancreatic differentiation with increases in insulin and Glut2 gene expressions, proinsulin and insulin protein levels, and insulin release in response to elevated glucose concentration. Adding FN or LAM induced activation of Akt and ERK. Blocking Akt or ERK by adding LY294002 (PI3K specific inhibitor, PD98059 (MEK specific inhibitor or knocking down Akt or ERK failed to abrogate FN or LAM-induced enhancement of IPC differentiation. Only blocking both of Akt and ERK or knocking down Akt and ERK inhibited the enhancement of IPC differentiation by adding ECM. Conclusions These data prove IPC differentiation by MSCs can be modulated by adding ECM, and these stimulatory effects were mediated through activation of Akt and ERK pathways.

  3. THE PRESSURE OF ANTHROPIC ACTIVITIES ON NATURAL CAPITAL OF SATU MARE COUNTY

    Directory of Open Access Journals (Sweden)

    VIOLETA BRAN

    2017-12-01

    Full Text Available The relationship between man and the natural environment, that provides the most valuable resources for existence, has transformed over time into an artificial and destructive manifestation. The encrease of the standard of living of society has been achieved through the drastic reduction of natural resources and the demage of the environment, endangering the welfare of future generations. Activities such as discharges of waste in the rivers, inappropriate use of land, uncontrolled deforestation, fragmentation of habitats due to infrastructure development pose the greatest risks to natural capital. This article aims to analyze by statistical methods, on the basis of the documents studied, the negative effects of anthropogenic activities on the natural capital of Satu Mare County.

  4. An in vitro comparative study of the antioxidant activity and SIRT1 modulation of natural compounds.

    Science.gov (United States)

    Fusi, Jonathan; Bianchi, Sara; Daniele, Simona; Pellegrini, Silvia; Martini, Claudia; Galetta, Fabio; Giovannini, Luca; Franzoni, Ferdinando

    2018-05-01

    Oxidative stress arises from an imbalance between the production of free radicals and antioxidant defences. Several studies have suggested that dietary antioxidants (such as polyphenols and berberine) may counteract oxidative stress through the involvement of the Sirtuin 1/Adenosine Monophosphate-Activated Protein Kinase (SIRT1/AMPK) pathway. The aim of this study was to evaluate the direct and specific antioxidant activity of some natural compounds, as well as their ability to modulate the expression of SIRT1 and the activation of AMPK. Quercetin, tyrosol, ferulic acid, catechin, berberine and curcumin were evaluated for their specific and direct antioxidant activity with TOSC assay. Their ability to modulate SIRT1 and AMPK was assessed by immunoblotting assay, while their cytotoxicity by CellTiter-Blue Cell Viability Assay. No statistically significant decrease (p > 0.05) in the number of viable cells was found upon challenging with the natural compounds. Quercetin exhibited the highest antioxidant activity against peroxyl radical and peroxinitrate derivates, while curcumin showed the best anti-hydroxyl activity with respect to the other compounds and, most importantly, respect to the reference antioxidants. Finally, all the tested compounds significantly increased the SIRT1 expression and the activation of AMPK. Our results clearly disclose the specific antioxidant activity of these natural compounds and their ability to increase SIRT1 expression and AMPK activation. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  5. An integrated study of natural hydroxyapatite-induced osteogenic differentiation of mesenchymal stem cells using transcriptomics, proteomics and microRNA analyses

    International Nuclear Information System (INIS)

    Zhang, Zhiwei; Wang, Jiandan; Lü, Xiaoying

    2014-01-01

    This work combined transcriptomics, proteomics, and microRNA (miRNA) analyses to elucidate the mechanism of natural hydroxyapatite (NHA)-induced osteogenic differentiation of mesenchymal stem cells (MSCs). First, NHA powder was obtained from pig bones and fabricated into disc-shaped samples. Subsequently, the proliferation and osteogenic differentiation of MSCs cultured on NHA were investigated. Then, proteomics was employed to detect the protein expression profiles of MSCs cultured on NHA, and the effect of NHA on MSCs was analyzed through an integrated pathway analysis (including proteomics and previous transcriptomics data) in which specific NHA-induced differentiation pathways were analyzed. The pathway nodes with expression data at both the mRNA and protein levels (mRNA–protein pairs) were filtered in differentiation-related pathways. miRNAs corresponding to these target mRNA–protein pairs were predicted, screened and tested, and the regulatory effects of miRNAs on mRNA–protein pairs were analyzed. Finally, the NHA-induced osteogenic pathways were verified. The results of an MTT assay and alkaline phosphatase (ALP) staining showed that the cell proliferation rate decreased and the osteogenic performance improved in the presence of NHA. By integrating transcriptomics and proteomics, the genes and proteins involved in 89 pathways were shown to be differentially expressed. Among them, 5 differentiation-associated pathways, in which 9 miRNAs and 8 regulated-target mRNA–protein zby inhibiting the target mRNA–protein pair HSPA8 in the MAPK signaling pathway, and miR-26a and miR-26b might inhibit adipogenic differentiation by repressing the target mRNA–protein pair HMGA1 in the adipogenesis pathway. A verification experiment for the osteogenic pathway indicated that the ERK1/2 or JNK MAPK pathways might play an important role in NHA-induced osteogenic differentiation. In conclusion, NHA affected MSCs at both the transcriptional and translational levels

  6. Activated NKT cells imprint NK-cell differentiation, functionality and education.

    Science.gov (United States)

    Riese, Peggy; Trittel, Stephanie; May, Tobias; Cicin-Sain, Luka; Chambers, Benedict J; Guzmán, Carlos A

    2015-06-01

    NK cells represent a vital component of the innate immune system. The recent discoveries demonstrating that the functionality of NK cells depends on their differentiation and education status underscore their potential as targets for immune intervention. However, to exploit their full potential, a detailed understanding of the cellular interactions involved in these processes is required. In this regard, the cross-talk between NKT cells and NK cells needs to be better understood. Our results provide strong evidence for NKT cell-induced effects on key biological features of NK cells. NKT-cell activation results in the generation of highly active CD27(high) NK cells with improved functionality. In this context, degranulation activity and IFNγ production were mainly detected in the educated subset. In a mCMV infection model, we also demonstrated that NKT-cell stimulation induced the generation of highly functional educated and uneducated NK cells, crucial players in viral control. Thus, our findings reveal new fundamental aspects of the NKT-NK cell axis that provide important hints for the manipulation of NK cells in clinical settings. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Atf4 regulates chondrocyte proliferation and differentiation during endochondral ossification by activating Ihh transcription.

    Science.gov (United States)

    Wang, Weiguang; Lian, Na; Li, Lingzhen; Moss, Heather E; Wang, Weixi; Perrien, Daniel S; Elefteriou, Florent; Yang, Xiangli

    2009-12-01

    Activating transcription factor 4 (Atf4) is a leucine-zipper-containing protein of the cAMP response element-binding protein (CREB) family. Ablation of Atf4 (Atf4(-/-)) in mice leads to severe skeletal defects, including delayed ossification and low bone mass, short stature and short limbs. Atf4 is expressed in proliferative and prehypertrophic growth plate chondrocytes, suggesting an autonomous function of Atf4 in chondrocytes during endochondral ossification. In Atf4(-/-) growth plate, the typical columnar structure of proliferative chondrocytes is disturbed. The proliferative zone is shortened, whereas the hypertrophic zone is transiently expanded. The expression of Indian hedgehog (Ihh) is markedly decreased, whereas the expression of other chondrocyte marker genes, such as type II collagen (Col2a1), PTH/PTHrP receptor (Pth1r) and type X collagen (Col10a1), is normal. Furthermore, forced expression of Atf4 in chondrocytes induces endogenous Ihh mRNA, and Atf4 directly binds to the Ihh promoter and activates its transcription. Supporting these findings, reactivation of Hh signaling pharmacologically in mouse limb explants corrects the Atf4(-/-) chondrocyte proliferation and short limb phenotypes. This study thus identifies Atf4 as a novel transcriptional activator of Ihh in chondrocytes that paces longitudinal bone growth by controlling growth plate chondrocyte proliferation and differentiation.

  8. Characterizing context-dependent differential firing activity in the hippocampus and entorhinal cortex.

    Science.gov (United States)

    Prerau, Michael J; Lipton, Paul A; Eichenbaum, Howard B; Eden, Uri T

    2014-04-01

    The rat hippocampus and entorhinal cortex have been shown to possess neurons with place fields that modulate their firing properties under different behavioral contexts. Such context-dependent changes in neural activity are commonly studied through electrophysiological experiments in which a rat performs a continuous spatial alternation task on a T-maze. Previous research has analyzed context-based differential firing during this task by describing differences in the mean firing activity between left-turn and right-turn experimental trials. In this article, we develop qualitative and quantitative methods to characterize and compare changes in trial-to-trial firing rate variability for sets of experimental contexts. We apply these methods to cells in the CA1 region of hippocampus and in the dorsocaudal medial entorhinal cortex (dcMEC), characterizing the context-dependent differences in spiking activity during spatial alternation. We identify a subset of cells with context-dependent changes in firing rate variability. Additionally, we show that dcMEC populations encode turn direction uniformly throughout the T-maze stem, whereas CA1 populations encode context at major waypoints in the spatial trajectory. Our results suggest scenarios in which individual cells that sparsely provide information on turn direction might combine in the aggregate to produce a robust population encoding. Copyright © 2014 Wiley Periodicals, Inc.

  9. Radionuclide detection and differential diagnosis of left-to-right cardiac shunts by analysis of time-activity curves

    International Nuclear Information System (INIS)

    Kim, Ok-Hwa

    1986-01-01

    The noninvasive nature of the radionuclide angiocardiography provided a useful approach for the evaluation of left-to-right cardiac shunts (LRCS). While the qualitative information can be obtained by inspection of serial radionuclide angiocardiograms, the quantitative information of radionuclide angiocardiography can be obtained by the analysis of time-activity curves using advanced computer system. The count ratios method and pulmonary-to-systemic flow ratio (QP/QS) by gamma variate fit method were used to evaluate the accuracy of detection and localization of LRCS. One hundred and ten time-activity curves were analyzed. There were 46 LRCS (atrial septal defects 11, ventricular septal defects 22, patent ductus arteriosus 13) and 64 normal subjects. By computer analysis of time-activity histograms of the right atrium, ventricle and the lungs separately, the count ratios modified by adding the mean cardiac transit time were calculated in each anatomic site. In normal subjects the mean count ratios in the right atrium, ventricle and lungs were 0.24 on average. In atrial septal defects, the count ratios were high in the right atrium, ventricle and lungs, whereas in ventricular septal defects the count ratios were higher only in the right ventricle and lungs. Patent ductus arteriosus showed normal count ratios in the heart but high count ratios were obtained in the lungs. Thus, this count ratios method could be separated normal from those with intracardiac or extracardiac shunts, and moreover, with this method the localization of the shunts level was possible in LRCS. Another method that could differentiate the intracardiac shunts from extracardiac shunts was measuring QP/QS in the left and right lungs. In patent ductus arteriosus, the left lung QP/QS was hight than those of the right lung, whereas in atrial septal defects and ventricular septal defects QP/QS ratios were equal in both lungs. (J.P.N.)

  10. Effects of autogamy in Paramecium tetraurelia on catalase activity and on radiosensitivity to natural ionizing radiations

    International Nuclear Information System (INIS)

    Croute, F.; Dupouy, D.; Charley, J.P.; Soleilhavoup, J.P.; Planel, H.

    1980-01-01

    Catalase activity of Paramecium tetraurelia decreased during autogamy and recovered to normal 5 days later. Autogamy also caused changes in the ciliate's sensitivity sensitivity to natural ionizing radiations - the decrease in cell growth rate previously described in shielded cultures did not occur when autogamous cells were used. Maximum effect of shielding was observed in 11-day-old postautogamous cells. The role of the catalase in the mechanism of natural irradiation effect is discussed

  11. Evaluation of antioxidant activity of natural products; Kosanka seibun no kino hyokaho

    Energy Technology Data Exchange (ETDEWEB)

    Miyazawa, T.; Nakagawa, K. [Tohoku Univ., Sendai (Japan)

    1998-10-20

    The methods for evaluating antioxidant property of natural products in in vitro and in vivo lipid peroxidation systems are reviewed. Antioxidant activity of tocopherols, carotenoids, flavonoids and curcuminoids have been demonstrated against lipid peroxidation induced in microsomes, erythrocytes, plasma lipoproteins and in animal trials. Recently, in vivo antioxidant function of natural products was extensively investigated in humans together with explanation of their absorbability and metabolic fate. 35 refs., 8 figs., 4 tabs.

  12. Importance of ERK activation in As2O3-induced differentiation and promyelocytic leukemia nuclear bodies formation in neuroblastoma cells.

    Science.gov (United States)

    Petit, A; Delaune, A; Falluel-Morel, A; Goullé, J-P; Vannier, J-P; Dubus, I; Vasse, M

    2013-11-01

    Neuroblastoma malignant cell growth is dependent on their undifferentiated status. Arsenic trioxide (As2O3) induces neuroblastoma cell differentiation in vitro, but its mechanisms still remains unknown. We used three human neuroblastoma cell lines (SH-SY5Y, IGR-N-91, LAN-1) that differ from their MYCN and p53 status to explore the intracellular events activated by As2O3 and involved in neurite outgrowth, a morphological marker of differentiation. As2O3 (2μM) induced neurite outgrowth in all cell lines, which was dependent on ERK activation but independent on MYCN status. This process was induced either by a sustained (3 days) or a transient (2h) incubation with As2O3, indicating that very early events trigger the induction of differentiation. In parallel, As2O3 induced a rapid assembly of promyelocytic leukemia nuclear bodies (PML-NB) in an ERK-dependent manner. In conclusion, mechanisms leading to neuroblastoma cell differentiation in response to As2O3 appear to involve the ERK pathway activation and PML-NB formation, which are observed in response to other differentiating molecules such as retinoic acid derivates. This open new perspectives based on the use of treatment combinations to potentiate the differentiating effects of each drug alone and reduce their adverse side effects. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Alkali-Activated Natural Pozzolan/Slag Binder for Sustainable Concrete

    Science.gov (United States)

    Najimi, Meysam

    This study aimed to fully replace Portland cement (PC) with environmentally friendly binders capable of improving longevity of concrete. The new binders consisted of different proportions of natural Pozzolan and slag which were alkaline-activated with various combinations of sodium hydroxide and sodium silicate. A step-by-step research program was designed to (1) develop alkali-activated natural Pozzolan/slag pastes with adequate fresh and strength properties, (2) produce alkali-activated natural Pozzolan/slag mortars to assess the effects of dominant variables on their plastic and hardened properties, and (3) finally produce and assess fresh, mechanical, dimensional, transport and durability properties of alkali-activated natural Pozzolan/slag concretes. The major variables included in this study were binder combination (natural Pozzolan/slag combinations of 70/30, 50/50 and 30/70), activator combination (sodium silicate/sodium hydroxide combinations of 20/80, 25/75 and 30/70), and sodium hydroxide concentration (1, 1.75 and 2.5M). The experimental program assessed performance of alkali-activated natural Pozzolan/slag mixtures including fresh properties (flow and setting times), unit weights (fresh, demolded and oven-dry), mechanical properties (compressive and tensile strengths, and modulus of elasticity), transport properties (absorption, rapid chloride penetration, and rapid chloride migration), durability (frost resistance, chloride induced corrosion, and resistance to sulfuric acid attack), and dimensional stability (drying shrinkage). This study also compared the performance of alkali-activated natural Pozzolan/slag concretes with that of an equivalent reference Portland cement concrete having a similar flow and strength characteristics. The results of this study revealed that it was doable to find optimum binder proportions, activator combinations and sodium hydroxide concentrations to achieve adequate plastic and hardened properties. Nearly for all studied

  14. Marine bioactive compounds: stereospecific anti-inflammatory activity of natural and synthetic cordiachromene A.

    Science.gov (United States)

    Benslimane, A F; Pouchus, Y F; Verbist, J F; Petit, J Y; Khettab, E N; Welin, L; Brion, J D

    1992-01-01

    A new synthesis is proposed for cordiachromene A (CCA), a bioactive component of the ascidian Aplidium antillense Gravier, using a method producing a racemic mixture. The anti-inflammatory activities of a natural extract and a chemically synthetic form of CCA were assessed in vivo by carrageenan-induced rat-paw edema. The activity of synthetic CCA was confirmed by a test on kaolin-induced granuloma in the rat. Strong activities were measured for both CCA, but comparison of results of the first test suggests that only the natural optically active isomer has an anti-inflammatory effect. CCA is similar to indomethacin in its effect on carrageenan-induced rat-paw edema and ten times as active as phenylbutazone.

  15. Naturally occurring genetic variability in expression of Gsta4 is associated with differential survival of axotomized rat motoneurons

    DEFF Research Database (Denmark)

    Mikael, Ström; Al Nimer, Faiez; Lindblom, Rickard

    2012-01-01

    A large number of molecular pathways have been implicated in the degeneration of axotomized motoneurons. We previously have demonstrated substantial differences in the survival rate of axotomized motoneurons across different rat strains. Identification of genetic differences underlying such natur...

  16. Differential associations between impulsivity and risk-taking and brain activations underlying working memory in adolescents.

    Science.gov (United States)

    Panwar, Karni; Rutherford, Helena J V; Mencl, W Einar; Lacadie, Cheryl M; Potenza, Marc N; Mayes, Linda C

    2014-11-01

    Increased impulsivity and risk-taking are common during adolescence and relate importantly to addictive behaviors. However, the extent to which impulsivity and risk-taking relate to brain activations that mediate cognitive processing is not well understood. Here we examined the relationships between impulsivity and risk-taking and the neural correlates of working memory. Neural activity was measured in 18 adolescents (13-18 years) while they engaged in a working memory task that included verbal and visuospatial components that each involved encoding, rehearsal and recognition stages. Risk-taking and impulsivity were assessed using the Balloon Analogue Risk Task (BART) and the adolescent version of the Barratt Impulsiveness Scale-11 (BIS-11A), respectively. We found overlapping as well as distinct regions subserving the different stages of verbal and visuospatial working memory. In terms of risk-taking, we found a positive correlation between BART scores and activity in subcortical regions (e.g., thalamus, dorsal striatum) recruited during verbal rehearsal, and an inverse correlation between BART scores and cortical regions (e.g., parietal and temporal regions) recruited during visuospatial rehearsal. The BIS-11A evidenced that motor impulsivity was associated with activity in regions recruited during all stages of working memory, while attention and non-planning impulsivity was only associated with activity in regions recruited during recognition. In considering working memory, impulsivity and risk-taking together, both impulsivity and risk-taking were associated with activity in regions recruited during rehearsal; however, during verbal rehearsal, differential correlations were found. Specifically, positive correlations were found between: (1) risk-taking and activity in subcortical regions, including the thalamus and dorsal striatum; and, (2) motor impulsivity and activity in the left inferior frontal gyrus, insula, and dorsolateral prefrontal cortex. Therefore

  17. Differential associations between impulsivity and risk-taking and brain activations underlying working memory in adolescents

    Science.gov (United States)

    Panwar, Karni; Rutherford, Helena J.V.; Mencl, W. Einar; Lacadie, Cheryl M.; Potenza, Marc N.; Mayes, Linda C.

    2014-01-01

    Increased impulsivity and risk-taking are common during adolescence and relate importantly to addictive behaviors. However, the extent to which impulsivity and risk-taking relate to brain activations that mediate cognitive processing is not well understood. Here we examined the relationships between impulsivity and risk-taking and the neural correlates of working memory. Neural activity was measured in 18 adolescents (13–18 years) while they engaged in a working memory task that included verbal and visuospatial components that each involved encoding, rehearsal and recognition stages. Risk-taking and impulsivity were assessed using the Balloon Analogue Risk Task (BART) and the adolescent version of the Barratt Impulsiveness Scale -11 (BIS-11A), respectively. We found overlapping as well as distinct regions subserving the different stages of verbal and visuospatial working memory. In terms of risk-taking, we found a positive correlation between BART scores and activity in subcortical regions (e.g., thalamus, dorsal striatum) recruited during verbal rehearsal, and an inverse correlation between BART scores and cortical regions (e.g., parietal and temporal regions) recruited during visuospatial rehearsal. The BIS-11A evidenced that motor impulsivity was associated with activity in regions recruited during all stages of working memory, while attention and non-planning impulsivity was only associated with activity in regions recruited during recognition. In considering working memory, impulsivity and risk-taking together, both impulsivity and risk-taking were associated with activity in regions recruited during rehearsal; however, during verbal rehearsal, differential correlations were found. Specifically, positive correlations were found between: (1) risk-taking and activity in subcortical regions, including the thalamus and dorsal striatum; and, (2) motor impulsivity and activity in the left inferior frontal gyrus, insula, dorsolateral and ventrolateral prefrontal

  18. Genetic variation in plant volatile emission does not result in differential attraction of natural enemies in the field.

    Science.gov (United States)

    Wason, Elizabeth L; Hunter, Mark D

    2014-02-01

    Volatile organic chemical (VOC) emission by plants may serve as an adaptive plant defense by attracting the natural enemies of herbivores. For plant VOC emission to evolve as an adaptive defense, plants must show genetic variability for the trait. To date, such variability has been investigated primarily in agricultural systems, yet relatively little is known about genetic variation in VOCs emitted by natural populations of native plants. Here, we investigate intraspecific variation in constitutive and herbivore-induced plant VOC emission using the native common milkweed plant (Asclepias syriaca) and its monarch caterpillar herbivore (Danaus plexippus) in complementary field and common garden greenhouse experiments. In addition, we used a common garden field experiment to gauge natural enemy attraction to milkweed VOCs induced by monarch damage. We found evidence of genetic variation in the total constitutive and induced concentrations of VOCs and the composition of VOC blends emitted by milkweed plants. However, all milkweed genotypes responded similarly to induction by monarchs in terms of their relative change in VOC concentration and blend. Natural enemies attacked decoy caterpillars more frequently on damaged than on undamaged milkweed, and natural enemy visitation was associated with higher total VOC concentrations and with VOC blend. Thus, we present evidence that induced VOCs emitted by milkweed may function as a defense against herbivores. However, plant genotypes were equally attractive to natural enemies. Although milkweed genotypes diverge phenotypically in their VOC concentrations and blends, they converge into similar phenotypes with regard to magnitude of induction and enemy attraction.

  19. Differential regulation of protease activated receptor-1 and tissue plasminogen activator expression by shear stress in vascular smooth muscle cells

    Science.gov (United States)

    Papadaki, M.; Ruef, J.; Nguyen, K. T.; Li, F.; Patterson, C.; Eskin, S. G.; McIntire, L. V.; Runge, M. S.

    1998-01-01

    Recent studies have demonstrated that vascular smooth muscle cells are responsive to changes in their local hemodynamic environment. The effects of shear stress on the expression of human protease activated receptor-1 (PAR-1) and tissue plasminogen activator (tPA) mRNA and protein were investigated in human aortic smooth muscle cells (HASMCs). Under conditions of low shear stress (5 dyn/cm2), PAR-1 mRNA expression was increased transiently at 2 hours compared with stationary control values, whereas at high shear stress (25 dyn/cm2), mRNA expression was decreased (to 29% of stationary control; Pmuscle cells, indicating that the effects of shear stress on human PAR-1 were not species-specific. Flow cytometry and ELISA techniques using rat smooth muscle cells and HASMCs, respectively, provided evidence that shear stress exerted similar effects on cell surface-associated PAR-1 and tPA protein released into the conditioned media. The decrease in PAR-1 mRNA and protein had functional consequences for HASMCs, such as inhibition of [Ca2+] mobilization in response to thrombin stimulation. These data indicate that human PAR-1 and tPA gene expression are regulated differentially by shear stress, in a pattern consistent with their putative roles in several arterial vascular pathologies.

  20. Carbonate Precipitation through Microbial Activities in Natural Environment, and Their Potential in Biotechnology: A Review

    Science.gov (United States)

    Zhu, Tingting; Dittrich, Maria

    2016-01-01

    Calcium carbonate represents a large portion of carbon reservoir and is used commercially for a variety of applications. Microbial carbonate precipitation, a by-product of microbial activities, plays an important metal coprecipitation and cementation role in natural systems. This natural process occurring in various geological settings can be mimicked and used for a number of biotechnologies, such as metal remediation, carbon sequestration, enhanced oil recovery, and construction restoration. In this study, different metabolic activities leading to calcium carbonate precipitation, their native environment, and potential applications and challenges are reviewed. PMID:26835451

  1. Carbonate precipitation through microbial activities in natural environment, and their potential in biotechnology: a review

    Directory of Open Access Journals (Sweden)

    Tingting eZhu

    2016-01-01

    Full Text Available Calcium carbonate represents a large portion of carbon reservoir and is used commercially for a variety of applications. Microbial carbonate precipitation (MCP, a by-product of microbial activities, plays an important metal coprecipitation and cementation role in natural systems. This natural process occurring in various geological settings can be mimicked and used for a number of biotechnology such as metal remediation, carbon sequestration, enhanced oil recovery and construction restoration. In this study, different metabolic activities leading to calcium carbonate precipitation, their native environment, and potential applications and challenges are reviewed.

  2. Foreign activities of German producers of petroleum and natural gas; Auslandsaktivitaeten deutscher Erdoel-ErdgasProduzenten

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    2010-04-15

    The contribution under consideration is engaged in the foreign activities of German producers of natural gas and oil: Wintershall Holding AG (Kassel), RWE DEA AG (Hamburg), Petro Canada Germany GmbH (Essen), E.ON Ruhrgas AG (Essen), VNG Norge AG (Leipzig), Bavaria gas GmbH (Munich) and EWE AG (Oldenburg). Data according to the petroleum of petroleum and natural gas abroad are published for the period between 2007 and 2009. Besides this, the activities of these companies in individual countries are specified exactly.

  3. Ecto-mesenchymal stem cells from dental pulp are committed to differentiate into active melanocytes

    Directory of Open Access Journals (Sweden)

    F Paino

    2010-10-01

    Full Text Available Dental pulp stem cells (DPSCs are multipotent stem cells derived from neural crest and mesenchyme and have the capacity to differentiate into multiple cell lineages. It has already been demonstrated that DPSCs differentiate into melanocyte-like cells but only when cultivated in a specific melanocyte differentiating medium. In this study we have shown, for the first time, that DPSCs are capable of spontaneously differentiating into mature melanocytes, which display molecular and ultrastructural features of full development, including the expression of melanocyte specific markers and the presence of melanosomes up to the terminal stage of maturation. We have also compared the differentiating features of DPSCs grown in different culture conditions, following the timing of differentiation at molecular and cytochemical levels and found that in all culture conditions full development of these cells was obtained, although at different times. The spontaneous differentiating potential of these cells strongly suggests their possible applications in regenerative medicine.

  4. Differential activation of airway eosinophils induces IL-13-mediated allergic Th2 pulmonary responses in mice.

    Science.gov (United States)

    Jacobsen, E A; Doyle, A D; Colbert, D C; Zellner, K R; Protheroe, C A; LeSuer, W E; Lee, N A; Lee, J J

    2015-09-01

    Eosinophils are hallmark cells of allergic Th2 respiratory inflammation. However, the relative importance of eosinophil activation and the induction of effector functions such as the expression of IL-13 to allergic Th2 pulmonary disease remain to be defined. Wild-type or cytokine-deficient (IL-13(-/-) or IL-4(-/-) ) eosinophils treated with cytokines (GM-CSF, IL-4, IL-33) were adoptively transferred into eosinophil-deficient recipient mice subjected to allergen provocation using established models of respiratory inflammation. Allergen-induced pulmonary changes were assessed. In contrast to the transfer of untreated blood eosinophils to the lungs of recipient eosinophil deficient mice, which induced no immune/inflammatory changes either in the lung or in the lung draining lymph nodes (LDLN), pretreatment of blood eosinophils with GM-CSF prior to transfer elicited trafficking of these eosinophils to LDLN. In turn, these LDLN eosinophils elicited the accumulation of dendritic cells and CD4(+) T cells to these same LDLNs without inducing pulmonary inflammation. However, exposure of eosinophils to GM-CSF, IL-4, and IL-33 prior to transfer induced not only immune events in the LDLN, but also allergen-mediated increases in airway Th2 cytokine/chemokine levels, the subsequent accumulation of CD4(+) T cells as well as alternatively activated (M2) macrophages, and the induction of pulmonary histopathologies. Significantly, this allergic respiratory inflammation was dependent on eosinophil-derived IL-13, whereas IL-4 expression by eosinophils had no significant role. The data demonstrate the differential activation of eosinophils as a function of cytokine exposure and suggest that eosinophil-specific IL-13 expression by activated cells is a necessary component of the subsequent allergic Th2 pulmonary pathologies. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Differential Activation of Airway Eosinophils Induces IL-13 Mediated Allergic Th2 Pulmonary Responses in Mice

    Science.gov (United States)

    Jacobsen, EA; Doyle, AD; Colbert, DC; Zellner, KR; Protheroe, CA; LeSuer, WE; Lee, NA.; Lee, JJ

    2015-01-01

    Background Eosinophils are hallmark cells of allergic Th2 respiratory inflammation. However, the relative importance of eosinophil activation and the induction of effector functions such as the expression of IL-13 to allergic Th2 pulmonary disease remain to be defined. Methods Wild type or cytokine deficient (IL-13−/− or IL-4−/−) eosinophils treated with cytokines (GM-CSF, IL-4, IL-33) were adoptively transferred into eosinophil-deficient recipient mice subjected to allergen provocation using established models of respiratory inflammation. Allergen-induced pulmonary changes were assessed. Results In contrast to the transfer of untreated blood eosinophils to the lungs of recipient eosinophildeficient mice, which induced no immune/inflammatory changes either in the lung or lung draining lymph nodes (LDLNs), pretreatment of blood eosinophils with GM-CSF prior to transfer elicited trafficking of these eosinophils to LDLNs. In turn, these LDLN eosinophils elicited the accumulation of dendritic cells and CD4+ T cells to these same LDLNs without inducing pulmonary inflammation. However, exposure of eosinophils to GM-CSF, IL-4 and IL-33 prior to transfer induced not only immune events in the LDLN, but also allergen-mediated increases in airway Th2 cytokine/chemokine levels, the subsequent accumulation of CD4+ T cells as well as alternatively activated (M2) macrophages, and the induction of pulmonary histopathologies. Significantly, this allergic respiratory inflammation was dependent on eosinophil-derived IL-13 whereas IL-4 expression by eosinophils had no significant role. Conclusion The data demonstrate the differential activation of eosinophils as a function of cytokine exposure and suggest that eosinophil-specific IL-13 expression by activated cells is a necessary component of the subsequent allergic Th2 pulmonary pathologies. PMID:26009788

  6. MicroRNA-9 promotes the neuronal differentiation of rat bone marrow mesenchymal stem cells by activating autophagy

    Directory of Open Access Journals (Sweden)

    Guang-yu Zhang

    2015-01-01

    Full Text Available MicroRNA-9 (miR-9 has been shown to promote the differentiation of bone marrow mesenchymal stem cells into neuronal cells, but the precise mechanism is unclear. Our previous study confirmed that increased autophagic activity improved the efficiency of neuronal differentiation in bone marrow mesenchymal stem cells. Accumulating evidence reveals that miRNAs adjust the autophagic pathways. This study used miR-9-1 lentiviral vector and miR-9-1 inhibitor to modulate the expression level of miR-9. Autophagic activity and neuronal differentiation were measured by the number of light chain-3 (LC3-positive dots, the ratio of LC3-II/LC3, and the expression levels of the neuronal markers enolase and microtubule-associated protein 2. Results showed that LC3-positive dots, the ratio of LC3-II/LC3, and expression of neuron specific enolase and microtubule-associated protein 2 increased in the miR-9 + group. The above results suggest that autophagic activity increased and bone marrow mesenchymal stem cells were prone to differentiate into neuronal cells when miR-9 was overexpressed, demonstrating that miR-9 can promote neuronal differentiation by increasing autophagic activity.

  7. When Should We Use Care Robots? The Nature-of-Activities Approach.

    Science.gov (United States)

    Santoni de Sio, Filippo; van Wynsberghe, Aimee

    2016-12-01

    When should we use care robots? In this paper we endorse the shift from a simple normative approach to care robots ethics to a complex one: we think that one main task of a care robot ethics is that of analysing the different ways in which different care robots may affect the different values at stake in different care practices. We start filling a gap in the literature by showing how the philosophical analysis of the nature of healthcare activities can contribute to (care) robot ethics. We rely on the nature-of-activities approach recently proposed in the debate on human enhancement, and we apply it to the ethics of care robots. The nature-of-activities approach will help us to understand why certain practice-oriented activities in healthcare should arguably be left to humans, but certain (predominantly) goal-directed activities in healthcare can be fulfilled (sometimes even more ethically) with the assistance of a robot. In relation to the latter, we aim to show that even though all healthcare activities can be considered as practice-oriented, when we understand the activity in terms of different legitimate 'fine-grained' descriptions, the same activities or at least certain components of them can be seen as clearly goal-directed. Insofar as it allows us to ethically assess specific functionalities of specific robots to be deployed in well-defined circumstances, we hold the nature-of-activities approach to be particularly helpful also from a design perspective, i.e. to realize the Value Sensitive Design approach.

  8. Differential hippocampal gene expression is associated with climate-related natural variation in memory and the hippocampus in food-caching chickadees.

    Science.gov (United States)

    Pravosudov, V V; Roth, T C; Forister, M L; Ladage, L D; Kramer, R; Schilkey, F; van der Linden, A M

    2013-01-01

    There is significant and often heritable variation in cognition and its underlying neural mechanisms, yet specific genetic contributions to such variation are not well characterized. Black-capped chickadees present a good model to investigate the genetic basis of cognition because they exhibit tremendous climate-related variation in memory, hippocampal morphology and neurogenesis rates throughout the North American continent, and these cognitive traits appear to have a heritable basis. We examined the hippocampal transcriptome profiles of laboratory-reared chickadees from the two most divergent populations to test whether differential gene expression in the hippocampus is associated with population differences in spatial memory, hippocampal morphology and adult hippocampal neurogenesis rates. Using high-resolution mRNA sequencing coupled to a de novo transcriptome assembly, we generated 23 295 consensus sequences, which predicted 16 206 protein sequences with 13 982 showing high similarity to known protein sequences or conserved hypothetical proteins in other species. Of these, we identified differential expression in nearly 380 genes, with 47 genes specifically linked to neurogenesis, apoptosis, synaptic function, and learning and memory processes. Many of the other differentially expressed genes, however, may be associated with other functions. Our study presents the first avian hippocampal transcriptome, and it is the first study identifying differential gene expression associated with natural variation in cognition and the hippocampus. Our results provide additional support to the hypothesis that population differences in memory, hippocampal morphology and neurogenesis in chickadees have likely resulted from natural selection that appears to act on memory and its underlying neural mechanisms. © 2012 Blackwell Publishing Ltd.

  9. Dopamine receptors D3 and D5 regulate CD4(+)T-cell activation and differentiation by modulating ERK activation and cAMP production.

    Science.gov (United States)

    Franz, Dafne; Contreras, Francisco; González, Hugo; Prado, Carolina; Elgueta, Daniela; Figueroa, Claudio; Pacheco, Rodrigo

    2015-07-15

    Dopamine receptors have been described in T-cells, however their signalling pathways coupled remain unknown. Since cAMP and ERKs play key roles regulating T-cell physiology, we aim to determine whether cAMP and ERK1/2-phosphorylation are modulated by dopamine receptor 3 (D3R) and D5R, and how this modulation affects CD4(+) T-cell activation and differentiation. Our pharmacologic and genetic evidence shows that D3R-stimulation reduced cAMP levels and ERK2-phosphorylation, consequently increasing CD4(+) T-cell activation and Th1-differentiation, respectively. Moreover, D5R expression reinforced TCR-triggered ERK1/2-phosphorylation and T-cell activation. In conclusion, these findings demonstrate how D3R and D5R modulate key signalling pathways affecting CD4(+) T-cell activation and Th1-differentiation. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Enhancement of human natural cytotoxicity by Plasmodium falciparum antigen activated lymphocytes

    DEFF Research Database (Denmark)

    Theander, T G; Pedersen, B K; Bygbjerg, I C

    1987-01-01

    Mononuclear cells (MNC) isolated from malaria immune donors and from donors never exposed to malaria were stimulated in vitro with soluble purified Plasmodium falciparum antigens (SPag) or PPD. After 7 days of culture the proliferative response and the cytotoxic activity against the natural killer...... were preincubated with interleukin 2 (IL-2) for one hour before the start of the cytotoxic assay. SPag activation did not enhance the cytotoxic activity of MNC which did not respond to the antigen in the proliferation assay, and preincubation of these cells with IL-2 did not increase the activity. PPD...

  11. Angiotensin II Regulates Th1 T Cell Differentiation Through Angiotensin II Type 1 Receptor-PKA-Mediated Activation of Proteasome.

    Science.gov (United States)

    Qin, Xian-Yun; Zhang, Yun-Long; Chi, Ya-Fei; Yan, Bo; Zeng, Xiang-Jun; Li, Hui-Hua; Liu, Ying

    2018-01-01

    Naive CD4+ T cells differentiate into T helper cells (Th1 and Th2) that play an essential role in the cardiovascular diseases. However, the molecular mechanism by which angiotensin II (Ang II) promotes Th1 differentiation remains unclear. The aim of this study was to determine whether the Ang II-induced Th1 differentiation regulated by ubiquitin-proteasome system (UPS). Jurkat cells were treated with Ang II (100 nM) in the presence or absence of different inhibitors. The gene mRNA levels were detected by real-time quantitative PCR analysis. The protein levels were measured by ELISA assay or Western blot analysis, respectively. Ang II treatment significantly induced a shift from Th0 to Th1 cell differentiation, which was markedly blocked by angiotensin II type 1 receptor (AT1R) inhibitor Losartan (LST). Moreover, Ang II significantly increased the activities and the expression of proteasome catalytic subunits (β1, β1i, β2i and β5i) in a dose- and time-dependent manner. However, Ang II-induced proteasome activities were remarkably abrogated by LST and PKA inhibitor H-89. Mechanistically, Ang II-induced Th1 differentiation was at least in part through proteasome-mediated degradation of IκBα and MKP-1 and activation of STAT1 and NF-κB. This study for the first time demonstrates that Ang II activates AT1R-PKA-proteasome pathway, which promotes degradation of IκBα and MKP-1 and activation of STAT1 and NF-κB thereby leading to Th1 differentiation. Thus, inhibition of proteasome activation might be a potential therapeutic target for Th1-mediated diseases. © 2018 The Author(s). Published by S. Karger AG, Basel.

  12. Human papillomavirus 16E6 and NFX1-123 potentiate notch signaling and differentiation without activating cellular arrest

    Energy Technology Data Exchange (ETDEWEB)

    Vliet-Gregg, Portia A.; Hamilton, Jennifer R. [Center for Global Infectious Disease Research, Seattle Children' s Research Institute, 1900 Ninth Ave., Seattle, WA 98101 (United States); Katzenellenbogen, Rachel A., E-mail: rkatzen@uw.edu [Center for Global Infectious Disease Research, Seattle Children' s Research Institute, 1900 Ninth Ave., Seattle, WA 98101 (United States); Department of Pediatrics, Division of Adolescent Medicine, University of Washington, Seattle WA (United States)

    2015-04-15

    High-risk human papillomavirus (HR HPV) oncoproteins bind host cell proteins to dysregulate and uncouple apoptosis, senescence, differentiation, and growth. These pathways are important for both the viral life cycle and cancer development. HR HPV16 E6 (16E6) interacts with the cellular protein NFX1-123, and they collaboratively increase the growth and differentiation master regulator, Notch1. In 16E6 expressing keratinocytes (16E6 HFKs), the Notch canonical pathway genes Hes1 and Hes5 were increased with overexpression of NFX1-123, and their expression was directly linked to the activation or blockade of the Notch1 receptor. Keratinocyte differentiation genes Keratin 1 and Keratin 10 were also increased, but in contrast their upregulation was only indirectly associated with Notch1 receptor stimulation and was fully unlinked to growth arrest, increased p21{sup Waf1/CIP1}, or decreased proliferative factor Ki67. This leads to a model of 16E6, NFX1-123, and Notch1 differently regulating canonical and differentiation pathways and entirely uncoupling cellular arrest from increased differentiation. - Highlights: • 16E6 and NFX1-123 increased the Notch canonical pathway through Notch1. • 16E6 and NFX1-123 increased the differentiation pathway indirectly through Notch1. • 16E6 and NFX1-123 increased differentiation gene expression without growth arrest. • Increased NFX1-123 with 16E6 may create an ideal cellular phenotype for HPV.

  13. Ihh enhances differentiation of CFK-2 chondrocytic cells and antagonizes PTHrP-mediated activation of PKA.

    Science.gov (United States)

    Deckelbaum, Ron A; Chan, George; Miao, Dengshun; Goltzman, David; Karaplis, Andrew C

    2002-07-15

    Indian Hedgehog (Ihh), a member of the hedgehog (HH) family of secreted morphogens, and parathyroid hormone-related peptide (PTHrP) are key regulators of cartilage cell (chondrocyte) differentiation. We have investigated, in vitro, the actions of HH signalling and its possible interplay with PTHrP using rat CFK-2 chondrocytic cells. Markers of chondrocyte differentiation [alkaline phosphatase (ALP) activity, and type II (Col2a1) and type X collagen (Col10a1) expression] were enhanced by overexpression of Ihh or its N-terminal domain (N-Ihh), effects mimicked by exogenous administration of recombinant N-terminal HH peptide. Moreover, a missense mutation mapping to the N-terminal domain of Ihh (W160G) reduces the capacity of N-Ihh to induce differentiation. Prolonged exposure of CFK-2 cells to exogenous N-Shh (5x10(-9) M) in the presence of PTHrP (10(-8) M) or forskolin (10(-7) M) resulted in perturbation of HH-mediated differentiation. In addition, overexpression of a constitutively active form of the PTHrP receptor (PTHR1 H223R) inhibited Ihh-mediated differentiation, implicating activation of protein kinase A (PKA) by PTHR1 as a probable mediator of the antagonistic effects of PTHrP. Conversely, overexpression of Ihh/N-Ihh or exogenous treatment with N-Shh led to dampening of PTHrP-mediated activation of PKA. Taken together, our data suggest that Ihh harbors the capacity to induce rather than inhibit chondrogenic differentiation, that PTHrP antagonizes HH-mediated differentiation through a PKA-dependent mechanism and that HH signalling, in turn, modulates PTHrP action through functional inhibition of signalling by PTHR1 to PKA.

  14. Class A scavenger receptor promotes osteoclast differentiation via the enhanced expression of receptor activator of NF-{kappa}B (RANK)

    Energy Technology Data Exchange (ETDEWEB)

    Takemura, Kenichi [Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556 (Japan); Department of Orthopaedic and Neuro-Musculoskeletal Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto (Japan); Sakashita, Naomi; Fujiwara, Yukio; Komohara, Yoshihiro; Lei, XiaoFeng; Ohnishi, Koji [Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556 (Japan); Suzuki, Hiroshi [National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Hokkaido (Japan); Kodama, Tatsuhiko [Department of Molecular Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo (Japan); Mizuta, Hiroshi [Department of Orthopaedic and Neuro-Musculoskeletal Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto (Japan); Takeya, Motohiro, E-mail: takeya@kumamoto-u.ac.jp [Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556 (Japan)

    2010-01-22

    Osteoclasts originate from bone marrow monocyte/macrophage lineage cells, and their differentiation depends on macrophage colony-stimulating factor (M-CSF) and receptor activator nuclear factor kappa B (RANK) ligand. Class A scavenger receptor (SR-A) is one of the principal functional molecules of macrophages, and its level of expression declines during osteoclast differentiation. To investigate the role of SR-A in osteoclastogenesis, we examined pathological changes in femoral bone and the expression levels of osteoclastogenesis-related molecules in SR-A{sup -/-} mice. The femoral osseous density of SR-A{sup -/-} mice was higher than that of SR-A{sup +/+} mice, and the number of multinucleated osteoclasts was significantly decreased. An in vitro differentiation assay revealed that the differentiation of multinucleated osteoclasts from bone marrow-derived progenitor cells is impaired in SR-A{sup -/-} mice. Elimination of SR-A did not alter the expression level of the M-CSF receptor, c-fms; however, the expression levels of RANK and RANK-related osteoclast-differentiation molecules such as nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) and microphthalmia-associated transcription factor (MITF) significantly decreased. Furthermore, acetylated low-density lipoprotein (AcLDL), an SR-A ligand, significantly increased the expression level of RANK and MITF during osteoclast differentiation. These data indicate that SR-A promotes osteoclastogenesis via augmentation of the expression level of RANK and its related molecules.

  15. Marine Natural Product Honaucin A Attenuates Inflammation by Activating the Nrf2-ARE Pathway.

    Science.gov (United States)

    Mascuch, Samantha J; Boudreau, Paul D; Carland, Tristan M; Pierce, N Tessa; Olson, Joshua; Hensler, Mary E; Choi, Hyukjae; Campanale, Joseph; Hamdoun, Amro; Nizet, Victor; Gerwick, William H; Gaasterland, Teresa; Gerwick, Lena

    2018-03-23

    The cyanobacterial marine natural product honaucin A inhibits mammalian innate inflammation in vitro and in vivo. To decipher its mechanism of action, RNA sequencing was used to evaluate differences in gene expression of cultured macrophages following honaucin A treatment. This analysis led to the hypothesis that honaucin A exerts its anti-inflammatory activity through activation of the cytoprotective nuclear erythroid 2-related factor 2 (Nrf2)-antioxidant response element/electrophile response element (ARE/EpRE) signaling pathway. Activation of this pathway by honaucin A in cultured human MCF7 cells was confirmed using an Nrf2 luciferase reporter assay. In vitro alkylation experiments with the natural product and N-acetyl-l-cysteine suggest that honaucin A activates this pathway through covalent interaction with the sulfhydryl residues of the cytosolic repressor protein Keap1. Honaucin A presents a potential therapeutic lead for diseases with an inflammatory component modulated by Nrf2-ARE.

  16. Natural products from Cuscuta reflexa Roxb. with antiproliferation activities in HCT116 colorectal cell lines.

    Science.gov (United States)

    Riaz, Muhammad; Bilal, Aishah; Ali, Muhammad Shaiq; Fatima, Itrat; Faisal, Amir; Sherkheli, Muhammad Azhar; Asghar, Adnan

    2017-03-01

    Parasitic Cuscuta reflexa Roxb. possesses many medicinal properties and is a rich source of a variety of biologically relevant natural products. Natural products are the prime source of leads, drugs, and drug templates, and many of the anticancer and antiviral drugs are either based on natural product or derived from them. Cancer is a devastating disease and one of the leading causes of death worldwide despite improvements in patient survival during the past 50 years; new and improved treatments for cancer are therefore actively sought. Colorectal cancer is the fourth most prevalent cancer worldwide and is responsible for nearly 9% of all cancer deaths. Our search for anticancer natural products from C. reflexa has yielded four natural products: Scoparone (1), p-coumaric acid (2), stigmasta-3,5-diene (3) and 1-O-p-hydroxycinnamoylglucose (4) and among them 1-O-p-hydroxycinnamoyldlucose (4) showed promising antiproliferative activities in HCT116 colorectal cell lines, whereas compounds 1-3 showed moderate activities.

  17. The Role of Biologically Active Ingredients from Natural Drug Treatments for Arrhythmias in Different Mechanisms.

    Science.gov (United States)

    Li, Jie; Hu, Dan; Song, Xiaoli; Han, Tao; Gao, Yonghong; Xing, Yanwei

    2017-01-01

    Arrhythmia is a disease that is caused by abnormal electrical activity in the heart rate or rhythm. It is the major cause of cardiovascular morbidity and mortality. Although several antiarrhythmic drugs have been used in clinic for decades, their application is often limited by their adverse effects. As a result, natural drugs, which have fewer side effects, are now being used to treat arrhythmias. We searched for all articles on the role of biologically active ingredients from natural drug treatments for arrhythmias in different mechanisms in PubMed. This study reviews 19 natural drug therapies, with 18 active ingredient therapies, such as alkaloids, flavonoids, saponins, quinones, and terpenes, and two kinds of traditional Chinese medicine compound (Wenxin-Keli and Shensongyangxin), all of which have been studied and reported as having antiarrhythmic effects. The primary focus is the proposed antiarrhythmic mechanism of each natural drug agent. Conclusion . We stress persistent vigilance on the part of the provider in discussing the use of natural drug agents to provide a solid theoretical foundation for further research on antiarrhythmia drugs.

  18. Natural resource management activities at the Savannah River Site. Environmental Assessment

    Energy Technology Data Exchange (ETDEWEB)

    1993-07-01

    This environmental assessment (EA) reviews the environmental consequences of ongoing natural resource management activities on the Savannah River Site (SRS). Appendix A contains the Natural Resources Management Plant (NRMP). While several SRS organizations have primary responsibilities for different elements of the plan, the United States Department of Agriculture (USDA), Forest Service, Savannah River Forest Station (SRFS) is responsible for most elements. Of the river scenarios defined in 1985, the High-Intensity Management alternative established the upper bound of environmental consequences; it represents a more intense level of resource management than that being performed under current resource management activities. This alternative established compliance mechanisms for several natural resource-related requirements and maximum practical timber harvesting. Similarly, the Low-Intensity Management alternative established the lower bound of environmental consequences and represents a less intense level of resource management than that being performed under current resource management activities. This alternative also established compliance mechanisms, but defined a passively managed natural area. The Proposed Action of this EA describes the current level of multiple-natural resource management. This EA reviews the proposed action, and the high and low intensity alternative scenarios.

  19. Evidence for similar patterns of neural activity elicited by picture- and word-based representations of natural scenes.

    Science.gov (United States)

    Kumar, Manoj; Federmeier, Kara D; Fei-Fei, Li; Beck, Diane M

    2017-07-15

    A long-standing core question in cognitive science is whether different modalities and representation types (pictures, words, sounds, etc.) access a common store of semantic information. Although different input types have been shown to activate a shared network of brain regions, this does not necessitate that there is a common representation, as the neurons in these regions could still differentially process the different modalities. However, multi-voxel pattern analysis can be used to assess whether, e.g., pictures and words evoke a similar pattern of activity, such that the patterns that separate categories in one modality transfer to the other. Prior work using this method has found support for a common code, but has two limitations: they have either only examined disparate categories (e.g. animals vs. tools) that are known to activate different brain regions, raising the possibility that the pattern separation and inferred similarity reflects only large scale differences between the categories or they have been limited to individual object representations. By using natural scene categories, we not only extend the current literature on cross-modal representations beyond objects, but also, because natural scene categories activate a common set of brain regions, we identify a more fine-grained (i.e. higher spatial resolution) common representation. Specifically, we studied picture- and word-based representations of natural scene stimuli from four different categories: beaches, cities, highways, and mountains. Participants passively viewed blocks of either phrases (e.g. "sandy beach") describing scenes or photographs from those same scene categories. To determine whether the phrases and pictures evoke a common code, we asked whether a classifier trained on one stimulus type (e.g. phrase stimuli) would transfer (i.e. cross-decode) to the other stimulus type (e.g. picture stimuli). The analysis revealed cross-decoding in the occipitotemporal, posterior parietal and

  20. Nature of the activates places of the acid solid catalysts of the sulphated metallic oxides type

    International Nuclear Information System (INIS)

    Gomez, Miguel A; Fontalvo Javier

    1998-01-01

    In this revision the state of the knowledge is presented with respect to the understanding of the nature of the active places for the strongly acid solid catalysts of the type sulphated metallic oxides. The results presented by means of models are based on the characterization of the properties physicochemical carried out by means of technical as XPS, to GO, NMR etc., and the evaluation of the catalytic activity in different applications

  1. Use of the painDETECT questionnaire to differentiate the nature of hip pain associated with a labrum tear

    Directory of Open Access Journals (Sweden)

    Mitsufumi Nakawaki

    2018-01-01

    Full Text Available The nature of pain associated with a labrum tear of the hip joint can vary widely among patients and does not always correlate with findings from diagnostic imaging. Identifying the components of the pain (nociceptive, neuropathic, or mixed pattern is important to direct treatment. This report aimed to describe the use of the painDETECT questionnaire as a screening tool in order to classify the nature of the pain in three patients who presented with pain that was atypical for a labrum tear. The painDETECT questionnaire was an effective tool to identify appropriate pain management strategies in each case.

  2. Synthesis and biological activity of chimeric structures derived from the cytotoxic natural compounds dolastatin 10 and dolastatin 15.

    Science.gov (United States)

    Poncet, J; Busquet, M; Roux, F; Pierré, A; Atassi, G; Jouin, P

    1998-04-23

    The natural cytotoxic compounds dolastatins 10 and 15 exhibit great similarities in structure and in their biological activity profiles. Two compounds (1 and 2) formed by interchanging the dolaisoleuine residue of dolastatin 10 and the MeVal-Pro dipeptide of dolastatin 15 were synthesized in order to evaluate the possible equivalence of these units. These compounds can be considered as chimeras of dolastatins 10 and 15 formed by the N-terminal part of the former and the C-terminal part of the latter and vice versa. Both analogues exhibited a marked decrease in their cytotoxic activity but showed similar differential cytotoxicity with regard to the cell lines assayed compared with the parent compounds. HT-29 cell line was the least sensitive one. However, this activity was in the nanomolar level and close to that of vincristine. The differences in their effect on tubulin polymerization were less pronounced. We confirmed the already known crucial role of the Dil residue in this assay. The nonequivalence of the Dil unit and the MeVal-Pro dipeptide probably reflects modification in the relative positions of the N-dimethylamino and the phenyl moieties.

  3. Differential flight responses of spring staging Teal Anas crecca and Wigeon A. penelope to human vs. natural disturbance

    DEFF Research Database (Denmark)

    Bregnballe, Thomas; Speich, Charlotte; Horsten, Anders

    2017-01-01

    (anglers, cyclists, farming activity) on the flight responses and displacement distances of ducks within uniform habitat along a public path were compared with the birds’ reaction to natural stimuli such as mammals or birds of prey. Excluding the controlled disturbance by a pedestrian, undertaken as part...... of the study, the main cause of flushing in Wigeon was a response to the movements of birds of prey and other birds, especially Lapwings Vanellus vanellus performing flight displays. For Teal, birds of prey accounted for around half of the flushes, with other birds accounting for one third of the flushes....... Wigeon and Teal were displaced significantly farther by human activities than by natural causes. We tested whether the ducks reacted differently to natural disturbances shortly after disturbance by a pedestrian by comparing response patterns to natural stimuli within the first hour following disturbance...

  4. Type 2 diabetes impairs venous, but not arterial smooth muscle cell function: Possible role of differential RhoA activity

    Energy Technology Data Exchange (ETDEWEB)

    Riches, Kirsten [Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, Health and Therapeutics (LIGHT), University of Leeds, Leeds (United Kingdom); Multidisciplinary Cardiovascular Research Centre (MCRC), University of Leeds, Leeds (United Kingdom); Warburton, Philip [Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, Health and Therapeutics (LIGHT), University of Leeds, Leeds (United Kingdom); O’Regan, David J. [Multidisciplinary Cardiovascular Research Centre (MCRC), University of Leeds, Leeds (United Kingdom); Department of Cardiac Surgery, The Yorkshire Heart Centre, Leeds General Infirmary, Leeds (United Kingdom); Turner, Neil A. [Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, Health and Therapeutics (LIGHT), University of Leeds, Leeds (United Kingdom); Multidisciplinary Cardiovascular Research Centre (MCRC), University of Leeds, Leeds (United Kingdom); Porter, Karen E., E-mail: medkep@leeds.ac.uk [Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, Health and Therapeutics (LIGHT), University of Leeds, Leeds (United Kingdom); Multidisciplinary Cardiovascular Research Centre (MCRC), University of Leeds, Leeds (United Kingdom)

    2014-04-15

    Background/purpose: Coronary heart disease is the leading cause of morbidity in patients with type 2 diabetes mellitus (T2DM), frequently resulting in a requirement for coronary revascularization using the internal mammary artery (IMA) or saphenous vein (SV). Patency rates of SV grafts are inferior to IMA and further impaired by T2DM whilst IMA patencies appear similar in both populations. Smooth muscle cells (SMC) play a pivotal role in graft integration; we therefore examined the phenotype and proliferative function of IMA- and SV-SMC isolated from non-diabetic (ND) patients or those diagnosed with T2DM. Methods/materials: SMC were cultured from fragments of SV or IMA. Morphology was analyzed under light microscopy (spread cell area measurements) and confocal microscopy (F-actin staining). Proliferation was analyzed by cell counting. Levels of RhoA mRNA, protein and activity were measured by real-time RT-PCR, western blotting and G-LISA respectively. Results: IMA-SMC from T2DM and ND patients were indistinguishable in both morphology and function. By comparison, SV-SMC from T2DM patients exhibited significantly larger spread cell areas (1.5-fold increase, P < 0.05), truncated F-actin fibers and reduced proliferation (33% reduction, P < 0.05). Furthermore, lower expression and activity of RhoA were observed in SV-SMC of T2DM patients (37% reduction in expression, P < 0.05 and 43% reduction in activity, P < 0.01). Conclusions: IMA-SMC appear impervious to phenotypic modulation by T2DM. In contrast, SV-SMC from T2DM patients exhibit phenotypic and functional changes accompanied by reduced RhoA activity. These aberrancies may be epigenetic in nature, compromising SMC plasticity and SV graft adaptation in T2DM patients. Summary: The internal mammary artery (IMA) is the conduit of choice for bypass grafting and is generally successful in all patients, including those with type 2 diabetes (T2DM). By contrast, saphenous vein (SV) is inferior to IMA and furthermore

  5. Meclozine facilitates proliferation and differentiation of chondrocytes by attenuating abnormally activated FGFR3 signaling in achondroplasia.

    Directory of Open Access Journals (Sweden)

    Masaki Matsushita

    Full Text Available Achondroplasia (ACH is one of the most common skeletal dysplasias with short stature caused by gain-of-function mutations in FGFR3 encoding the fibroblast growth factor receptor 3. We used the drug repositioning strategy to identify an FDA-approved drug that suppresses abnormally activated FGFR3 signaling in ACH. We found that meclozine, an anti-histamine drug that has long been used for motion sickness, facilitates chondrocyte proliferation and mitigates loss of extracellular matrix in FGF2-treated rat chondrosarcoma (RCS cells. Meclozine also ameliorated abnormally suppressed proliferation of human chondrosarcoma (HCS-2/8 cells that were infected with lentivirus expressing constitutively active mutants of FGFR3-K650E causing thanatophoric dysplasia, FGFR3-K650M causing SADDAN, and FGFR3-G380R causing ACH. Similarly, meclozine alleviated abnormally suppressed differentiation of ATDC5 chondrogenic cells expressing FGFR3-K650E and -G380R in micromass culture. We also confirmed that meclozine alleviates FGF2-mediated longitudinal growth inhibition of embryonic tibia in bone explant culture. Interestingly, meclozine enhanced growth of embryonic tibia in explant culture even in the absence of FGF2 treatment. Analyses of intracellular FGFR3 signaling disclosed that meclozine downregulates phosphorylation of ERK but not of MEK in FGF2-treated RCS cells. Similarly, meclozine enhanced proliferation of RCS cells expressing constitutively active mutants of MEK and RAF but not of ERK, which suggests that meclozine downregulates the FGFR3 signaling by possibly attenuating ERK phosphorylation. We used the C-natriuretic peptide (CNP as a potent inhibitor of the FGFR3 signaling throughout our experiments, and found that meclozine was as efficient as CNP in attenuating the abnormal FGFR3 signaling. We propose that meclozine is a potential therapeutic agent for treating ACH and other FGFR3-related skeletal dysplasias.

  6. Meclozine Facilitates Proliferation and Differentiation of Chondrocytes by Attenuating Abnormally Activated FGFR3 Signaling in Achondroplasia

    Science.gov (United States)

    Matsushita, Masaki; Kitoh, Hiroshi; Ohkawara, Bisei; Mishima, Kenichi; Kaneko, Hiroshi; Ito, Mikako; Masuda, Akio; Ishiguro, Naoki; Ohno, Kinji

    2013-01-01

    Achondroplasia (ACH) is one of the most common skeletal dysplasias with short stature caused by gain-of-function mutations in FGFR3 encoding the fibroblast growth factor receptor 3. We used the drug repositioning strategy to identify an FDA-approved drug that suppresses abnormally activated FGFR3 signaling in ACH. We found that meclozine, an anti-histamine drug that has long been used for motion sickness, facilitates chondrocyte proliferation and mitigates loss of extracellular matrix in FGF2-treated rat chondrosarcoma (RCS) cells. Meclozine also ameliorated abnormally suppressed proliferation of human chondrosarcoma (HCS-2/8) cells that were infected with lentivirus expressing constitutively active mutants of FGFR3-K650E causing thanatophoric dysplasia, FGFR3-K650M causing SADDAN, and FGFR3-G380R causing ACH. Similarly, meclozine alleviated abnormally suppressed differentiation of ATDC5 chondrogenic cells expressing FGFR3-K650E and -G380R in micromass culture. We also confirmed that meclozine alleviates FGF2-mediated longitudinal growth inhibition of embryonic tibia in bone explant culture. Interestingly, meclozine enhanced growth of embryonic tibia in explant culture even in the absence of FGF2 treatment. Analyses of intracellular FGFR3 signaling disclosed that meclozine downregulates phosphorylation of ERK but not of MEK in FGF2-treated RCS cells. Similarly, meclozine enhanced proliferation of RCS cells expressing constitutively active mutants of MEK and RAF but not of ERK, which suggests that meclozine downregulates the FGFR3 signaling by possibly attenuating ERK phosphorylation. We used the C-natriuretic peptide (CNP) as a potent inhibitor of the FGFR3 signaling throughout our experiments, and found that meclozine was as efficient as CNP in attenuating the abnormal FGFR3 signaling. We propose that meclozine is a potential therapeutic agent for treating ACH and other FGFR3-related skeletal dysplasias. PMID:24324705

  7. Bisphenol A differentially activates protein kinase C isoforms in murine placental tissue

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Wenjuan; Huang, Hui; Wang, Yanfei [Biochemistry Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T. (Hong Kong); Wong, Tsz Yan [Food and Nutritional Sciences Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T. (Hong Kong); Wang, C.C. [Department of Obstetrics and Gynecology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T. (Hong Kong); Leung, Lai K., E-mail: laikleung@cuhk.edu.hk [Biochemistry Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T. (Hong Kong); Food and Nutritional Sciences Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T. (Hong Kong)

    2013-06-01

    Bisphenol A is utilized to make polycarbonate plastics and is an environmental pollutant. Recent research has indicated that it is an endocrine disruptor and may interfere with reproductive processes. Our lab has previously shown that bisphenol A could regulate corticotrophin releasing hormone and aromatase in cultured placental cells. In the present study, the effect of bisphenol A on these two genes in the placenta was investigated in mice. Pregnant ICR mice were gavaged with bisphenol A at 2, 20 and 200 mg/kg body weight/day from E13 to E16 and were euthanized at E17. Compared to the control mice, increased plasma estrogen and corticotrophin releasing hormone were observed in bisphenol A-treated mice. Messenger RNA quantification indicated that placental crh but not cyp19 was induced in mice treated with bisphenol A. Tracking the related signaling pathway, we found that protein kinase C ζ/λ and δ were activated in the placentas of bisphenol A-treated mice. As the gene promoter of crh contains CRE and the half site of ERE, either phospho-PKC or estrogen could stimulate the gene transactivation. These results indicate that bisphenol A might increase plasma concentrations of estradiol, testosterone, corticotrophin releasing hormone and placental phospho-PKC ζ/λ and δ in mice. Ultimately, the incidence of premature birth in these mice could increase. - Highlights: • The pollutant bisphenol A differentially activated PKC isoforms in the placenta. • CRE-binding activity in the nuclear protein of placenta was increased. • Bisphenol A induces CRH mRNA expression in mice.

  8. MIDAS: Mining differentially activated subpaths of KEGG pathways from multi-class RNA-seq data.

    Science.gov (United States)

    Lee, Sangseon; Park, Youngjune; Kim, Sun

    2017-07-15

    Pathway based analysis of high throughput transcriptome data is a widely used approach to investigate biological mechanisms. Since a pathway consists of multiple functions, the recent approach is to determine condition specific sub-pathways or subpaths. However, there are several challenges. First, few existing methods utilize explicit gene expression information from RNA-seq. More importantly, subpath activity is usually an average of statistical scores, e.g., correlations, of edges in a candidate subpath, which fails to reflect gene expression quantity information. In addition, none of existing methods can handle multiple phenotypes. To address these technical problems, we designed and implemented an algorithm, MIDAS, that determines condition specific subpaths, each of which has different activities across multiple phenotypes. MIDAS utilizes gene expression quantity information fully and the network centrality information to determine condition specific subpaths. To test performance of our tool, we used TCGA breast cancer RNA-seq gene expression profiles with five molecular subtypes. 36 differentially activate subpaths were determined. The utility of our method, MIDAS, was demonstrated in four ways. All 36 subpaths are well supported by the literature information. Subsequently, we showed that these subpaths had a good discriminant power for five cancer subtype classification and also had a prognostic power in terms of survival analysis. Finally, in a performance comparison of MIDAS to a recent subpath prediction method, PATHOME, our method identified more subpaths and much more genes that are well supported by the literature information. http://biohealth.snu.ac.kr/software/MIDAS/. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Bisphenol A differentially activates protein kinase C isoforms in murine placental tissue

    International Nuclear Information System (INIS)

    Tan, Wenjuan; Huang, Hui; Wang, Yanfei; Wong, Tsz Yan; Wang, C.C.; Leung, Lai K.

    2013-01-01

    Bisphenol A is utilized to make polycarbonate plastics and is an environmental pollutant. Recent research has indicated that it is an endocrine disruptor and may interfere with reproductive processes. Our lab has previously shown that bisphenol A could regulate corticotrophin releasing hormone and aromatase in cultured placental cells. In the present study, the effect of bisphenol A on these two genes in the placenta was investigated in mice. Pregnant ICR mice were gavaged with bisphenol A at 2, 20 and 200 mg/kg body weight/day from E13 to E16 and were euthanized at E17. Compared to the control mice, increased plasma estrogen and corticotrophin releasing hormone were observed in bisphenol A-treated mice. Messenger RNA quantification indicated that placental crh but not cyp19 was induced in mice treated with bisphenol A. Tracking the related signaling pathway, we found that protein kinase C ζ/λ and δ were activated in the placentas of bisphenol A-treated mice. As the gene promoter of crh contains CRE and the half site of ERE, either phospho-PKC or estrogen could stimulate the gene transactivation. These results indicate that bisphenol A might increase plasma concentrations of estradiol, testosterone, corticotrophin releasing hormone and placental phospho-PKC ζ/λ and δ in mice. Ultimately, the incidence of premature birth in these mice could increase. - Highlights: • The pollutant bisphenol A differentially activated PKC isoforms in the placenta. • CRE-binding activity in the nuclear protein of placenta was increased. • Bisphenol A induces CRH mRNA expression in mice

  10. Evaluation of the differential energy distribution of systems of non-thermally activated molecules

    International Nuclear Information System (INIS)

    Rogers, E.B.

    1986-01-01

    A non-thermally activated molecule may undergo pressure dependent deactivation or energy dependent decomposition. It should be possible to use the pressure dependent stabilization/decomposition yields to determine the energy distribution in non-thermal systems. The numerical technique of regularization has been applied to this chemical problem to evaluate this distribution. The resulting method has been tested with a number of simulated distributions and kinetic models. Application was then made to several real chemical systems to determine the energy distribution resulting from the primary excitation process. Testing showed the method to be quite effective in reproducing input distributions from simulated data in all test cases. The effect of experimental error proved to be negligible when the error-filled data were first smoothed with a parabolic spline. This method has been applied to three different hot atom activated systems. Application to 18 F-for-F substituted CH 3 CF 3 generated a broad distribution extending from 62 to 318 kcal/mol, with a median energy of 138 kcal/mol. The shape of this distribution (and those from the other applications) indicated the involvement of two mechanisms in the excitation process. Analysis of the T-for-H substituted CH 3 CH 2 F system showed a more narrow distribution (56-218 kcal/mol) with a median energy of 79.8 kcal/mol. The distribution of the T-for-H substituted CH 3 CH 2 Cl system, extending from 54.5 to 199 kcal/mol was seen to be quite similar. It was concluded that this method is a valid approach to evaluating differential energy distributions in non-thermal systems, specifically those activated by hot atom substitution

  11. Anti-oxidation activity of different types of natural Cordyceps sinensis and cultured Cordyceps mycelia.

    Science.gov (United States)

    Li, S P; Li, P; Dong, T T; Tsim, K W

    2001-05-01

    Cordyceps, one of the well-known traditional Chinese medicines, consists of the dried fungus Cordyceps sinensis growing on the larva of the caterpillar. It is commonly used for the replenishment of body health. One of the known pharmacological effects is its anti-oxidation activity. However, there is a great variation of the quality in different sources of Cordyceps. Here, the water extracts of various sources of natural C. sinensis and cultured Cordyceps mycelia were analyzed for their anti-oxidation activity by using three different assay methods such as the xanthine oxidase assay, the induction of hemolysis assay and the lipid peroxidation assay. The results showed that Cordyceps, in general, possesses a strong anti-oxidation activity in all assays tested. However, both natural and cultured Cordyceps showed the lowest inhibition in the lipid peroxidation when compared with the other two assay methods. The cultured Cordyceps mycelia had equally strong anti-oxidation activity as compared to the natural Cordyceps. Besides, the anti-oxidation activities were increased to 10-30 folds in the partially purified polysaccharide fractions from the cultured Cordyceps mycelia, which suggested that the activity could be derived partly from Cordyceps polysaccharides.

  12. Biglycan deficiency increases osteoclast differentiation and activity due to defective osteoblasts

    DEFF Research Database (Denmark)

    Bi, Yanming; Nielsen, Karina L; Kilts, Tina M

    2006-01-01

    to be independent of the differential production of soluble RANKL and OPG and, instead, due to a decrease in osteoblast maturation accompanied by increase in osteoblastic proliferation. In addition to the imbalance between differentiation and proliferation, there was a differential decrease in secretory leukocyte......Bone mass is maintained by a fine balance between bone formation by osteoblasts and bone resorption by osteoclasts. Although osteoblasts and osteoclasts have different developmental origins, it is generally believed that the differentiation, function, and survival of osteoclasts are regulated...... by osteogenic cells. We have previously shown that the extracellular matrix protein, biglycan (Bgn), plays an important role in the differentiation of osteoblast precursors. In this paper, we showed that Bgn is involved in regulating osteoclast differentiation through its effect on osteoblasts...

  13. Sensitivity to Disgust and Perceptions of Natural Bodies of Water and Watercraft Activities

    Science.gov (United States)

    Robert D. Bixler; Gwynn Powell

    2003-01-01

    A written 7-item self-report scale on sensitivity to disgust and participation in watercraft activities was administered to 450 seasonal park employees. Correlations indicate that nonparticipation in seven different watercraft sports was weakly related with reactions of disgust to contact with natural bodies of water (rpbis...

  14. Increase in natural killer cell activity during diethylcarbamazine treatment of patients with filariasis

    DEFF Research Database (Denmark)

    Pedersen, B K; Bygbjerg, Ib Christian; Svenson, M

    1987-01-01

    Two patients, one with Bancroftian filariasis and the other with onchocerciasis, and two healthy controls were treated with diethylcarbamazine (DEC). The natural killer (NK) cell activity of the two patients increased during DEC treatment to 2.5 and 2.8 times, respectively, while that of the cont...

  15. “Environmental Psychology” the mental benefits of physical activities in natural settings

    OpenAIRE

    De Dominicis, Stefano

    2017-01-01

    Practicing sports and physical activities has a huge positive impact on physiological and psychological wellbeing of individuals. Drawing from Environmental and Positive psychology, the idea presented in this paper highlight the even stronger psychological benefits related to training, exercising and playing sports in natural environments. Specifically, given their intrinsic characteristics, such contexts are more prone then urban environments to foster positive emotions, controlled cognition...

  16. Activating Metaphors: Exploring the Embodied Nature of Metaphorical Mapping in Political Discourse

    Science.gov (United States)

    Giovanelli, Marcello

    2016-01-01

    Metaphor is generally understood as the process of understanding one thing in terms of another. The activity described here is designed to make use of the principles of embodied cognition and meaning, and specifically the embodied nature of metaphor, to explore political discourse and communication. With high-school junior or senior students in…

  17. Hydrogen Adsorption on Activated Carbon an Carbon Nanotubes Using Volumetric Differential Pressure Technique

    Science.gov (United States)

    Sanip, S. M.; Saidin, M. A. R.; Aziz, M.; Ismail, A. F.

    2010-03-01

    A simple hydrogen adsorption measurement system utilizing the volumetri differential pressure technique has been designed, fabricated and calibrated. Hydroge adsorption measurements have been carried out at temperatures 298 K and 77 K on activate carbon and carbon nanotubes with different surface areas. The adsorption data obtained will b helpful in understanding the adsorption property of the studied carbon materials using th fundamentals of adsorption theory. The principle of the system follows the Sievert-type metho The system measures a change in pressure between the reference cell, R1 and the sample cell S1, S2, S3 over a certain temperature range. R1, S1, S2, and S3 having known fixed volume The sample temperatures will be monitored by thermocouple TC while the pressures in R1 an S1, S2, S3 will be measured using a digital pressure transducer. The maximum operatin pressure of the pressure transducer is 20 bar and calibrated with an accuracy of ±0.01 bar. Hig purity hydrogen is being used in the system and the amount of samples for the study is betwee 1.0-2.0 grams. The system was calibrated using helium gas without any samples in S1, S2 an S3. This will provide a correction factor during the adsorption process providing an adsorption free reference point when using hydrogen gas resulting in a more accurate reading of th adsorption process by eliminating the errors caused by temperature expansion effects and oth non-adsorption related phenomena. The ideal gas equation of state is applied to calculate th hydrogen adsorption capacity based on the differential pressure measurements. Activated carbo with a surface area of 644.87 m2/g showed a larger amount of adsorption as compared to multiwalled nanotubes (commercial) with a surface area of 119.68 m2/g. This study als indicated that there is a direct correlation between the amounts of hydrogen adsorbed an surface area of the carbon materials under the conditions studied and that the adsorption significant at 77

  18. Hydrogen Adsorption on Activated Carbon an Carbon Nanotubes Using Volumetric Differential Pressure Technique

    International Nuclear Information System (INIS)

    Sanip, S. M.; Saidin, M. A. R.; Aziz, M.; Ismail, A. F.

    2010-01-01

    A simple hydrogen adsorption measurement system utilizing the volumetric differential pressure technique has been designed, fabricated and calibrated. Hydrogen adsorption measurements have been carried out at temperatures 298 K and 77 K on activate carbon and carbon nanotubes with different surface areas. The adsorption data obtained will be helpful in understanding the adsorption property of the studied carbon materials using the fundamentals of adsorption theory. The principle of the system follows the Sievert-type method. The system measures a change in pressure between the reference cell, R1 and the sample cell S1, S2, S3 over a certain temperature range, R1, S1, S2, and S3 having known fixed volume. The sample temperatures will be monitored by thermocouple TC while the pressures in R1 an S1, S2, S3 will be measured using a digital pressure transducer. The maximum operating pressure of the pressure transducer is 20 bar and calibrated with an accuracy of ±0.01 bar. High purity hydrogen is being used in the system and the amount of samples for the study is between 1.0-2.0 grams. The system was calibrated using helium gas without any samples in S1, S2 an S3. This will provide a correction factor during the adsorption process providing an adsorption free reference point when using hydrogen gas resulting in a more accurate reading of the adsorption process by eliminating the errors caused by temperature expansion effects and other non-adsorption related phenomena. The ideal gas equation of state is applied to calculate the hydrogen adsorption capacity based on the differential pressure measurements. Activated carbon with a surface area of 644.87 m 2 /g showed a larger amount of adsorption as compared to multiwalled nanotubes (commercial) with a surface area of 119.68 m 2 /g. This study als indicated that there is a direct correlation between the amounts of hydrogen adsorbed an surface area of the carbon materials under the conditions studied and that the adsorption

  19. Natural products induce a G protein-mediated calcium pathway activating p53 in cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Ginkel, Paul R. van; Yan, Michael B. [UW Carbone Cancer Center, University of Wisconsin, Madison, WI 53792 (United States); Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792 (United States); Bhattacharya, Saswati [UW Carbone Cancer Center, University of Wisconsin, Madison, WI 53792 (United States); Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792 (United States); Department of Pediatrics, University of Wisconsin, Madison, WI 53792 (United States); Polans, Arthur S., E-mail: aspolans@wisc.edu [UW Carbone Cancer Center, University of Wisconsin, Madison, WI 53792 (United States); Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792 (United States); Kenealey, Jason D. [UW Carbone Cancer Center, University of Wisconsin, Madison, WI 53792 (United States); Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792 (United States); Department of Nutrition, Dietetics and Food Science, Brigham Young University, Provo, UT 84602 (United States)

    2015-11-01

    Paclitaxel, etoposide, vincristine and doxorubicin are examples of natural products being used as chemotherapeutics but with adverse side effects that limit their therapeutic window. Natural products derived from plants and having low toxicity, such as quercetin, resveratrol, epigallocatechin gallate and piceatannol, have been shown to inhibit tumor cell growth both in vitro and in pre-clinical models of cancer, but their mechanisms of action have not been fully elucidated, thus restricting their use as prototypes for developing synthetic analogs with improved anti-cancer properties. We and others have demonstrated that one of the earliest and consistent events upon exposure of tumor cells to these less toxic natural products is a rise in cytoplasmic calcium, activating several pro-apoptotic pathways. We describe here a G protein/inositol 1,4,5-trisphosphate pathway (InsP3) in MDA-MB-231 human breast cancer cells that mediates between these less toxic natural products and the release of calcium from the endoplasmic reticulum. Further, we demonstrate that this elevation of intracellular calcium modulates p53 activity and the subsequent transcription of several pro-apoptotic genes encoding PIG8, CD95, PIDD, TP53INP, RRM2B, Noxa, p21 and PUMA. We conclude from our findings that less toxic natural products likely bind to a G protein coupled receptor that activates a G protein-mediated and calcium-dependent pathway resulting selectively in tumor cell death. - Highlights: • Natural products having low toxicity increase cytoplasmic calcium in cancer cells. • A G-protein/IP{sub 3} pathway mediates the release of calcium from the ER. • The elevation of intracellular calcium modulates p53 activity. • p53 and other Ca{sup 2+}-dependent pro-apoptotic pathways inhibit cancer cell growth.

  20. Natural products induce a G protein-mediated calcium pathway activating p53 in cancer cells

    International Nuclear Information System (INIS)

    Ginkel, Paul R. van; Yan, Michael B.; Bhattacharya, Saswati; Polans, Arthur S.; Kenealey, Jason D.

    2015-01-01

    Paclitaxel, etoposide, vincristine and doxorubicin are examples of natural products being used as chemotherapeutics but with adverse side effects that limit their therapeutic window. Natural products derived from plants and having low toxicity, such as quercetin, resveratrol, epigallocatechin gallate and piceatannol, have been shown to inhibit tumor cell growth both in vitro and in pre-clinical models of cancer, but their mechanisms of action have not been fully elucidated, thus restricting their use as prototypes for developing synthetic analogs with improved anti-cancer properties. We and others have demonstrated that one of the earliest and consistent events upon exposure of tumor cells to these less toxic natural products is a rise in cytoplasmic calcium, activating several pro-apoptotic pathways. We describe here a G protein/inositol 1,4,5-trisphosphate pathway (InsP3) in MDA-MB-231 human breast cancer cells that mediates between these less toxic natural products and the release of calcium from the endoplasmic reticulum. Further, we demonstrate that this elevation of intracellular calcium modulates p53 activity and the subsequent transcription of several pro-apoptotic genes encoding PIG8, CD95, PIDD, TP53INP, RRM2B, Noxa, p21 and PUMA. We conclude from our findings that less toxic natural products likely bind to a G protein coupled receptor that activates a G protein-mediated and calcium-dependent pathway resulting selectively in tumor cell death. - Highlights: • Natural products having low toxicity increase cytoplasmic calcium in cancer cells. • A G-protein/IP 3 pathway mediates the release of calcium from the ER. • The elevation of intracellular calcium modulates p53 activity. • p53 and other Ca 2+ -dependent pro-apoptotic pathways inhibit cancer cell growth.

  1. Differentially expressed genes linked to natural variation in long-term memory formation in Cotesia parasitic wasps

    NARCIS (Netherlands)

    Vugt, van J.J.F.A.; Hoedjes, K.M.; Geest, van de H.C.; Schijlen, E.G.W.M.; Vet, L.E.M.; Smid, H.M.

    2015-01-01

    Even though learning and memory are universal traits in the Animal Kingdom, closely related species reveal substantial variation in learning rate and memory dynamics. To determine the genetic background of this natural variation, we studied two congeneric parasitic wasp species, Cotesia glomerata

  2. Differentially expressed genes linked to natural variation in long-term memory formation in Cotesia parasitic wasps

    NARCIS (Netherlands)

    Van Vugt, Joke J. F. A.; Hoedjes, Katja M.; Van de Geest, Henri C.; Schijlen, Elio W. G. M.; Vet, Louise E. M.; Smid, Hans M.

    2015-01-01

    BACKGROUND: Even though learning and memory are universal traits in the Animal Kingdom, closely related species reveal substantial variation in learning rate and memory dynamics. To determine the genetic background of this natural variation, we studied two congeneric parasitic wasp species, Cotesia

  3. Asymmetric localization of natural antisense RNA of neuropeptide sensorin in Aplysia sensory neurons during aging and activity

    Directory of Open Access Journals (Sweden)

    Beena eKadakkuzha

    2014-04-01

    Full Text Available Despite the advances in our understanding of transcriptome, regulation and function of its noncoding components continue to be poorly understood. Here we searched for natural antisense transcript for sensorin (NAT-SRN, a neuropeptide expressed in the presynaptic sensory neurons of gill-withdrawal reflex of the marine snail Aplysia californica. Sensorin (SRN has a key role in learning and long-term memory storage in Aplysia. We have identified NAT-SRN in the central nervous system (CNS and have confirmed its expression by northern blotting and fluorescent RNA in situ hybridization. Quantitative analysis of NAT-SRN in micro dissected cell bodies and processes of sensory neurons suggest that NAT-SRN is present in the distal neuronal processes along with sense transcripts. Importantly, aging is associated with reduced levels of NAT-SRN in sensory neuron processes. Furthermore, we find that forskolin, an activator of CREB signaling, differentially alters the distribution of SRN and NAT-SRN. These studies reveal novel insights into physiological regulation of natural antisense RNAs.

  4. Asymmetric localization of natural antisense RNA of neuropeptide sensorin in Aplysia sensory neurons during aging and activity.

    Science.gov (United States)

    Kadakkuzha, Beena M; Liu, Xin-An; Narvaez, Maria; Kaye, Alexandra; Akhmedov, Komolitdin; Puthanveettil, Sathyanarayanan V

    2014-01-01

    Despite the advances in our understanding of transcriptome, regulation and function of its non-coding components continue to be poorly understood. Here we searched for natural antisense transcript for sensorin (NAT-SRN), a neuropeptide expressed in the presynaptic sensory neurons of gill-withdrawal reflex of the marine snail Aplysia californica. Sensorin (SRN) has a key role in learning and long-term memory storage in Aplysia. We have now identified NAT-SRN in the central nervous system (CNS) and have confirmed its expression by northern blotting and fluorescent RNA in situ hybridization. Quantitative analysis of NAT-SRN in micro-dissected cell bodies and processes of sensory neurons suggest that NAT-SRN is present in the distal neuronal processes along with sense transcripts. Importantly, aging is associated with reduction in levels of NAT-SRN in sensory neuron processes. Furthermore, we find that forskolin, an activator of CREB signaling, differentially alters the distribution of SRN and NAT-SRN. These studies reveal novel insights into physiological regulation of natural antisense RNAs.

  5. Differentiate responses of soil structure to natural vegetation and artificial plantation in landslide hazard region of the West Qinling Mountains, China

    Science.gov (United States)

    Wang, X.; Huang, Z.; Zhao, Y.; Hong, M.

    2017-12-01

    Natural vegetation and artificial plantation are the most important measures for ecological restoration in soil erosion and landslide hazard-prone regions of China. Previous studies have demonstrated that both measures can significantly change the soil structure and decrease soil and water erosion. Few reports have compared the effects of the two contrasting measures on mechanical and hydrological properties and further tested the differentiate responses of soil structure. In the study areas, two vegetation restoration measures-natural vegetation restoration (NVR) and artificial plantation restoration (APR) compared with control site, with similar topographical and geological backgrounds were selected to investigate the different effects on soil structure based on eight-year ecological restoration projects. The results showed that the surface vegetation played an important role in releasing soil erosion and enhance soil structure stability through change the soil aggregates (SA) and total soil porosity (TSP). The SArestoration and conservation in geological hazard-prone regions.

  6. Natural and anthropogenic radionuclide activity concentrations in the New Zealand diet.

    Science.gov (United States)

    Pearson, Andrew J; Gaw, Sally; Hermanspahn, Nikolaus; Glover, Chris N

    2016-01-01

    To support New Zealand's food safety monitoring regime, a survey was undertaken to establish radionuclide activity concentrations across the New Zealand diet. This survey was undertaken to better understand the radioactivity content of the modern diet and also to assess the suitability of the current use of milk as a sentinel for dietary radionuclide trends. Thirteen radionuclides were analysed in 40 common food commodities, including animal products, fruits, vegetables, cereal grains and seafood. Activity was detected for (137)Caesium, (90)Strontium and (131)Iodine. No other anthropogenic radionuclides were detected. Activity concentrations of the three natural radionuclides of Uranium and the daughter radionuclide (210)Polonium were detected in the majority of food sampled, with a large variation in magnitude. The maximum activity concentrations were detected in shellfish for all these radionuclides. Based on the established activity concentrations and ranges, the New Zealand diet contains activity concentrations of anthropogenic radionuclides far below the Codex Alimentarius guideline levels. Activity concentrations obtained for milk support its continued use as a sentinel for monitoring fallout radionuclides in terrestrial agriculture. The significant levels of natural and anthropogenic radionuclide activity concentrations detected in finfish and molluscs support undertaking further research to identify a suitable sentinel for New Zealand seafood monitoring. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Activation of peroxisome proliferator-activated receptor gamma bypasses the function of the retinoblastoma protein in adipocyte differentiation

    DEFF Research Database (Denmark)

    Hansen, Jacob B.; Petersen, R K; Larsen, B M

    1999-01-01

    The retinoblastoma protein (pRB) is an important regulator of development, proliferation, and cellular differentiation. pRB was recently shown to play a pivotal role in adipocyte differentiation, to interact physically with adipogenic CCAAT/enhancer-binding proteins (C/EBPs), and to positively...

  8. Natural products and biological activity of the pharmacologically active cauliflower mushroom Sparassis crispa.

    Science.gov (United States)

    Kimura, Takashi

    2013-01-01

    Sparassis crispa, also known as cauliflower mushroom, is an edible mushroom with medicinal properties. Its cultivation became popular in Japan about 10 years ago, a phenomenon that has been attributed not only to the quality of its taste, but also to its potential for therapeutic applications. Herein, I present a comprehensive summary of the pharmacological activities and mechanisms of action of its bioactive components, such as beta-glucan, and other physiologically active substances. In particular, the immunomodulatory mechanisms of the beta-glucan components are presented herein in detail.

  9. Natural Products and Biological Activity of the Pharmacologically Active Cauliflower Mushroom Sparassis crispa

    Directory of Open Access Journals (Sweden)

    Takashi Kimura

    2013-01-01

    Full Text Available Sparassis crispa, also known as cauliflower mushroom, is an edible mushroom with medicinal properties. Its cultivation became popular in Japan about 10 years ago, a phenomenon that has been attributed not only to the quality of its taste, but also to its potential for therapeutic applications. Herein, I present a comprehensive summary of the pharmacological activities and mechanisms of action of its bioactive components, such as beta-glucan, and other physiologically active substances. In particular, the immunomodulatory mechanisms of the beta-glucan components are presented herein in detail.

  10. Natural isothiocyanates express antimicrobial activity against developing and mature biofilms of Pseudomonas aeruginosa.

    Science.gov (United States)

    Kaiser, Stefan J; Mutters, Nico T; Blessing, Brigitte; Günther, Frank

    2017-06-01

    The antimicrobial properties of natural isothiocyanates (ITCs) found in plants such as nasturtium (Tropaeolum majus) and horseradish (Armoracia rusticana), and the need of new chemotherapeutic options for treatment of infections caused by multidrug-resistant and biofilm-forming Gram-negative bacteria such as Pseudomonas aeruginosa (Pa), led us to evaluate the effects of three major ITCs, allylisothiocyanate (AITC), benzylisothiocyanate (BITC), and phenylethyl-isothiocyanate (PEITC), and a mixture (ITCM) adapted to the ITC composition after release of active components out of natural sources. Out of 105Pa isolates 27 isolates with increased biofilm formation were selected for testing. The effects of ITCs on Pa were evaluated regarding (1) planktonic bacterial proliferation, (2) biofilm formation, (3) metabolic activity in mature biofilms, and (4) synergism of ITCs and antibiotics. (1) Each ITC had anti-Pa activity. Mean minimum inhibitory concentrations (MICs) were (μg/ml, mean±standard deviation): AITC 103±6.9; BITC, 2145±249; PEITC 29,423±1652; and ITCM, 140±5. (2) Treating bacteria with PEITC and ITCM in concentrations below the MIC significantly inhibited biofilm formation. Particularly, ITCM reduced biofilm mass and bacterial proliferation. (3) ITCs significantly inhibited metabolic activity in mature biofilms. (4) Combining ITCs with meropenem synergistically increased antimicrobial efficacy on Pa biofilms. ITCs represent a promising group of natural anti-infective compounds with activity against Pa biofilms. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Differential Cytotoxic Activity of Essential Oil of Lippia citriodora from Different Regions in Morocco.

    Science.gov (United States)

    Oukerrou, Moulay Ali; Tilaoui, Mounir; Mouse, Hassan Ait; Bouchmaa, Najat; Zyad, Abdelmajid

    2017-07-01

    The aim of this work was to investigate the cytotoxic effect of the essential oil of dried leaves of Lippia citriodora (H.B. & K.) harvested in different regions of Morocco. This effect was evaluated against the P815 murine mastocytoma cell line using the MTT assay. Interestingly, this work demonstrated for the first time that these essential oils exhibited a strong cytotoxic activity against the P815 cell line, with IC 50 values ranging from 7.75 to 13.25 μg/ml. This cytotoxicity began early and increased in a dose- and time-dependent manner. The chemical profile of these essential oils was analyzed by gas chromatography coupled to mass spectrometry. Importantly, the difference in terms of major components' contents was not significant suggesting probably that the differential cytotoxicity between these essential oils could be attributed to the difference in the content of these essential oils in minor compounds, which could interact with each other or with the main molecules. Finally, this study demonstrated for the first time that essential oils of L. citriodora from different regions in Morocco induced apoptosis against P815 tumor cell line. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

  12. miR-378 attenuates muscle regeneration by delaying satellite cell activation and differentiation in mice.

    Science.gov (United States)

    Zeng, Ping; Han, Wanhong; Li, Changyin; Li, Hu; Zhu, Dahai; Zhang, Yong; Liu, Xiaohong

    2016-09-01

    Skeletal muscle mass and homeostasis during postnatal muscle development and regeneration largely depend on adult muscle stem cells (satellite cells). We recently showed that global overexpression of miR-378 significantly reduced skeletal muscle mass in mice. In the current study, we used miR-378 transgenic (Tg) mice to assess the in vivo functional effects of miR-378 on skeletal muscle growth and regeneration. Cross-sectional analysis of skeletal muscle tissues showed that the number and size of myofibers were significantly lower in miR-378 Tg mice than in wild-type mice. Attenuated cardiotoxin-induced muscle regeneration in miR-378 Tg mice was found to be associated with delayed satellite cell activation and differentiation. Mechanistically, miR-378 was found to directly target Igf1r in muscle cells both in vitro and in vivo These miR-378 Tg mice may provide a model for investigating the physiological and pathological roles of skeletal muscle in muscle-associated diseases in humans, particularly in sarcopenia. © The Author 2016. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Profiles of Nature Exposure and Outdoor Activities Associated With Occupational Well-Being Among Employees

    Science.gov (United States)

    Hyvönen, Katriina; Törnroos, Kaisa; Salonen, Kirsi; Korpela, Kalevi; Feldt, Taru; Kinnunen, Ulla

    2018-01-01

    This research addresses the profiles of nature exposure and outdoor activities in nature among Finnish employees (N = 783). The profiles were formed on the bases of nature exposure at work and the frequency and type of outdoor activities in nature engaged in during leisure time. The profiles were investigated in relation to work engagement and burnout. The latent profile analysis identified a five-class solution as the best model: High exposure (8%), Versatile exposure (22%), Unilateral exposure (38%), Average exposure (13%), and Low exposure (19%). An Analysis of Covariance (ANCOVA) was conducted for each well-being outcome in order to evaluate how the identified profiles related to occupational well-being. Participants with a High, Versatile, or Unilateral exposure profile reported significantly higher work engagement in the dimensions of vigor and dedication than did the participants with a Low exposure profile. The participants with the High exposure profile also reported lower burnout in the dimensions of cynicism and professional inadequacy than the participants with the Low exposure profile. Nature exposure during the workday and leisure time is an under researched but important aspect in promoting occupational well-being. PMID:29867699

  14. Natural AMPK Activators: An Alternative Approach for the Treatment and Management of Metabolic Syndrome.

    Science.gov (United States)

    Sharma, Hitender; Kumar, Sunil

    2017-01-01

    This review covers recent discoveries of phytoconstituents, herbal extracts and some semi-synthetic compounds for treating metabolic syndrome with AMPK activation as one of their mechanisms of action. Recent researches have demonstrated AMPK activation to ameliorate multiple components of metabolic syndrome by regulating a balance between anabolic and catabolic cellular reactions. The review attempts to delineate the AMPK activation by natural agents from the perspective of its functional consequences on enzymes, transcription factors and signaling molecules and also on other potential factors contributing in the amelioration of metabolic syndrome. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Screening of medicinal natural extracts for their antibacterial activity against salmonella species

    International Nuclear Information System (INIS)

    Yousaf, A.; Latif, Z.

    2014-01-01

    The present study was aimed to screen out natural crude extracts exhibiting antibacterial activity against Salmonella causing gastrointestinal problems in humans. Fifteen Salmonella species were isolated from uncooked chicken, polluted water, rotten potatoes, beef, rotten eggs etc. Aqueous plant extracts of Allium sativum (garlic), Nigella sativa (kalvanji), Azadirachta indica (neem), Ficus carica (anjeer), and Trigonella foenum-graecum (methi) were checked against Salmonella species by well plate method. In addition to plant extract, Honey was also used for antibacterial activity. Inhibition zones ranging from 2mm to 20mm were obtained with different concentration of plant extracts and honey. The antibacterial sensitivity pattern was in the order of kalvanji > garlic > honey > anjeer > methi > neem. The standard antibiotics such as Ceftriaxone and Ciprofloxacin were also used for comparison with natural extract for antibacterial activity. The extracts of Allium sativum, Nigella sativa and Honey were found to be more effective against Salmonella species for which even Ceftriaxone was found ineffective. (author)

  16. Screening of medicinal natural extracts for their antibacterial activity against salmonella species

    Energy Technology Data Exchange (ETDEWEB)

    Yousaf, A.; Latif, Z. [University of the Punjab, Lahore (Pakistan). Dept. of Microbiology

    2014-12-15

    The present study was aimed to screen out natural crude extracts exhibiting antibacterial activity against Salmonella causing gastrointestinal problems in humans. Fifteen Salmonella species were isolated from uncooked chicken, polluted water, rotten potatoes, beef, rotten eggs etc. Aqueous plant extracts of Allium sativum (garlic), Nigella sativa (kalvanji), Azadirachta indica (neem), Ficus carica (anjeer), and Trigonella foenum-graecum (methi) were checked against Salmonella species by well plate method. In addition to plant extract, Honey was also used for antibacterial activity. Inhibition zones ranging from 2mm to 20mm were obtained with different concentration of plant extracts and honey. The antibacterial sensitivity pattern was in the order of kalvanji > garlic > honey > anjeer > methi > neem. The standard antibiotics such as Ceftriaxone and Ciprofloxacin were also used for comparison with natural extract for antibacterial activity. The extracts of Allium sativum, Nigella sativa and Honey were found to be more effective against Salmonella species for which even Ceftriaxone was found ineffective. (author)

  17. Investigation of coagulation activity of natural coagulants from seeds of different leguminose species

    Directory of Open Access Journals (Sweden)

    Šćiban Marina B.

    2005-01-01

    Full Text Available The ability of seeds of plants: Phaseolus vulgaris, Robinia pseudoacacia Ceratonia siliqua and Amorpha fruticosa, to act as natural coagulants was tested using synthetic turbid water. This water was prepared by adding kaolin into tap water, just before the test. Active components were extracted from ground seeds with distilled water. The coagulation ability of this extract was assessed by the use of standard jar test measurements in water with various initial turbidity. Investigation of these natural coagulants was confirmed their positive coagulation activity. Of all plants that have been examined, the seed extract from Ceratonia siliqua appeared to be one of the most effective coagulants for water treatment. A dose of 20 mg/l of this coagulant resulted in 100% coagulation activity for clarification of water with 17.5 NTU initial turbidity.

  18. Staurosporine induces ganglion cell differentiation in part by stimulating urokinase-type plasminogen activator expression and activation in the developing chick retina

    International Nuclear Information System (INIS)

    Kim, Yeoun-Hee; Chang, Yongmin; Jung, Jae-Chang

    2012-01-01

    Highlights: ► Staurosporine mediates stimulation of RGC differentiation in vitro cultured retinal neuroblasts. ► Staurosporine mediates uPA activation during RGC differentiation in vitro. ► Inhibition of uPA blocks the staurosporine mediated RGC differentiation both in vitro and in ovo. ► Thus, uPA may play a role in the staurosporine-mediated stimulation of RGC differentiation. -- Abstract: Here, we investigated whether staurosporine-mediated urokinase-type plasminogen activator (uPA) activation is involved in retinal ganglion cell (RGC) differentiation. Retinal cells were isolated from developing chick retinas at embryonic day 6 (E6). Relatively few control cells grown in serum-free medium started to form processes by 12 h. In contrast, staurosporine-treated cells had processes within 3 h, and processes were evident at 8 h. Immunofluorescence staining showed that Tuj-1-positive cells with shorter neurites could be detected in control cultures at 18 h, whereas numerous Tuj-1 positive ganglion cells with longer neuritic extensions were seen in staurosporine-treated cultures. BrdU-positive proliferating cells were more numerous in control cultures than in staurosporine-treated cultures, and the BrdU staining was not detected in post-mitotic Tuj-1 positive ganglion cells. Western blotting of cell lysates showed that staurosporine induced high levels of the active form of uPA. The staurosporine-induced uPA signal was localized predominantly in the soma, neurites and axons of Tuj-1-positive ganglion cells. Amiloride, an inhibitor of uPA, markedly reduced staurosporine-induced Tuj-1 staining, neurite length, neurite number, and uPA staining versus controls. In developing retinas in ovo, amiloride administration remarkably reduced the staurosporine-induced uPA staining and RGC differentiation. Taken together, our in vitro and in vivo data collectively indicate that uPA plays a role in the staurosporine-mediated stimulation of RGC differentiation.

  19. Natural variation in the VELVET gene bcvel1 affects virulence and light-dependent differentiation in Botrytis cinerea.

    Science.gov (United States)

    Schumacher, Julia; Pradier, Jean-Marc; Simon, Adeline; Traeger, Stefanie; Moraga, Javier; Collado, Isidro González; Viaud, Muriel; Tudzynski, Bettina

    2012-01-01

    Botrytis cinerea is an aggressive plant pathogen causing gray mold disease on various plant species. In this study, we identified the genetic origin for significantly differing phenotypes of the two sequenced B. cinerea isolates, B05.10 and T4, with regard to light-dependent differentiation, oxalic acid (OA) formation and virulence. By conducting a map-based cloning approach we identified a single nucleotide polymorphism (SNP) in an open reading frame encoding a VELVET gene (bcvel1). The SNP in isolate T4 results in a truncated protein that is predominantly found in the cytosol in contrast to the full-length protein of isolate B05.10 that accumulates in the nuclei. Deletion of the full-length gene in B05.10 resulted in the T4 phenotype, namely light-independent conidiation, loss of sclerotial development and oxalic acid production, and reduced virulence on several host plants. These findings indicate that the identified SNP represents a loss-of-function mutation of bcvel1. In accordance, the expression of the B05.10 copy in T4 rescued the wild-type/B05.10 phenotype. BcVEL1 is crucial for full virulence as deletion mutants are significantly hampered in killing and decomposing plant tissues. However, the production of the two best known secondary metabolites, the phytotoxins botcinic acid and botrydial, are not affected by the deletion of bcvel1 indicating that other factors are responsible for reduced virulence. Genome-wide expression analyses of B05.10- and Δbcvel1-infected plant material revealed a number of genes differentially expressed in the mutant: while several protease- encoding genes are under-expressed in Δbcvel1 compared to the wild type, the group of over-expressed genes is enriched for genes encoding sugar, amino acid and ammonium transporters and glycoside hydrolases reflecting the response of Δbcvel1 mutants to nutrient starvation conditions.

  20. Identifying group-sensitive physical activities: a differential item functioning analysis of NHANES data.

    Science.gov (United States)

    Gao, Yong; Zhu, Weimo

    2011-05-01

    The purpose of this study was to identify subgroup-sensitive physical activities (PA) using differential item functioning (DIF) analysis. A sub-unweighted sample of 1857 (men=923 and women=934) from the 2003-2004 National Health and Nutrition Examination Survey PA questionnaire data was used for the analyses. Using the Mantel-Haenszel, the simultaneous item bias test, and the ANOVA DIF methods, 33 specific leisure-time moderate and/or vigorous PA (MVPA) items were analyzed for DIF across race/ethnicity, gender, education, income, and age groups. Many leisure-time MVPA items were identified as large DIF items. When participating in the same amount of leisure-time MVPA, non-Hispanic blacks were more likely to participate in basketball and dance activities than non-Hispanic whites (NHW); NHW were more likely to participated in golf and hiking than non-Hispanic blacks; Hispanics were more likely to participate in dancing, hiking, and soccer than NHW, whereas NHW were more likely to engage in bicycling, golf, swimming, and walking than Hispanics; women were more likely to participate in aerobics, dancing, stretching, and walking than men, whereas men were more likely to engage in basketball, fishing, golf, running, soccer, weightlifting, and hunting than women; educated persons were more likely to participate in jogging and treadmill exercise than less educated persons; persons with higher incomes were more likely to engage in golf than those with lower incomes; and adults (20-59 yr) were more likely to participate in basketball, dancing, jogging, running, and weightlifting than older adults (60+ yr), whereas older adults were more likely to participate in walking and golf than younger adults. DIF methods are able to identify subgroup-sensitive PA and thus provide useful information to help design group-sensitive, targeted interventions for disadvantaged PA subgroups. © 2011 by the American College of Sports Medicine

  1. The discriminating nature of dopamine transporter image in parkinsonism: the competency of dopaminergic transporter imaging in differential diagnosis of parkinsonism {sup 123}I-FP-CIT SPECT study

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Bom Sahn; Jang, Sung June; Eo, Jae Seon; Park, Eun Kyung; Kim, Yu Kyeong; Kim, Jong Min; Lee, Won Woo; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2007-08-15

    The aim of this study was to evaluate the discriminating nature of {sup 123}I-FP-CIT SPECT in patients with parkinsonism. {sup 123}I-FP-CIT SPECT images acquired from the 18 normal controls; NC (60.4 {+-} 10.0 yr) and 237 patients with parkinsonism (65.9 {+-} 9.2 yr) were analyzed. From spatially normalized images, regional counts of the caudate, putamen, and occipital lobe were obtained using region of interest method. Binding potential (BP) was calculated with the ratio of specific to nonspecific binding activity at equilibrium. Additionally, the BP ratio of putamen to caudate (PCR) and asymmetric index (ASI) were measured. BPs of NC (3.37 {+-} 0.57, 3.10{+-} 0.41, 3.23 {+-} 0.48 for caudate, putamen, whole striatum, respectively) had no significant difference with those of essential tremor; ET (3.31 {+-} 0.64, 3.06 {+-} 0.61, 3.14 {+-} 0.63) and Alzheimer's disease; AD (3.33 {+-} 0.60, 3.29 {+-} 0.79, 3.31 {+-} 0.70), but were higher than those of Parkinson's disease; PD (1.92 {+-} 0.74, 1.39 {+-}0.68, 1.64 {+-} 0.68), multiple system atrophy; MSA (2.36 {+-} 1.07, 2.16 {+-} 0.91, 2.26 {+-} 0.96), and dementia with Lewy body; DLB (1.95{+-} 0.72, 1.64 {+-} 0.65, 1.79 {+-} 0.66)({rho} < 0.005). PD had statistically lower values of PCR and higher values of ASI than those of NC ({rho} < 0.005). And PD had significantly lower value of PCR, higher ASI and lower BP in the putamen and whole striatum than MSA ({rho} < 0.05). Dopamine transporter image of {sup 123}I-FP-CIT SPECT was a good value in differential diagnosis of parkinsonism.

  2. Angiocrine factors from Akt-activated endothelial cells balance self-renewal and differentiation of haematopoietic stem cells

    Science.gov (United States)

    Kobayashi, Hideki; Butler, Jason M.; O'Donnell, Rebekah; Kobayashi, Mariko; Ding, Bi-Sen; Bonner, Bryant; Chiu, Vi K.; Nolan, Daniel J.; Shido, Koji; Benjamin, Laura; Rafii, Shahin

    2010-01-01

    Endothelial cells establish an instructive vascular niche that reconstitutes haematopoietic stem and progenitor cells (HSPCs) through release of specific paracrine growth factors, known as angiocrine factors. However, the mechanism by which endothelial cells balance the rate of proliferation and lineage-specific differentiation of HSPCs is unknown. Here, we demonstrate that Akt activation in endothelial cells, through recruitment of mTOR, but not the FoxO pathway, upregulates specific angiocrine factors that support expansion of CD34−Flt3− KLS HSPCs with long-term haematopoietic stem cell (LT-HSC) repopulation capacity. Conversely, co-activation of Akt-stimulated endothelial cells with p42/44 MAPK shifts the balance towards maintenance and differentiation of the HSPCs. Selective activation of Akt1 in the endothelial cells of adult mice increased the number of colony forming units in the spleen and CD34−Flt3− KLS HSPCs with LT-HSC activity in the bone marrow, accelerating haematopoietic recovery. Therefore, the activation state of endothelial cells modulates reconstitution of HSPCs through the upregulation of angiocrine factors, with Akt–mTOR-activated endothelial cells supporting the self-renewal of LT-HSCs and expansion of HSPCs, whereas MAPK co-activation favours maintenance and lineage-specific differentiation of HSPCs. PMID:20972423

  3. Engineered Biomaterials Control Differentiation and Proliferation of Human-Embryonic-Stem-Cell-Derived Cardiomyocytes via Timed Notch Activation

    Directory of Open Access Journals (Sweden)

    Jason C. Tung

    2014-03-01

    Full Text Available For cell-based treatments of myocardial infarction, a better understanding of key developmental signaling pathways and more robust techniques for producing cardiomyocytes are required. Manipulation of Notch signaling has promise as it plays an important role during cardiovascular development, but previous studies presented conflicting results that Notch activation both positively and negatively regulates cardiogenesis. We developed surface- and microparticle-based Notch-signaling biomaterials that function in a time-specific activation-tunable manner, enabling precise investigation of Notch activation at specific developmental stages. Using our technologies, a biphasic effect of Notch activation on cardiac differentiation was found: early activation in undifferentiated human embryonic stem cells (hESCs promotes ectodermal differentiation, activation in specified cardiovascular progenitor cells increases cardiac differentiation. Signaling also induces cardiomyocyte proliferation, and repeated doses of Notch-signaling microparticles further enhance cardiomyocyte population size. These results highlight the diverse effects of Notch activation during cardiac development and provide approaches for generating large quantities of cardiomyocytes.

  4. Lipid-lowering Activity of Natural and Semi-Synthetic Sterols and Stanols.

    Science.gov (United States)

    Taha, Dhiaa A; Wasan, Ellen K; Wasan, Kishor M; Gershkovich, Pavel

    2015-01-01

    Consumption of plant sterols/ stanols has long been demonstrated to reduce plasma cholesterol levels. The objective of this review is to demonstrate the lipid-lowering activity and anti-atherogenic effects of natural and semi-synthetic plant sterols/ stanols based on evidence from cell-culture studies, animal studies and clinical trials. Additionally, this review highlights certain molecular mechanisms by which plant sterols/ stanols lower plasma cholesterol levels with a special emphasis on factors that affect the cholesterol-lowering activity of plant sterols/stanols. The crystalline nature and the poor oil solubility of these natural products could be important factors that limit their cholesterol-lowering efficiency. Several attempts have been made to improve the cholesterol-lowering activity by enhancing the bioavailability of crystalline sterols and stanols. Approaches involved reduction of the crystal size and/or esterification with fatty acids from vegetable or fish oils. However, the most promising approach in this context is the chemical modification of plant sterols /stanols into water soluble disodium ascorbyl phytostanyl phosphates analogue by esterification with ascorbic acid. This novel semi-synthetic stanol derivative has improved efficacy over natural plant sterols/ stanols and can provide additional benefits by combining the cholesterol-lowering properties of plant stanols with the antioxidant potential of ascorbic acid. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  5. Lifestyles and mental health status are associated with natural killer cell and lymphokine-activated killer cell activities.

    Science.gov (United States)

    Morimoto, K; Takeshita, T; Inoue-Sakurai, C; Maruyama, S

    2001-04-10

    We investigated the association of lifestyle and mental health status with natural killer (NK) cell and lymphokine-activated killer (LAK) cell activities in healthy males. NK cell activity was determined in 105 male workers and LAK cell activity was determined in 54 male workers. Peripheral blood was obtained from each subject and peripheral blood mononuclear cells (PBMC) were isolated from the blood. These PBMC were used as effector cells. LAK cells were generated by incubation of PBMC with interleukin-2 for 72 h. NK cell activity against NK-sensitive K562 cells and LAK cell activity against NK-resistant Raji cells were examined by 51Cr release assay. Overall lifestyles were evaluated according to the answers on a questionnaire regarding eight health practices (cigarette smoking, alcohol consumption, eating breakfast, hours of sleep, hours of work, physical exercise, nutritional balance, mental stress). Subjects with a good overall lifestyle showed significantly higher NK cell (P mental status had significantly lower NK cell activity than those who reported stable mental status. When subjects were divided into four groups by lifestyle and mental health status, subjects who had poor or moderate lifestyle and reported unstable mental status showed the lowest NK cell activity and subjects who had good lifestyle and reported stable mental status showed the highest NK cell activity among four groups.

  6. GDNF/GFRα1 Complex Abrogates Self-Renewing Activity of Cortical Neural Precursors Inducing Their Differentiation

    Directory of Open Access Journals (Sweden)

    Antonela Bonafina

    2018-03-01